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ZILELE INSTITUTULUI ONCOLOGIC „PROF. DR. ION CHIRICUŢĂ” CLUJ-NAPOCA 13 14 iunie 2014

REZUMATE

ABSTRACTS

Organizator Institutul Oncologic „Prof. Dr. Ion Chiricuţă” Cluj-Napoca

Președinte de onoare Alexandru Irimie

Comitet de Organizare Patriciu Achimaș Cadariu Ioana Berindan Neagoe Anca Burca Anca Bojan Cristian Nemeș Rodica Cosnarovici Cosmin Lisencu Ovidiu Coza Alexandru Eniu Vlad Schiţcu

Secretariat Catalin Vlad Monica Groza Laura Sabău Liliana Policiuc Claudia David Alexandra Tolnai Anca Salanţă

*În Volumul de rezumate sunt cuprinse lucrări ale căror titlu şi respectiv rezumat au fost predate secretariatului acestei manifestări ştiinţifice până la data menţionată în primul anunţ. Cele predate sau ajunse ulterior acestei date au fost publicate în măsura posibilităţilor tehnice.

Stimați colegi,

Stima ț i colegi, De 85 de ani Institutul Oncologic ”Prof.dr. Ion Chiricu ț ă din

De 85 de ani Institutul Oncologic ”Prof.dr. Ion Chiricuță din Cluj-Napoca” face toate eforturile pentru a reda speranța persoanelor care se confruntă cu afecțiunile oncologice, fiind unul dintre primele institute de acest gen din Europa. La ceas aniversar, avem deosebita onoare de vă invita să luați parte alături de noi la Zilele Institutului Oncologic ”Prof. Dr. Ion Chiricuţă”, o sărbătoare dedicată generațiilor medicale trecute, spre consolidarea celor prezente și deschiderea celor viitoare, totul în beneficiul pacienților

noștri. În acelaşi timp, IOCN este gazda unui eveniment internaţional de anvergură organizat în premieră în România - OECI (Organization of European Cancer Institutes) Oncology Days & General Assembly. Sub deviza ”Istorie, Tradiție, Profesionalism”, Zilele IOCN 2014 prezintă bilanțul ultimilor cinci ani și cuprinde Gala de Excelență, documentare în premieră, simpozioane științifice pe tema principalelor tipuri de tumori canceroase, precum și evenimente conexe dedicate presei, pacienților și publicului larg. Sperăm să fiți alături de noi în semn de solidaritate cu oncologia europeană, oncologia românească și cu persoanele pentru care luptăm în fiecare zi.

Vă așteptăm cu drag! Conf.dr. Patriciu Achimaș-Cadariu Manager Institutul Oncologic ”Prof.dr. Ion Chiricuță” Cluj-Napoca

drag! Conf.dr. Patriciu Achima ș -Cadariu Manager Institutul Oncologic ”Prof.dr. Ion Chiricu ț ă” Cluj -Napoca

Cuprins

CANCERUL MAMAR COMUNICĂRI ORALE

CANCERUL PULMONAR COMUNICĂRI ORALE

CANCERELE DIGESTIVE COMUNICĂRI ORALE POSTERE

CANCER ŞI DIABET COMUNICĂRI ORALE

CANCERELE GINECOLOGICE COMUNICĂRI ORALE

CANCERELE UROLOGICE COMUNICĂRI ORALE POSTERE

HEMATOLOGIE ŞI ONCOPEDIATRIE COMUNICĂRI ORALE POSTERE

DISCIPLINE FUNDAMENTALE COMUNICĂRI ORALE POSTERE

CANCERELE TIROIDIENE ŞI SFERA ORL COMUNICĂRI ORALE POSTERE

ANESTEZIE ŞI TERAPIE INTENSIVĂ COMUNICĂRI ORALE

ASISTENŢI COMUNICĂRI ORALE POSTERE

ISTORIA MEDICINII COMUNICARE ORALĂ

REZIDENŢI ŞI DOCTORANZI

COMUNICĂRI ORALE POSTERE

STUDENŢI

POSTERE

CANCERUL MAMAR

COMUNICĂRI ORALE

1. Hipertermia ca tratament al cancerului

Autori: Radu Tanasescu Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Rezumat:

Alaturi de metodele terapeutice standard, hipertermia si-a castigat un loc bine conturat in formele avansate si metastatice ale diverselor localizari maligne. La Institutul Oncologic “Ion Chiricuta” beneficiem de o instalatie de hipertermie prin microunde, care asigura penetrarea pana la o profunzime de 3-4 cm, ceea ce face posibil tratamentul tumorilor situate superficial (san, sfera ORL, cutanat etc). In lucrare este prezentata cazuistica personala a autorului, intre 2011-2013. Au fost tratati 221 pacienti, cancerul mamar fiind majoritar, cu 77 de paciente. Cei mai multi pacienti au beneficiat doar de hipertermie singura (124), asocierea hipertermie-radioterapie la 79 de pacienti iar asocierea cu chimioterapia a fost utilizata la 18 pacienti. S-au obtinut raspunsuri obiective importante, (complet-4%, partial-33% si stationar-46%) ceea ce recomanda aceasta metoda nu numai in tratamentul paliativ al cancerului, ci si integrarea sa in tratamentul curativ al formelor avansate locoregional.

2. Impact of boost dose on local control and survival in breast conserving therapy of early breast cancer: from theory to practice

Autori: Carmen Popa, Anamaria Sipos, Luca Abrudan, Radu Tanasescu, Daniela Martin Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie:

Rezumat:

3. Breast Angiosarcoma After Breast Cancer: 2 case experience;

Autori: C. Zlătescu, R. Elisei, F. Bogdan, M-A. Mureşan Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie:

Rezumat:

Background: Breast conserving therapy has become an important treatment option for primary breast cancer. Most patients undergo postoperative radiation therapy. Angiosarcoma arising in the irradiated breast is being reported with increasing frequency. It has been estimated to occur in 0.05- 0.2 % of patients treated with adjuvant radiotherapy after breast cancer. Methods: We reviewed the clinical history, treatment plans and followed 2 patients diagnosed in our service with Angiosarcoma of the breast. Both cases have arisen in patients treated with conservative surgery and adjuvant radiotherapy after primary breast cancer. Conclusions: Breast angiosarcoma is an aggressive tumor. This calls for vigilance regarding the skin changes in patients treated with breast conserving therapy. The aggressive nature of this tumor demands further investigation regarding therapy to control local recurrence.

4.

Molecular and cellular mechanisms of chemotherapy resistance in triple negative

breast cancer cells Autori: Oana Tudoran, Olga Soritau, Loredana Balacescu, Otilia Barbos, Roxana Cojocneanu- Petric, Ovidiu Balacescu, Ioana Berindan-Neagoe Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: microarray, triple negative breast cancer, cancer stem-like cells, treatment resistance

Rezumat:

Introduction: Breast cancer is the leading causes of cancer mortality in women worldwide. Triple negative breast tumors are characterized by an aggressive phenotype, develop at early ages and have the poorer prognosis and overall survival among the breast cancer subtypes. Therefore, efforts are being focused on describing the molecular mechanisms of therapy resistance with a view to identify new targeting strategies. Materials and methods: Triple negative MDA-MB-231 breast cancer cells and Estrogen/Progesteron positive MCF7 breast cancer cells were treated with doxorubicin and carboplatin and analyzed for changes in gene expression using whole human genome Agilent microarrays. The molecular and functional classification of the identified genes was done using Ingenuity Pathway Analysis software. Biological effects were measured in hanging drop and mammosphere assays to monitor the treatment influence on stem-like associated proprieties. Results: In triple negative MDA-MB-231 breast cancer cells, microarray analysis revealed transcriptional alterations of 5943 genes in response to doxorubicin and 1137 genes in response to carboplatin, while in ER, PR positive MCF 7 breast cancer cells, doxorubicin treatment induced changes in the expression of 3880 genes and carboplatin induced changes for 1740 genes. Functional analysis revealed that several of the altered genes are involved in stem cells related signaling. Both doxorubicin and carboplatin treatments affected the MCF7 cells ability to survive in anchorage independent growth conditions, while the MDA-MB-231 cells remained unaffected. Discussions and conclusions: In comparison to ER/PR positive breast cancer cells, our results suggest that one of the chemotherapy resistance mechanisms of triple negative breast cancer cells is through the modulation of stem cells signaling pathways to maintain survival and self- renewal.

5. Rolul imagisticii intervenţionale în patologia glandei mamare

Autori: Carmen Lisencu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

6. Evolution of some quality indicators of DCIS treatment in a decade at the Oncology

Institute „Prof Dr Ion Chiricuta” Cluj-Napoca Autori: Cosmin-Codruţ Nistor-Ciurba Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: DCIS, quality indicators, surgery Rezumat:

Evolution of DCIS treatment imposed quality indicators to measure the quality of both diagnostic and therapeutic procedures. In Europe the most used are EUSOMA (2010) Quality Indicators for DCIS treatment, which set standards for the diagnostic and therapeutic procedures involved in DCIS treatment. Our study analyses the evolution of quality indicators from international literature(1,2) in a 10 years period studying by comparison 2 series of DCIS’s treated in the Oncology Institute „Prof Dr Ion Chiricuta” Cluj – Napoca (IOCN) between 2000 2002 and 2010 1012.

Our results show statistic significant differences in improving quality indicators as: percent of DCIS’s smaller than 2 cm treated by conservative surgery, a mammogram no older than 6 months prior to surgery, cases referral to radiation-therapist, clear mention of dimensions, histological grade, nuclear grade hormonal receptors status and status of resection margins in pathologic reports. Our study also identifies cases treated by conservative surgery who skipped the radiation therapy due to the usage of VNPI (3) or due to refuse or inaccessibility of the treatment.

7. Molecular characterization of peripheral blood immunological profile of breast cancer

patients Autori: Oana Virtic 1 , Oana Tudoran 2 , Loredana Balacescu 2 , Gabriela Morar Bolba 2 , Ovidiu Balacescu 2 , Ioana Berindan-Neagoe 1,2 Instituţie: 1- Iuliu HatieganuUniversity of Medicine and Pharmacy, Cluj-Napoca 2- The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: breast cancer, cytokines, peripheral blood Rezumat:

Introduction: Breast cancer is the worldwide leading cause of cancers in female population. Current approaches of cancer treatment are oriented towards more effective targeted therapies. In order to understand the underlying pathogenic mechanisms of breast carcinogenesis and tumor progression we need to accomplish a better evaluation of the tumor microenvironment and its link to inflammation. Cytokines are key signaling molecules, released by immune cells that are involved in complex modulating inflammatory microenvironment responses to antitumor therapy. The aim of this study is to investigate a panel of pro-inflammatory mediators in the peripheral blood cells of patients with breast cancer with different response to the therapy. Materials and methods: Forty patients with two different subtypes of breast cancer were enrolled in this study. The two groups were defined by their prognosis according to their hormonal estrogen and progesterone receptors(ER, PR) expression in primary tumors at diagnosis, both groups lacking Her2 expression. Eighty-four genes including pro-inflammatory mediators, cytokines and chemokines were investigated in the peripheral blood circulating cells (PBCs) by PCR array. Data were analyzed with Web-designed software Cataloged and Custom Arrays for expression levels and IPA software for functional analysis. Molecular data were correlated with clinical-pathological characteristics. Results and discussions: We identified 15 genes that were significantly expressed between the two groups based on ER/PR expression. These genes are involved in regulating of inflammatory responses through cell-to-cell interactions and signaling. Likewise cytokines manifest pleiotropic actions with functions and implications in innate and adaptive immune responses. An association of molecular data with clinical and histopathological characteristics was established for both breast cancer subtypes. In conclusion, we believe that analyzing the immunobiological pathways of PBCs may yield important information data with impact for therapy and prognosis.

8. A survey of the needs of women suffering from breast cancer

Autori: Alexandra-Ana Tolnai, Florina Pop Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: cancer, psychosocial intervention, anxiety, depression, QOL Rezumat:

Introduction A lot of the patients diagnosed with breast cancer experience a myriad of psychological, medical and social challenges. Recent studies have showed that psychosocial problems are very common in patients throughout their treatment. Therefore, the aim of this paper is to configures a survey of the needs of women suffering from breast cancer and to propose psychosocial intervention strategies meant to improve their quality of life. Material and method: In all, 15 patients suffering from breast cancer agreed to participate in the survey. As such, they have completed the functional assessment of cancer therapy for breast

cancer (FACT-B) form, (Romanian version), and a 20 question questionnaire regarding their specific needs (NEQ) at the moment of its completion. Results: The FACT-B Trial Outcome Index (TOI) showed that 3 patients (20%) had a score of ≥72, 13 patients (86,67%) had a score of ≥48 and 2 patients (13,33%) had a score of <48. Moreover, the FACT-G total score showed that non of the respondents have a maximum of 108 score, but there were 3 (33,33%) patients that scored ≥81. Finally, the FACT-B total score showed that 5 patients (33,33%) had a score of ≥111, but non of them reached the maximum of 148. Discutions: The FACT-B is appropriate for use in oncology clinical trials, as well as in clinical practice. It demonstrates ease of administration, brevity, reliability, validity, and sensitivity to change. On the other hand, the NEQ showed that psychosocial strategies, if carried out on regular basis, proved their validity for the patients. Conclusion: Overall, psychosocial care during breast cancer treatment, as an important cure strategy, should be carried out in routine clinical practice. What is more, family support was the most important source of support for patients protecting them from psychological distress, anxiety and depression.

CANCERUL PULMONAR

COMUNICĂRI ORALE

1. Milestones in the management of lung cancer and treatment algorithm

Autori: Dana Iancu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

According to Globocan 2008, in Romania 70,300 new patients with cancer and 46,300 cancer deaths were eccountered.Lung cancer is most frequently in both men and women and remains the leading cause of death. Incidence of lung cancer was 10,384 new cases and mortality was 9,427 cases. The death rates are now falling because of declining cigarette smoking and more effective cancer management. The last 50 years have seen a real progress in the development of effective treatment for lung cancer with significant and meaningful improvements in both quantity and quality of life. The surgical techniques for resection have evolved; relationship between cigarette smoking and lung cancer has been defined; efficacy of chemotherapy in advanced lung cancer has been recognized; role of adjuvant therapy following resection has been established; identification and targeted treatment as well as identification and understanding of oncogenic drivers have become possible, a CT scan screening was recently introduced for early detection of disease. Due to this progress, the treatment algorithms were developed for both non small cell and small cell lung cancer.

2. Pulmonary resection in pulmonary tumors. Anesthetic management

Autori: Laura Săndoiu Instituţie: “Leon Daniello” Hospital, Cluj-Napoca, Cuvinte cheie: pulmonary cancer, anesthetic management, one lung ventilation, pulmonary resection, acute lung injury. Rezumat:

Pulmonary cancer incidence has increased alarmingly in recent decades. In Romania, pulmonary cancer showed a significant increase,occupied first place for men and 3rd place for women after the breast and uterus. Pulmonary cancer is a tumor that is extremely severe because clinical signs often appear late, evolving asmptomatic for a long period of time.At the time of diagnosis only one third of cases are found useful therapy . Pulmonary cancer is the leading indication for elective surgery in the field of thoracic surgery, often questionable in terms of possible therapeutic alternatives untill now. A resectable cancer patient of severe local neoplastic or loco-regional, can be operated with an acceptable risk. Should be kept in mind that only 13% of patients will benefit from a radical surgery and cure survival rate from the remaining 87 % with unfavorable outcome. Histopathological pulmonary cancer is divided into small pulmonary cell cancer of 20-25% or without small cell (squamous - adenocarcinoma with enlarge cell) 75-80 %, smoking is responsible for about 90 % of pathology. Small cell Cancer has survival rate of max.10 % of treatment because of limited to chemo / radiotherapy. Frequently is associated with paraneoplastic syndromes (SIADH, Chusing syndrome or miasteniform Eaton-Lambert syndrome). cancer without small cell has a five year survival rate after surgery in approximately 40 %. More primary thoracic carcinoid tumors are mostly benign , five year survival over 90% and pleural tumors ( malignant mesothelioma does not respond to treatment, interventions are risky and have an average survival rate of one year).

Responsibility of anesthesiologist before surgery is to check all preoperative investigations performed by pulmonologist and surgeon to establish perioperative risk, and to calculate the risk / benefits so that they can focus more resources on higher -risk patient.

3. The role of radiotherapy in modern treatment of lung cancer

Autori: Petronela Rusu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

The principles and role of Radiation Therapy for Lung Cancer are reviewed according to updated guidelines, the NCCN Guidelines version 3.2014, and ESMO Guidelines 2013. Radiotherapy has a potential role in all stages of NSCLC and SCLC and is definitive or palliative as part of multidisciplinary treatment. The appropriateness is made by board certified radiation oncologists who perform lung cancer radiotherapy as a part of their practice. The critical goals of modern RT are to maximize tumor control and to minimize treatment toxicity. Recommendations and techniques are reviewed for early stage, locally advanced and metastatic NSCLC, as well as for limited stage and extended stage SCLC. A minimum technologic standard is CT-planned 3D-CRT. More advanced technologies, which proved to reduce toxicity and improve survival in nonrandomized comparisons, include 4D- CT and/or PET-CT simulation, IMRT/VMAT, IGRT, motion management and proton therapy, which are also reviewed.

4. Maximum-tolerated dose reached with dose escalation using 3DCR

Autori: Petronela Petronela Rusu 1 , Tudor E. Ciuleanu 1,2 , Nicolae Todor 1 , Ioana Lupse 1 ,Tiberiu

Guttman 1 Instituţie: 1 The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca; 2 Iuliu HatieganuUniversity of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: locally advanced NSCLC, dose escalation 3DCRT, concurrent chem Rezumat:

Purpose: In order to improve local and distant control, we aimed to evaluate the maximum- tolerated dose (MTD) and efficacy of dose escalation using three-dimensional conformal Radiotherapy (3DCRT) in concurrent setting with vinorelbine (Vrb) and Cisplatin (DDP) or Carboplatin (CBDCA) in locally advanced non-small cell lung cancer (NSCLC), in a phase I-II study.

Patients and methods: 84 patients (pts) were included from 09.02.2005 to 05.11.2012 with median age 57.5 (41-74), M/F=77/7, PS 1/2=60/24, stage IIIA/IIIB=15/69, squamous cell carcinoma 66, adenocarcinoma 10, large cell carcinoma 3, “non-small” cell carcinoma 5. Pts who fulfilled the dose-volume histogram constraints underwent dose escalation of radiotherapy, if no more than two grade 3 or one grade 4 (non-hematological or hematological toxicities lasting more than 2 weeks or complicated with fever or bleeding) occurred, until MTD. If there were one grade 3 and one grade 4 toxicities, further expansion continued by 6 more pts. Chemotherapy consisted of 6 cycles of Vrb (25 mg/sqm, d1, 8, q21) and DDP (100 mg/sqm, d1, q21), or CBDCA (AUC 5, d1, q21). In concurrent setting, doses were reduced: Vrb 15 mg/sqm, d1, 8, q21, DDP 80 mg/sqm, d1, q21 or CBDCA AUC 4, d1, q21. Results: 69 pts underwent dose escalation in nine cohorts from 64Gy to 80Gy. For each dose level up to 7 pts were enrolled, with further expansion by 6 pts at 70 Gy dose level, as one grade 3 pulmonary toxicity and one grade 4 neutropenia lasting more than two weeks occurred. At the 80 Gy dose level, one grade 3 esophagitis and two grade 3 pulmonary toxicities occurred, so the MTD was set at 78Gy. Severe acute grade 3 and 4 toxicities were: esophagitis 6%, pulmonary toxicity 12%, digestive toxicity 4%, neutropenia 17% of the pts.

The phase II portion of the study was delayed after detailed evaluation of the late toxicities. So far, severe late esophageal adverse events occurred in 5 pts (7%), grade 3 pulmonary fibrosis in 8 pts (12%), myocardial infarction in 1 pts, fatal hemoptysis in 4 pts (6%), at a time when progression of the disease occurred. Objective response rate was 78%. With a median follow-up of 26.5 months, median survival was 27.6months the 1 and 2.5-year survival rates were 87% and 46% ( CI 34%- 59%). Progression free survival at 1 year was 68%, at 2.5 years 26% (CI: 17%-39%) and mTTP 14.7 months. Local-regional progression- free survival at 1 year was 84%, at 2.5 years 38% ( CI:

25%-52%).

Conclusions: MTD was reached during dose escalation and set at 78 Gy using 3D-CRT with concurrent Vrb and a platinum compound. RR and Survival data were promising in these cohorts, but late toxicities need further evaluation.

5. Translating lung cancer biology to the clinical setting

Autori: Claudia Burz Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie:

Rezumat:

Cancerul de plămân reprezintă o cauză importantă de deces prin cancer, adesea datorita stadiului avansat în care este diagnosticat. Prin studii de biologie moleculară se incearcă identiificarea indivizilor susceptibili de a dezvolta această neoplazie dar, și descifrarea mecanismelor moleculare responsabile de apariția fenotipului malign. Cele mai frecvente mutații genice identificate în cancerul de plămân afectează gena EGFR, K-RAS, BKL-ALK, Her2, BRAF, FGF1, VEGF, incidența lor fiind diferită în tipurile histopatologice cunoscute. Terapia individualizată prin administrarea unor produse care țintesc modificările genice este tot mai utilizată în managementul cancerului de plămân.

the

international lung cancer research scene. Autori: TE Ciuleanu, P Rusu, D Iancu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: NSCLC, SCLC, multicentre clinical studies Rezumat:

The purpose of this presentation is to review the involvement of the Institute of Oncology “Prof. Dr. Ion Chiricuță” Cluj Napoca (IOCN) in the active clinical research in lung cancer in the last 10 years. From 2004 to 2009, among 9129 patients included in selected prospective multicentric lung cancer phase II&III studies, where IOCN took part, 549 (6%) were treated at IOCN. The range of participation in different studies was among 2,2% and 39,2%. Briefly, the topics and results were as follows:

6. Presence

of

the

Institute

of

Oncology

“Prof.

Dr.

Ion

Chiricuţă”

on

NSCLC studies:

-demonstration of the benefit of adjuvant chemotherapy in prolonging survival (IALT study, NEJM, 974 citations). -survival benefit for erlotinib over placebo as rescue treatment (BR21 study, NEJM 2744 citations). -lack of benefit for gefitinib as rescue treatment in an unselected patient population (ISEL study, Lancet: 1146 citations). -demonstration of the predictive role of EGFR activating mutations for gefitinib response (J Clin Oncol, 454 citations). -value of maintenance therapy in NSCLC pts. for pemetrexed (JMEN study, Lancet: 388 citări) and erlotinib (SATURN study, Lancet Oncol: 359 citations), in terms of overall survival. -limited benefit for gemcitabine maintenance (CECOG study, Lung Cancer, 131 citations).

-equivalent efficacy for eroltinib versus docetaxel or pemetrexed in 2nd line treatment (TITAN study, Lancet Oncol: 43 citations). -no advantage for paclitaxel-poliglumex + platinum versus paclitaxel plus platinum as first line treatment (STELLAR 3 study, J Thorac Oncol: 52 citations). -no benefit adding cediranib to pacltaxel and carboplatin first line therapy (BR 24 study, J Clin Oncol: 97 citations). SCLC studies -survival benefit for oral topotecan vs best suportive care as rescue treatment (O’Brien study, J Clin Oncol: 143 citations). -25 Gy/ 10 fractions remains the standard prophylactic whole brain radiotherapy, less toxic and as efficient as higher doses (PCI 99-01 study, Lancet Oncol: 73 citations). -pemetrexed is inferior to etoposid, in combination with platinum as first line treatment in extended disease (J Clin Oncol: 43 citations). Conclusions: The participation of IOCN to multicentric clinical studies was active and consistent. Some of these trials resulted in the first time registration of new molecules (such as erlotinib, oral topotecan) or indications (maintenance for pemetrexed and erlotinib) or decisively contributed to the acceptance by the medical community of a new treatment strategy (such as adjuvant and maintenance chemotherapy in NSCLC, second line treatment in SCLC).

CANCERELE DIGESTIVE

COMUNICĂRI ORALE

1. MRI evaluation in rectal cancer

Autori: C. Popiţa¹´², Anca-Raluca Popiţa¹´², Ramona Boja², Adina Andrei² Instituţie: 1 – The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca 2 Phoenix Diagnostic Clinic, Cluj-Napoca, Romania Cuvinte cheie: Magnetic Resonance, rectal cancer, pelvic MRI Rezumat:

Rectal cancer is a common malignancy, representing one of the most common causes of cancer death. The subsequent evolution of patients is variable, local pelvic recurrence after surgical resection being a negative prognostic factor. The success rate of surgical excision depends on the accuracy of staging.

Studies to date have indicated that the assessment of tumor invasion of perirectal fat and of the mesorectal fascia are important factors for the T staging and for choosing the optimal treatment plan.

Due to the high contrast resolution, magnetic resonance imaging (MRI) is nowadays increasingly used to assess operability and to determine which of the patients will be treated surgically and which will require adjuvant radiotherapy. In this paper we present MRI findings encountered in patients with rectal cancer, at initial staging. The MRI exams were performed on a Siemens Avanto 1.5 T unit in the Phoenix Diagnostic Clinic, in Cluj-Napoca. The protocol used for evaluating the patients included T2-weighted sequences - in the long axis of the tumor and perpendicular to the longitudinal axis of the tumor - diffusion sequence with ADC map and T1 sequences before and after administration of contrast material. The histopathological confirmation of the rectal cancer was obtained in all patients included in the study. We correlated the MRI findings with the surgical and histopathologic data. Magnetic Resonance is an examination that allows reproducible assessment of surgical circumferential resection margins and extramural tumor extension. Pelvic MRI is used increasingly frequently in the preoperative staging of rectal cancer, as its accuracy allows choosing the appropriate therapeutic approach.

2. Morphopathological prognostic factors in rectal cancer. The experience of a tertiary

oncology center. Autori: C. Vlad, P. Achimaş-Cadariu, C. Lisencu, E. Puscas, F. Ignat, T. Criste, A. Oltean, A. Irimie Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: rectal cancer, prognostic factors, TNM stage, lymphatic invasion, perineural invasion. Rezumat:

Introduction: Despite the progresses of genetics and mollecular biology in the last decades, morphopatologic factors remain primordial in the prognosis of colorectal cancer. This study evaluates the most important morphopatologic prognostic factors and the link with rectal cancer. Material and method: We have retrospectively analyzed a group of 317 patients with rectal cancer resected at The Oncology Institute ”Prof. Dr. Ion Chiricuţă” Cluj-Napoca (IOCN), between January 2000 and December 2008. Patients data was statistically analyzed. Results: The 5-year overall survival rate was 55.6%. The univariated analysis revealed that all morphopathologic factors had a prognostic significance in rectal cancer, respectively the radial resection margin (p=0.038), TNM stage (p<0.001), ganglionary insvasion (p<0.001), venous invasion (p=0.01), limphatic invasion (p<0.001), perineural invasion (p=0.014) şi degree of tumor

differentiation (p=0.019). Venous invasion is frequently associated with advanced disease stages, with high degree differentiation tumours and distant metastasis, and the lymphatic and perineural invasion is associated with relapse and positive nodes. The multivariate analysis revealed independent prognostic factors for global survival: tumor degree, (p = 0.0142), node invasion (p = 0.0135), venous invasion (p = 0.0174), limphatic invasion (p = 0.0001) and perineural invasion (p =

0.0082).

Conclusions: Apart from TNM stage and ganglionary insvasion, it was proved that venous, limphatic and perineural invasions are also prognostic factors in rectal cancer. It is necessary to identify an optimal therapeutic protocol according to all analyzed prognostic factors.

3. Rectal cancer extended to the adjacent anatomic structures: pathology features and

surgical implications Autori: R. Simescu 1,2 , O. Fabian 1,2 , M. Cazacu 1,2 , I. Domsa 3 , A. Zolog 3 , A. Mihailov 1,2 , G. Petre 1,2 , I. Simon 1,2 , T. Oniu 1,2 , C. Lungoci 1,2 , D. Deceanu 1,2 , R. Galasiu 1,2 , C. Radu 1,2 , V.

Muntean 1,2 Instituţie:

1 CF Clinical Hospital

2 “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca

3 CF Clinic Cluj-Napoca

Cuvinte cheie: rectal cancer, local extension, surgical treatment Rezumat:

Introduction: Surgery of rectal cancer invading adjacent structures (T4b) is still controversial. Morbidity and mortality subsequent to R0 resections (multi-organ resections or total pelvectomies) are considerable and often radio-chemotherapy and palliative surgery are the preferred options. Patients and method: Patients with rectal cancer extended to adjacent anatomical structures (T4b) were compared with patients without extra-rectal extension (T1-T4a) and with ones having serosal invasion (T4a). Information was drawn from a prospective database including operative protocols, specimen pathology findings and follow-up data. The study included only patients who had undergone elective surgery and whose database records were complete. Statistical analysis was performed with Microsoft Excel and OpenEpi. Rates were compared using the chi-square test; p values under 0,05 were considered statistically significant. Results: Over 10 years (2004-2013) 268 patients with recto-sigmoid and rectal cancer were

treated.

Of the 237 eligible patients, 52 had adjacent structures invasion (pT4b). 185 patients didn’t show extra-colic extension (pT1-pT4a), 30 of them had invasion in the serosa (pT4a). Compared with T1-T4a tumors, T4b had statistically significant venous invasion and low tumor grade; there were no significant differences regarding growth pattern, inflammatory infiltrate, lymph node metastases or lymphatic and perineural invasion. No statistically significant evidence was found between pT4b and pT4a groups. 43% of the pT4a and 38% of the pT4b cases were N0M0. For anterior rectal and abdomino-perineal resections there was no significant difference between the three groups of patients regarding type of resection performed (R0, R1 or R2), morbidity and immediate perioperative mortality. Morbidity in pT4b patients with total pelvectomies was significantly increased. Conclusions: Rectal tumors extended to adjacent structures show a locally and regionally increased invasion pattern. Multiorgan R0 resections are justified whenever perioperative morbidity and mortality can be maintained within acceptable ranges. Regarding T4bN0M0 cases, R0 resection should be performed in all patients with good operative risk.

4.

Tailoring treatment in rectal cancer

Autori: Alina-Simona Muntean Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: radiochemotherapy, chemotherapy, rectal cancer, prognostic factors Rezumat:

Overview : Rectal cancer treatment was improved in the last five decades. Surgery and chemo (radiotherapy) remain the key elements of multimodality management of locally advanced rectal adenocarcinoma (LARC). Improvement in surgical techniques with implementation of total mesorectal excision (TME) dropped the local recurrence to 10-15% vs 50% in blunt dissection era. Also, radiotherapy alone or combined with chemotherapy resulted in improvement of locoregional control, but no differences in overall survival were reported. The optimum sequence of surgery, combined modality treatment, radiotherapy and induction or adjuvant chemotherapy has been addressed in several trials with the aim of reducing local failure and increase overall survival. In 1990, National Institute of Health Consensus Conference established adjuvant 5 FU- based radiotherapy as standard of care in patients with pT3, T4 N0 or any T and positive lymph nodes. After 15 years, German Rectal trial CAO/ARO/AIO -94 demonstrated that preoperative chemoradiotherapy (CRT) is better than postoperative therapy in terms of local control (6% vs 13%, p= 0,006), acute toxicity ( 27% vs 40%, p=0.001), chronic toxicity ( 14% vs 24%, p=0,012), sphincter sparing surgery in patients judged initially to require an abdomino-perineal resection (39% vs 19%, p=0,005). Due to these results, preoperative concomitent chemoradiotherapy was established as standard of care in LARC. Four randomized phase III trials have added oxaliplatin to 5-FU or to capecitabine based preoperative radiotherapy. Three of these trials demonstrates that oxaliplatin does not improve the endpoints of these studies : pathologic response rate, sphincter preservation and disease-free survival but increases the toxicity and concluded that oxaliplatin has no role in preoperative combined modality treatment. The next step is to identify and to select patients for ideal treatment who must be adapted to the tumor location, stage and to the individual patient's risk factors. The option of nonoperative therapy in patients with pCR particularly in patients with distal rectal cancers who required an abdominoperineal resection and permanent colostomy, assure a better quality of life. However the majority of local recurrences occur in the first 3 years after treatment, therefore a close surveillance and longer follow-up is needed. The selective use of chemoradiotherapy is also investigated in patients treated with induction chemotherapy. Preoperative chemoradiotherapy is the current standard, but to apply these treatment to all patients with stage II / III needs to be examined in perspective. Avoiding radiotherapy or surgery remains investigational and are the endpoints of phase II/III trials.

5. Predictors of response to neoadjuvant induction chemotherapy and chemoradiation in

rectal cancer. A prospective observational study. Autori: Fekete Zsolt 1,2 , Muntean Alina 2 , Irimie Alexandru 1,2 , Hica Ştefan 1 , Rancea Alin 1,2, Resiga Liliana 2 , Nagy Viorica Magdalena 1,2

Instituţie: 1. “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca 2. The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: rectal adenocarcinoma, chemoradiation, down-staging, prognostic factors Rezumat:

Introduction: The purpose of this prospective study was to analyze the prognostic factors associated with a good response to induction chemotherapy and chemoradiation in the neoadjuvant treatment of locally advanced rectal adenocarcinoma. Material and methods: Between 03/2011-10/2013 we have included 88 patients in the study. We have analyzed tumor and lymph node down-staging and the histological tumor response grade as defined by the 7th edition of the TNM staging of the AJCC.

Results: The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01) and higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05). TRG correlated with T-down-staging. Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). A smaller yN stage was encountered in 49/73 patients (67.1%); 10 patients (13.7%) had N0 both on the initial and post-CRT staging; 11 patients had stable N stage (15.1%) and 3 patients (4.4%) a higher N stage. Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Discussions: There are several factors which anticipate a suboptimal response to neoadjuvant treatment and intensification of the neoadjuvant protocol for patients with negative prognostic factors for down-staging worth consideration in well designed prospective studies. Conclusions: Almost 50% of patients had T-down-staging and 78% N-down-staging. The rate of complete response in this mixed cohort was 11%. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA and the number of Oxaliplatin cycles.

6. Locally advanced gastric cancer: pathological particularities and surgical implications

Autori: D. Constantinescu, O. Fabian, I. Domsa, A. Zolog, A. Mihailov, R. Toganel, F. Muresan, O. Cebotari, E. Patrut, V. Muntean Instituţie: Surgery IV Clinic, CF Clinical Hospital, Cluj-Napoca Cuvinte cheie: gastric cancer, locally advanced, surgical treatment Rezumat:

Introduction: Surgical treatment for locally advanced gastric cancer (T4) was limited for a long period to palliative resections. Association of radio-chemotherapy and identification of patients with a better prognosis among the T4 group, could sustain the therapeutic benefit of R0 resections and justify the increased perioperative morbidity and mortality. Patients and methods: Pathological examination and clinical data of patients with locally advanced gastric cancer (T4) were compared with data from patients with tumor extension limited to the stomach (T1-T3). Data were extracted from a prospective database, which includes operative and pathological reports, as well as postoperative follow up. The study included only patients with complete records, who underwent elective surgery. Statistical analysis was performed using Microsoft Excel an Open Epi. Frequencies were compared using Chi square test; p values under 0.05 were considered significant. Results: Over a period of 10 years (2004-2013) 248 patients with gastric cancer underwent surgical resection.

The study included 200 patients, 100 patients for each half of the above mentioned period (2004-2008, 2009-2013 respectively): 114 patients (92 / 22 from the first, respectively second period) were pT1-pT3, and 86 patients pT4 (8 / 78). Compared with T1-T3 tumors, T4 tumors had a better histological differentiation grade, while peritumoral inflammatory infiltrate and tumor necrosis were significantly reduced. Metastases in regional lymph nodes, lymphatic emboli and perineural invasion were significantly higher in T4 tumors compared with T1-T3; no significant differences regarding tumor growth pattern and venous tumor emboli were observed. There were no significant differences in pathological parameters between T4a and T4b tumors. Regarding the type of surgery, between 2009-2013 there were more D1+ and D2 lymphadenectomies performed, compared with 2004-2008 period (with a significantly higher number of resected lymphnodes), without a significant difference in the type of resection performed: R0, R1 or R2 (which could be explained by the higher number of locally advanced tumors resected during the second period). Perioperative morbidity was significantly increased in patients with T4b tumors and in patients who underwent D1+ or D2 lymphadenectomies, while immediate perioperative mortality remained unchanged. Conclusions: While perioperative mortality

and morbidity remain acceptable, multiorgan R0 resection and D1+ or D2 lymphadenectomy could bring a therapeutic benefit in selected patients with locally advanced gastric cancer with favorable biological characteristics of tumor growth

7. Modern Chemotherapy in stomach cancer after surgery

Autori: Cainap C, Muntean A, Lisencu C, Achimas P, Nagy V Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Rezumat:

Gastric cancer remains one of the most difficult tumour type despite his relative reduction of his global incidence, it remains on of the most deadly cancer. The latest advances in therapy of the gastric cancer ameliorate the results in terms of survival. In our study which is a prospective nonrandomised one, we enrolled 40 patients with gastric adenocarcinoma stage IB to IV (M0) who was operated, chemoradioterapy treated, but with the chemotherapy compound modified with ECX regimen(epirubicine, cisplatine, xeloda) which is now considered standard in metastatic setting. We report the toxicities and posible predictive factors to toxicity. The ECX regimen seems to be a reliable alternative to the clasic regimen with convienient toxicity and therapeutical index.

8. PanINs in chronic pancreatitis: to resect or not to resect?

Autori: S.T. Barbu, I. Domsa, M. Cazacu Instituţie: Univeristy of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca Cuvinte cheie: pancreatic cancer, precursor lesions, pancreatic intraepithelial neoplasia, chronic pancreatitis Rezumat:

Introduction: Although pancreatic intraepithelial neoplasia (PanIN) are well-documented precursor lesions of pancreatic cancer, there are few available data about their natural history and rate of progression. As PanIN3 is carcinoma “in situ” and evolves toward invasive ductal adenocarcinoma (IDC), such data would help to decide the surgical attitude when PanIN3 are found.

Methods: We describe herein a patient with PanIN3, in whom IDC manifested in the remnant pancreas 7.5 years after distal pancreatectomy for chronic pancreatitis (CP). We found 8 more documented cases in the literature. Furthermore, we analyzed 11 partial pancreatectomy samples from CP patients operated in our Clinic for the presence, grade and number of PanIN foci. Cases were graded by the highest PanIN grade focus identified. All patients were followed- up yearly, until December 2013, or last personal contact or death. Statistical PanIN correlations with clinical independent variables (age, sex, smoking, diabetes, alcohol consumption, calcifications, CP duration) were calculated. Results: In the 9 documented patients from the literature (including our patient) where PanIN3 was found in partial pancreatectomy specimens, IDC manifested in the pancreatic remnant 17 months to 29 years after surgery (mean = 8.85 years). In our 11 CP pancreatectomy samples, PanIN was present in 7 (58.4%). Pathology grading was PanIN1 in 4 (36.36%), PanIN2 in 2 (18.18%) and PanIN3 in 1 (9.1%). No other IDC developed on PanIN in 7.3 years mean follow-up. PanIN3 presence was correlated with advanced age and smoking more than 20 cigarettes/day for more than 10 years. Conclusion: PanIN is a frequent founding in advanced CP. Progression to IDC may take many years, pleading rather for a close follow-up than for total pancreatectomy in debilitated, malnourished, CP patients. To individualize indication for surgery, further studies are needed, looking for risk factors like molecular or genetic alterations that accelerate PanIN3 progression.

9.

Human bile contains microRNA-laden extracellular vesicles that can be used for

cholangiocarcinoma diagnosis Autori: Ciprian Tomuleasa, Ioana Berindan-Neagoe, Florin Selaru Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary Sclerosing Cholangitis (PSC) patients pose a particularly difficult clinical dilemma, since they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. Conclusion: We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers and size distribution of human biliary EVs. Utilizing Multivariate Organization of Combinatorial Alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis which demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 patients with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 patients with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility.

POSTERE

1. Pseudomyxoma peritonei: A Case Report and the Management of Disease

Autori: Ababneh Rami, Pompiliu Piso, Dumitrovici Anca, Burz Claudia Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Pseudomyxoma peritonei, cytoreductive surgery , HIPEC Rezumat:

Pseudomyxoma peritonei (PMP) is a rare condition characterized by intra abdominal extracellular gelatinous fluid collections and non-invasive mucinous implants on the peritoneum containing mucus-producing epithelium. This disease affecting 1 per million population with an estimated incidence of 2 cases per 10000 laparotomies, The etiology is a mucinous neoplasm, most often arising in the appendix. The treatment protocol for PMP focuses on cytoreductive surgery combined with intraperitoneal chemotherapy (more latterly hyperthermic intraperitoneal chemotherapy). We herein describe a case of pseudomyxoma peritonei diagnosed in a 44 year-old man. The patient was treated with aggressive Cytoreductive surgery in combination with intraoperative HIPEC and HITHOC followed by systemic chemotherapy, with good tolerability.

2.

Scintigraphy versus ultrasonography in assessment of liver tumors

Autori: Ioana Grigorescu 1 , Oliviu Pascu 2 , Radu Badea 2 , Zeno Spârchez 2 , Mircea Dragoteanu 2 ,

Cecilia Pîgleşan 2 , Dan Lucian Dumitraşcu 1 Instituţie:

1 II Medical Clinic. University of Medicine and Pharmacy “Iului Hatieganu” Cluj-Napoca,

2 Regional Institute for Gastroenterology and Hepatology “O. Fodor” Cluj-Napoca

Cuvinte cheie: Ultrasonography, scintigraphy, liver nodules Rezumat:

Aim: assessment of complementary contribution of the data offered by ultrasonography (US) and scintigraphy, in order to establish the positive and differential diagnosis of liver focal lesions, both in normal liver and in CLD (chronic liver diseases). Methods: 238 patients (23 having at the same time 2 different types of tumors) with 261 hepatic tumors, were evaluated by: grey-scale and DopplerUS, Scintigraphy; some patients underwent also: contrast-enhanced US (CEUS), Power-Doppler (PD), B-flow, hepatic angioscintigraphy (HAS) „in vivo”-labeled-RBC-SPECT. The final diagnosis was established after correlating US-scintigraphic data with other imaging methods (CT, MR), clinical, laboratory, intraoperatory and histological aspects. Results: Doppler-US revealed in 81.85% cases the classical criteria of hyperechoic, well defined mass without vascular signal. Gray-scale, Doppler-US and CEUS had high specificities (94,87%) in small hemangiomas in normal liver. CEUS established real positive diagnosis in 87.5%cases. Cavernous hemangiomas with non-enhancing central areas (central necrosis/ thrombosis/sclerosis) arised problems of differentiation with necrosis in malignancy. Similar did high-shunt-flow hemangiomas because of the hypoenhancement (late phase). False negative diagnosis of non-hemangiomatous tumor(n=5) might be explained by the correlation between fibrotic stage and presence of sclerosis; US-scintigraphic concordances were found in 68.83% hemangiomas, while non-concordances could be caused by: lack of scintigraphic performances in tumors<2cm, decreased rate of detectability of isoechoic+ deep seated lesions. Angioscintigraphy revealed a good correlation of tumoral volume and the increased HPI in hemangiomas (r=0.378 p=0.000) and FNH ( r=0.712 p=0.021). HPI≤45% suggests benign lesions but can be found also in metastatic carcinoids; higher HPI>45% were correlated with malignancy, but also with voluminous benign tumors (r=0,313; p=0.000). Conclusion: US and scintigraphy are complementary diagnostic methods, US representing the standard investigation for cysts, while HAS and labeled-RBC-SPECT are useful in hemangiomas and FNH. Atypical features require often further investigations (CT, MR or histology) to allow benign-malignant differentiation.

3. Tonic-Clonic Seizures During Chemotherapy Regimen in Gastric

Autori: Crinela Lupu, Blag Dorel, Burz Claudia Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: seizures, gastric cancer, chemotherapy Rezumat:

Due to late diagnosis, gastric cancer remains a severe disease, with a 5-year survival of 15% for all stages. Surgery is the only curative treatment. Radiotherapy and chemotherapy used as neoadjuvant or adjuvant regimens, alone or in combination, have yielded encouraging results. Regarding metastatic gastric cancer a slow but indisputable progress of palliative chemotherapyis observed. The main chemotherapy regimens used for the advanced stages of the disease are ECF (epirubicin, cisplatin, 5 fluorouracil), EOX (epirubicin, oxaliplatin, capecitabine), DCF (docetaxel, cisplatin, 5 fluorouracil), FOLFOX (5 fluorouracul, folinic acid, oxaliplatin), XELOX (oxaliplatin, capecitabine), with an inclination towards EOX due to low toxicity and overall survival improvement.

Chemotherapy is a systemic treatment which causes a large number and a variety of side effects to the body. The toxicity limits the dose and rate of cytostatic administration. In this study we report a case of a 34 year old patient, without a personal history of pathologic disease, who developed seizures after the 4th EOX cycle for gastric cancer. After eliminating other causes through cerebral CT and IRM scans, lumbar puncture and neurological examination, it was considered that the seizures were caused by the chemotherapeutic drugs Epirubicin or Oxaliplatin.

4. Central pancreatectomy with Roux en y duct to mucosa pancreatico-jejunostomy for

neuroendocrine tumor of the pancreatic body Autori: D. Munteanu, J.Serhal, P. Pădurean, Al. Munteanu, C. Iancu Instituţie: Regional Institute for Gastroenterology and Hepatology “O. Fodor”, Cluj Napoca Cuvinte cheie: pancreatic benign tumors, resection. Rezumat:

Background: To analyse and discuss the particularities, clinic-pathological features and technical aspects of a case of pancreatic body neuroendocrine tumor. Method: The case of a 54 years old caucasian female patient with a pancreatic body neuroendocrine tumor is discussed. Clinical features, intraoperative findings and technical solutions are debated on. Results: At a routine percutaneous abdominal ultrasound examination the suspicion of a 10 mm pancreatic body “cyst” was raised. A subsequend CT scan revealed a pancreatic body solid tumor, 10-11 mm in diameter, well delimited, with the imagistic features of a neuroendocrine tumor. After admittance in our institute, a further endosonography excluded the invasion of the adjacent vascular structures. Surgery has confirmed the diagnosis. A central pancreatectomy with bilateral 1 cm security margins and preservation of both splenic vein and artery was performed; the cephalic pancreatic stump was sutured after separate closure of the Wirsung duct. The left pancreatic body stump was termino-lateral anastomosed to a Roux en Y transmesocolic loop, in the duct-to-mucosa manner (Wirsung duct dilated 3-4 mm in diameter). The outcome was uneventful. Conclusions: -Central pancreatectomy the save procedure when well indicated; in neuroendocrine benign tumors that cannot be enucleated it allowes a significant pancreatic parenchyma preservation, as an alternative to a classic splenopancreatectomy of the entire tail and body of the gland, thus preventing exo- and endocrine pancreatic insufficiency; preservation of the spleen represents another important advantage. In cases with ductal dilation, duct-to-micosa pancreatico-jejunostomy offers very good long term functional results.

5. Neuroendocrine carcinoid tumor associated with right heart failure, treatment options.

A Case Report Autori: C. Radu, R. Simescu, G. Petre, V. Muntean Instituţie: CF Clinical Hospital, Department of Surgery, University of Medicine “Iuliu Haţieganu” Cluj-Napoca, Romania Cuvinte cheie: carcinoid tumors, carcinod syndrome, right heart failure, Sandostatin Rezumat:

Introduction: Carcinoid tumors are rare neuroendocrine tumors with hormonal patterns which differ depending on their site. Diagnosis is usually incidental. The carcinoid syndrome is the clinical expression of systemic release of bioactive proteins, such as serotonin or histamine. Right heart failure is common in patients with carcinoid syndrome, the left heart being protected by the pulmonary inactivation of serotonin. Patients and method: This is the case report of a 62 years old female patient with no surgical history or comorbidities, presenting diffuse abdominal pain, important weight loss, appetite loss, asthenia and facial flush. The patient had been incidentally diagnosed with hepatic lesions, which were biopsied revealing neuroendocrine tumor metastases. Subsequent investigations led to the diagnosis of a stage IV ascending colon neuroendocrine tumor with liver metastases, six months

prior to admission in the CF Clinical Hospital. The patient underwent two cycles of chemotherapy (Carboplatin with Etoposide) and was also administered Sandostatin (Octreotide). Abdominal and pelvic CT scan showed a para-caecal mass, multiple hepatic lesions and a moderate basic pleural effusion. In December 2013 a right hemicolectomy was performed. During surgery the patient had oscillating blood pressure and high pulmonary resistance to ventilation, both of which subsided after the administration of Sandostatin. Pathology analysis of the tumor described a neuroendocrine carcinoma G1, pT2N1M1L1V0. Post-operative the patient developed right heart failure which subsided after the administration of Sildenafil (Viagra 25 mg tid); central venous pressure oscillations and hyperglycemia normalized after administration of Sandostatin. Conclusion: In patients with neuroendocrine tumors and carcinoid syndrome the intraoperative hemodynamic instability and high respiratory resistance can be controlled with Sandostatin. Right heart failure due to high pulmonary pressure can be efficiently controlled with Sildenafil.

CANCERELE GINECOLOGICE

COMUNICĂRI ORALE

1) Raportul Unităţii Regionale de Nord-Vest de management al programului de screening pentru cancerul de col uterin rolul specialistului ginecolog Autori: Florian Al. Nicula, Alexandru Irimie, Patriciu Achimaș-Cadariu Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: screening, cancer de col uterin Rezumat:

În perioada 2002-20014, 1 din 2 din femeile din judeţul Cluj şi o medie de 2 din 10 femei din judeţele Regiunii NV cu vîrste cuprinse între 25-64 de ani ( 762.558), au beneficiat de teste gratuite Babeş-Papanicolaou în cadrul programelor de screening al cancerului de col uterin organizate de Unitatea de Management din cadrul Departamentului de Prevenire şi Control al Cancerului IOCN ( 75.568 teste în pilotul regional 2002-2008 şi 87.305 îm programul naţional 2012-2014 ). Toate aceste activităţi au creat o povară de prelevare de frotiuri (76% din totalul de frotiuri în pilotul regional 2002-2008 şi 66% în programul naţional 2012-2014) reţelei de ginecologie, la care s-a cumulat şi povara evaluării celor mult peste 10 mii de displazii înregistrate la registrul de screening, din care o mare parte au beneficiat de colposcopii, biopsii, tratamente şi urmăriri în timp ( activităţi suplimentare celor curative corespunzătoare numărului de peste 300 de cazuri noi de cancere de col uterin operabile anual înregistrate de Registrul de Cancer NV - 67% din total ). Medicul ginecolog are în programul de screening misiunea majoră de a asigura calitatea finalizării, motiv pentru care am diseminat protocoale specifice de evaluare, tratament şi urmărire în timp a displaziilor.

2) Evaluarea rezultatelor oncologice a tratamentului displaziilor agravate de col uterin sau carcinom microinvaziv printr-o tehnică mai simplă de conizaţie Autori: P. Achimas-Cadariu, C. Vlad, T. Criste, C. Lisencu, E. Puscas, F. Ignat, A. Irimie Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: displazii de col uterin, carcinom microinvaziv de col uterin, conizatie, rezultate oncologice. Rezumat:

Obiective: Obiectivele principale ale studiului de fata au constat in evaluarea rezultatelor oncologice, respectiv supravietuire si calitatea vietii, la pacientele cu displazii agravate de col uterin sau carcinoame microinvazive, tratate printr-o tehnică mai simplă de conizaţie (descrisa de Ostergard, Berman si Yee in Atlas of Gynecologic surgery). Material si metoda: Acest studiu retrospectiv a cuprins un numar de 211 paciente cu displazii agravate de col uterin sau carcinoame microinvazive, tratate chirurgical prin conizatie. Dintre acestea, un numar de 104 paciente au beneficiat de conizatie prin tehnica descrisa mai sus, iar 107 de conizatie prin tehnica Green. Au fost analizate durata interventiei chirurgicale, complicatiile, pierderea de sange, marginile de rezectie chirurgicala, rezultatele obstetricale, rata de recidiva. De asemenea, folosind chestionarul EORTC QOL-C30 si un model de ecuatie structurala, s-a evaluat si calitatea vietii (functia fizica, cognitiva, emotionala, sociala si sexuala) pacientelor luate in studiu. Rezultate: Nu au existat diferente semnificative statistic in ceea ce priveste rata complicatiilor (o stenoza cervicala in primul grup), intre cele 2 grupuri. Durata interventiei chirurgicale a fost semnificativ mai mica pentru noua tehnica (P<0.01), la fel ca si pierderea de sange. Din cele 104 paciente ce au beneficiat de prima tehnica a conizatiei, 11 au ramas insarcinate si au nascut 11 copii sanatosi. In ceea ce priveste recidiva, au existat doua paciente cu recidiva, ambele din primul grup, respectiv o pacienta cu tulpini HPV 16, 31 pozitive si o pacienta cu tulpini HPV 18, 31 pozitive.

Nu au existat diferente semnificative statistic in ceea ce priveste calitatea vietii intre cele doua grupuri de paciente. Concluzii: Tehnica mai simpla de conizatie pare fezabila, mai rapida din punct de vedere al duratei interventiei chirurgicale, iar in ceea ce priveste rezultatele oncologice, nu au existat diferente semnificative statistic intre cele doua grupuri de paciente, rezultatele fiind similare cu cele publicate in literatura de specialitate.

3) Progresses in the multidisciplinary treatment of cervical cancer at the Institute of Oncology “Prof. Ion Chiricuta” Autori: Viorica Nagy, Claudia Ordeanu, Ovidiu Coza, Alin Rancea, Alexandru Traila, Rares Buiga, Adriana Tudosescu, Nicolae Todor Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: cervical cancer, concomitant radiochemotherapy , surgery Rezumat:

Cervical cancer is the second most common malignancy in Institute of Oncology Cluj-

Napoca (IOCN), which explains the constant preoccupation of the institute’s specialists for improving results.

A randomized phase III trial carried out in the IOCN between 1999-2002, in which 566

patients were involved, proved the obvious superiority of cisplatin (CDDP)-based concomitant radiochemotherapy (RCT) versus radiotherapy alone (RT) (5-year-survival rate 74% vs 64%, p<0.05), and thus concomitant RCT became standard treatment for locally advanced cervical cancer in the institute. In 2003, a phase 3 randomized study was started in our institute, which proposed the comparison of two CDDP-based RCT regimens and in which 326 patients with stage IIB-IIIB cervical cancer were involved. The results demonstrate that RCT with cisplatin 20 mg/ m²x5 days

every 21 days, is superior regarding local efficacy (5-year local relapse-free survival 87% vs 77%, p<0.01), the patients’ quality of life and is less toxic compared with the 40 mg/m²/weekly chemotherapy regimen.

In 2006, a third randomised institutional study was begun, in which 111 patients in stage IIB

were included with the aim to compare exclusive RCT with RCT associated with surgery. The results show no statistically significant differences between the two treatment modalities, with

regard to overall survival (92% vs. 89%), disease free survival (89% vs 88%) and treatment failure.

In 2010, a nonrandomized feasibility study started with the aim of assessing neoadjuvant CT

(NACT) associated with RCT in locally advanced cervical cancer. The preliminary results show that NACT administered before RCT brings a high response rate (68% negative surgical specimen) with manageable toxicity, but randomized, larger number and long term evaluation trials are necessary in order to confirm these data.

4)

A new challenge: gynecological examination - TRUS - MRI

Autori: C.Ordeanu, D.C.Pop, R.Badea, C.Csutak, N.Todor, R.Kerekes, O.Coza, V.Nagy, A.Irimie Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: cervical cancer, transrectal ultrasound, MRI Rezumat:

Objective: The aim of this study was to analyze the accuracy of TRUS (Transrectal Ultrasound) in comparison to MRI (Magnetic Resonance Imaging) and clinical gynecological examination estimation, in the evaluation of tumor dimensions and identification of residual tumor in advanced cervical cancer. Methods: The patients’ inclusion criterion was pathologically confirmed squamous cell carcinoma (by tumor biopsy), the exclusion criterias were patients who didn’t undergo BT and treated with palliative intent. We offer two types of treatment for locally advanced cervical cancer: (a) radiochemotherapy followed by surgery and (b) exclusive radiochemotherapy. The treatment schedule consists of

EBRT (External Beam Radiotherapy) to the pelvic region with 15/16 MV X-Rays, adding Cisplatin

as radiosensitizer and a boost by HDR BT (High Dose Rate Brachytherapy). At 46 Gy given to the

pelvis we do reevaluation of the patient and according to tumor response and/or patients option the treatment continues with radiochemotherapy (RCT) up to 60 Gy or with surgery (after 4-6 weeks interval). Imaging tests follow the presence of tumor and tumor size (width and thickness). Each examination (gynecological, TRUS and MRI) was performed by a different physician that had no knowledge of each other’s findings. The TRUS and MRI were performed outside our institution, according to the standard protocols of our collaborators. All patients underwent MRI prior to EBRT while 18 of them also at the time of the first brachytherapy application. For the analysis we used a measure of linear correlation between two variables x and y giving a value between GYN-MRI-TRUS: R - Pearson correlation coefficient. The dimensions that we used for the comparison were AP (anterior-posterior) and LL (latero-lateral). Results: Between January-August 2013, 26 patients with cervical cancer were included. A

number of 44 gynecological examinations were performed, 44 MRI’s and 18 TRUS’s.

The median tumor thickness for the first gynecological examination was 32.5 mm, for TRUS was 33.5 mm and for MRI was 35 mm. The median tumor width for the first gynecological examination was 40 mm, for TRUS was 34 mm and for MRI was 37.5 mm. For the comparisons prior to EBRT the correlation coefficient between TRUS vs. MRI was

R = 0.79 for AP and R=0.83 for LL, for GYN vs. MRI was R= 0.6 for AP and R = 0.75 for LL.

Prior to BT for GYN vs. MRI, R was 0.6 respectively 0.63 for AP and LL; for GYN vs. TRUS, R was 0.56 respectively 0.78 for AP and LL. Conclusions: A high correlation between the 3 examinations (gynecological, TRUS and MRI) was obtained for the width of the tumor. TRUS is less expensive than MRI, a relatively quick procedure, it has a widespread availability and it is recommended to be the imagistic technique in the countries with low-income facilities. TRUS can be considered a suitable method in the evaluation of tumor dimensions (width and thickness) for patients with cervical cancer, and can be an alternative imaging method to MRI.

5) A model of immunohistochemical score useful in endometrioid tumors characterisation Autori: Ignat F., Fetica B., Fit Ana Maria, Lisencu C., Achimas-Cadariu P., Puscas E., Vlad C., Irimie A. Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: endometrial cancer, biomarkers, immunohistochemical score Rezumat:

The risk stratification of patients with endometrial cancer is generally based on histo- pathological evaluation of surgical specimens. To improve the therapeutic management of these patients a wide range of molecular markers are currently investigated and some researchers are trying to some extent to determine their role in the attempt to individualise treatment. The challenge of the moment in international research is the validation of such biomarkers, detectable in the preoperative biopsy material, to be useful parameters in stratifing patients with endometrial cancer to risk groups. The objective of this study is to evaluate biomarkers ER, PR, P53, P16, Her2 and Ki -67 and their ability to predict the dissemination of lymph nodes and the utility of the examined immunohistochemical panel to stratify risk groups of patients with endometrial cancer by cuantification of data in a immunohistochemical score. 62 patients were included in the study distributed as follows: 31 patients in the study group (group A node positive patients) and 31 patients in the control group (group B node negative patients). All patients were surgically staged at the Oncology Institute "Prof. Dr. Ion Chiricuţă" in Cluj- Napoca (IOCN) by total hysterectomy with bilateral adnexectomy, peritoneal procedures and retroperitoneal procedures (pelvic and/or para-aortic lymphadenectomy).

6)

Rolul angiogenezei în cancerul ovarian

Autori: Milan-Paul Kubelac, Bogdan Fetica, Annamaria Fulop, Ioan-Catalin Vlad, Alexandru Irimie, Patriciu Achimas-Cadariu Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: angiogeneză, cancer ovarian, proteinele ID, microarray Rezumat:

Introducere: Angiogeneza tumorală reprezintă un element cheie în progresia cancerului ovarian, iar rezultatele studiilor pe această temă validate prin intervenții terapeutice în trialuri clinice au arătat o îmbunătățire a intervalului liber de boală sau a supraviețuirii globale. Proteinele ID (inhibitor of DNA binding), reprezintă factori de transcripție din clasa HLH (helix-buclă-helix), au deja un rol stabilit în carcinogeneză. Până în prezent expresia ID-1 a fost puţin evaluată în

cancerul ovarian în corelație cu neoangiogeneza tumorală. Materiale şi metode: Am analizat cazuistica Institutului Oncologic “Prof. Dr. Ion Chiricuţă” pe o perioadă de 7 ani ce a cuprins 933 de pacienţi. În urma aplicării criteriilor de includere şi de excludere, prin tehnologia de tissue microarray, s-au efectuat colorații imunohistochimice pentru evidențierea proteinei ID-1 și a vaselor de neoformație pe blocurile de parafină corespunzătoare. Datele obținute au fost corelate cu variabilele pacientelor obținute din foile de observație. Rezultate: La majoritatea pacientelor, diagnosticul a fost stabilit în timpul menopauzei. Scorul imunohistochimic pentru ID-1 cât şi microvascularizaţia tumorală au fost semnificativ statistic mai mari în cazul pacienţilor cu stadii avansate de boală. În timpul perioadei de urmărire, majoritatea pacienților au prezentat reluarea bolii. Supravieţuirea medie la 5 ani a fost de 45%. Concluzii: Expresia ID-1 a fost pozitivă într-un număr mare de cazuri examinate, mai ales în stadiile avansate de boală, arătând astfel o corelaţie cu istoria naturală a bolii, o verigă patogenetică care poate prezenta interes, atât prin prognosticul infaust al unei cascade angiogenetice abundente cât şi ca o posibilă ţintă terapeutică în viitor.

7) Surgical management of uterine sarcomas ten year experience of a single tertiary center of cancer care Autori: Lisencu C, Sfîra Adriana, Ignat F, Achimaș P, Pușcaș EM, Vlad C, Mureșan MȘ, Pătcaș S, Deac Daniela, Cheregi C, Irimie A. Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: Uterine sarcomas, total hysterectomy +/- bilateral adenexectomy Rezumat:

Background: Uterine sarcomas are stromal-derived endometrial cancers with increased aggressiveness and unfavorable prognosis. In most of the cases, definitive diagnosis is established after surgery for supposedly benign uterine pathology. Preoperative diagnosis is rarely stated, and in such situations it is achieved either by uterine hysteroscopic biopsy or by uterine chiurettage. Clinical and radiology findings are unspecific. Surgical treatment varies with the patient’s history, hormonal status and locoregional extension. The aim of the study was to evaluate the outcomes of uterine sarcoma therapy of a single tertiary center of cancer care. Materials and methods: We have performed a descriptive ten-year-retrospective study (2002-2012) of patients treated for uterine pathology at “Prof. Dr. Ion Chiricuta” Oncology Institute, Cluj-Napoca, Romania. The parameters followed were: preoperative histology findings, surgical management, postoperative histology findings. Results: Out of 1401 cases of uterine malignant tumors treated in our service, 121 (8.7%) were uterine sarcomas and 115 (8.2%) were carcinosarcomas. The highest incidence was found for 40-60 years of age group. Out of the 115 cases of uterine sarcoma, only 22 (18.18%) of patients had preoperative diagnosis. For 77 of the patients (63.63%), the preferred surgical intervention was total hysterectomy with bilateral adenexectomy (THBA), for the remaining 36.36%, THBA was

associated with multiorgan resection/ilio-pelvic or paraaortic lymphadenectomy. 58.6% of the postoperative histology consisted of endometrial stromal sarcoma, 26.4% - of leiomyosarcoma and 14.8% of undifferentiated sarcoma. Discussion: The aim of surgery in uterine sarcomas is to achieve an R0 resection. Routine lympadenectomy is not recommended. No specific symptoms or radiological findings link with the disease. In most of the situations, preoperative histology is not achieved, mainly because of the indication to operate of a benign uterine pathology. Conclusions: Uterine sarcomas are rare forms of uterine cancer. Elective surgical treatment involves total hysterectomy +/- bilateral adenexectomy. Due to the local extension of the disease, it is sometimes necessary to perform multiorgan resection.

8)

Immediate and long-term results in 80 patients with pelvic exenterations

Autori: V. Muntean 1 , A. Mihailov 2 , I. Domsa 1 , A. Zolog 1 , O. Fabian 1 , O. Cebotari 1 , F. Muresan 1 ,

G. Petre 1 , R. Simescu 1 , M.V.Muntean 1,2 . Instituţie:

1CF Clinical Hospital,

2 University of Medicine “Iuliu Haţieganu” Cluj-Napoca

Cuvinte cheie: pelvic exenteration, five-year survival, disease-free survival, progression-free survival Rezumat:

Introduction: Pelvic exenteration is now largely accepted, with clearly defined roles in the multidisciplinary treatment of locally advanced or recurrent pelvic cancer. The purpose of the study was to analyze the immediate and long-term results in patients with pelvic exenterations performed in a community hospital. Patients and method: A cross-sectional population analysis of the prospectively maintained database was performed, including surgical and pathological reports and follow up recordings.

Results: In a 15-year interval (19982012), 152 multiorgan pelvic resections were performed for locally advanced or recurrent cancers, 80 of which fulfilled the criteria of pelvic exenterations (≥2 pelvisubperitoneal organs resected): 36 ano-rectal, 25 cervical, 4 uterine, 6 ovary,

4 urinary bladder, 2 prostate, and 3 pelvic sarcoma; 9 anterior, 20 posterior and 51 total; 11 with

sacrectomy and 28 with additional resections of abdominal organs. Major morbidity was recorded in 29 patients (36.25%), with 13 reinterventions (16.25%). In the follow-up period, 3 out of the 80 patients died in the first 30 postoperative days (operative mortality 3.75%) and 48 afterwards, 43 of cancer and 5 of reasons unrelated to cancer. Of the 29 patients still alive, 25 are disease free and 5 show progressive disease. In the 55 patients with R0 resections, the median disease-free survival interval was 22 months. In the 22 patients with R1-R2 resections the median progression-free interval was 3 months. 37 patients had a follow-up longer

than 5 years and 12 are alive (five-year survival 32%). In the 24 R0 patients, the five-year survival was 50% and the median disease-free survival interval 38 months. For the 13 patients with palliative (R1-R2) resections, the five-year survival was 0 and the median progression-free interval

3 months. Conclusions: Careful patient selection, R0 resections and quality surgery are the key to good results after pelvic exenteration.

9)

Pelvic and perineal reconstruction in 98 patients with pelvic exenterations

Autori: M.V. Muntean, I. Tichil, O. Fabian, G. Petre, F. Muresan, R. Simescu, V. Muntean Instituţie: CF Clinical Hospital Cluj-Napoca “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: pelvic exenteration, pelvic perineal reconstruction, greater omentum, TRAM flap Rezumat:

Introduction: Pelvic exenteration along with neo-adjuvant chemo-radiotherapy is considered to be the standard treatment for locally advanced or recurrent pelvic malignancy. This

leads to a large, non-collapsible dead space and poor vascularity of the irradiated surrounding tissue, which is the most important source of postoperative complications. The purpose of the study was to analyze the results of pelvic and perineal floor reconstruction in patients operated in a community hospital. Patients and methods: A cross-sectional population analysis of the prospectively maintained database, including surgical, pathological reports and follow up recordings, was performed during a 16 year interval, between 1998 and 2013. Results: 172 multiorgan pelvic resections have been performed for locally advanced or recurrent cancers, 98 of which fulfilled the criteria of pelvic exenterations (≥2 pelvisubperitoneal organs resected). The greater omentum was used for pelvic dead space filling in 86 patients; perineal reconstruction was necessary in 22 patients, with TRAM flap in 16 and Gluteus Maximus Flap in 6. Vaginoplasty was performed in 38 patients, TRAM in 17, VRAM in 5, DIEP in 8,

Gracilis in 4 and Posterior perineal in 4. Major morbidity was recorded in 12 patients (12.2%), with

8 reinterventions (8.2%) for intestinal obstruction and pelvic abscesses. In the 56 patients with

myocutaneous flaps there were 18 partial necrosis and 1 complete flap necrosis, with more favourable results for TRAM, DIEP and Gluteus Maximus. In the follow-up, 28 patients with vaginoplasty (73.7%) have resumed vaginal intercourse. Conclusions: In patiens with pelvic exenteration, pelvic and perineal reconstruction is necessary in all patients. Its impact on patient’s quality of life, body image and sexual function is substantial, as well as the benefits of improving primary healing and reducing the rate of intestinal complications and pelvic abscess. Careful selection of reconstructive method and good technique are key to achieving good results.

10) Long-term results of exclusive adjuvant vaginal brachytherapy Autori: Ovidiu Coza 1,2 , Claudia Ordeanu 2 , Diana Pop 2 , Patriciu Achimaş 1,2 , Dan Eniu 1,2 , Ştefan Hica 2 Instituţie:

1 “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca,

2The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: HDR-VBT, vaginal cylinder, endometrial carcinoma Rezumat:

Introduction: This paper represents a retrospective non-randomized study designed to analyze the results of high-dose rate vaginal brachytherapy (HDR-VBT) as exclusive adjuvant treatment in postoperative management of endometrial carcinoma. Material and method: Our study includes 208 patients - median age of 60 (38-79) years - treated in our Institute in the period January 2006 - December 2012 for stage IA-IIB endometrial carcinoma. All patients were submitted to radical surgery, followed after a median free interval of 49 days, by endocavitary brachytherapy. HDR-VBT was performed with vaginal cylinder: two weekly insertions at 72 hours interval, for a total dose of 28 - 30 Gy/ 4 to 6 fractions. The dose prescription was at 5 mm from the vaginal cylinder surface, with a median active length of 40 mm. The brachytherapy total duration was 15 days. Results: After a median follow-up of 24 (3-85) months, we observed 9 treatment failures (4,32%): 3 local vaginal recurrences; another 3 patients presented with lymphnoderelapse (pelvic & retroperitoneal); 2 patients developed distant hematogenous metastases (lung and liver), and one case with multiple peritoneal disease. The local control was obtained in 98% of the included patients. As for the late adverse effects (AE): we observed in 10 patients vaginal toxicity - 3 G1, 7 G2; another patient with G1 bladder AE and one patient with a rectal G2 late toxicity (CTCAE v

4.03).

Conclusions: Postoperative exclusive HDR-VBT in selected patients with endometrial carcinoma represents an efficient treatment method. Main advantages are the low incidence of late morbidity (5,77%) and that it can be performed in an outpatient basis for a reasonable period of time.

CANCERELE UROLOGICE

COMUNICĂRI ORALE

1. Conformal irradiation in prostate cancer - 5 years experience

Autori: Andreea Marita 1 , Raluca Stahiescu 1 , Anamaria Rusu 1 , Victor Bogdan 1 , Dan Dordai 1 , Gabriel Kacsó 1,2 Instituţie: 1 The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca 2 Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie:

Rezumat:

Purpose: evaluation of efficacy and toxicity of conformal radiotherapy (CRT) for prostate adenocarcinoma (ADKP) Material and Methods: From 2005 to 2011, 300 patients were treated with CRT at the Oncologic Institute Cluj., The dose was 66 to 70 Gy after radical prostatectomy, 70-72Gy/25-26fr for low-risk patients and 45-46 Gy/23-25fr associated with 110 Gy permanent implant or 74-76Gy / 37-38fr for high and intermediate risk group. Dose-volume constraints were pre-defined for bladder and rectum. Acute and late toxicities were assessed using CTC 3.0 scale. Biochemical relapse was defined as an 2 ng/ml increase above PSA nadir. Results: With a median follow-up of 30 months [12-102], the overall survival and specific survival was 93.6% and 98.9%, whereas the biochemical relapse free survival was 87.4%. According to the D'Amico classification: 17 (5%) were low risk , 37 (11%) intermediate, 214 (74%) high risk patients, 2% with unknown risk group and 25 (8%) patients received CRT adjuvant or as salvage after radical prostatectomy. There were 38 (12.6%) biochemical relapses of which 18 (47%) local recurrences, 14 (37%) metastases and 6 (16%) "occult". Of them, 21 patients were high risk, 3 intermediate, 1 low risk, 10 in the prostatectomy subgroup and 2 patients with unknown risk; Hormonal therapy was given for 87.3% of patients. Severe acute urinary (U) and digestive (D) toxicity (G3) was 11% and 2%. The severe late toxicity was 3 % for U, 0% for D. Conclusion: CRT is a reliable method as curative treatment of T1-3NoMo ADKP with low toxicity and a medium term specific survival of 98.9%.

2. Case report: multidisciplinary approach to poor prognosis renal cancer

Autori: Paula Pruteanu 1 , Laura Ardelean 1 , Crinela Lupu 1 , Horatiu-Mircea Stan 3,2 , Petre Kiss 3 , Petrut Bogdan 1,2 , Claudia Burz 1,2 Instituţie: 1 The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca, 2 Universitatea de Medicina si Farmacie Iulius Hatieganu, Cluj-Napoca, 3 Clinica de Neurochirurgie, Cluj-Napoca Cuvinte cheie:

Rezumat: Din punct de vedere epidemiologic, cancerul renal se situeaza pe locul 8, incidenta sa fiind crecuta la persoane in varsta. De multe ori pacientul este diagnosticat in faza metastatica , cand prognosticul pacientilor ramane rezervat . Prezentam cazul unui pacient de 44 ani care s-a prezentat in Institutul Oncologic Cluj cu cefalee, tulburari de vedere ochi stang, vertig, sindrom astenic simptomatologie care a debutat in urma cu un an anterior prezentarii. Evaluarea imagistica a evidentiat o formatiune tumorala la nivel occipital stang de aprox. 6 cm, care a fost rezecata in totalitate in serviciul de neurochirurgie cu rezultat histopatologic de carcinom renal cu celule clare. In cadrul bilantului preterapeutic s-a efectuat o tomografie abdomino-pelvina care a decelat o formatiune tumorala renala dreapta de 12 cm, fara plan de clivaj fata de ficat, adenopatii metastatice retroperitoneale , inter-aortico-cave. Datorita prezentei factorilor de prognostic rezervati s-a initiaza terapie tinta cu Temsirolimus. Pe parcursul terapiei starea generala a pacientului s-a ameliorat, iar evaluarea efectuata dupa administrarea a 6 cicluri a aratat raspuns partial la nivelul formatiunilor tumorale. S- a intervenit chirurgical practicandu-se nefrectomie dreapta, limfadenectomie retroperitoneala, cu

excizie lambou de vena cava si cavorafie. Rezultatul histopatologic a confirmat prezenta carcinomului renal cu celule clare grad IV Fuhrman, cu infiltrarea venei cave, stadiul pT3cN1MxL1V1. Recuperarea postoperatorie dificila cu infectii severe la nivelul plagii nu au permis continuarea tratamentului oncologic postinterventie chirurgicala. La 3 luni postinterventie chirurgicala pacientul revine in IOCN cu deficit motor brusc instalat, imagistic decelandu-se formatiune tumorala frontala stanga. Se intervine chirurgical practicandu-se ablatia formatiunii tumorale. Se reinitiaza terapia cu Temsirolimus datorita evolutiei la distanta, asociat cu radioterapie pe calota craniana. La doi ani de la diagnostic, pacientul este cu stare generala buna, in tratament cu Temsirolimus.

3. Stage I testicular seminoma: results of survival and risk factors for relapse

Autori: Nicoleta Zenovia Antone, Cristina Ligia Cebotaru, Monica Groza, Nicolae Todor Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: survival, risk factor, seminoma Rezumat:

Objective: evaluation of adjuvant treatment and risk factors for relapse for stage I testicular seminoma. Material and methods: retrospective study evaluated 112 patients aged between 18 and 78 years (median age-37,4 years) stage I testicular seminoma between January 1982-January 2007, treated at The Oncology Institute Prof Dr Ion Chiricuta, Cluj-Napoca, Romania. The median follow-up duration was 135,8 months (range 3 - 233 months). Demographic, clinical and paraclinical parameters of patients were observed. Chemotherapy regimen administered in adjuvant setting was 1 cycle Carboplatin AUC 7 or 2 cycles Carboplatin AUC 6 in 31 (27,68%) patients for stage I seminoma, 44 (39,29%) patients were treated with adjuvant radiotherapy and 37 (33,04) were managed by surveillance. Results: Overall survival at 10 years was 92%(CI: 85%-96%). Eighty seven seminoma patients (77,68%) have not presented relapse, metastatic relapse was observed in 5 patients (4,46%), pelvic or lumboaortic lymph nodes was present in 17 cases (15,18%), metastatic and adenopathy relapse in 2 patients (1,79%) and seric relapse in 1

patient(0,89%).

Risk factors evaluated for relapse were age at presentation (p=0,1), performance status(p<0,01), stage of disease at presentation(p<0,01) and presence of markers(p=0,1). Chemotherapy toxicity was moderate, main toxicity for Carboplatin was thrombocytopenia (6,67%), anemia(3,7%), leucopenia (3,33%), and nausea and vomiting (3,33%). Conclusion: Stage I seminoma tumor prognosis is excellent. The rate of curability with adjuvant treatment is high, the overall survival at 10 years with adjuvant chemotherapy is 96%, followed by adjuvant radiotherapy 93% and overall survival for patients treated with orchiectomy alone followed by surveillance is 41%.

4. Laparoscopic Adrenalectomy

Autori: Alexandra Alb, Maximilian Hogea, Vlad Schitcu, Dragos Feflea, Vasile Buda, Denes Kaba, Vlad Hardo, Bogdan Petrut Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Laparoscopic Adrenalectomy learning curve Rezumat:

Introduction: The adrenal gland is especially suited for laparoscopic surgery because of its relative small and difficult retroperitoneal access. The minimally invasive approach allows for lower perioperative morbidity, decreased blood loss, less pain relief medication need, shorter hospital stay and faster recovery. Objective: We aim to present our experience with the laparoscopic approach to adrenal

masses.

Material and method: Data was analyzed for patients undergoing laparoscopic surgery for adrenal masses. Demographic characteristics and perioperative parameters are described in relation to the learning curve for the procedure. All patients underwent laparoscopic adrenalectomy either through a retroperitoneoscopic or transperitoneal approach. Results: From 2010 until April 2014, 18 patients were operated in our institution for adrenal masses, 14 women and 4 men. The pathological stage was pT1 pT2. Average tumor diameter was 53mm. Pathology showed 4 cases (22.22%) of benign masses, 3 cases (16.67%) of pheochromocitoma and 4 proved to be metastatic tumors. Surgical margins were negative in all cases of primary adrenal lesions, and positive in 3 out of 4 cases of metastatic disease. Average operation time decreased from 192 min (first 5 cases) to 137 min in latest 5 (overall average duration 153 min). Average blood loss decreased as well with experience gain, with an average of 1.2 units of RBC for the first 5 cases to under 0.2 units. Hospital stay was constant, independent of the learning curve - average 6 days. Conclusion: Laparoscopic adrenalectomy is a safe and effective surgical technique for the management of adrenal masses, with the added benefits of a minimally invasive approach. Adequate patient selection and surgical expertise are required for favorable patient outcomes.

perioperative

outcomes Autori: A. Boc, N. Crișan, P. Prunduș, V.D. Stanca, R.T. Coman, I. Coman. Instituţie: Secția Clinică Urologie, Spitalul Clinic Municipal Cluj-Napoca, România. Cuvinte cheie: Laparoscopic Adrenalectomy learning curve Rezumat:

Introduction: Open radical cystectomy remains the gold standard treatment for muscle- invasive bladder cancer. Following the wide spread of robotic radical prostatectomy, robotic techniques are now increasingly being applied to radical cystoprostatectomy. Robotic radical cystectomy provides the potential benefit of lower complications while maintaining functional and oncological outcomes. We report our experience, perioperative and pathological results, presenting step by step our technique of radical cystectomy and the variants of urinary diversions used. Material and method: We perform robotic radical cystectomy, extended lymphadenectomy and urinary diversion. Orthotopic ileal neobladder is created extracorporeal or totally intracorporeal. When the extracorporeal urinary diversion is chosen, the uretro-neobladder anastomosis is done using the robotic system after re-docking the robotic cart. We use a laparoscopic stapler device for reestablishing bowel continuity in order to reduce the operative time. Our surgical technique is presented in the accompanying video. Results: From January 2010 to February 2014 we performed 11 robotic radical cystectomies. Mean patients age was 60.1 years (range 52 to 73). 5 patients underwent cutaneous ureterostomy and 6 received an orthotopic ileal neobladder. In three cases the neobladder was created extracorporeal and in the other three totally intracorporeal. Mean operative time was 6.5 hours and mean blood loss 378 ml. In 7 cases tumor stage was T2 or less and in 3 cases T3. A mean of 16 lymph nodes were removed. There were no positive lymph node cases. In all cases surgical margins were negative. Three patients presented grade II complications and one patient grade III complications. Conclusions: We have presented our technique of RRC with different types of urinary diversions. Robot-assisted radical cystectomy can be accomplished safely with encouraging perioperative and pathological outcomes and acceptable morbidity.

5.

Robotic

radical

cystectomy:

operative

technique,

pathological

and

6.

Overall survival and prognostic factors in metastatic renal cell carcinoma patients

treated with cytokines and targeted therapies at the “Prof. Dr. Ion Chiricuţă” Institute of Oncology Autori: Cristina Ligia Cebotaru, Elena Diana Olteanu, Cristina Mocan, Nicolae Todor Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: renal cell carcinoma, prognostic factors, targeted therapies Rezumat:

Background: Survival in metastatic renal cell carcinoma (mRCC) has been definitely improved by targeted therapies. This is a retrospective study to assess prognostic factors for survival in mRCC/advanced patients treated with targeted therapies at the `Prof Dr Ion Chiricuta` Institute of Oncology, Cluj Napoca. Patients and methods: We retrospectively analysed the baseline characteristics, response to targeted therapies and survival in 90 mRCC patients that were treated in our Institute between 2005- 2011. Stratification was made for histology: clear cell histology: 70 pts.(92%), sex: M=70 (80%), nephrectomy: 67 (77%), ECOG PS: 0/1=61 pts. (74%), unique metastatic site: 64 pts.(74%) vs. multiple = 23 sites of metastases LDH, anemia, number of thrombocytes, lymphocytes, calcemia, alkaline phosphatase, interval from diagnosis to progression, number of therapy lines, and Motzer prognosis criteria. A number of 48 patients received targeted therapy in the first line, 34 received it as second line and only 8 in the third. Altogether, 33 patients received sunitinib, 5 bevacizumab+ interferon, 10 temsirolimus and none sorafenib in the first line. Sorafenib was only given in second and third line. We analyzed the overall survival (OS) and progression free survival (PFS) according prognostic factors. Toxicities were also reported. Results: The median OS since the diagnosis of the metastasis was 23,36 months (95%CI:

18,51-28,24). One patient obtained complete response, after targeted therapy in the first line and 1 after the second line. In the uni- and multivariate analysis, independent prognostic factors for outcome were: the risk group according to Motzer criteria, the presence of anaemia. The sequence of targeted therapies was as per guidelines. Conclusion: Our study showed improved survival for patients with advanced/mRCC treated with targeted therapies with mild and manageable toxicities.

7. Laparoscopic radical prostatectomy - operative and perioperative parameters analysis

of the first 100 cases Autori: V Schiţcu, M Hogea, D Feflea, V Buda, D Kaba, V Hardo, Alexandra Alb, DS Popescu, B Petruţ Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: radical lapascopic prostatectomy Rezumat:

Radical prostatectomy continues to represent the gold standard of surgical treatment of organ confined prostate cancer. The minimally invasive alternatives to the open approach have already been proven to offer comparable oncological and functional outcomes. In spite of the technical drawbacks and inherent difficulty, the prohibitive price of robot assistance still drives urologists to overcome the steep learning curve of conventional laparoscopy. This presentation aims to analytically describe perioperative parameters of the the first 100 cases, in order to quantify progress on the learning curve, in the experience of the urologic team of the Oncology Institute „Prof. Dr. I. Chiricuţă” Cluj-Napoca.

8.

Alternativa laparoscopică în nefrectomia parţială – particularităţi şi avantaje

Autori: V Buda, M Hogea, V Schiţcu, D Feflea, D Kaba, V Hardo, B Petruţ Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

În mâini experimentate, laparoscopia reprezintă o opţiune viabilă în tratamentul tumorilor renale ce se pretează la chirurgia de prezervare nefronală. Abordul laparoscopic prezintă anumite particularităţi tehnice ce sporesc gradul de dificultate al intervenţiei, limitând accesabilitatea metodei la centre cu experienţă şi volum crescut de pacienţi. Lucrarea de faţă îşi propune prezentarea parametrilor operatori şi rezultatelor oncologice a nefrectomiei parţiale laparoscopice într-o manieră descriptivă a curbei de învăţare, în experienţa Institutului Oncologic „Prof Dr I

Chiricuță” Cluj-Napoca.

9. Risk factors and long term survival in stage I germ cell tumors

Autori: Cristina Ligia Cebotaru, Nicoleta Zenovia Antone, Monica Groza, Nicolae Todor, Maximilian Hogea Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: survival, risk factor, germ cell tumor Rezumat:

Objective: evaluation of adjuvant treatment and risk factors for relapse in stage I germ cell

tumors.

Material and methods: retrospective study evaluated 253 patients aged between 14 and 78 years (median age - 33,9 years) with stage I germ cell testicular tumors, between January 1982- January 2007, treated at The Oncology Institute Prof Dr Ion Chiricuta, Cluj-Napoca. The median follow-up time was 126 months (range 3 - 285 months). Demographic, clinical and paraclinical parameters of patients were observed. The histological classification consisted of 126 patients with seminoma (50%), and nonseminoma (choriocarcinoma, embryonal carcinoma, Yolk sac tumor, teratoma and malignant mixed germ cell tumor). Chemotherapy regimens administered in adjuvant setting were Carboplatin AUC 7 for stage I seminoma, EP and BEP for nonseminoma. VAB6 protocol was used before the BEP era. Results: Overall survival at 10 years was 93% (CI: 89%-96%). Ninety nine seminoma patients (78,57%) presented relapse, metastatic relapse was observed in 5 patients (3,97%), pelvic or lumboaortic lymph nodes was present in 19 patients (15,08%), metastatic and adenopathy relapse in 2 patients (1,59%) and seric relapse in 1 patient(0,79%). For nonseminoma patients the relapse was present in 11 cases (8,66%). Risk factors evaluated for relapse were age at presentation (p=0,1), performance status(p<0,01), stage of disease at presentation(p<0,01) and presence of markers(p=0,1). Chemotherapy toxicity was moderate, main toxicity for Carboplatin was thrombocytopenia (6,67%), and for the BEP protocol - leucopenia (4,76%), anemia(4,76%) and nausea and vomiting

(11,9%).

Our results are superposable with literature data. Conclusion: Germ cell tumor prognosis is excellent. The rate of curability for adjuvant treatment is high, the overall survival at 10 years being 93% (CI: 89%-96%).

10. Anterograde and retrograde nerve-sparing in robot-assisted radical prostatectomy surgical technique Autori: H. Logigan, Iulia Pop, C.D. Pop, R. Coman, C. Manea, N. Crişan, I. Coman Instituţie: Department of Urology, Clinical City Hospital, Cluj-Napoca, România Cuvinte cheie:

Rezumat:

Introduction and objectives: Nerve-sparing (NS) in radical prostatectomy accounts for being one of the most challenging surgical techniques where an expert knowledge of neurovascular bundle anatomy is essential. The purpose of this paper is presenting the anterograde and retrograde nerve-sparing techniques used in our service. Material and methods: The retrograde approach to nerve-sparing implies the dissection of the anterior and lateral aspects of the prostate with the identification of the surgical planes between the prostate and nerurovascular bundles, that is continued by the Denonvillier fascia. After performing the dissection in the mid-lateral aspect of the prostate, the lateral prostatic pedicles are clipped and the dissection is continued towards the apex of the prostate. When the antegrade approach is considered, the posterior aspect of the prostate is dissected from the anterior aspect of the Denonvillier fascia, laterally with the identification of the surgical plane between rectum and posterior aspect of the prostate. The dissection is continued using this plane towards the prostate apex until the neurovascular bundles are completely detached. In order to avoid positive resection margins, frozen sections are performed and in case of malignant involvement, the homolateral bundle is sacrificed. Results: Among the 102 patients with localized stage prostate adenocarcinoma, there were 49 cases where bilateral NS was performed and 29 where one bundle was preserved. Continence progressively improved and the results at 1, 6 and 24 months follow-up time for both groups (bilateral and one sided NS) were 58%, 74% and respectively 93%. Regarding sexual function, results at 6, 12 and 24 months follow-up were 45.4%, 67.4% and respectively 79% in the case of bilateral bundle preservation and 20%, 28% and respectively 51% for unilateral NS, with or without 5-PDE inhibitor therapy. Conclusion: The robot-assisted surgery allows for a more accurate development of the anterograde and retrograde nerve-sparing techniques with a beneficial impact on functional outcomes.

11. Nefrectomia radicală laparoscopică - analiza curbei de învățare prin prisma parametrilor operatori Autori: D Feflea, M Hogea, V Schiţcu, V Buda, D Kaba, V Hardo, B Petruţ Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: nefrectomia radicala laparoscopica curba invatare Rezumat:

Nefrectomia radicală laparoscopică a devenit standardul de aur în tratamentul tumorilor renale în stadiile în care prezervarea parenchimului renal nu este fezabilă. Abordul minim invaziv oferă avantaje multiple din punct de vedere al morbidităţii postoperatorii, duratei spitalizării şi cosmetice, cu rezultate oncologice şi funcţionale comparative cu abordul clasic. Scopul acestei prezentări este analiza acestor parametri în funcţie de avansarea pe curba de învăţare a echipei operatorii urologice a Institutului Oncologic „Prof. Dr. Ion Chiricuță”, în raport cu datele existente în literatură.

12. Modular teaching program for laparoscopic radical cystectomy at the Institute of Oncology “Prof. Dr. Ion Chiricuţă” Autori: Maximilian Hogea, Vlad Schitcu, Dragos Feflea, Alexandra Alb, Vasile Buda, Vlad Hardo, Denes Kaba, Bogdan Petrut Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: laparoscopy, radical cystectomy, teaching Rezumat:

Introduction: Radical cystectomy and pelvic lymph node dissection currently represents the criterion standard for determining accurate pathologic staging, optimizing curative potential, and minimizing the risk recurrence of bladder cancer. The laparoscopic approach is a challenging procedure with a difficult learning curve that demands a high degree of technical skill. Objective: The aim of this paper is to evaluate the surgical parameters and the oncological results of laparoscopic radical cystectomy (LRC) performed in steps by trainer and trainees during the modular training program implemented in our institution. Methods: Our training program divides trainees depending on their expertise. The surgical maneuvers are also grouped by degree of difficulty in three levels. When the proficiency of the trainee is attested by objective parameters, they move on to perform surgical steps from the next difficulty level. 6 LRC were performed in this fashion at our institution. 2 trainees from intermediate level group acted as first assistants and performed obturatory lymphadenectomy during the LRC. Previous surgical laparoscopic training was correlated with the surgical parameters. Results: Performing the LRC with the same team the operative the operative time decreased from 300 min to 210 min. When the first assistant was changed, the operative time increased to 240 min. The time to perform obturatory lymphadenectomy saw a decrease from 25 to 15 min for one assistant and 20 min for the second. These times were correlated with previous surgical training. There were no intraoperative or postoperative complications. The surgical margins were negative in all cases, and all lymph nodes removed were negative. Conclusion: Our mentor assisted modular training program allows the trainees to perform independently, under mentor guidance, steps of the procedure according to their training level, while simultaneously maintaining the standard of excellence and safety of the procedure, without compromising the functional or oncological results.

13. Prostate cancer control following high intensity focused ultrasound (HIFU) by means of robotically assisted laparoscopic radical prostatectomy (RALP) Autori: C. Manea, N. Crisan, H. Logigan, T. Coroi, C. Ivan, I. Coman Instituţie: Department of Urology, Clinical City Hospital, Cluj-Napoca, România Cuvinte cheie:

Rezumat:

Introducere: Implementarea terapiei High Intensity Focused Ultrasound (HIFU) pentru cancerul prostatic localizat este in crestere. La cazurile atent selectionate, rezultatele oncologice si functionale pe termen mediu sunt comparabile cu rezultatele chirurgiei de exereza. In cazul recidivei tumorale locale, exista alternative terapeutice fezabile pentru controlul patologiei neoplazice Material si metoda: Din 189 de pacienti cu adenocarcinom prostatic tratati HIFU, la 4 cazuri cu recidiva locala post HIFU s-a efectuat prostatectomie radicala laparoscopica asistata robotic. Prezentam timpii operatori ai tehnicii de exereza radicala a ,,bontului” prostato-veziculo- deferential Rezultate: Conversia la chirurgia clasica nu a fost necesara la niciuna din interventiile efectuate. Timpul operator mediu a fost de 115 minute, pierderea medie de sange a fost de 110 ml si niciun pacient nu a fost transfuzat. Rezultatul histopatologic descris a fost stadiul pT2a la un caz, pT2b doua cazuri si pT2cun caz. Scorul Gleason a fost 7 (3+4) pentru 3 pacienti si 7 cu pattern

primar 4 la cel de-al patrulea pacient. Marginile de rezectie au fost negative. Un caz este continent si a obtinut erectie la 3 saptamani postoperator, iar celelalte 3 cazuri au prezentat incontinenta urinara doar la efort, fara functie erectila. Timpul mediu de monitorizare prospectiva este de 4 luni. Concluzii: Controlul adenocarcinomului prostatic prin prostatectomia radicala asistata robotic este posibil la pacientii tratati initial prin tehnica HIFU. Tehnica de disectie si izolare a blocului prostato-veziculo-deferential este mult mai dificila decat in abordul primar. Utilizarea chirurgiei robotice creste siguranta in exereza piesei, prin disectia magnificata si minutioasa si astfel se evita aparitia marginilor de rezectie pozitive. Numarul mic de cazuri si perioada scurta de monitorizare limiteaza precizarea gradului morbiditatilor ulterioare, comparativ cu indicatia primara de prostatectomie radicala

14. Chemotherapy in urinary bladder cancer an overview of the treatment in IOCN of the last 5 years

Autori: Cainap C, Campean C,Feflea D, Petrut B Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: bladder cancer, chemotherapy, neoadjuvant, adjuvant, intravesical Rezumat:

Cancer is a major problem for health systems all over the world. With an increasing incidence which will arrive at 19,3 millions new cases every year by 2020 (estimated by GLOBOCAN) the importance of cancer management is growing. Bladder cancer is situated in the first ten primary tumours in the world with more than 400000 new cases per year, males beeing more affected than females. Surgery remains the cornerstone of the correct oncological approach; radiotherapy and chemotherapy are underused despite the fact that they are improuving the general prognosis of the patients. In this presentation we will make an overview of the treatments in our institute for bladder cancer patients: intravesical, neoadjuvant, adjuvant or metastatic setting. We will present the hysthological types, types of medical treatments used, toxicities and prognostic factors in correlations with previous published data.

POSTERE

1. Circulating tumor cells in testicular germ cell tumors

Autori: Cristina Cebotaru, Elena Diana Oteanu, Rares Buiga, Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: circulating tumor cells, testicular cancer Rezumat:

Aim: Circulating tumor cells (CTCs) are rare malignant cells found in the peripheral blood. As poor-prognosis germ-cell tumors patients still have a 50% `chance` to die of their disease with standard treatment, we tested the hypothesis that CTCs detection could predict clinical, serologic, radiologic and pathologic response, in order to guide treatment. Patients and methods: In this prospective pilot study, in two poor-prognosis germ-cell tumor patients, we isolated and enumerated the CTCs in the peripheral blood at baseline, after one cycle, and at the end of first-line chemotherapy (BEP regimen), and correlations were made with serum markers, radiologic and pathologic response. CTCs were measured using a density gradient centrifugation separation technique and an immunocytochemistry technique ( citokeratinAE1/AE3). Radiologic assessments consisted of CT-scans and PET-CTs, and pathology report was obtained either from resected specimen or biopsy of persistent tumors with negative serum markers or metabolic inactive PET-images. Results: Enumeration of CTCs in the peripheral blood at baseline and after chemotherapy correlated with serum markers decrease and radiologic and pathologic response. For the first patient, the decrease of CTCs was slower than for the second patient, and correlated with the response: partial response with positive serum markers versus partial response with negative markers. The first patient had positive PET-CT and the second patient had negative PET images. Biopsy from resected specimen PET-negative (second patient) showed no viable tumor. After 12 months the first patient was alive, with active disease and the second patient was alive, disease free with stable PET-negative images. Conclusion: The first results suggest that the number of CTSs might provide prognostic information as their decrease after chemotherapy correlates well with clinical assessment, serum markers, imaging, post-chemotherapy pathologic response and outcome.

HEMATOLOGIE ŞI ONCOPEDIATRIE

COMUNICĂRI ORALE

1. Indolent non-Hodgkin lymphomas - Clinical course and response to treatment -

Experience of the Haematology Department of the “Ion Chiricuta” Oncology Institute in Cluj-Napoca Autori: Anca Bojan 2 , Anca Vasilache 1 , Andrei Cucuianu 2 , Laura Urian 2 , Mariana Patiu 1 , Carmen Basarab 1 , Bogdan Fetica 1 , Calin Coldea 1 , Tunde Torok 2 , Mihnea Zdrenghea 2 , Andrada Parvu 2 , Ljubomir Petrov 1 .

Instituţie:

1- The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

2 - University of Medicine and Pharmacy “Iuliu Haţieganu” Cluj-Napoca

Cuvinte cheie: follicular lymphoma, marginal zone lymphoma, lymph node Rezumat:

Introduction: Indolent lymphomas are often insidious, presenting only with slow growing lymphadenopathy, hepatomegaly, splenomegaly, or cytopenias. Examples of lymphomas that typically have indolent presentations include follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, and marginal zone lymphoma (MALT). This study represents a non-randomized retrospective study aimed to evaluate the incidence of different forms and the treatment outcome in the Haematology department of the “Ion Chiricuta” Oncology Institute in Cluj-Napoca. Methods: 122 patients with indolent lymphomas were treated in the Haematology department of the Oncology Institute of Cluj-Napoca, in the last 10 years, between 2003 and 2012. Diagnosis was made by lymph node biopsy for follicular lymphoma, nodal marginal zone lymphoma, histology of the spleen in splenic marginal zone lymphoma and gastric, intestinal, parotid, thyroidal, lung, rhinopharinx etc. biopsy in MALT lymphomas. The prognostic evaluation was done according to the FLIPI score for follicular lymphoma. Results: 122 patients with indolent lymphomas were included in the study: 41% with follicular lymphoma, 37% with lymphocytic lymphoma, 5% lymphoplasmacytic lymphoma, 9% MALT lymphomas, 4% splenic marginal zone lymphoma. 24 patients with follicular lymphoma had a FLIPI score >3 and 80% were treated with CHOP-based regimens as first-line therapy. The overall survival in patients with follicular lymphomas was significantly higher in patients with stage I or II, FLIPI score<3 and complete remission after first line therapy. Conclusion: Indolent lymphomas are characterized by a long median survival, are usually in an advanced stage, respond to therapy, but relapse and the therapeutic options are increasing:

monoclonal antibody, radioimmunotherapy interferons, stem cell transplantation.

2. Prognostic significance of ZAP-70 and CD38 expression in Chronic Lympocytic

Leukemia Autori: Ana-Maria Fit 1 , Laura Maja2, 2Gabriel Tanu, 3Delia Dima, 3Liubovici Petrov, 3Andrei Cucuianu, 3Mihnea Zdrenghea, 4Luminita Blaga, 2Bogdan Fetica

Instituţie:

1 Clinical Emergency Hospital, Cluj-Napoca,

2 The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

Cuvinte cheie: chronic lymphocytic leukemia, CD38, ZAP-70, EBER Rezumat:

Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Among useful markers in identifiyng patients with poor outcome are unmutated IgVH, ZAP-70 and CD38 expression. Both ZAP-70 and CD38 were shown to be capable of identifying aggressive CLL.

We analysed data from 39 patients with CLL: 24 cases diagnosed by lymph node biopsy and 15 cases diagnosed by bone marrow biopsy. The clinical and immunophenotypic criteria (C23+, CD5+, CD20+, CD10-, CD3-, cyclinD1-) for B-cell CLL were achieved in all 39 patients. The median age of patients was 60 years and we noted a slight male predominance. Cytoplasmic ZAP-70 and surface CD38 expression were evaluated by immunohistochemistry and correlated with clinical course. In addition in-situ hybridization for EBER-1was evaluated. Prognostic information given by ZAP-70 and CD38 could be used in guiding treatment decisions and they probably should be recommended to all patients with B-CLL in trying to obtain a more clear profile of the disease at the time of diagnostic.

3. Anemia aplastica (AA). Actualitati in etiopatogeneza si tratament. Aplastic Anemia

(AA). Recent advances in pathogenesis and treatment. Autori: L. Petrov Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Aplastic anemia, etiologic agent, pathogenesis, treatment Rezumat:

Aplastic anemia is defined as pancitopenia with a hipocellular bone marrow without an increase of reticulin or fibrosis and no morphologically anormal cells in blood or marrow. The pathophysiology of AA is not entirely clear. There is a deficiency in the number of hematopoetic stem cells. The nature of damage is nuclear. There is a growing evidence of the role of cell-mediated damage of stem cells. Although acquired aplastic anemia has been causally associated with many agents (drugs, benzene, insecticides and viruses) no etiologic agent can be identified in most cases. The severity of bone marrow failure is reflected by the depression of the peripheral blood counts and is closely related to the prognosis. First line treatment is determined by the severity of the marrow failure, the age of the patient, the availability of a suitable donor and presence of comorbidity. Young patients transplanted from HLA matched sibling donors have about 80-90% disease free survival. Event free survivals falls to <50% in patients > 40 years. Succesfull outcome of transplant diminishes with matched unrelated donors and with any degree of HLA mismatch. Immunosupressive therapy with antithymocyte globulin (ATG) and cyclosporine (CSA) is used in patients who are not candidates for bone marrow transplantation. The response rates with ATG/CSA ranged between 60 and 80% with 5 year survival comparable to BMT. Persistent cytopenia is common and many patients relapse, become dependent on CSA or develop secondary clonal disease (PNH or MDS). High dose cyclophosphamide without BMT can be used to treat AA. There are no standard treatment for managing refractory and relapsed patients after ATG/CSA treatment. Therapeutic options include allogenic SCT, retreatment with ATG/CSA or high dose cyclophosphamide.

4. Monoclonal B cell lymphocytosis in patients with hepatitis C virus infection:

prevalence, demographyc and laboratory correlations Autori: Tünde Tőrők-Vistai , Anca Bojan , Manuela Sfichi , Cristina Pojoga Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: monoclonal B lymphocytosis, hepatitis C virus, nonhodgkin lymphoma, chronic lymphocytic leukemia

Rezumat:

Introduction: Several studies have demonstrated an increased prevalence of HCV infection in patients with B-cell nonhodgkin lymphoma. Monoclonal B lymphocytosis (MBL) is

characterized by the presence of a clonal B-cell population which might evolve into malignant B- cell lymphoproliferative disease. MBL can be detected in approximately 3.5% of healthy individuals, but in HCV-infected patients it can be identified at a higher frequency. We aimed to quantify monoclonal B-cell populations in patients with HCV and to identify demographyc and laboratory features of patients with MBL. Methods: We conducted a prospective study on 50 consecutive patients with chronic hepatitis or cirrhosis. For detection of MBL we performed a four-colour flow cytometry. Statistical analysis was performed using the Statistical Package for Social Sciences. The level of statistical significance was set at p<0.05. Results: Flow cytometric analysis revealed MBL in 22% of the patients. Prevalence of MBL was higher in patients with cirrhosis then in those with hepatitis. In patients with MBL the leucocyte count was significantly lower (p=0.04) and increased liver echogenicity was more frequent (p=0.02). Discussion: The prevalence of MBL in patients with HCV infection is significantly higher then in the general population, sustaining the pathogenetic role of HCV in B-cell lymphoma. Comparing patients with or without MBL, we didn’t find statistically significant demographyc differences. Data differed only in terms of the leucocyte count and liver echogenicity. Conclusions: In accordance to other studies, we have found a high prevalence of MBL in patients with HCV infection. While in the general population, it is known that the rate of progression of MBL to CLL is about 1.1% /year, in HCV infected patients further studies are needed to investigate the rate of progression into lymphoprolyferative disease.

5. Prognostic Factors in Acute Myeloblastic Leukemia in Children

Autori: Popa Gheorghe Instituţie: University of Medicine and Pharmacy “Iuliu Haţieganu” Cluj-Napoca Cuvinte cheie: leukemia, child, prognostic factors Rezumat:

Acute myeloblastic leukemias are a heterogenous group of hematologic malignancies. They are rare in children and progress in diagnosis and treatment are recent. The identification of some specific molecular markers allowed the new WHO classification since 2008 that distinguishes subtypes defined by molecular markers. The author analyses the prognostic factors that have particular significance: host factors, response to induction chemotherapy, cytogenetic changes and molecular abnormalities in patients with normal karyotype. The personal experience in the diagnosis and therapeutic strategy is presented, based upon the current knowledge about prognostic factors.

6. Management decisions and outcome in bilateral Wilms tumor

Autori: Emilia Mihut, Rodica Cosnarovici, Stefania Neamtu, Popita Vasile Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat: Management of bilateral Wilms tumor is very challenging, focused on the eradication of tumor and preservation of renal function. We report two cases of bilateral Wilms tumor with discussion of its treatment and management. Although Wilms tumor is one of the most common solid malignancies in children, bilateral disease is rare and is seen in only 5% of all patients. The management of bilateral Wilms tumor depends on the individual clinical scenario and requires a multidisciplinary clinic approach by a highly experienced team.

7. Realitate şi perspective în oncologia pediatrică

Autori: Rodica Cosnarovici Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

Cuvinte cheie:

Rezumat:

POSTERE

1. Systematic clinical, hematological, cytogenetic and molecular follow-up of chronic phase CML patients treated with TKIS. Impact on treatment Autori: Dima D, Cucuianu A, Patiu M, Trifa A, Selicean C, Balacescu O, Lelutiu L, Frinc IC, Pavel C, Rosu I, Petrov L Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: mutation, imatinib, leukemia, T315I Rezumat:

Introduction. Since the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), a dramatic improvement in hematologic, cytogenetic and molecular responses was noted. Also, the overall survival increased significantly. Unfortunately, in certain patients, resistance to TKI develops relatively early, especially due to point mutations in the ABL kinase domain, among which the T315I mutation confers resistance to all three currently available TKIs (imatinib, dasatinib, nilotinib). Methods. We performed a prospective study on 74 patients diagnosed with chronic phase CML, for whom we analyzed the T315I mutation. Mutational analysis was performed using ARMS-PCR (with subsequent confirmation by direct sequencing) at regular intervals of 6 months or in case of suboptimal response, loss of response or progression. Correlations between the T315I mutation and disease characteristics, response to treatment and survival were analyzed. A comparative analysis between patients positive and negative for the mutation was performed. The patients were followed and evaluated according to European Leukemia Net (ELN) criteria. Results. T315I mutation was detected in 3 patients (4.05%) and its presence was correlated with younger age at diagnosis, second line TKI therapy, progressive disease and decreased survival from the moment of detection. Conclusions. ARMS-PCR is a sensitive, easy to use method for the detection of T315I mutation in chronic phase CML patients.

2. Prognostic value of the International Staging System in multiple myeloma. Comparison with the Salmon Durie staging system Autori: Rosu A, Frinc IC, Tomuleasa C, Pavel C, Bibirigea A, Rosu I, Dima D, Selicean CE, Patiu M, Cucuianu A Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Multiple myeloma, staging, ISS, Salmon Durie Rezumat:

Background: Multiple myeloma (MM) is a malignant monoclonal gammopathy characterized by bone pain, lytic bone lesions, hypercalcemia, anemia, impaired renal function, bone marrow plasmacytosis. Since 1975 the Salmon Durie staging (SDS) system has the been used for the evaluation of prognosis of these patients, a staging system that takes into account the clinical features listed above. The subjectivity of the interpretation of bone lesions, an important part of the staging system, and the poor positive predictive value of the Salmon Durie system has led to the design of a new staging system, the International Staging System (ISS) in 2005. ISS takes into consideration the serum levels of beta 2 microglobulin and albumin. Several comparisons of the two systems have demonstrated the superiority of ISS. Aim: To compare the prognostic value of the ISS and Salmon Durie staging system for patients with multiple myeloma treated in the hematology department in Cluj-Napoca Material and method: The study is a prospective analytic study of the prognostic value and survival rates of 57 MM patients treated in 2012-2014 in the hematology department in Cluj- Napoca, that were grouped according to both systems. 33 patients (59%) were female and the median age was 60 years (range 4282) Evaluation of response included immunoglobulin levels,

serum and urine immunofixation, radiologic evaluation of the plasmacytoma, bone marrow aspiration/biopsy plasmacytosis, and were done at the end of 8 cycles of chemotherapy. Results: According to the Salmon Durie staging system, 9% of our patients were stage I, 30% stage II, and 61% stage III. Using the ISS, 27% of the patients were stage I, 33% stage II and 40% stage III. Until now 37 patients had undergone one or two evaluations, 12 of which had a complete response and have stopped treatment. Among the complete responders, 8 patients were in stage III, 3 patients were in stage II and 1 in stage I SDS, while according to ISS, 6 patients were in stage I, 3 patients were in stage II and 3 patient was in stage 1. The non-responder group was formed of 25 patients who had stable disease (15 in stage III SDS and 7 in stage II and 3 stage I SDS); according to ISS, 8 patients were stage III, 11 patients were stage II and 6 patient was stage I) and continue treatment with 2-nd or 3-nd line therapy. One patient, who initially had a complete response (stage IIIB SDS and stage III ISS) had an early relapse (6 months after autologous stem cell transplantation). Fifty five patients are currently alive and continuing observation regularly; one patient (stage IIIB SDS and stage III ISS) died 18 months after diagnosis. Conclusions: Between the responders group and the non responders group there were no differences according to Salmon Durie system, stage III patients forming the majority in both groups (66.6% and 60%), while, according to the ISS there were differences between the two groups: in the responders group the majority were stage I (50%), while in the non responders group stage II formed the majority of patients (44%). Therefore, the Salmon Durie staging system has a poorer prognostic value than the ISS, because it tends to confer a poor prognosis to the majority of patients.

3. Mutatia JAK2V617F in trombocitemia esentiala

Autori: Laura Urian, L. Petrov,A. P. Trifa, A. Bojan, A. Cucuianu, C. Basarab, M. Patiu, A. Vasilache, M. Zdrenghea, T. Torok, D Gavril Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: trombocitemie esentiala, mutatia JAK2 Rezumat:

Introduction: Essential thrombocythemia (ET) is a clonal myeloproliferative disease involving a hematopoietic stem cell and, manifesting predominantly as thrombocythosis, and it is associated with thrombohemorrhagic complications and myeloid transformation to diseases such as myelofibrosis and acute myeloid leukemia. In 2005 a unique acquired clonal mutation in JAK2 was found. This mutation was observed in the majority of polycythemia vera patients and in about half of ET or primary myelofibrosis patients.Methods We analyzed 107 cases of ET, from a single institution to determine the prevalence of JAK2V617F mutation and the clinical correlations. Mutation screening was performed on genomic DNA from peripheral blood from all 107 patients. Results: The JAK2V617F mutation was found in 51,4% of cases. 7,2% were homozygous for the mutant allele (>75%). Conclusions Patients with JAK2V617F positive had higher haematocrit, leucocytes levels and advanced age.

4. Rare association of chronic myelomonocytic leukemia, hypereosinophilic syndrome

and aggressive systemic mastocytosis diagnostic and therapeutic challenges Autori: Anca Vasilache, Radu Dancu, Carmen Basarab, Muntean Lavinia Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: CMML, systemic mastocytosis, hypereosinophilic syndrome Rezumat:

We present the case of a 52 years old man, who presented in our service in October 2011, with a splenomegaly detected at a routine ultrasound exam. He was than suspected to have CML but finally a diagnosis of Ph negative CMPS/CMML was made. After one year of unmonitored evolution and no treatment, he associated a hypereosinophilic syndrome (α -PDGFR negative, lack of response to imatinib 100 mg/day) and then aggressive systemic mastocytosis with abrupt onset

(important hepatosplenomegaly, enlarged lymph nodes, pleural effusion, positive histology in the lymph node and bone marrow, c-Kit positive and elevated serum tryptase). He had no response to cladribine and for a short time his disease was relatively stable with IFN-α, hydroxiureea and intermittent corticosteroids. In September 2013, the CMML entered a myeloblastic phase, resistant to aggressive chemotherapy and the patient died with hemorrhagic stroke.

The association of myeloproliferative disease or CMML with hypereosinophilic syndrome or systemic mastocytosis is noted in the literature but the association of the three conditions is rare. We also considered the end as particular, due to the blastic phase of the CMML and not to the aggressive systemic mastocytosis.

5. Dynamics of pediatric oncological pathology within 30 years

Autori: Ştefania Neamţu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: pediatric malignancy, distribution, survival, complications Rezumat:

Purpose: Retrospective evaluation of uni-institutional pediatric malignancy during a period of 30 years. Material and Method: 3 groups have been compared, representing new cases of children diagnosed and treated at the Oncology Institute “Prof.dr.Ion Chiricuta” Cluj-Napoca. The first cohort consisted of 787 children (1983-1992), the second one consisted of 908 children, out of which only 881 complied with the evaluation criteria (1993-2002) and the third cohort consisted of 760 children, out of which only 725 complied with the evaluation criteria (2003-2012). We studied the annual pathology distribution, survival rate, and development of late complications. Conclusions:The number of cases has increased in the second decade, with the decrease in the average age of disease manifestation, from 7, 8 years to 4, 7 years. The structure of the treated casuistry has changed a decreasing in the number of the malignant hemopathy has been registered and the increasing number of malignant solid tumors, especially thyroid and CNS tumors. There has been an increasing of the cases complexity and the diagnosis of rare pediatric tumors. Survival rate has improved, and late side effects decreased.

6. Improved hematological and clinical responses in MDS with combination therapy:

blood transfusion and chelation. Case report. Autori: Rosu A, Frinc IC, Tomuleasa C, Pavel C, Bibirigea A, Rosu I, Dima D, Selicean CE, Patiu M, Cucuianu A. Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: SMD, iron chlelation, transfusion Rezumat:

Introduction: The myelodysplastic syndrome (MDS) is a heterogeneous group of diseases of the hematopoietic stem cell, characterized by infective hematopoiesis and increased risk of acute leukemia transformation. The treatment varies from supportive care to potentially curative treatment such as allogeneic bone marrow transplantation. For most patients, the elective supportive treatment is packed red cell transfusions. Unfortunately, iron overload is an inevitable complication to multiple transfusions. This complication has recently and successfully been addressed with oral chelation therapy. Case presentation. VI, 61 years old, orderly, presents in our clinic in December 2006 with fatigue and dyspnea at slight effort. The symptomatology was present for several months. The patient used to be an alcoholic but has been abstinent for the past 7 years. The physical exam revealed severe pallor. The initial workout consisted of severe anemia (Hgb 6 g/dl) with normal WBC 6x10³/µl and PLT count 367x10³/µl, low reticulocyte count 9%o. The blood smear showed

poikilocytosis with codocytes and erythrocytes with basophilic stippling with a normal leucocyte differential count. The bone marrow aspiration revealed a hypercellular marrow with left shift of the granulocytic series with 4% blasts, 11% promyelocytes; the erythrocyte series represented 26% of nucleated cells with binucleated erythroblast, internuclear bridging, numerous codocytes and basophilic stippling . The Prussian blue stain showed 20% ring sideroblasts. The karyotype was normal and the JAK2V617F mutation was negative. Biochemically, there were no abnormalities and the ferritin level was 250 µg/l. The diagnosis of MDS- RARS, IPSS low risk was established and blood transfusions were recommended. The patient had since received 2-4 units of red cells monthly. A treatment with vitamin B6 250 mg/day was given between January 2007 and March 2007. During May-July 2007, a treatment with erythropoietin was given with no response. Three years after the diagnosis, the patient complained of increased fatigue, dyspnea and lower limbs edema. There were no changes on the ECG, but the echocardiogram showed restrictive dysfunction.

A diagnosis of congestive heart failure, NYHA II was established. At the time, the ferritin level was

1800 µg/l. Given the heart condition, treatment with deferasirox 40 mg/kgc/day was started in

September 2010. The clinical, biochemical and hematological evolution was favorable. The patient

is still given 2-3 units of red cells every month to maintain a Hgb level of 8-9g/dl, but he has no

symptoms under minimum cardiological treatment. The ferritin level is <1000 µg/l. and there are no signs of leukemic transformation. Conclusions. Iron overload is an independent negative prognostic factor, especially in low risk MDS patients. In MDS patients receiving red cell transfusions, the quality of life and survival can be improved with correct chelation treatment. The patient is still in good clinical condition at 8 years after diagnosis and his hematological and biochemical parameters are stable. There might also be a role for deferasirox in the hematological response. We expect a good overall survival for this patient.

7. Primary non-Hodgkin’s lymphoma of the orbit presenting with massive bilateral periorbital tumors Autori: Tünde Tőrők-Vistai, Anca Bojan, Anca Vasilache, Laura Urian, Andrei Cucuianu, Delia Dima, Andrada Pirvu, Daniela Gavril, Andrea Zsoldos Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: non-Hodgkin’s lymphoma, orbital tumors, vision loss. Rezumat:

Extranodal onset can be seen in approximately 25-40% of the cases of nonohodgkin lymphomas and diagnosis is often difficult due to nonspecific symptoms. Orbital lymphomas represent approximately 50% of the orbital malignancies., Common symptoms and signs at presentations are: palpable tumor, exophtalmos, dyplopia and decreased vision. Diagnosis can be made only by biopsy and early treatment is important in order to increase the chance of cure. We present the case of a patient whose diagnosis and treatment were delayed due to refusal of biopsy and, although complete remission of lymphoma was obtained, the vision loss was permanent because of prolonged compression on the optic nerves. A particularity of this case is the presence of massive periorbital tumors on admision to the hospital, incorporating the eye globes completely and causing impressive facial deformity.

8.

Difficult diagnosis in a case of large granular lymphocyte leukemia

Autori: Cristina Băgăcean 1 , Mariana Patiu 1 , Horia Bumbea 2 , Bogdan Fetica 1 , Jean-Michel

Picquenot 3 , Mihaela Groșan 1 , Mihnea Zdrenghea 1 Instituţie:

1. The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca and Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca, Romania

2. University Hospital Bucharest, Romania and Carol Davila University of Medicine and Pharmacy Bucharest

3. Centre Henri Becquerel, Rouen, France

Rezumat:

Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder thought to arise from transformed NK or T cells and is one example of chronic exposure to a pro- inflammatory cytokine, IL-15, being clearly implicated in cancerogenesis. This pathogenetic feature explains why treatment of T-LGLL is based on immunosuppressive therapy. However, the pathways of cytokine signals fitting into the bigger picture of malignant transformation are unclear. Molecular pathways that co-operate for malignant transformation downstream of prolonged IL-15 receptor signaling have been recently described. Proteasome inhibitor bortezomib is known to target some of these pathways and has been proposed as therapy in LGLL. Diagnosis of the majority of T-LGLL is established by documentation of increased numbers of clonal large granular lymphocytes in peripheral blood by specific morphology and phenotype. We here report the case of a 60-year-old patient with a history of chronic neutropenia of unknown origin since 2007, investigated in several hematology departments without the establishment of a diagnosis, referred to us in 2013 because of recurrent respiratory infections with severe neutropenia. The patient underwent a full diagnostic checkup including cytological and histological examination of bone marrow, which were at first attempt inconclusive, but cytology pointed towards the presence of unidentified nuclei infiltrating the marrow and led to bone marrow flow cytometric analysis, which finally allowed for the establishment of diagnosis. The patient was treated in first line with bortezomib, with inconclusive results, but responded to a second line of methotrexate in immunosuppressive doses.

9. Loss of CD20 tumoral expression after rituximab and chemotherapy in a nodular

follicular lymphoma Autori: Cristina Băgăcean 1,2 , Adrian Tempescul 3 , Mihnea Zdrenghea 1

Instituţie:

1. The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj -Napoca

2. Iuliu HațieganuUniversity of Medicine and Pharmacy, Cluj-Napoca, Romania,

3. Institute of Cancerology and Hematology, Brest University Medical School, France

Rezumat:

A humanized chimaeric antibody targeting CD20, rituximab is the first monoclonal antibody approved in cancer treatment, and is currently used in practically all B cell malignancies. Expression of CD20 is limited to mature and precursor B cells, and the histological and/or immunophenotypic demonstration of its presence in a tumor warrants the inclusion of rituximab in its therapy. However, repeated administration of rituximab can lead to the disappearance of CD20 molecule expression at B cell surface, rendering the drug useless. Despite this phenomenon being reported in B cell lymphoma since the advent of the drug, awareness among hematology practicians is still limited. We here present a case of nodular follicular lymphoma, treated with four courses of chemoimmunotherapy or immunotherapy with rituximab alone, showing CD20 expression loss at relapse. Our report emphasizes the importance of re-biopsy and CD20 expression assessment at relapse/progression.

10. Hemophagocytic syndrome secondary to common variable immunodeficiency. Case report. Autori: Frinc IC, Dima D, Patiu M, Selicean CE, Pavel C, Bibirigea A, Fetica B, Tomuleasa C, Cucuianu A Instituţie: The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca Rezumat:

Introduction: Common variable immunodificiency (CVID) is a heterogenous group of genetically determined primary humoral immune defects, manifested mainly in young adults, resulting in increased susceptibility to infections. Hemophagocytic syndrome (HS) is a potentialy lethal hyperinflamation syndrome caused by increased secretion of cytokines due to excessive but inefficient immune stimulation. Although there are cases of inherited HS, most cases are acquired, secondary to infections, immunodeficiency, autoimmunity or cancer. Case presentation: OL, 34 years old, presented in June 2013 at our clinic with high fever (40 0 C), altered general status, fatigue and diahreea. Since April 2013, the patient was hospitalized in various clinics with the same symptoms. He was treated with antibiotics and short courses of corticosteroids with good, but short responses. The clinical exam revealed hepatomegaly 4 cm and splenomegaly 6 cm under the costal margin. The hematological examination showed severe normocytic normochromic anemia (Hgb 5.3 g/dl) and increased ESR (143mm at 1h). Biochemically, there were signs of hepatic failure: AST 222 UI/l, ALT 210UI/l, ALP 1080 UI/l, hypoproteinemia with hypoalbuminemia (total proteins 5,3 g/dl, albumin 2.3 g/dl), increased ferritin (9770 microg/dl), increased procalcitonin (7,76 ng/mL) and hypogammaglobulinemia (IgG 548,6mg/dl, IgA 50,2mg/dl, IgM 7mg/dl), hypertriglyceridemia (344 mg/dl). The bone marrow aspiration revealed a hypercellular marrow with granulocytic hyperplasia with a left shift, toxic granulations within the neutrophils and frequent histio-monocytic cells with important hemophagocytosis of erythrocytes, leukocytes, platelets, erythroblasts and neutrophils. Some of the histiocytic cells displayed digestive vacuoles. The screening tests for HCV, HBV, HIV, EBV and CMV were negative. The stool was positive for Clostridium difficile. The hemocultures were also positive for Staphylococcus saprophyticus. A diagnosis of Common variable immunodeficiency complicated with hemophagocytic syndrome, septicemia with Staphylococcus saprophyticus and acute enterocolitis with Clostridium difficile was established. The patient was treated with antibiotics, antifungals, corticoids, red cell transfusions and intravenous immunoglobulins (10g). The response to therapy was good with resolution of fever, improvement of hematological and biochemical parameters and normalization of spleen volume. The patient was subsequently referred to Medical Clinic III, Immunopathology Dept. for continuation of treatment with immunoglobulins. Unfortunately, the patient was hospitalized again in less than a month due to reappearance of fever, anemia, and splenomegaly. Biochemically there was worsening of hepatic failure, increased ferritin (17000 microg/dl). The CT scan showed left lobar pneumonia, multiple mediastinal and abdominal adenopathies, hepatomegaly, ascites, bilateral pleural effusions and splenomegaly with hypodense nodules. Treatment with antibiotics, antifungals, red cell transfusions and corticosteroids was reinitiated, but the patient’s status deteriorated, with the occurrence of seizure, coma and death shortly afterwards. Conclusions. This case illustrates the difficult management and severe outcome of CVID complicated with HS, due to repetead severe infections and multiple organ failure.

11. Late

diagnosis

of

Hodgkin’s

lymphoma:

paraneoplastic,

immune

complications and fatal outcome. Case report.

and

infectious

Autori: Pavel C, Patiu M, Fetica B, Dima D, Frinc IC, Rosu A, Rosu I, Bibirigea A, Selicean CE, Tomuleasa C, Cucuianu A Instituţie: The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca Reyumat:

Introduction. Hodgkin’s lymphoma is a neoplasm of the lymphoid tissue characterized by the presence of malignant Reed-Sternberg and Hodgkin cells of germinal center origin in a specific microenvironment composed by T, B cells, neutrophils, eosinophils, plasma cells, histiocytes. With combination treatment- chemotherapy and radiotherapy, the survival expectation at 10 years for patients under the age of 65, is 70-80%. Case presentation. HAR, 42 years old presents at our clinic in February 2014 with altered general status, marked fatigue, important weight loss (17 kg) and persistent laterocervical adenopathy. The symptomatology was present for 2 months. The patient has also complained of persistent diarrhea, cough, fever and edema in lower limbs. The patient has presented a laterocervical adenopathy for 4 years. There were 2 biopsies performed, both revealed a reactive lymphoid tissue. At clinical exam: an important right cervical adenopathy 6/7 cm and lower limb edema. Hematological exam shows moderate hemolytic anemia (Hgb 7.3 g/dl, reticulocyte count 140%o) and thrombocytopenia (Plt 90x10ᵌ/µl). Biochemically, there was severe hypoporotidemia secondary to nephrotic syndrome, hypogamaglobulinemia, increased ferritin and cholestasis. Bone marrow aspiration reveals hypercellular marrow with left shift of granulocytic series and histio-monocytic cells with hemophagocytic activity. The CT of thorax and abdomen did not show other lymphadenopathies, but revealed effusions both pleural and ascites. The stool was positive for Clostridium difficile. The bacteriologic exam of sputum was positive for Pseudomonas aeruginosa and Candida albicans. There was a third biopsy of the lymphadenopathy perfomed and it has showed an infiltration of Reed Sternberg cells. The diagnosis of HL stage I Bulky was established, complicated with nephotic syndrome, autoimmune hemolytic anemia, hemophagocytic syndrome, acute enterocolitis with Clostridium difficile and acute pneumonia with Pseudomonas aeruginosa and Candida albicans. The patient has received antibiotherapy, antifungals, corticotherapy, intravenous albumin and packed red cell transfusions. The general and bioumoral status of the patient have improved. At that time chemotherapy was offered. Considering the prognosis of the patient, a cycle of BEACOPP chemotherapy was administered. The patient was discharged in good general health. Soon after the chemotherapy, the patient presents another infectious complication that is treated in another hospital with no response and alteration of general status and exitus. Conclusions. The goal of treatment in Hodgkin’s lymphoma is cure, possible with current combination therapy. Delayed diagnosis of HL is associated with advanced disease, complications such as: paraneoplastic manifestations, immune deficiency, infectious complications and finally, severe outcome despite aggressive chemotherapy.

DISCIPLINE FUNDAMENTALE

COMUNICĂRI ORALE

1. Comparison of one- and two-color microarray experiments, within Agilent platform

Autori: Loredana Balacescu 1 , Oana Tudoran 1 , Ovidiu Balacescu 1 , Ioana Berindan-Neagoe 1,2 Instituţie: 1- The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca 2- “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: one-color design, two-color design, microarray, Agilent Rezumat:

Introduction. Agilent microarrays platforms allow both one- and two-color labeling of samples to detect changes in gene expression. Although the performance of these approaches has been widely demonstrated, there are advantages and disadvantages of each labeling design. In this study we compared the results obtained from one- and two-color microarray experiments, performed on Agilent platform. Material and methods. Total RNA was isolated from negative- and PDGFBB-siRNA treated Ca Ski cells, obtained in three independent experiments. PDGFBB inhibition upon siRNA treatment was confirmed by qRT-PCR. The same three cell line replicates for each condition were used for both one- and two-color experiments, negativetreated cell lines considered as reference. Feature Extraction software were used to quantify the fluorescent images. For both experiments, microarray data analysis was performed in R, using suitable methods for each design. Results. The data were evaluated in terms of reproducibility and accuracy to determine if this two approaches provide comparable results. Using one-color design, we identified 58 genes whose differential expression exceeded 1.3-fold (adjusted p-value < 0.05) in PDGFBB-siRNA treated compared to negativesiRNA treated Ca Ski cells. A very different transcriptional profile was obtained using two-color design. The data analysis highlighted 671 differentially expressed genes between PDGFBB-siRNA treated and negativesiRNA treated Ca Ski cells (Fc > 1.3, adjusted p-value < 0.05). Of the 58 genes that were found to be differentially expressed in one-color experiment, 52 genes were also identified in the two-color experiment. Significant down-regulation of PDGFBB upon siRNA treatment, previously demonstrated by qRT-PCR, was observed just in two-color experiment. Conclusions. Our data showed a significant difference in the number of changing genes detected with the two approached. The results indicate that two-color microarray experiments have an increased power to find differentially expressed genes between groups with small differences in expression.

2. The relationship between FA/BRCA pathway and therapy failure in advanced squamous

cervical cancer. Autori: Ovidiu Balacescu 1 , Loredana Balacescu 1,2 Rares Buiga 1 , Oana Tudoran 1,2 , Nicolae Todor 1 , Viorica Nagy 1,2 , Claudia Ordeanu 1,2 , Ioana Berindan-Neagoe 1,2 Instituţie: 1- The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca 2- “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca Cuvinte cheie: FANCD2, RAD51, BRCA1, BRIP1, cervical cancer, treatment prediction

Rezumat:

Introduction: Cervical cancer, the third most commonly diagnosed cancer in women, represents a major problem in oncology. About half of the patients with advanced cervical cancer will develop recurrence or metastasis in the first 2 years after completion of therapy. The aim of this study is to identify new prognostic factors that could distinguish between patients with unfavorable prognoses from others with better prognoses. Material and methods: Forty five patients with locally advanced squamous cell carcinoma were enrolled in this study. Fresh primary biopsies from twenty-one patients harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months

clinical response. The rest of twenty-four FFPE primary biopsies were used for independent validation of the proteins of interest. Results: One hundred and twenty four genes involved in DNA replication, recombination and repair were activated (92 were over-expressed and 32 were down-regulated) for patients with unfavorable prognoses compared with that with better prognoses. Role of BRCA1 in DNA Damage Response was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262. Conclusions: Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the patients at risk for treatment failure.

3. Titanocene nanostructures modulate PARP-1 and Bax-α expression

Autori: E.Fischer-Fodor, S.Gomez-Ruiz, J.Ceballos-Torres, P.Virag, M.Cenariu, S.Prashar, M. Fajardo Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: antitumor, nanostructures, apoptosis, PARP-1, metallodrug Rezumat:

Chemotherapeutic treatments based on metallodrugs, traditionally platinum complexes has a relatively high number of side effects and this opened up interest in the use of other metal complexes with similar antineoplastic properties. Thus, we focused our efforts on the design of a novel synthesized titanocene compounds series grafted onto a nanostructured porous material, which act as vectors for the delivery of the metallodrug and as a protector of the active species for the enhancement of its anti-cancer action. A very high in vitro activity has been observed against colon, ovary and breast cancer cells. Their inhibitory effect is much higher than the majority of the titanocene derivatives reported before and present superior cytotoxic activity and selectivity. From studies of the apoptosis induction capacity, evaluation of the modulator effect on the intrinsic apoptotic pathway (through Bax-α and Bcl-xL) and apoptosis regulation at the DNA level, one can conclude that the dynamics of apoptotic morphological and functional changes is modified when the active titanocenes are incorporated onto mesoporous materials. Compounds are able to induce programmed cell death in tumor cell populations, by impairing the damaged DNA repair mechanisms by PARP-1 inhibition and by up-regulation of intrinsic and extrinsic apoptotic signaling pathways. The compounds are acting as Trojan horses for the incorporation of the active species into the cells, leading to enhanced cellular uptake. Therefore, these nanostructures are good candidates for targeted anti-cancer therapy, because of their interesting biological properties and because the higher permeation of the membranes of cancer cells in comparison with healthy cells and this may advantageous for the specific use of these materials in chemotherapy.

3. Rectal cancer extended to the adjacent anatomic structures: pathology features and surgical implications Autori: R. Simescu 1,2 , O. Fabian 1,2 , M. Cazacu 1,2 , I. Domsa 3 , A. Zolog 3 , A. Mihailov 1,2 , G.

Petre 1,2 , I. Simon 1,2 , T. Oniu 1,2 , C. Lungoci 1,2, D. Deceanu 1,2 , R. Galasiu 1,2 , C. Radu 1,2 , V. Muntean 1,2 Instituţie: 1 - CF Clinical Hospital

2 - “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca

3 - CF Clinic Cluj-Napoca

Cuvinte cheie: colon cancer, invasive cancer, surgical treatment Rezumat:

Introduction: Surgical treatment of the colon cancer invading adjacent anatomical structures (T4b) remains a controversy. R0 resections go only by laborious surgery. Subsequent morbidity and mortality cannot be justified unless there is significant therapeutical benefit. Patients and method: Patients with colon cancer extended to adjacent anatomical structures (T4b) were compared with patients without extracolonic extension (T1-T4a) and with ones having invasions of the serosal layer (T4a). Information was drawn from a prospective database, including operative protocols, specimen pathology findings and follow-up data. Only patients who underwent elective surgery and with complete database information were included in the study. Statistical analysis was performed using Microsoft Excel and OpenEpi. Rates were compared using the chi- square test; p values under 0,05 where considered statistically significant. Results: During a 10-year period (2004-2013) 498 colon cancer patients were treated. Out of the 462 patients included in the study, 161 had tumors invading adjacent structures (pT4b); 301 had no extracolonic invasion (pT1-pT4a), out of which 65 presented serosal invasion (pT4a). Compared with T1-T4a, T4b tumors presented statistically significant low tumor grade (G), infiltrative growth pattern, no increased inflammatory infiltrate, more frequent lymph node metastases and venous, lymphatic and perineural invasion. As compared to T4a, T4b tumors presented statistically significant low tumor grade (G), increased peritumoral inflammatory infiltrate and venous invasion. One third of pT4b tumors were N0M0 (IIC stage; Dukes B; MAC B3). There was no statistically significant difference between the three study groups regarding the type of resection (R0, R1 or R2), morbidity and immediate perioperative mortality. Conclusions: Colon tumors extended to the adjacent anatomical structures show a locally and regionally increased invasion pattern. Multiorgan resections R0 are justified whenever perioperative morbidity and mortality remain within acceptable ranges. In what regards cases classified as T4bN0M0 (MAC B3), any palliative surgery would be inacceptable.

4. Nanotechnology in conversion of cancer stem cell resistance to chemotherapy

Autori: Soriţău O 1,2 , Tomuleasa C 1,2 , Orza A, Petrushev B, Aldea M 3 , Florian S 2 , Kacso G 1 , Irimie

A 1,2

Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca,

2 - “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca,

3 - Babeş-Bolyai University Cluj-Napoca

Cuvinte cheie: gold nanoparticles, cancer stem cells Rezumat:

The lack of efficacious pharmacological treatments in cancer has been recently attributed to the presence, within the tumour, of cancer stem cells (CSC), which are poorly responsive to the antineoplastic drugs because of their chemoresistant properties and ability to stimulate neoangiogenesis. Glioblastoma is an example of oncological localization with high resistance to chemotherapy. Recently, gold nanoparticles (GNPs) have developed into an attractive candidate for the specific delivery of complex drugs, molecules, and/or biomolecules. Because of their ability to accumulate selectively in tumor tissue, GNPs can serve as detectors of cancer cells or as targeted drug delivery agents.

Glioma cancer stem cells were found to interact strongly with GNPs-based drug delivery vectors. Phase contrast microscopy showed that GNP-L-aspartate was internalized within the first hour. After 24 hours, the drug delivery vector affected the number of cells, their rate of proliferation, and their shape, suggesting that the cells entered a pre-apoptotic stage. Measurements of in vitro cytotoxicity and apoptosis indicate that combination with GNPs facilitated the ability of temozolomide to deliver into CSC and to alter the resistance of these cells to therapy. Temozolomide-loaded GNPs were able to reduce the CSC chemoresistance and destroy 82.7% of CSC compared with a 42% destruction rate using temozolomide alone. This approach based on nanotechnology proposes a novel chemotherapy strategy with minimal toxicity and increased efficacy profiles for the destruction of cancer stem cells for patients with unresectable recurrent malignant glioma.

5. Potential biomarkers for therapeutic response in colorectal cancers

Autori: P. Virag, I. Brie, E. Fischer-Fodor, O. Barbos, G. Chereches, Zs. Fekete, C. Cainap, E. Cojocaru, A. Muntean Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: GDF-15, Treg, colorectal cancer, markers, therapeutic response Rezumat:

Background: The outcome of the treatment of colorectal cancers (CRC) and the severity of the delayed adverse effects impose the identification of potential markers of therapeutic response (TR) in order to establish individually tailored therapies. Lately, a special interest was paid for the growth and differentiation factor-15 (GDF-15), member of the TGF-beta superfamily, which regulates the inflammatory and apoptotic processes in injured tissues, being proposed as biomarker of the activation of the p53 pathway in some cancers. The TR is also influenced by the status of the immune system; one of the responsibles for the immune suppression during the tumor progression is the Treg subpopulation (CD4+, CD25+, FOXP3+). The aim of this study was to analyze the ratio of the Treg subpopulation and the serum level of GDF-15 as potential TR markers in vivo. Patients and methods: 25 patients with loco-regional advanced CC and a group of 6 healthy volunteers were included in this study. Blood samples were collected before therapy and after radio- and chemotherapy (RT/ChT). Lymphocytes were isolated in density gradient for Treg subpopulation establishment by flow-cytometry. Blood serum was also separated and stored until ELISA was performed for the GDF-15 assessment. Results: Significant increases were registered both in the Treg subpopulation and GDF-15 level after RT/ChT in the patients’ group vs before treatment (p<0.05 and p<0.0001, respectively). Significant differences in the basal levels of the Treg cells and GDF-15 were observed in the patients’ group as compared to the healthy volunteers’ with interindividual variations in the patients’ group. Conclusion: These results support the idea that correlations may exist between the basal levels of the tested parameters and the clinical evolution of the disease which might be exploited in the establishment of TR markers in CC.

6. Introduction of personalized therapy in Romania

Autori: Tudor E. Ciuleanu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: personalized therapy, clinical research, pivotal trials Rezumat:

As of May 2014, the recognized “official” standard of care in cancer is still represented by the 2009 edition of the ESMO guidelines. Cancer treatment is free, as the National Program of Oncology covers the budget for all cytotoxic agents and targeted therapy. However, reimbursement for several expensive drugs for solid tumors such as bevacizumab, cetuximab, erlotinib, imatinib, pemetrexed, sorafenib, sunitinib, trastuzumab, is individually approved by a centralized commission with monthly reunions. Analyses of biomarkers are not covered by the insurance companies or the state budget. Some of them are sponsored by the pharmaceutical industry (such as HER2 FISH

testing, mutational status for EGFR or KRAS). All the new drugs registered in Europe by a common procedure by the European Medicines Agency are concomitantly authorized for medical

use in Romania. However, no new drugs (such as abiraterone, afatinib, aflibercept, axitinib, cabazitaxel, cabozantinib, catumaxomab, crizotinib, dabrafenib, degarelix, denosumab, enzalutamide, eribulin, everolimus, gefitinib, ipilimumab, lapatinib, panitumumab, pazopanib, pertuzumab, regorafenib, sipuleucel, trabectedin, trastuzumab emtansine, vandetanib, vemurafenib, vinflunine, vismodegib) and no new indications (such as 1st line TKIs or maintenance treatment in NSCLC, trastuzumab in early breast cancer or advanced gastric cancer, bevacizumab in gynecological cancers, sunitinib in neuroendocrine tumors) were accepted for reimbursement since

2008.

On the other hand, clinical research is rapidly growing and Romanian centers demonstrate a high recruitment rate in pivotal trials, despite initial delays due to a slow approval of the studies by the competent authorities.

8. Validation of molecular profiles in cancer through independent studies

Autori: Ioana Berindan Neagoe 1,2 , Ovidiu Bălăcescu 1 , Cornelia Braicu 2 , Oana Tudoran 1 , Loredana Bălăcescu 1 , Roxana Ilies 2 , Emilian Neagoe 1 , Alexandru Irimie 1,2 Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca, 2 – “Iuliu HatieganuUniversity of Medicine and Pharmacy Cluj-Napoca Cuvinte cheie: molecular profiling, breast cancer subtypes patterns, bioinformatic data Rezumat:

The development of new genomics throughout technologies in cancer research brought the data generation facilities as one of the most important issue in the interpretation and generation of a specific molecular profile pattern. Breast cancer is one of the most studied due to the heterogeneous molecular subtypes and the number of new cases and death each year worldwide. The concept of molecular profiling has fundamentally changed our understanding of breast cancer in the last decade by creating a new genetics of breast cancers based on the expression patterns. Actual we are looking into molecular profiles of breast cancer defined as distinct breast cancer subgroups (luminal type A/B, HER2-enriched type, basal-like type). The use of gene microarray approaches revealed individual properties of the intrinsic subgroups regarding the clinical course and the responsiveness to chemotherapy. The new gene expression profile-based morphology of breast cancer address as a major breakthrough on the way to individually tailored therapies. However, validation of the gene signatures in prospective studies is necessary before accepting these new technologies in daily clinical practice. The current data regarding the breast cancer subtypes and the associated clinical implications as well as the methodology of molecular profiling and complex use of bioinformatics data in identifying common patterns for different subtypes come into discussion.

9. Mutation analysis of triple negative breast cancer patients using next generation sequencing

Autori: Laura Pop, Roxana Petric, Oana Virtic, Ioana Berindan-Neagoe Instituţie: Iuliu HatieganuUniversity of Medicine and Pharmacy Cluj-Napoca Cuvinte cheie: triple negative breast cancer, mutations, next generation sequencing Rezumat:

Introduction: Despite the intense research in the field of breast cancer, this disease still remains the second most common cancer in women worldwide, being the first cause of death in women in Romania. Among the different subtypes of breast cancer, triple negative breast cancer (TNBC) needs a special attention due to its limitations in therapy and to its aggressiveness. Several studies have tried to identify different new mutation both in oncogenes and tumor suppressor gene in order to explain these limitations of TNBC treatment. The present study was aimed at the identification of mutations in 46 genes involved in cancer in 31 patients with TNBC operated at the Institute of Oncology ”Prof. Dr. I. Chiricuta”, Cluj-Napoca between 2006-2007, using Next Generation Sequencing.

Material and methods: We used FFPE tissue samples, from which we extracted the DNA, which was sequenced using the Ion Torrent Personal Genome Machine and the Ion Reporter 1.6 software for data analysis. Discussions: After data analysis we obtained 103 mutations in 34 genes of the 46 studied. The clinical assessment of the identified mutations showed that three mutations were benign, one was likely benign, 42 were likely pathogenic, 28 were pathogenic and 29 had no assessment. This study also identified KDR, TP53, PIK3CA, FGFR3 and FGFR2 genes as being the most frequently mutated genes. Conclusions: Our results show that TNBC has specific mutations leading to resistance to therapy and poor outcome of these patients.

10. TGF-β siRNA therapy enhance doxorubicine antitumoral therapy in triple negative breast cancer model Autori: Cornelia Braicu 1 , Eve Ponthière 1,2 , Mahafarin Maralani 3 , Roxana Petric 1 , Valentina Pileczki 1,4 , Gherman Claudia 1,5 , Ioana Berindan-Neagoe 1,5,7 Instituţie:

1 - Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu HatieganuUniversity of Medicine and Pharmacy,

2 - Haute École Louvain en Hainaut, Fleurus, Belgique

3 - Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey

4-Faculty of Pharmacy, Iuliu HatieganuUniversity of Medicine and Pharmacy

5 - Department of Functional Genomics and Experimental Pathology, The Oncology Institute Prof. Dr. Ion ChiricutaCluj-Napoca

6 - National Institute for Research and Development in Animal Biology and Nutrition (IBNA)

7 - Department of Immunology, Faculty of Medicine, Iuliu HatieganuUniversity of Medicine and

Pharmacy Cluj-Napoca Cuvinte cheie: TGF-β siRNA , doxorubicine, triple negative breast cancer Rezumat:

Doxorubicine is a chemotherapeutic agent routinely used for triple negative breast cancer (TNBC) therapy. TNBC is characterized by the absence of estrogen, progesterone, and HER-2 receptors and a reduced response to classical therapy. Therefore, new therapeutic strategies should be tested. In the present study was tested the combinatorial effect of doxorubicine with RNA interference (RNAi) therapy. RNAi is a natural mechanism in which a double-stranded RNA causes degradation of the complementary mRNA. TGF-β siRNA in combination with doxorubicine was tested on the Hs578T cells. The magnitude of cellular effects was tested using MTT test, invasion capacity using matrigel assay and gene expression alteration was evaluate using PCR-array technology (Breast cancer Panel, Qiagen cat no. PAHS-131Z). TGF-β downregulation was connected with an increased reduction of cell proliferation and a decreased invasion capacity as we were able to observe by fluorescence staining. Doxorubicin therapy is associated with undesired pathological characteristics characteristics like, epithelial- mesenchymal transition (EMT) or drug resistance. Our experimental data suggest that TGF-β inhibition in the presence of doxorubicine leads to an enhanced antitumor theraphy via preventing drug resistant mechanism and modulation of immune response.

11. In house informatics a framework for conducting clinical trial Autori: Nicolae Todor Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: medical informatics, oncology project methodology Rezumat:

Introduction. Firstly is presented “in house” informatics system of Institute "Prof. Dr. Ion Chiricuţă" (IOCN). It consists of a complete informatic medical system adapted to the requirements of modern oncology. Clinical trials have unfourtunately a precisely limited target but the information is often difficult to retrieve. Material and methods. The framework provided by us with the informatics “in house” system allows instant access to all the information making it a very powerful tool in the hands of investigators. Now a set of modules cover all functional areas of IOCN excepting Brachytherapy and hematology laboratory where we have only ongoing solutions. Results. In IOCN these studies are used extensively for doctoral works, residents and seniors works or in IOCN projects as: BREAST-IMPACT, CERVIX-ARRAY, ANGIOCOL, etc. Through these examples drawn from IOCN’s panel studies practical aspects of such an approach are presented. Discussions. Oncology centers in the world have such facilities since 70s, the era of computer punch card, our solution taking advantage of the facilities present in IOCN rises to the accepted standards in modern oncology. Conclusions. Studies and projects successfully modular integrated until now increases our confidence that chosen approach allows simple further development of the system.

POSTERE

1. Circulating tumor cells: a novel method of detection

Autori: Otilia Bărbos, Gabriela Cherecheş, R. Buigă, T.E.Ciuleanu, D.Eniu, Cristina Cebotaru Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: metoda, CTC, cancer Rezumat:

The detection of circulating tumor cells (CTCs) in the peripheral blood of cancer patients holds great promise but remains technically challenging. Many research groups are currently assessing the clinical utility of CTCs for prognosis and monitoring response to systemic therapies. We present here a novel method of detection, developed in our laboratory, performed on different types of cancer cells wich were obtained from the blood of colorectal, breast and testicular cancer patients and also from the lymph of operated breast cancer patients. CTC analysis will contribute to a better understanding of the complex metastatic process in cancer patients, which might unravel new strategies to eradicate metastatic cells or control their outgrowth into life-threatening overt metastases.

2. Detection of Circulating Tumor Cells (CTCs) on metastatic colorectal cancer patients

Autori: G.Chereches, O. Barbos, R. Buiga, T.E. Ciuleanu, D. Iancu, V. Manolescu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: circulating, tumor, cells, chemotherapy Rezumat:

Circulating tumor cells (CTCs) are released into the blood from primary and metastatic tumors and have high clinical diagnostic potential in oncology. Enumeration of CTCs as a prognostic and predictive factor of survival an overall disease progression in advanced colorectal cancer patients has been reported in several studies. We present a novel method of detection, performed on 50 cases of metastatic colorectal cancer patients, following chemotherapy. 6ml of blood samples have been collected at baseline, after 3 cycles of chemotherapy and a third one after completing 5 cycles of therapy. Each sample was treated with a red blood cells (RBC) hemolysis solution, blood smears were than imunohistochemic stained, followed by microscopic evaluation. The integration of present method into routine immuno-chemotherapy could be suggested for the research of the metastatic process and the determination of an eventual correlation between circulating tumor cells and metastases in humans.

3. NextGen Sequencing: a tool for deciphering the BRCA1/2 and TNBC relationship

Autori: Roxana Cojocneanu Petric 2 , Laura Pop 1 , Ioana Berindan Neagoe 1 Instituţie: 1 - “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, 2 Babeş-Bolyai University Cluj-Napoca Cuvinte cheie:

Rezumat:

Introduction. Although during recent years science and technology have generated a great deal of progress in medicine, breast cancer still is the most common malignancy and the leading cause of death by cancer in women. Triple negative breast cancer (TNBC), characterized by the absence of Estrogen and Progesterone receptors and Her2/neu, affects 15-20% of breast cancer patients, has a more aggressive phenotype and occurs at younger ages. Because of its therapeutic limitations, TNBC needs to be investigated in more detail with the help of new technologies. Materials and method. Our study focuses on exploring the mutation status of BRCA1/2 genes involved in hereditary breast cancer, and with known mutations in TNBC. This retrospective study on 30 TNBC patients who underwent surgery at The Oncology Institute “Prof. Dr. I. Chiricuta” Cluj-Napoca was conducted with the help of the next generation sequencing platform Ion Torrent PGM. The biological material consisted of FFPE tissue from which we extracted the

DNA necessary for subsequent library preparation, amplification and sequencing. Results. After data analysis, we observed that 20 of the 30 patients presented germline BRCA1/2 mutations, of which seven in BRCA2, 10 in BRCA1, and three in both genes. We identified two mutations that are frequent in patients of European descent with hereditary breast cancers, two that are similar to mutations identified in families of Swedish origin, and several other new mutations. Conclusions. This is the first study that investigates BRCA1/2 mutations in TNBC patients in Romania, and proves that NextGen Sequencing is a competitive and cost-effective BRCA screening method especially in low-income countries where patients cannot afford early breast cancer diagnosis.

4. 40 years of population-based Cancer Registration in the frame of 85 excellence years of

the Oncology Institute “Prof. Ion Chiricuta”, Cluj-Napoca Autori: Coza D. 1 , Nicula F. Al. 1 , Șuteu O. E. 1,2 , Blaga L. M. 1 , Todescu Al. 1 , Marton A. 1 , Lovasz

L. 1 , Sîrbu M. 1 , Achimaș-Cadariu P 1,2 ., Irimie Al. 1,2

Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

2 – “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca

Cuvinte cheie: cancer, registry, incidence, registration, population-based Rezumat:

Introduction: Oncology Institute, set-up in 1929, had always a major field of interest in cancer prevention and registration. Population-based cancer registration in Cluj County, started in 1974, supervised by Institute’s Department of Prevention and Cancer Control, 6 years before it became compulsory by law, in Romania. Cancer data were used internationally, published in WHO’s Monography Cancer Incidence in Five Continents (CIV) volumes IV, V, VI, (1974-1987) and considered for national cancer estimates in GLOBOCAN 2008 and 2012 and EUCAN databases (2000-2010). Material and method: We analyzed average age-standardized incidence (ASRW), for five years intervals, for Cluj County, since 1974 to 1987 and 2001 to 2010. The source of information was CIV published data (1974-1987) and Cluj Cancer Registry (2001-2010). We computed percent changes in incidence and hierarchy of the main primary sites, by sex. Results: Overall, the number of new cancer cases almost doubled (96% increase) in the last period compared with the first one (in men 8137/4151, in women 7587/3866), with an increase ASRW of 40.3% in men (287.2/204.8) and 37% in women (227.4/166). The hierarchy of first five primaries changed between first and last interval, in men, from stomach, lung, liver, prostate, rectum to lung, prostate, stomach, colon, rectum and in women from breast, cervix, stomach, liver, ovary to breast, cervix, colon, corpus uteri and thyroid. Discussions: With few exceptions all cancer sites showed an increase in incidence, during the 40 years, both in men and in women, the most significant concerned bladder, prostate and colon in men and thyroid and colon in women. Stomach and liver cancers decreased with 48.5%, respectively 13%, in men and 59.8% respectively 48.1%in women. Conclusions: The overall burden of cancer continued to raise in Cluj County, partially due to growth and ageing population, improvement in diagnostic methods and in cancerregistration.

5. Modulation of apoptotic mechanisms in ovarian cells A2780 and A2780 cisplatin

resistant cells Autori: Claudia Gherman 1 , Maralani Mahafarin 2 , Flaviu Drigla 1 , Ovidiu Leonard Braicu 3 , Ioana

Berindan-Neagoe 1,3 Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

2 - Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey

3 - “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: CAPE, ovarian cancer, apoptotic mechanisms

Rezumat:

Introduction. Ovarian carcinoma is still considered one of the most lethal gynecological cancers. In this context, the chemoresistance to treatment is a clinical issue that drastically limits the therapy success. We investigated the effect of caffeic acid phenethyl ester (CAPE), a major component of propolis, in ovarian cancer cell lines. Materials and methods. We used A2780 and A2780 cisplatin resistant cells to examine the cell viability using MTT test, evaluation of apoptosis by flow cytometry and invasion assay with Matrigel, followed by qRT-PCR to observe the expression of relevant apoptotic genes. Results and discussions. As was expected, we have a significant reduction of cell proliferation in both cell lines, due to the activation of the apoptotic mechanisms. qRT-PCR data shows that CAPE was able reduce the expression of the proinflammatory phenotype, particularly in the case of cisplatin resistant cells. The proapoptotic effect in both cell lines is also due to the interaction with the TGF-β pathways. Conclusions. CAPE alone or in combination might be implemented in the advancement of anticancer therapies in ovarian cancer, particularly for the cisplatin-resistant tumours.

6. Pretherapeutic evaluation of lymphocyte radiosensitivity as a biomarker in cervix carcinoma Autori: Ioana Brie 1 , Nicolae Todor 1 , Piroska Virag 1 , Maria Perde-Schreppler 1 , Alexandra Ticle 2 , Viorica Nagy 1,2 Instituţie: 1 - The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca 2 - University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca Cuvinte cheie: radiosensitivity, in vitro, comet assay, cervix carcinoma Rezumat:

Background. The modern radiotherapy techniques and association of chemotherapy or surgery (SY) improved the therapeutic results in cervix cancer. However, it remains the unsolved problems of the increased rate of local failures, ranging between 20% and 30%, and of the late side effects of radiotherapy. This raise the problem of finding new predictive and prognostic factors that can be utilized for choosing the most efficient therapeutic modality for each patient. Among the radiosensitivity (RS) tests, very promising are the DNA lesion assays such as the comet assay (CA) - a sensitive and reproducible method which detects DNA alterations induced by radiation and other genotoxic agents. CA is a fast, reproducible and relatively low-cost method that has the potential to evaluate the basal level of DNA lesions as well as their induction and repair. Aim. The aim of the present study was to test if the in vitro parameters of radiosensitivity (RS) measured by Comet Assay in lymphocytes from patients with cervix carcinoma were able to predict their clinical outcome and the late complications after radiochemotherapy (RCT). Patients and methods. The study analyses 83 patients with stage IIB cervix carcinoma that were included between 2006-2008 in a prospective randomized phase III trial with 2 arms: RCT alone (41 patients) and RCT followed by SY (42 patients). Using comet assay, 3 parameters of in vitro lymphocytes RS were determined before the beginning of therapy: the basal level of DNA alterations, the induction of new lesions by irradiation and the repair capacity. The outcome of patients (local, regional or distant relapse) was clinically assessed by regular controls after the end of the treatment. Normal tissues late reactions were evaluated on the base of Common Toxicity Criteria for Adverse Effects (CTCAE vs. 2.0). In vitro lymphocytes RS was correlated with patients outcome and with the late normal tissues complications. Results. With a median follow-up period of 69 month, 10 relapses were registered in the group of 83 patients (12,05%). The rate of late complications (rectal and bladder side effects, vaginal fibrosis and lymphoedema) was 19,28%. Using ROC analysis, significant correlations between the late side effects of RCT (especially fibrosis) and 2 parameters of lymphocytes RS were found in operated patients, who received lower doses of radiotherapy: the level of DNA lesions at 2 hours after in vitro irradiation (p = 0.02) and the DNA repair capacity (p = 0.03). Significant correlations were also found between the locoregional tumor control and other 2 parameteres of

lymphocytes RS: the basal level of DNA alterations (p = 0.03) and the induction of supplementary DNA lesions by in vitro irradiation (p=0.02). Conclusions. Pre-therapeutic evaluation of lymphocytes RS predicts the individual clinical outcome and late toxicity after RCT in patients with stage IIB cervix carcinoma. Determination of lymphocytes RS by CA can be a simple, rapid and useful method for tailoring treatments in order to obtain better results and a reduced complication rate with impact on patients survival and quality of life.

7. Carbapenem-resistance in non-fermentative species and in Enterobacteriaceae isolates

from hospitalized patients Autori: Mihaela Ionescu 1,2 , Dan Neagoe 2 , Claudia Chiorean 2 , Loredana Dumitras 2 , Aurelia Rus 2 Instituţie: 1 - “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca,

2 - County Emergency Clinic Cluj-Napoca Cuvinte cheie: β-lactamase, carbapenems, antibiotic resistance, Gram-negative Rezumat:

Aim. Nosocomial Gram-negative bacilli infections carbapenem-resistant strains among hospitalized patients have become an increasing cause of concern. This study was focused in evaluating carbapenem-resistance occurrence at hospitalized patients in various clinical wards. Materials and methods. From January 2012 to November 2013, we evaluated 654 Gram- negative bacilli strains isolated from patients hospitalized in County Emergency Clinical Hospital Cluj-Napoca in different clinical wards: surgery, anesthesia and intensive therapy unit, neurosurgery, internal medicine, gynecology, dermatology, orthopedic unit, oto-rhino-laryngology, and ophthalmology. The collection includes unique bacterial isolates and excludes duplicate isolates. All isolates were tested and analyzed according to their antibiotic resistance phenotypic pattern.

Results. We analyzed three non-fermentative species - Acinetobacter spp. (161; 24.61%), Pseudomonas aeruginosa (62; 9.48%), and Stenotrophomonas maltophilia (6; 0.91%) and the following Enterobacteriaceae - Escherichia coli (213; 32.56%), and Klebsiella spp. (130; 19.87%), Enterobacter spp. (6; 0.91%), Proteus spp. (42; 6.42%), Providencia spp. (17; 2.59%), Morganella spp. (6; 0.91%), Citrobacter spp. (7; 1.07%), and Serratia spp. (4; 0.61%). One hundred forty-five ESBL strains (22.17%) were identified. Among 654 isolates, 192 (29.35%) carbapenem- resistant/intermediate strains were detected: 154 (23.54%) Acinetobacter spp., 33 (5.04%) Pseudomonas aeruginosa, 2 (0.31%) Escherichia coli, 2 (0.31%) Klebsiella spp., and 1 (0.15%) Serratia spp. Among 192 carbapenem-resistant/intermediate strains (137; 71.35%) were isolated from from anesthesia and intensive therapy units. Our data showed a predominant carbapenem resistant Acinetobacter spp. strain in intensive care units. The main mechanism associated with carbapenem resistance could be production of carbapenemase in combination with impermeability. In the clinical laboratory the accurate identification is carbapenem-resistant strains can be difficult to achieve due methodological limitations. In our study we do not identify any stains that exhibit resistance at colistin. Conclusions. Our study demonstrates that the carbapenem resistance of Gram-negative bacilli is wide spread among non-fermenters species isolated from the patients hospitalized in intensive care units.

8.

Double knockdown of apoptotic genes and their relationship with other mechanisms

involved in tumor cell survival Autori: Valentina Pileczki 1 , Laura Pop 1 , Cornelia Braicu 1,2 , Mahafarin Maralani 3 , Ioana Berindan Neagoe 1,2 Instituţie: 1 – “Iuliu HatieganuUniversity of Medicine and Pharmacy, Cluj-Napoca

2 - The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca

3 - Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey

Cuvinte cheie: apoptosis, triple negative breast cancer, RNA silencing Rezumat:

Introduction: Triple negative breast cancer (TNBC) presents one of the worst prognoses due to the potential aggressive nature of the malignant illnesses, high rate of visceral metastasis and limited therapeutic options. Therefore, in this experiment we directed our attention toward the knockdown activity of the siRNA molecules, by simultaneously blocking the expression of the p53 gene and of the tumor necrosis factor alpha (TNF-α). Material and methods: In our experiment we used a triple negative breast cancer cell line (Hs578T) that was reverse transfected with p53 and TNF-α siRNA. After 24 hours from the treatment, cells were harvested and the total RNA was extracted. RT-PCR array technology was used in order to evaluate the most relevant genes involved in apoptosis. Viability and autophagy assays were performed after 24 and 48 h from the treatment in order to give more relevant assistance with the interpretation of the PCR data. Results and discussions: After analyzing the transcript quantification data by using the ΔΔCT formula, we calculated the fold-changes of each sample and obtained statistical relevant results for 16 genes, of which 4 were down-regulated and 12 up-regulated. The effects of p53 and TNF-α silencing led to the loss of cell viability first observed at 24 h, and increased at 48h. The simultaneous inhibition of the two genes after 48 h led to the activation of autophagy machinery, as it is known that defective autophagy plays a significant role in cancer induction. Conclusion: A full comprehension of p53 and TNF biology using preclinical models supports the development of novel and efficient therapeutic strategies in TNBC. Integrating the expression profiles of Hs578T untreated cells with those from simultaneous p53 and TNF knock- down provided us with a network-based platform.

9. Novel Approaches in Testing BRCA Deleterious Mutation Related to Breast and

Ovarian Cancers Autori: Madalina Stanciu, Gabriela Teodorescu Instituţie: AstraZeneca Medical Department Cuvinte cheie: BRCA mutation, PARP inhibitors Rezumat:

Introduction: In women with a known BRCA mutation, the risk of developing breast cancer increases to 45%-65% by age 70 and the risk for ovarian cancer increases to 10-17% by age 70. Women who are BRCA1 mutation carriers have approximately 40 % lifetime risk for ovarian cancer and increased risk for other cancer types, such as breast, prostate or pancreatic cancer. Objective: of this literature review is to discuss criteria of testing BRCA mutations in women with a family history of breast or ovarian cancer, as well as in patients already diagnosed with cancer. Background: BRCA1/2 (“breast cancer, early onset.”) are human genes that codify tumor suppressor proteins involved in normal DNA repair. Deleterious mutations of BRCA1/2 produce abnormal proteins causing defects in DNA repair. Another crucial factor in DNA repair is PARP (Poly-ADP-ribose polymerase), which becomes the preferential pathway in BRCA mutated cells. Discussion: until now, individuals at 10% risk of carrying a mutation have been eligible for BRCA testing. BRCA testing has also become available to patients with serous and endometrioid ovarian cancer under 65 years. Meanwhile, there is an increasing number of data supporting

therapeutic benefit of testing BRCA mutations. Several drugs that specifically inhibit PARP are currently being tested in clinical studies and patients with BRCA mutations respond better to PARP inhibitors than patients without this mutation. Conclusions: currently the main goal is to test more genes in more people, a flexible, patient-centered testing pathway for a novel therapeutic approach: genetic counseling, prophylactic surgery, and chemoprevention.

10. Incidence trends of liver and biliary tract cancers in cluj county, 2000-2010

Autori: Ofelia Şuteu 1,2 , Daniela Coza 1 , Luminiţa Blaga 1 , Florian Nicula 1 , Alexandru Irimie 1,2

Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca, 2 - ”Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: Liver, biliary tract cancers, incidence, trends Rezumat:

Introduction. There is little information on the epidemiology of liver and biliary tract cancers (LBTC) available in Romania. We aimed to examine and provide detailed data on the incidence trends for liver and biliary tract cancers (BTC) between 2000-2010, in Cluj County. Material and method. We calculated directly age-standardized incidence rates (world standard population) by subsite for cancers of LBTC in Cluj County, using data provided by the North-Western Cancer Registry. Time trends were expressed as the annual percent change (APC). Results. A total of 673 (55.5%) male and 540 (44.5%) female LBTC cases were reported; liver cancer was the most common subsite in both sexes: 80% in males and 59% in females. The incidence of LBTC increased from 6.13%000 to 10.62%000 in males and from 4.92%000 to 6.41%000 in females, with a 3.22% APC (p=0.007). Hepatocellular carcinoma (HCC) increased by 3.55% APC (p=0.03) in both sexes and extrahepatic bile duct cancers increased in females by 0.10% APC (p=0.05) and by 0.05% APC in males (p=0.07). Gallbladder (GB) in men, intrahepatic bile duct (IHBD) and ampulla of Vater cancers increased, while GB in women and BTC not specified decreased, but these trends were not statistically significant. The agreement between subsite and histological type showed that 90% in females and around 72% in males of cholangiocarcinomas were coded as IHBD cancer and 100% of HCC were coded as liver cell cancer.

Discussion. Except for hepatocellular cancer, BTC are rare but trends are upward by increased diagnosis and certification of the disease. Increased surveillance of cirrhotic patients and the substantial improvements in the detection affected the incidence trends of liver cancer. Conclusions. From a public health perspective, the upward trends of hepatocellular cancers are likely to be, at least partially, real, although our study cannot directly examine the causes for this ascending trend.

11. Novel antitumor immunomodulatory metallodrugs

Autori: C.Tatomir 1 , E. Fischer 1 , N. Miklasova, P.Virag 1 , M. Perde 1 , C. Precup, F. Devinsky Instituţie: 1 - The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: antitumor, immunomodulatory,palladium, curcumin Rezumat:

The use of metal - based anticancer agents is an important part for treatment of cancer of various types. Complexes with cis-platinum compounds have been used for the prevention and treatment of cancers but cause several side effects and their success rate is limited in some malignant casuistic. On the base of the structural analogy between Pt(II) and Pd(II) complexes, some studies of palladium compounds as suitable drugs have been carried out. Geometry and complex forming processes of palladium(II) are very similar to those of platinum(II) therefore it was speculated that palladium complexes may also have antitumour activities and serve as good models for the understanding of more inert platinum(II) anticancer drugs. We tested the in vitro/ex vivo biologic response triggered by six Pd(II) curcumine complexes on human cell lines and primary cell cultures. Antiproliferative effects of the palladium compounds was evaluated using a

system based on the tetrazolium yellow dye MTT. SEM electron microscopy were used for determination in ultrasructural changes. Inhibition of tumor growth and the antitumoral immune response was evaluated on peripheral mononuclear blood cell subpopulations by flow-cytometry. Pro-apoptotic (Bax) and anti-apoptotic (Bcl-xL) molecules was determined using Elisa technique. The Palladium complexes are cytotoxic against various tumor cell lines, they cause massive DNA damages, which leads to programmed cell death. They show selectively low toxicity against normal cell lines and human lymphocytes, while modulating the expression of molecules implicated in antitumoral response. All these biologic effects emphasize the prodrug potential of palladium curcumin complexes and their applicability in cancer care.

12. ”Artificial blood”- newly developed blood substitutes tested on laboratory animals and cell culture. Preliminary results Autori: Vlad-Alexandru Toma 1,2 , Anca-Daniela Farcaş 1,2 , Ioana Roman 1 , Denisa-Gabriela Hathazi 2 , Eva Fischer-Fodor 3 , Bogdan Sevastre 4 , Radu Lucian Silaghi-Dumitrescu 2 Instituţie: 1 Biological Research Institute, Cluj-Napoca, Romania 2 Babeş-Bolyai University, School of Chemistry and Chemical Engineering Cuvinte cheie: Blood substitutes, hemoglobin, hemerythrin, laboratory animals. Rezumat:

Introduction. Newly developed blood substitutes are based on two different proteins, hemoglobin and hemerythrin, respectively. In this paper we present the impact of the newly developed blood substitutes based on hemoglobin in Wistar rats and also we mention that this research is an explorative study. Hemoglobin-based blood substitutes are infusible oxygen-carrying liquids, obtained from bovine blood. This blood substitutes have no need for refrigeration or cross- matching, and are ideal for treating hemorrhagic shock in remote situations. Materials and methods. The experiment was performed in six Wistar male groups:

Control, Native Hemoglobin, Polymerized Hemglobin, Copolymerized Hemoglobin with BSA, Copolymerized Hemoglobin with Rubrerythrin, Copolymerized Hemoglobin with Rubrerythrin- NROR and Polymerized Hemoglobin with o-ATP. All gropus received regular food and water ad libitum. The animals were healthy males, weighting 230±20 g and hosted in zoohygienical conditions into the zoobase of the Biological Research Institute from Cluj-Napoca. The blood substitutes were administrated via intravenous injection. The experiment lasted two days. The invitro tests were developed on human lymphocytes and their subpopulations also on the human vascular endothelial cells. Results and discussions. All the analyses that we have studied suggest a very good collaboration between the newly developed hemoglobin blood substitutes and in vivo and in vitro models used. The most important aspect of these tests is the fact that all blood substitutes do not produce any significant immunological reaction and also there is no any toxicity on human cell cultures. The biochemical and hematological tests do not suffer any significant changes. Conclusions. All the parameters that we have studied encourage us to continue this experiment we have already started. Acknowledgements to Florina Violeta Scurtu for the material support.

13. Reality Map of Integrated Oncology and Palliative Care in Romanian Cancer Centers Autori: Patriciu Ahimaş-Cadariu, Anca Burcă, Florina Pop, Alexandra Tolnai, Armeana Zgâia Instituţie: The Oncology Institute “Prof. Dr. Ion ChiricutaCluj-Napoca Cuvinte cheie: palliative care, reality map, international partnership Rezumat:

The joint partnership has a duration of 3 years and the research group consists of 18 people. Our group aims to collect original data (“reality map”) about the implementation of defined KI-PCC and specific outcome quality indicators. The hypothesis is that both predefined cofactors and

appropriately delivered KI-PCC will predict quality of individual patient’s care, measured as composite endpoint. The results will provide the basis for further research on implementation of tailored interventions of palliative care procedures provided by oncologists and other health care professionals. In the care of advanced incurable cancer patients medical oncologists and other cancer- related healthcare professionals play a sentinel role in not only providing tumor directed treatment, but also in identifying and treating palliative care needs. Models of integrating oncology and palliative care are developing, but require local and national adaption of processes. The Swiss- Romanian partnership grant offers an opportunity to investigate this approach further. The partnership involves 4 more Romanian centers: Alba, Braşov, Bucharest and Iaşi and managed to create a strong liaison between each center on the basis of the common shared believe the every life worth fighting for. The benefits of engaging in international collaboration are as follows: access foreign or joint facilities and equipment, access techniques and skills, increase knowledge capacity, cultural and personal experience, access foreign markets. What we have learned from this collaboration so far is that it can increase the quality of research and builds an understanding for palliative care rationale.

14. Identification of novel target networks as response to zearalenone mycotoxin exposure Autori: Cornelia Braicu 1,2 , Valentina Pileczki 1,3 , Ovidiu Balacescu 3 , Daniela Martin 4 , Ionelia Taranu 4 , Ioana Berindan-Neagoe 1,3,5 Instituţie:

1 - Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu

Hatieganu University of Medicine and Pharmacy

2 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca

3 - Faculty of Pharmacy, Iuliu HatieganuUniversity of Medicine and Pharmacy,

4 - National Institute for Research and Development in Animal Biology and Nutrition (IBNA)

5 - Department of Immunology, Faculty of Medicine, Iuliu HatieganuUniversity of Medicine and

Pharmacy Cuvinte cheie: zearalenone, mycotoxin, microarray, gene expression Rezumat:

Introduction. Zearalenone (ZEA) toxin is secondary fungal metabolite produced by Fusarium species. ZEA proved to be an estrogenic mycotoxin. Most of the investigations are focused on the cytotoxic or effect of this mycotoxin, but the precise mechanism of action of ZEA still remains to be deciphered. Materials and methods. Two-colour microarray (Agilent technology) was used for screening the altered genes as response to a single dose of 10 µM ZEA, at 24 h post treatment. Results. ZEA 10 µM was showed no cytotoxic effect, despite of that the microarray evaluation selecting a fold change cut-off of ±1.5 and a p-value of <0.05 reveals a panel of 790 genes overexpressed and 1164 downregulated. Discussion. In order to identify the modified key processes from the microarray data, we used the Gene Ontology (GO) analysis of gene expression. The results showed some anticipated gene class associations, such as apoptosis, cell cycle, differentiation and proliferation, as well as others that were unforeseen, like cell invasion and adhesion molecules. Interpreting and integrating these results by means of interaction network analysis of the genes that presented statistically significant p-value give us the instruments for predicting the negative effects of this mycotoxin. Conclusion. The effects of ZEA are complexes as we were able to see from the bioinformatics analysis. The altered genes were connected with several key pathways even for the case of a non-cytotoxic dose of this mycotoxin.

15. In vitro effects of noble metal nanoparticles Autori: M.Perde-Schrepler, E.Fischer-Fodor, G.Chereches, O.Barbos, I.Brie, C.Tatomir, L.David, L. Olenic Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Nanoparticles, in vitro, green synthesis Rezumat:

Nanoparticles (NP) are used nowadays in several biomedical fields as antimicrobian agents, transfection vectors, fluorescent markers, etc. Despite the tremendous progresses made so far, there are still big question marks regarding their potential adverse effects. The intracellular behavior, and also their metabolic and immunologic effects are far from being completely understood. The development of green processes for the synthesis of NP represents an important progress having many advantages such as simplicity, rapid synthesis rate, eco-friendliness and economic viability. The aim of our study was to evaluate the effects of some new biomaterials based on silver and gold nanoparticles synthesized with polyphenols rich natural extracts on normal and tumoral human keratinocytes. The effects were assessed by the evaluation of NPs internalization, modifications in cell morphology (TEM), cytotoxicity (MTT), the generation of reactive oxygen species (ROS) and the modulation of the secretion of inflammatory cytokines: Il1 α, IL6 and TNF α both in basal condition and after the induction of inflammation by exposure to UVB radiation (ELISA). All NPs were in the range of 20-100 nm and had almost spherical shape. They had different effects on the morphology of the treated cells and could be visualized in the treated keratinocytes by TEM. The toxicity of NPs was dose- dependent and was also depending on the metal employed. Their presence had a significant effect on the release of ROS and also they modulated the release of inflammatory cytokines.

CANCERELE TIROIDIENE ŞI SFERA ORL

COMUNICĂRI ORALE

1. How to diagnose and treat thyroid cancer in 2014?

Autori: V. Muntean 1 , I. Domsa 1 , A. Zolog 1 , R. Simescu 1,2 , G. Petre 1,2 , C. Radu 1,2 , D. Constantinescu 1 , M.V.Muntean 1 , O. Fabian 1,2 Instituţie: 1 - CF Clinical Hospital 2 - “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: thyroid cancer, diagnosis, surgical treatment Rezumat:

Introduction: Starting with 2010, a modified surgical protocol of differentiated thyroid cancers has been applied systematically in our Surgery Department: total thyroidectomy in all patients; frozen-section examination in all clinical, imagistic and macroscopic suspicious lesions; central compartment lymphadenectomy (CCL) in all patients with malignant confirmed tumors and selective cervical lymphadenectomy (SCL) for ultrasound-modified or intraoperative confirmed malignant lymph nodes. Patients and method: Pathology findings and clinical data were compared in patients with thyroid cancer operated on before and after application of the new protocol. Information was drawn from a prospective database including operative protocols, specimen pathology findings and follow- up data. Statistical analysis was performed with Microsoft Excel and OpenEpi. Rates were compared using the chi-square test; p values under 0,05 were considered statistically significant. Results: The study included 200 patients operated for differentiated thyroid cancer: 100 during 2004-2009 (Group 1) and 100 during 2013-2014 (Group 2). The two groups were similar, with no statistically significant differences of age, sex, clinical and imagistic diagnosis, pathology findings, tumor size and multicentricity. The number of total thyroidectomies was significantly higher in recently operated patients (98 against 85), with a decrease in the number of reinterventions for initially incomplete operations (14 against 0). The number of lymphadenectomies was significantly higher in Group 2 compared to Group 1 (44 vs 15 CCL and 17 vs 10 SCL). The study evidenced less stage I and II and more stage III in recently operated patients due to the increase of T3 and IVA patients, as well as due to the higher number of N1a and N1b patients. Conclusions: Systematic use of the new treatment protocol led to the disappearance of reinterventions and to an improved staging of the disease. The therapeutic benefits of the new protocol remain uncertain and are to be confirmed by patient follow-up.

2. Second malignancies in patients with differentiated thyroid carcinoma treated with

low - medium I-131 doses Autori: Doina Piciu Instituţie: The Oncology Institute “Prof. Dr. Ion Chiricuta” Cluj-Napoca Cuvinte cheie: thyroid cancer, second malignancies Rezumat:

Background. Differentiated thyroid cancers represent the most frequent endocrine tumors, with a 10-years overall survival of more than 90%. During the long-term follow-up these patients may present other primary malignancies. The aim of the study is to demonstrate if there is a risk for the development of second primary malignancies after low and medium radioiodine doses used during the treatment of thyroid cancers. Methods and patients. Second primary malignancies after differentiated thyroid cancer was determined in 1990 patients diagnosed between 1970 and 2003 being in the database of the Ion Chiricuta Institute of Oncology Cluj-Napoca (IOCN). This number represented 37.9% from all the patients with thyroid cancer from our evidences. The long-term follow-up of these patients was carried out exclusively in same center and it was of minimum 10 years, respectively 120 months, with a mean of 202 months (range, 120516 months). We analyzed the relation between the risk of

second malignancy and the radioiodine dose used for the therapy of differentiated thyroid cancer. Results. The group had a ratio of female/male of 8:1, and a mean age of 47.2 years at the moment of the thyroid cancer diagnostic. A percent of 51.7% of the patients were in stage I, 19.6% in stage II, 17.5% of the cases were in stage III and 11.2% were in stage IV. The radioiodine as adjuvant therapy was administrated in all these cases and the mean dose was 63.2 mCi (2338 MBq) I-131, with a range between 30 mCi (1111 MBq) and 90 mCi (3330 MBq); all other cases treated with higher dose were excluded. The overall survival rate was 94.7% at 10 years. There were identified 93 patients with second primary malignancies: breast carcinoma, lung carcinoma, malignant melanoma, Hodgkin lymphoma, cervix carcinoma, colorectal cancer, hepatocarcinoma, leiomyosarcoma, larynx carcinoma, basocellular carcinoama, pancreatic neuroendocrine cancer. The risk compared with the general population was not increased for none of these cases. Conclusions: The overall risk of second primary malignancies was not related to the low and medium doses of radioiodineadministered as adjuvant therapy in differentiated thyroid cancers.

3. Management of thyroid carcinoma a long term single tertiary cancer center study

Autori: C Lisencu, S Pătcaș, Doina Piciu, F Ignat, P Achimaș, E Pușcaș, C Vlad, C Bădulescu, MȘ Mureșan, Adriana Sfîra, Daniela Deac, C Cheregi, A Irimie. Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: thyroid carcinoma Rezumat:

Background: Thyroid carcinoma was considered to be a rare form of cancer, but its’ incidence has grown in the past decade, mainly because of increased exposure to ionizing radiation. The management of thyroid carcinoma relies upon the dominant histology and the risk factors associated with the disease. The aim of the present study was to evaluate the standard of care for thyroid carcinoma treated at Oncology Institute “Prof. Ion Chiricuta”, Cluj-Napoca (IOCN), over a period of 42 years. Materials and methods: We have performed a 42-year retrospective descriptive and analytical study of 4774 thyroid carcinoma patients treated at IOCN between 1970 and 2012. The parameters followed were: mean 5-year and 10-year overall survival rate, 5-year and 10-year disease free interval, comparison of mean survival rate between gender, age, pathology results patients group clusters. Results: Thyroid carcinoma is the 4th most commonly treated cancer type in our institution. The female:male incidence ratio is 7:1, with a peak of incidence for the over 45 year age group. Today’s thyroid carcinoma incidence is 43 times larger than the one from 1980. Almost 3000 cases were papillary carcinomas. The overall gender-related-10 year-survival rate was 89.4%, with better outcome for female patients (93.2%) vs. male patients (81.87%). The overall age-related-10 year- survival rate was 89.4% (91.7% for under 45 years vs. 87.8% for patients over 45 years). Global histology-related-10 year-survival rate was 77.3% (80.4% papillary carcinoma vs 70% follicular carcinoma vs 66.7% medullary carcinoma). Discussion: In the past decades the incidence of thyroid carcinoma has exponentially increased. The most frequent types are differentiated histologies (papillary and follicular). The increase in incidence could be linked to better and sooner diagnosis measures and/or increased ionizing radiation exposure. Conclusions: Low risk thyroid carcinoma patients (young, differentiated histology, localized disease) prove to have better survival outcome at 10 year follow-up interval.

4.

The increase in thyroid carcinoma frequency after the Chernobyl nuclear accident. A

study conducted in the The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Prezintă: Avram Manea Autori: Cosmin Ioan Lisencu, Manea Avram, Ioan Claudiu Bădulescu, Patriciu Achimaş Cadariu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Carcinom tiroidian, microcarcinom, Cernobîl Rezumat:

Accidentul de la Cernobal petrecut in 1986 a avut numeroase urmari atat imediate cat si pe termen lung. Dintre efectele pe termen lung, cresterea incidentei cancerului tiroidian a fost demonstrata prin multe studii realizate in alte tari afectate. Acest studiu evidentiaza evolutia incidentei cancerului tiroidian pentru 2948 de pacientii operati de tiroida in Institutul Oncologic Cluj Napoca , intre 2008 si 2012. Acestia au fost impartiti in 3 grupe de varsta fata de momentul incidentului de la Cernobil: A(persoane >18 ani), B(0-18 ani), C (nenascuti in momentul accidentului). Comparativ cu frecventa cancerului tiroidian la grupul A, procentul cancerului tiroidian a inceput sa creasca in grupul B ajungand pana la 41,4% in grupul C. Ca si alte studii facute in unele tari afectate de asemenea de radiatiile eliberate dupa accident,acest studiul a demonstrat o crestere semnificativa statistic a incidentei diferitelor forme de cancer tiroidian atat la cei care erau copii sau adolescenti in cat si la cei nascuti dupa evenimentul nuclear.

5. Incidentaloamele tiroidiene şi asocierea cu tiroidita autoimună Hashimoto

Autori: Iulian-Claudiu Badulescu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: carcinom tiroidian, tiroida , tiroidita Hashimoto Rezumat:

Introduction: Thyroid microcarcinoma accidentally discovered after surgery of the thyroid, represents an increasingly common clinico-pathological entity. This study evaluates the incidence of the thyroid microcarcinoma with all histopathological subtypes, particularly papillary form and also the coexistence with autoimmune Hashimoto's thyroiditis, which may require attention in the management of this chronic disease. Methods: This is a retrospective analytical study, made out of Oncological Institute(IOCN) of Cluj-Napoca casuistry, based on the analysis of the Institutional Register of Cancer surgery protocols and histopathological results. Out of a total of 2961 thyroid surgeries performed between 2008-2012 2778 were performed for presumed benign thyroid pathology.Total tyroidectomies or thyroid lobectomy were performed. Results: Out of the total cases (2778) with benign presumed pathology, 506 cases were confirmed to be carcinomas on histopathological results, out of which 305 were microcarcinomas. There were found 207 (67,86%) papillary microcarcinoma and 43 (14,09%) multifocal micropapillary thyroid cancer. Out of the 376 cases of Hashimoto autoimmune thyroiditis, 54 (14,36%) were associated with thyroid carcinoma. Conclusion: This study confirms the recent years increased frequency of the thyroid carcinoma and microcarcinoma incidentally discovered, especially papillary form, among the supposedly benign cases ,as well as associating between Hashimoto thyroiditis and malignant thyroid pathology. This suggests the need for a more thorough (surgical and endocrinological) approach for the apparently benign thyroid cases.

6.

Head and neck vascular masses

Prezintă: Vasile Popita Autori: Vasile Popita, Magdalena Chirila, Elisabeta Ciuleanu, Valentin Cernea, Octavian Chis, Dan Gheorghiu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: vascular masses, head and neck Rezumat:

Vascular masses of the head and neck region are a heterogeneous group of lesions with different histology, clinical picture and variable treatment options. These type of lesions can be subdivided in three categories: benign lesions, malignant lesions and congenital or acquired vascular masses. We need to use the imaging technique suitable to clinical symptoms to establish a correct diagnosis.In this paper, we illustrate some cases of vascular masses of the head and neck region, presenting clinical features, imaging methods used for diagnosis, imaging findings with emphasis on the particularity of the cases and subsequent evolution of patients.

7. Data on the treatment and survival of patients with parotid cancer at the Oncology

Institute “Prof. I. Chiricuţă” in Cluj-Napoca Autori: Octavian Chiş, Silviu Albu, Georgia Cirebea, Marilena Cheptea, Corina Vernic, Ciuleanu Elisabeta, Gheorghiu Dănuţ, Sava Alexandru, Stănculescu Horaţiu, Chiş Amalia Andreea Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: primary parotid cancer, surgery, radiotherapy, post-therapeutic survival, significance factors Rezumat:

Introduction. The cancer of the parotid gland, a major pair salivary gland, is considered a rare entity, dealt with in surgery and oncology centers of head an neck. Material and methods. The authors analyze data recorded for 135 patients suffering from primary parotid cancer, selected according to the criteria chosen for the inclusion in the present study. The treatment consisted of surgery or surgery followed by radiotherapy and was administered between 1995 and 2008 at the “Prof. Dr. I. Chiricuţă” Institute of Oncology in Cluj-Napoca. Both univariate and multivariate methods of statistic analysis have been employed. Results. The authors conclude that the disease-free interval after 3 years was of 78.5% with a general survival rate of 88%, while after 5 years, these variables had the value of of 71.5% and 80.7% respectively. Conclusion. The results indicate that the post-therapeutic interval at 3 years was significantly influenced by parameters pT and pN, at 5 years by age and pT, while the survival rate at 3 years was influenced, with statistic relevance, by age, pstage, pT, category pN, and the perineural invasion, while at 5 years by age and pT.

8. Treatment results in Nasopharyngeal Carcinoma

Autori: Elisabeta Ciuleanu, Valentin Cernea, Tudor Eliade Ciuleanu, Danut Gheorghiu, Octavian Chis Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Nasopharyngeal Carcinoma Rezumat:

Aim of the study: to present o retrospective analysis of the cases with nasopharyngeal carcinoma treated in the Oncology Institute „Prof. Dr. I. Chiricuta” Cluj, between 2006-2011. The end points of the study were: response rate (RR), overall survival (OS), time to progression (TTP) and the analyses of prognostic factors for RR, OS and TTP. Material and methods: 163 patients with nasopharyngeal carcinoma were treated. Median age was 44 years (range 15-78), 36,2% were female, 63,8% were male; 78,5% of them had an

undifferentiated cc., 14,1% had a nonkeratinizing cc. and 7,3 % epidermoid cc.; 2,5 % of patients were stage I, 21,4% stage II, 41% stage III, 20,8 % stage IVA, and 14 % stage IVB. Results: 92,6 % of patients had induction chemotherapy (IC)(Epirubicin and Cisplatin - 90,7% or Cisplatin and 5-Fluorouracil 6,6%). All pts had RT; 86% of them with Cisplatin as radiosensitizer. Median follow up was 51 months. RR at the end of primary treatment was 93,86 % (89,57% CR; 4,29 % PR). RR was significantly influenced by: the stage (I, II, III vs IV) p<0.01; level of Hb (<10 gr vs >10gr) p<0.01; ESR value (<40 vs >40) p<0,01. There was a trend towards improved RR function of age (<45 vs >45) not reaching significant statistical value p=0,06;

5 year-OS was 78% (IC:70% - 85%). 5 year-OS was significantly influenced by: the stage (I, II, III

vs IV) p<0.01; Hb level (<10 gr vs >10gr) p<0.01; ESR value (<40 vs >40) p<0.01.There was a trend towards improved OS for undifferentiated cc. and nonkeratinizing cc vs epidermoid

cc.(p=0,06)

5 year-TTP was 71%. It was significantly influenced by the stage (I, II, III vs IV) p<0.01 and was a trend towards improved TTP for VSH value <40 vs >40, p<0.08.

Conclusions: RR and OS were significantly influenced by the stage, level of Hb and ESR value. There was a trend towards improved OS for undifferentiated cc. and nonkeratinizing cc vs epidermoid cc. TTP was significantly influenced by the stage.

9. The treatment of cervical lymph nodes metastasis from an unknown primary site

Autori: D. Gheorghiu, Elisabeta Ciuleanu, V. Cernea, O. Chiş, Diana Spârchez, N. Todor Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Cervical lymph node metastasis from unknown primary site, radio-surgical therapy, prognostic factors Rezumat:

Purpose: Cervical lymph node metastasis from unknown primary site represents a heterogenic and pathological class without having unanimous consensus treatment. This study aimed to analize the results and prognostic factors in a series of patients treated by means of radio- surgical therapy. Methods and materials: A chart review was performed on 29 patients with cervical lymph node metastasis from unknown primary site between14.10.2004 and 04.12.2009. 13 patients (45%) had squamos cell carcinoma and 16 patients (55%) had nonkeratinizing or undifferentiated carcinoma. 22 patients were treated with curative and 7 with palliative intent. For the patients treated with curative intent, the treatment was represented by surgery, followed by radiotherapy. Concomitant chemotherapy or induction chemotherapy was associated with radiotherapy. Results: The 3-year overall survival rate for the entire group was 50% and the disease-free survival rate was 39%, the group with undifferentiated carcinoma had a survival rate of 59%. The univariate analysis reflected that the curative intention treatment and the absence of the extracapsular spread were favorable prognostic factors for the radio-surgical therapy. Conclusions: Patients with cervical lymph node metastasis from unknown primary site have similar prognostic in comparison to patients with other head and neck carcinoma. The strategy of curative therapy which includes neck-dissection with extensive irradiation of bilateral neck and pharyngeal mucosa has shown the best results.

10. Voice rehabilitation after laryngectomy using self retaining prosthesis (Provox) Autori: Alma Maniu, Relu Marin, Marcel Cosgarea Instituţie: Department of Otorhinolaryngology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca Cuvinte cheie: laryngeal carcinoma, total laryngectomy, voice restoration, voice prosthesis Rezumat:

Introduction: The introduction of tracheoesophageal voice restoration by Blom and Singer has provided laryngectomy patients with a successful alternative to the use of artificial larynx and esophageal speech. Objective: To evaluate the indications, complications, and device life of the Provox prostesis in a case series of 6 patients at the Department of Otorhinolaryngology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca. Methods: We reviewed the records of patients who used the Provox prostesis for general indicators, device life, and complications All patients had advanced laryngeal squamous cell carcinoma. Two patients had primary voice prosthesis inserted and four patients had a tracheo- esophageal puncture (TEP) carried out as a secondary procedure. Results: All the patients from both the primary insertion or the secondary insertion group, developed good and understood speech using the prosthesis. No significant difference in quality of speech was found between the two subgroups. Two patients required replacement of the prosthesis at intervals of 8 and 10 months after insertion, because of salivary leakage and granulation formation around the fistula. Conclusions: TEP puncture and prosthesis insertion is a relatively simple, safe and effective surgical procedure for voice restoration after laryngectomy. Provox voice prosthesis is a new and useful modified device that has overcome the previous prosthesis drawbacks, is well tolerated by the patients and can be easily changed via the front-loading technique.

11. Vaccination with quadrivalent HPV (type 6/11/16/18) vaccine in patients with Recurrent Respiratory Papillomatosis Autori: Magdalena B.Chirila, Sorana D. Bolboaca Instituţie: “Iuliu HatieganuUniversity of Medicine and Pharmacy Cuvinte cheie: respiratory papillomatosis, HPV, vaccine Rezumat:

Introduction: The aim of the study was to assess the clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis (RRP). Material and Method: This was a prospective study of patients with RRP treated from January 2009 to July 2012 at the Ear, Nose and Throat Department of the Emergency County Hospital of Cluj-Napoca, Romania. Demographic characteristics, onset of RRP, HPV typing, use and number of cidofovir injections, number of surgeries for RRP per year, and use of human papillomavirus vaccine (types 6, 11, 16, 18) (recombinant, adsorbed)/Silgard® were considered from all the patients included in the study. Charts were reviewed for follow-up after diagnosis, after cidofovir, and after Silgard; all the statistical tests were applied at a significance level of 5 %. Results: The recurrences were observed within 27.53 ± 11.24 days after intralesional cidofovir injection. Thirteen patients with recurrence after cidofovir agreed and received Silgard® vaccine. 85 % [54.4499.41] of patients had no recurrences during 1-year follow-up. The recurrence of papillomas was observed in two patients (15 %, 95 % CI [0.5945.56]), one with adult-onset RRP and one with juvenile-onset RRP. Both recurrences appeared after the first Silgard dose; one month after the third vaccine dose each patient underwent a new surgery for remaining papillomas with no recurrences at 1-year follow-up visit. Conclusions: Silgard® vaccination had a good effect and proved to be efficient in the treatment of our patients with RRR without appearance of recurrence in 85 % of the patients during 1-year follow-up.

POSTERE

1. The Expression of Epidermal Growth Factor Receptor in Glioblastomas - a preliminary study Autori: Morosanu Cezar Octavian 1 , Cioca Andreea 2 , Vasiu Renata 2 , Pop Bogdan 2 , Cilean Ioana 2 , Florian Ioan Stefan 1 Instituţie: 1. “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 2. Department of Pathology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cuvinte cheie: glioblastoma, epidermal growth factor receptor, immunohistochemistry Rezumat:

Introduction. Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumor, with a severe malignant progression. Overall survival of patients under the current treatment of radio/chemotherapy and surgical interventions is very poor and the high recurrence rate renders every therapy as being futile. New therapeutical avenues are being investigated in the light of molecular and cellular advancements targeting the growth factors implicated in epidermal proliferation. Epidermal Growth Factor Receptor (EGFR) stimulates cell growth and differentiation, and its overexpression can indicate variations in tumor pathology. The purpose of the study was to analyze the expression of EGFR in patients with newly diagnosedGBM and in the recurrent tumor of those patients. Material and methods. Our study included a total of 48 samples collected from 24 patients diagnosed with GBM. Immunohistochemical expression of EGFR was compared between primary and recurrent tumor after surgery, chemotherapy and radiotherapy. The clinicopathological data including sex, age, treatment and tumor type (primary/secondary) wererecorded from the Institute database. The intensity of EGFR staining was scored on a scale of 13+ (weak, intermediate and strong).

Results. Using immunohistochemical detection for EGFR with monoclonal human antibody (clone EGFR.25), we found overexpression in 23 patients (96%), including strong reactivity in cases 11 cases (46%), intermediate positivity in 9 (37%), and weak positivity in 4 (17%). Conclusion. Our results suggest that EGFR is overexpressed in GBM and contributes to more advance disease. Further studies are required for the full comprehension of the mechanism that can eventually lead to new anti-tumoral strategies.

2.

Calculation of I-131 activity administrated in hyperthyroidism

Autori: A. Sabo, C. Peştean, M. Cheptea, M.I. Larg, M. Crisan, C. Moisescu-Goia, E. Barbus, D. Piciu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: hyperthyroidism, radioiodine, radionuclide treatment, I-131. Rezumat:

Aim. The aim of the study is to demonstrate the utility of a personalized formula in order to calculate the optimal activity to be administrated with the intention to treat hyperthyroidism, in comparison with the empirical method where fixed activities are administrated to the patients with hyperthyroidism. Methods. The study was performed in the Nuclear Medicine department of the Oncology Institute “Prof. dr. Ion Chiricuţă” Cluj-Napoca, over a period of 18 months. We included in our study 60 patients with hyperthyroidism who received radioactive iodine treatment. Before iodine treatment each patient underwent a clinical evaluation. The patients were divided into two groups. First group G1 consists of 30 patients who received personalized activities calculated and the second group G2 who received fixed empirical activities. Results. For the both groups the age distribution is uniform. The average activity (expressed in Mbq) for the G1 is 313.39±38.03:IC and for the G2 is 252.58±82.82:IC. It was noted a difference with strong statistical significance between the average administrated activities of iodine for the G1 in comparison with G2. The recurrence of disease is higher for G2 (23.33.0%) in comparison with

G1 3.33% (p=0.04). The odds ratio (OR) regarding the recurrence in the two groups is 8.82 and the 95% of coincidence interval of OR is between 1.01 to 76.96. Conclusions. The therapeutic success is assessed related to the number and the frequency of recurrence. OR value showed that in G2 the recurrence is higher comparative to G1 which demonstrates the superiority of the method with personalized calculated activities, because it has a higher success rate According to the results we may conclude that the presented personalized calculation formula for the administrated radioiodine activities in hyperthyroidism is an efficient method that improves the clinical response of patients undergoing radioiodine treatment for hyperthyroidism.

3. 131 I - optimization diagnosis and treatment in thyroid pathology

Autori: Cristina Moisescu, Doina Piciu, Alexandrina Sabo, Claudiu Pestean, Iulia Maria Larg, Crisan Monica Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: radioiodine, thyroid carcinoma, and radiation protection Rezumat:

Introduction: Patients treated with radioiodine present a radiation hazard and precautions are necessary to limit the radiation dose to family members, nursing staff and general population. The precautions advised are usually based on instantaneous dose rates or iodine retention and do not take into account the time spent in close proximity with a patient. Methods: After I-131 oral administration the gamma radiation from patients was detected using a radioiodine uptake station (RIC) anterior or linear scanner. The thyroid cancer investigation, based on whole body scan scintigraphy (WBS) after I-131 administration, was applied. The scan is performed with collimated gamma camera with High Energy, and highlights residues of thyroid tissue, cervical metastasis and slight metastasis of thyroid cancer. We have combined whole-body dose rate measurements taken from 132 thyroid cancer patients after radioiodine administration with known data on nursing and social contact times to calculate the cumulative dose that may be received by an individual in contact with a patient. These estimates dose have been used to calculate restrictions to patients' behavior to limit received doses to less than 1 mSv. We have also measured urinary iodide excretion in 19 patients to estimate the potential risk from the discharge of radioiodine into the domestic drainage system. Results: The dose rate decay was biexponential for patients receiving radioiodine to ablate the thyroid after surgery (the ablation group, A) and monoexponential for these receiving subsequent treatments for residual or recurrent disease (the follow-up group, FU). These values are important because they depend on the future in terms of patient’s radiation and their family. Advice given to patients receiving radioiodine therapy is based on retained activity or instantaneous dose rate measurement and takes little or no account of patient behavior. The doses received by staff, members of the public and family will be influenced by the patients' retained activity and the length and proximity of contact with those individuals. Discussion: RIC values recorded at 24 hours on the thyroid and at thigh indicate the charging level and the presence of the radioisotopes in the bloodstream. The faster clearance in the follow-up patients generally resulted in less stringent restrictions than those advised for ablation patients. For typical activities of 1850 MBq for the ablation patients and 3700 MBq for the persistent disease, the following restrictions were advised. Patients could travel in a private car for up to 8 h on the day of treatment (for an administered activity of 1850 MBq in group A) or 4 h (for activities of 3700 in group FU) respectively. Patients should remain off work for 3 days (1850 MBq/group A) or 2 days (up to 3700 MBq/group FU). Partners should avoid close contact and sleep apart for 16 days (1850 MBq/group A) or 4-5 days (3700 MBq/group FU). Contact with children should be restricted according to their age, ranging from 16 days (1850 MBq/group A) or 4-5 days (3700 MBq in group FU) for younger children, down to 10 days (1850 MBq/group A) or 4 days (up to 3700 MBq/group FU) for older children.

Conclusion: The main advantage of 131 I isotope consists in the fact that is strictly for cell tropism of thyroid. This is the reason of radioiodine use with great success in thyroid diseases, especially in the treatment of thyroid cancer. Sensible guidelines can be derived to limit the dose received by members of the public and staff who may come into contact with cancer patient treated with radioiodine to less than 1 mSv. The rapid clearance of radioiodine in patients treated on one or more than one occasion means that therapy could be administered at home to selected patients with suitable domestic circumstances. In most cases the restriction times, despite the high activities, are less than those for patients treated for thyrotoxicosis. The concentration of radioiodine in domestic drainage systems should not pose a significant risk.

ANESTEZIE ŞI TERAPIE INTENSIVĂ

COMUNICĂRI ORALE

1. Intravenous lidocaine infusion in the management of acute and chronic oncologic pain

Autori: Adela Hilda Onuţu Instituţie: Emergency Clinical County Hospital, Orthopedic and Trauma Clinic Cuvinte cheie: lidocaine infusion, acute pain, cancer pain Rezumat:

Lidocaine is known as a local anesthetic and an antiarrhythmic drug.Used for almost two decades in the acute neuropathic pain management lidocaine infusion proved its usefulness in the preventive analgesia strategy being recognized as an adjuvant analgesic and recommended in the certain multimodal analgesic regimens, in the perioperative period. Lidocaine infusion provides analgesia, anti-inflammatory and anti-hyperalgesic effects. The analgesic effect is the result of the nociceptive blockade, by inhibition of the voltage dependent sodium channels and G-coupled receptors. Anti-inflammatory effects are attributable to reduced neurogenic inflammation and to the inhibition of the migration and adhesion of granulocytes, that secondary leads to lower levels of pro-inflammatory cytokines. Acting as antagonist of the NMDA receptors lidocaine, suppresses central sensitization phenomena and leads to an anti-hyperalgesic effect.

Current evidence shows that in major abdominal surgery perioperative lidocaine infusion (1,5-3 mg/kg/h) provides intraoperative anesthetic consumption reduction, lower postoperative 24- hour opioid consumption, reduced postoperative pain scores, faster recovery of the bowel function and a shorter time to patient discharge. At the moment there are recommendation regarding lidocaine infusion use for patients with colon, breast and prostatic cancer surgery. Several studies showed lidocaine infusion efficacy in the management of refractory neuropathic cancer pain, providing reduced morphine consumption and a better level of patient satisfaction. Chemotherapy-induced peripheral neuropathy, plexopathies and other categories of pain could benefit of the complex analgesic effect of lidocaine infusion but supplementary research is still needed. Lidocaine infusion is recognized as a valuable adjuvant analgesic, with good results as a part of multimodal analgesic regimens in order to reduce opioid consumption, in acute and chronic pain management. The lecture will go further in order to emphasize the aspects discussed above and will give supplementary data from recent literature and personal experience.

2. Profilaxia trombembolismului venos, noi protocoale, noi substante, noi tendinte?

Autori: Camelia Pascaru Instituţie: Hospital for Medical Recovery, Cluj-Napoca Cuvinte cheie:

Rezumat:

Datele stiintifice noi, din ce in ce mai numeroase si experienta medicala acumulata, au condus la o abordare, in parte diferita, a diagnosticului, tratamentului si profilaxiei trombozei, in general, si a TEV. Astazi este unanim acceptat ca preventia TEV este mai eficace decat tratamentul TEV constituit. Noile anticoagulante orale aparute in ultimii 4-5 ani tind sa inlocuiasca clasicele AVK. Eficienta si siguranta lor in terapie este dovedita. Noile antitrombotice, altele decat antifactorXa si antitrombinice sunt in cercetare avansata si pot schimba orientarile in TEV. In recomandarile actuale pentru tromboprofilaxie, dar si pentru tratamentul TEV sunt luati in considerare atat factori de risc pentru tromboza cat si factori de risc pentru sangerare. Au aparut noi scoruri de risc (Padua, Rogers, Caprini) si scoruri pentru sangerare. Folosirea acestor scoruri in practica clinica sporeste baza stiintifica a tromboprofilaxiei (relatia eficienta/risc). S-au conturat mai bine domeniile in care tromboprofilaxia are rol esential. Va voi prezenta cateva date

epidemiologice, date despre motivatia tromboprofilaxiei, stratificarea riscului de TEV, strategia profilaxiei TEV, durata profilaxiei TEV, screeningul pentru TEV cat si metode de profilaxie. Voi detalia despre profilaxia TEV la pacientii oncologici si la pacientii supusi chirurgiei non-ortopedice (urologie, ginecologie, chirurgia gastro-intestinala, chirurgia vasculara, chirurgia bariatrica, chirurgia reconstructiva). Factorii de risc generali si specifici la pacientii cu tumori maligne sunt multipli si au pondere variabila. In ultimii ani au fost publicate mai multe ghiduri de profilaxie si tratament al TEV la pacientii oncologici: ghidul ASCO 2007 (American Society of Clinical Oncology), ghidul NNCN 2008 (National Comprehensive Cancer Network), ghidul ACCP 2012 (American College Chest Physicians). La pacientii supusi chirurgiei non-ortopedice fara profilaxie adecvata incidenta TEV este de 10-40%. Toate ghidurile publicate considera ca profilaxia adecvata (modalitate, doza, durata) reprezinta cea mai eficienta strategie in prevenirea TEP. La pacientii operati factorii de risc sunt produsi direct de interventia chirurgicala (staza, leziune, hipercoagulare) la care se adauga factorii ce tin de unele manevre terapeutice, comorbiditati, prezenta factorilor mosteniti. Noile ghiduri ACCP au folosit impartirea pacientilor pe grupe de risc si recomandarea masurilor de profilaxie fiecarei grupe. S-au elaborat doua scale de risc: scala Rogers si scala Caprini. Aplicarea recomandarilor din ghiduri la patul bolnavului s-a dovedit a fi cel mai dificil de realizat, de aceea, prin prezentarea mea doresc sa va prezint principalele tendinte in tromboprofilaxie in practica actuala.

3. Perioperative management of pregnant women with renal tumor

Autori: T. Tat, B. Petruţ, I. Gădălean, V. Schiţcu Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie:

Rezumat:

The association of pregnancy with renal tumors is rare in cancer pathology. Pregnant patient, diagnosed with left renal tumor, is subject to partial nephrectomy. Laparoscopic surgery was chosen considering its benefits. Management case involving: compensation fluid loss, position the patient on the operating table, deep vein thrombosis prophylaxis, prevention triggering premature birth, postoperative pain therapy.

4. Studiu prospectiv, longitudinal, multicentric, international, cu privire la situatia reala

a integrari ingrijirilor paliative in centrele oncologice - Raport al IOCN Autori: Zgaia A., Pop F., Tolnai A., Irimie A., Achimas-Cadariu P Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: palliative care, oncology, evaluation of needs Rezumat:

Introducere. Pacientul oncologic reprezinta o provocare pentru sistemul sanitar datorita numarului in crestere permanenta, a resurselor limitate si variabilitatii in furnizarea serviciilor oncologice si paleative. Pentru pacienti oncologici in stadii avansate, rolul medicilor este esential in oferirea unui tratament tintit spre tumora dar si in identificarea si abordarea nevoilor de ingrijire paleativa. Acest studiu ofera oportunitatea investigarii aceastei abordari in detaliu. Scop. Evidentierea situatiei reale a ingrijirilor oncologice paleative si a indicatorilor de calitate asociati pentru o populatie specifica unei institutii, pentru a planifica in viitor interventii adecvate. Material si metoda. Studiul este prospectiv, longitudinal, multicentric si consta in colectarea de date in cinci institutii oncologice din Romania si o institutie din Elvetia, pentru o perioada de sase luni sau pana la deces. Se utilizeaza instrumente validate pentru evaluarea nevoilor paliative şi indicatori de calitate definiţi rezultaţi.Criteriile de includere sunt: pacienti cu orice tip de cancer, stadiu IV, ECOG 1-3 care au cel putin nevoi paleative minimale, definite ca ≥ 3 itemi pe IPOS ≥ 2.

Criteriile de excludere sunt: prognostic mai mic de 1 lună, deficite cognitive evidente, vârstă sub 18 ani, ECOG 0 şi 4. Rezultate. Studiul este in desfasurare.Vom prezenta datele obtinute pana in prezent in IOCN. Sunt luati in studiu 74 pacienti care s-au prezentat la cabinetele ambulatorii sau pentru internare in sectiile chimioterapie si radioterapie, in perioada noiembrie 2013- februarie 2014 . Majoritatea pacientilor au avut diferite nevoi paleative. Discutii. Rezultatele obtinute vor contura ‘realitatea’ nevoilor paleative.Vor fi evidentiate caracteristici regionale pe baza carora se va realiza un program pentru corectarea deficientelor constatate. Concluzii. Ingrijirea pacientului oncologic terminal in Romania este deficitara. Proiectul actual creaza premisele unei analize minutioase in domeniu si a crearii unui program menit sa alinieze standardele nationale in ingrijirea pacientului oncologic din Romania la standardele internationale.

ASISTENŢI

COMUNICĂRI ORALE

1. Interventii nutritionale in cancer

Autori:. Gyongyi Brigitta Szekely Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: malnutrition, nutritional intervention, quality of life Rezumat:

One of the most important aspects of the treatment of the cancer patient is an adequate nutrition to prevent malnutrition and the increase the quality of life. Malnutrition is a common condition among cancer patients due to side effects of surgery, chemo- and radiotherapy. Managing side effects which can influence the nutritional status of the patient is the main theme of this paper. Nutritional intervention and monitoring the patient in early stages and during treatment can positively influence the patient outcome and most importantly the quality of life.

2. Combined epidural and general anesthesia versus general anesthesia in colorectal

cancer patients Autori: Lia Iulia Alba 1 , Ioana Gădălean 1 , Simona Angheloiu 2 , D. Blag 1 , T. Tat 1 , Simona Mărgărit² Instituţie: 1 - The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca 2 ICU Clinic, Cluj-Napoca Cuvinte cheie: epidural, general anesthesia, colorectal cancer Rezumat:

Introduction: Rapid postoperative rehabilitation after colorectal surgery is one of the goals of modern surgery and is influenced by anesthesia and analgesia techniques used. Objectives: The aim of this study is to compare two different methods of anesthesia and analgesia used for elective surgery in patients with colorectal cancer and to compare postoperative recovery in the first 48 hours postoperatively Methods: The prospective study was conducted on two groups of patients with colorectal cancer admitted to the Institute "Prof. Dr. I. Chiricuţă "C. The first group (PG=42) received general anesthesia combined with epidural anesthesia, followed by postoperative epidural analgesia, and the second group (G=44) received general anesthesia followed by IV multimodal analgesia. Results: The dose of fentanyl administered intraoperatively was lower for PG group (110 ± 30 µg) than in group G (160 ± 80 µg). Number of patients who required additional boluses of morphine in the first hour after surgery was lower in the group PG (18) than in group G (40). Bowel movement into the first 24 hours was resumed to 15 patients in group PG compared with no patients in group G. Postoperative nausea and vomiting into the first 24 postoperative hours were present in 18,2% of patients in group G compared with no patients in group PG. Conclusions: General anesthesia combined with epidural anesthesia and analgesia provides a better control of postoperative pain and a faster recovery compared with general anesthesia and IV analgesia.

3.

Evaluation of patient satisfaction in an oncological ICU

Autori: Ioana Gadalean, Marilena Cheptea Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: nursing, patient satisfaction, quality Rezumat:

Introduction. Patient satisfaction may influence the results of medical care and their impact. Patient experience can be evaluated by different questionnaires or by direct observation. The purpose of this study was to evaluate the satisfaction of the patients admitted in ICU and to detect the most important insatisfaction factors. Materials and methods. 106 patients admitted in ICU of the Oncological Institute were included in the this prospective non-international study. Patients were given a questionnaire 24 hours after discharge. The original questionnaire included a Lickert scale with 5 grades for evaluation of patient satisfaction as well as a list with the most frequent satisfaction and insatisfaction factors as reported by patients in previous studies or identified by staff. The results were statistically analyzed (SPSS software).To detect relationships/ associations between qualitative variables the Chi-Square test was used. A p ≤ 0.05 was considered significant. Results. Only two degrees of satisfaction were chosen on the Lickert scale. 53,8% of the patients were very satisfied, respectively 46.2% were satisfied. The most important insatisfaction factors were: lack of communication, accommodation facilities, factors arising from the lack of personal , pain and lack of sleep. Conclusions. We consider that patients’ satisfaction score in our study was good. The study detected the most important 5 factors of discomfort for the patients; thus measures that may be taken to ameliorate them. Patients’ satisfaction evaluation should be done periodically to detect both improvements of the satisfaction, and to detect insatisfaction factors that can be further improved.

4. Infectious complications in cancer patients

Autori: Edit Boglár Tasnadi-Gazsi, Zsolt Fekete, Viorica Nagy, Alina Chezan Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: cancer patient, infection prevention, nursing care Rezumat:

Infections are the most common life-threatening complications in oncology patients with advanced disease, the leading cause of death accounting for about 70% of patients with acute leukemia and 50% of deaths in patients with lymphomas and solid tumors. Hygiene and infection prevention measures have the greatest impact in combating them. Factors favoring the infections: people over the age of 65, immobilized patients, diabetes, kidney diseases, metastatic diseases, chemotherapy and neutropenia in history. One of the most important factors favoring infection is neutropenia, which changes the epidemiology of infections and the resistance to the antibiotics. Often the only sign of infection in immunocompromised patients is fever. Pathogen agents may be of bacterial, fungal or viral nature. Empirical treatment may be PO and IV (depending on individual factors) but preferably based on antibiotic treatment. Use of granulocyte colony stimulating factor is based on strict guidelines. The requirements for a successful program of outpatient therapy of patients with fever, neutropenia, but at low risk are: a dedicated medical team (doctors, nurses, pharmacists), adequate institutional infrastructure, monitoring and rechecking, motivated patients, families and other care- givers.

Conclusions: Neutropenia and infectious complications are important problems in oncology. With proper patient education and individualizing therapy for pathogens the impact of these problems can be reduced.

5.

Principles of medical pain therapy

Autori: Eliza Ciglenean Instituţie: The Oncology Institute "Prof. Dr. Ion Chiricuta" Cluj-Napoca Cuvinte cheie: Pain, medical pain therapy, opioids-nonopioids Rezumat:

Pain is a complex physiological and emotional experience, which induces depression, exacerbates anxiety, causes sleep disturbances, and contributes to fatigue and general deterioration.

At the time of diagnosis, one-third of cancer patients suffer from pain; in advanced stages, at least two-thirds suffer. The World Health Organization published the guideline on cancer pain therapy. Medical pain therapy adheres to certain principles:

- Priority of oral administration: oral administration of drugs has proven to be safe, effective, and easy, supporting the autonomy of patients.

- Drugs are administered according to the duration of their activity. This means that medication needs to be taken at fixed time intervals.

- Pain therapy is built up stepwise. Pain therapy is initiated with nonopioids. Weak opioids are

added in step II. If pain control remains insufficient, weak opioids are replaced by strong opioids. Nonopioids should be continued in step II and III.

- Depending on the pain modality, coanalgesic drugs can be added at each level. Frequent and

serious unwanted side effects should be treated prophylactically.

- Breakthrough pain requires additional treatment in accordance with pain type. In the course of treatment, efficacy, tolerability and safety should be reassessed. This can be done with diaries or ranking scales. Adhering to these recommendations permits adequate pain control in 80-90% of patients b