ORIGINAL ARTICLES

Putative Predictive Parameters for the Outcome of Laparoscopic Splenectomy

A Multicenter Analysis Performed on the Italian Registry of Laparoscopic Surgery of the Spleen
Marco Casaccia, MD,* Paolo Torelli, MD, Ambra Pasa, PhD, Maria Pia Sormani, PhD, Edoardo Rossi, MD, and the IRLSS Centers
any studies suggest that laparoscopic splenectomy (LS) represents the gold standard for the treatment of benign hematologic diseases, with or without splenomegaly.1,2 Although the most common indication for LS is idiopathic thrombocytopenic purpura, many other benign or malignant hematologic diseases derive benet from this procedure. However, the role of laparoscopy for many hematologic malignancies (HM) is complex, and the benets should be carefully weighed against the risks. In fact, patients with malignant disease tend to have larger spleens than patients with benign disorders. Since the advent of laparoscopic surgery, patients with enlarged spleens presented the greatest challenge for surgeons.3,4 Currently, technical development and improved skills have expanded the number of LS indications in HM cases, independent of the associated splenomegaly.57 However, these conditions are still under discussion and their treatment require further studies. Questions have already been raised about patient selection and operative technique. In view of these problems, the Italian Registry of Laparoscopic Surgery of the Spleen (IRLSS) was developed to provide an informative tool at the national level for performing multicenter studies in the eld of laparoscopic surgery of the spleen.8 In 2008, a contribution to drawing up the clinical practice guidelines of the European Association for Endoscopic Surgery with respect to LS9 was made by a preliminary analysis of the IRLSS data.10 In this study, a wide cohort of patients with splenic diseases was investigated for potential predictive parameters that can affect intraoperative or immediate postoperative outcome.

Objective: To identify predictive risk factors for conversion to open splenectomy and postoperative complications in patients undergoing elective laparoscopic splenectomy. Background: The laparoscopic approach represents the gold standard for splenectomy, but its use in the treatment of splenomegaly and malignant disease is controversial. Factors that inuence immediate outcome are clinical, anatomic, and pathologic. Methods: Univariate and multivariate analyses of data from the Italian Registry of Laparoscopic Surgery of the Spleen, a multicenter database supported by 25 referral centers. Analysis of data (19932007) was performed on a series of patients (n 676) undergoing elective laparoscopic splenectomy. Demographic data, the operative indications, the surgical technique applied, and any intra- and/or postoperative complications with respect to the patients were assessed. Records were analyzed retrospectively using the Student t test, the 2 test, and logistic regression. Results: Conversion to open splenectomy was necessary in 39 cases (5.8%). Perioperative deaths occurred in 3 cases (0.4%). There were no complications in 560 patients (82.8%), with a mean hospital stay of 5 days (range, 254). Overall, morbidity occurred in 116 patients (17.2%). Multivariate analysis found that the body mass index (P 0.01) and the presence of hematologic malignancy (P 0.001) were independent predictors for intraoperative complications and surgical conversion. Spleen longitudinal diameter (P 0.001) and surgical conversion (P 0.001) were independent predictors for the occurrence of postoperative complications. Conclusions: This large multicenter study provides evidence for the significance of predictive risk factors for intra- and postoperative complications in laparoscopic splenic surgery. Besides splenic dimensions, other factors like the patients habitus and the specic underlying hematologic pathology should be recognized by the surgeon to reduce complications and initiate adequate treatment. (Ann Surg 2010;251: 287291)

PATIENTS AND METHODS

In December 2000, IRLSS was formally launched under the auspices of the Italian Society for Endoscopic Surgery and New Technologies (SICE). Adherence to the IRLSS is on a voluntary basis. Starting from 2001, 13 laparoscopic centers asked to participate in the Registry. At the end of the data analysis period (October 2007), 25 centers from all over the country contributed to the Registry. Data collection (19932000), initially through questionnaires, has been subsequently performed by using a specic database developed in MS Access (Microsoft Corporation, Redmond, WA, USA). This database can be downloaded from the SICE Web site (available at: http://www.siceitalia.com/db_on-line_milza.htm). Patients treated with elective LS for different benign or malignant hematologic diseases were eligible for inclusion in the study. Indications for splenectomy are reported in details in Table 1. Patients were assessed for demographic data, operative indications, type of approach and technique, and intra- and postoperative complications. A preoperative measurement of spleen longitudinal diameter (SLD) dened as interpole length was obtained by computed tomography or ultrasonography. Splenic weight was the agwww.annalsofsurgery.com | 287

From the *Advanced Laparoscopy Unit, Department of General Surgery and Transplant, San Martino University Hospital, University of Genoa, Genoa, Italy; General and Minimally-Invasive Surgery Unit, Sanremo Hospital, Sanremo, Italy; Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy; and Department of Hematology and Oncology, San Martino University Hospital, University of Genoa, Genoa, Italy. Supported by the Italian Society for Endoscopic Surgery and New Technologies (SICE; http://www.siceitalia.com). Reprints: Marco Casaccia, MD, Advanced Laparoscopy Unit, Department of General Surgery and Transplant, San Martino University Hospital, Monoblocco IV Piano, Largo R. Benzi 10, 16132 Genoa, Italy. E-mail: marco. casaccia@unige.it. Copyright 2010 by Lippincott Williams & Wilkins ISSN: 0003-4932/10/25102-0287 DOI: 10.1097/SLA.0b013e3181bfda59

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TABLE 1.

Clinical Indications of Laparoscopic Splenectomy

676 246 169 37 2 38 222 140 38 12 7 7 18 142 62 30 12 38 66 19 10 3 34

N TP Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura HIV-related thrombocytopenia Other thrombocytopenia HM Non-Hodgkin lymphoma Hodgkin lymphoma Idiopathic myelobrosis Chronic lymphatic leukemia Hairy cell leukemia Other HM HA Hereditary spherocytosis Major beta-thalassemia Autoimmune hemolytic anemia Other HA OP Splenic cyst Splenic angioma Splenic artery aneurysm Unknown

mobilized. For this dissection, the most commonly used tool was the ultrasonic dissector (65.9%). Next, the short gastric vessels were cut after successful achievement of hemostasis with clips. The hilar splenic vessels were freed and hemostasis was achieved with a stapler. The spleen was put in a plastic bag and extracted by fragmentation and subsequent passage through the lumen of the 15-mm trocar. For cases involving larger spleens and those requiring pathologic examination of the surgical specimen for determination of the underlying hematologic disease, a minilaparotomy was performed through a left subcostal incision or through an upper midline/ Pfannenstiel incision. A drain was left in situ in 514 (76%) patients. The spleen was retained for histopathologic examination. The results are expressed as mean SD. All comparisons between groups were performed using the Student t test or the Mann-Whitney U test. The 2 test was used to assess the relationships between categorical variables. A logistic regression model was used to identify variables affecting the probability of a conversion and of postoperative complications in univariate analysis. At univariate analysis, all parameters with a P 0.05 were included in a multivariate model through a backward selection procedure to evaluate potential independent predictors for conversion and postoperative complications. Statistical analysis was performed using the software package SPSS Version 13.0 (SPSS Inc, Chicago, IL).

Statistical Analysis

HM indicates hematologic malignancy; TP, thrombocytopenic purpura; HA, hemolytic anemia; HIV, human immunodeciency virus; OP, other pathologies.

gregate weight of the morcellated splenic tissue as measured in the pathology laboratory. A maximum of 146 parameters were collected for each patient.

Surgical Procedures
The fully laparoscopic approach was the preferred technique, with the hand-assisted approach used for only 43 patients (6.4%). The right hemilateral decubitus position was used for 432 patients (63.9%), with the surgeon and the assistant on the right side of the patient. In general, 4 trocars and a 30 optic were necessary. After exploration of the abdominal cavity (liver and lymph nodes in particular) and exclusion of an accessory spleen, the left colic angle was lowered and the inferior pole of the spleen was TABLE 2.

A group of 676 patients (mean age, 42 20 years; range, 4 84 years; male/female, 333/343) treated with LS between February 1993 and October 2007 was entered into the IRLSS. Of these, 90 patients operated on prior to Registry institution (December 2000) and for whom a complete set of data was available, were entered in the IRLSS. The patients were classied according to the American Society of Anesthesiologists (ASA) score as follows: ASA1, n 279 (41.3%); ASA2, n 308 (45.6%); ASA3, n 93 (13.8%); and ASA4, n 5 (0.7%). About 56 patients (8.3%) had a body mass index (BMI) greater than 30 kg/m2. Previous abdominal surgery before LS was performed in 138 patients (20.4%). Administration of pneumococcal, meningococcal, and antihaemophilus vaccine was reported in 549 patients (81.2%). The main anatomic and clinical parameters of the patients who underwent LS and the results for each pathology are shown in Table 2.

RESULTS

Demographics and Clinical Characteristics of Patients

Overall TP 246 40 18 88/158 24.5 5.1 1.6 0.7 12.0 2.5 329 238 122 48 9 (3.6) 54 33 (13.4) 0 HM 222 56 14 143/79 24.6 3.9 2.1 0.7 19.2 5.9 1776 1368 152 58 26 (11.7) 64 55 (24.7) 3 (1.3) HA 142 23 16 67/75 21.6 3.8 1.5 0.6 16.7 3.7 767 512 142 54 4 (2.8) 52 20 (14) 0 OP 66 46 17 31/35 24.6 3.3 1.6 0.7 13.2 3.7 692 333 145 59 0 51 8 (12.1) 0 676 42 20 333/343 24.0 4.4 1.8 0.7 15.4 5.3 905 1023 138 55 39 (5.8) 54 116 (17.2) 3 (0.4)

N Age (yr) Men/woman (n) BMI ASA score SLD (cm) Spleen weight (g) Operative time (min) Conversion (%) Hospital stay (d) Morbidity (%) Mortality (%)

TP indicates thrombocytopenic purpura; HM, hematologic malignancy; HA, hemolytic anemia; OP, other pathologies; BMI, body mass index; ASA, American Society of Anesthesiologists; SLD, spleen longitudinal diameter.

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The overall operative time was 138 55 minutes, and the ndings showed a signicant difference between HM (152 58 minutes) and non-HM (131 52 minutes; P 0.001) patients. The operative time for entirely laparoscopic operations (136 53 minutes) was shorter than for cases that required an open conversion (164 71 minutes), the difference being statistically signicant (P 0.001). Analogously, obesity was found to be a factor signicantly affecting the operative time (154 65 minutes in patients with BMI 30 vs, 136 53 minutes in patients with BMI 30; P 0.04). The ASA score was signicantly higher for HM patients (2.1 0.7) than for non-HM patients (1.6 0.7; P 0.001), as was the BMI (24.6 3.9 vs. 23.7 4.8, respectively; P 0.038). A cholecystectomy was associated with the procedure for 32 cases of hemolytic anemia and 10 cases of thrombocytopenic purpura. In the HM group, LS was associated to a lymph node biopsy (11) or a liver biopsy (15) for diagnostic or disease-staging purposes. One or more accessory spleens were found and removed in 64 patients (9.5%). The overall spleen weight was 1191 1046 g (range, 80 4600), whereas SLD was 15.4 5.3 cm (range, 6 35 cm). In HM patients, both spleen weight (1776 1368 g) and SLD (19.2 5.9 cm) reached signicantly higher values than in non-HM patients (508 417 g and 13.6 3.7 cm, respectively), with both comparisons bearing statistical signicance (P 0.001). The estimated blood loss was less than 100 mL in 64.3% patients, between 100 and 500 mL in 26% patients, and more than 500 mL in 9.7% patients. HM patients had signicantly greater estimated blood loss (more than 500 mL: 12.6%) than non-HM patients (more than 500 mL: 3.9%; P 0.001). A conversion from LS to open splenectomy was required for 39 patients (5.8%). Surgical conversion was made in the presence of hemorrhagic problems involving the hilar splenic vessels (53.1%), massive splenomegaly (21.8%), strong diaphragmatic adhesions (15.6%), or advanced local malignant disease with nearby organ involvement (9.3%). When conversion rate according to hematologic diseases was considered, it was found to be 4-fold higher in the malignant group (11.7%) than in the benign group (3.2%), with the difference reaching statistical signicance (P 0.001). The ndings showed that 13.6% of the patients who experienced a conversion from LS to open splenectomy were obese, as compared with 5.7% of the patients who underwent completed laparoscopic procedures (P 0.05). The postoperative hospital stay was 5 4 days. This parameter was signicantly greater after surgical conversion (9 6 days) than after laparoscopically completed splenectomy (5 4 days, P 0.001), and similarly greater for HM patients (6 4 days) than for non-HM patients (5 4 days, P 0.001). Altogether, 138 postoperative complications occurred in 116 patients (morbidity 17.2%). The most common surgical complications were pleural effusion (n 31), and actual or suspected hemorrhage (n 30), commonly requiring reintervention (n 26). The detailed postoperative complications are listed in Table 3. Postoperative complications occurred for 47.1% converted patients as compared with 21.6% patients without surgical conversion, the difference reaching statistical signicance (P 0.001). A signicant difference was also found in morbidity rate between HM patients and non-HM patients (24.7% vs. 13.9%, respectively; P 0.001). Perioperative deaths were observed in 3 patients (0.4%). One patient affected by idiopathic myelobrosis died 15 days after surgery as a consequence of secondary blast crisis. One perioperative death attributable to myocardial infarction occurred for an 2010 Lippincott Williams & Wilkins

TABLE 3.

Postoperative Complications
138 (20.4) 31 (22.5) 30 (21.7) 17 (12.3) 16 (11.6) 14 (10.1) 11 (8) 7 (5) 5 (3.6) 7 (5) 22 (15.9)

N (%) Pleural effusion Bleeding* Abdominal uid collection Isolated fever Splenic/portal vein thrombosis Surgical site infection Pneumonia Pancreatitis Other More than 1 complication
*Requiring reintervention in 26 cases.

TABLE 4. Univariate and Multivariate Logistic Regression Analysis of Parameters Associated With Surgical Conversion
Univariate Analysis Parameter Patient age Patient sex Female Male Pathology Non-HM HM ASA score BMI (kg/m2) SLD (cm) Spleen weight (kg) OR 95% CI P 0.001 Multivariate Analysis OR 95% CI P

1.03 1.011.05 1 1.46 0.731.94 1 4.23 2.22 1.1 1.08 1.31

0.285

Not entered

2.048.77 0.001 4.15 1.948.91 0.001 1.403.52 0.001 1.031.17 0.007 1.1 1.021.18 0.01 1.011.15 0.018 0.881.15 0.018 Not entered

OR indicates odds ratio; CI, condence interval; HM, hematologic malignancy; ASA, American Society of Anesthesiologists; BMI, body mass index; SLD, spleen longitudinal diameter.

80-year-old patient affected by non-Hodgkin lymphoma. One patient with non-Hodgkin lymphoma died 23 days after splenectomy from sepsis.

Multivariate Predictors of Surgical Conversion and Morbidity

Logistic regression analysis was performed to evaluate patient characteristics that can potentially affect conversion from LS to open-surgery splenectomy. The parameters included in the model are shown in Table 4. Univariate analysis showed that patient age (odds ratio OR, 1.03; P 0.001), BMI (OR, 1.1; P 0.007), ASA score (OR, 2.22; P 0.001), SLD (OR, 1.08; P 0.018), and pathology type (HM vs. non-HM; OR, 4.23; P 0.001) were signicantly associated with the risk of surgical conversion. The type of pathology was coded as a binary variable (HM vs. non-HM patients) because the risk of a conversion was similar for all non-HM patients. No signicant correlation was found for patient sex (gender) and spleen weight. At univariate analysis, all the variables with P 0.05 were entered into a multivariate model. The nal model retained pathology type (OR, 4.15 for HM vs. non-HM, P 0.001) and BMI (OR, 1.1 for each 1-point increase; P 0.01). www.annalsofsurgery.com | 289

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TABLE 5. Univariate and Multivariate Logistic Regression Analysis of Parameters Associated With Morbidity
Univariate Analysis Parameter Patient age Patient sex Female Male Pathology Non-HM HM ASA score BMI (kg/m2) SLD (cm) Spleen weight (kg) Conversion No Yes OR 95% CI P Multivariate Analysis OR 95% CI P

1.02 1.021.03 0.001 1 1.06 0.721.58 1 2.09 1.53 1.01 1.1 1.44

0.765

Not entered

1.393.14 0.001 1.162.02 0.003 0.971.06 0.549 1.061.5 0.001 1.12 1.071.95 0.017

Not entered 1.051.2 0.001

1 2.83 1.395.74

0.004 9.34

2.4439.75

0.001

OR indicates odds ratio; CI, condence interval; HM, hematologic malignancy; HA, hemolytic anemia; TP, thrombocytopenic purpura; ASA, American Society of Anesthesiologists; BMI, body mass index; SLD, spleen longitudinal diameter.

Univariate and multivariate analyses of parameters affecting the risk of postoperative complications are shown in Table 5. In the univariate analysis, patient age (OR, 1.02; P 0.001), ASA score (OR, 1.53; P 0.003), SLD (OR, 1.1; P 0.001), spleen weight (OR, 1.0; P 0.02), pathology type (HM vs. non-HM; OR, 2.09; P 0.001), and need for surgical conversion (OR, 2.83; P 0.004) were signicantly associated with the risk of having a postoperative complication. At univariate analysis, all the variables with P 0.05 were entered into a multivariate model. The nal model retained SLD (OR, 1.12; P 0.001) and surgical conversion occurrence (OR, 9.34; P 0.001).

DISCUSSION
The IRLSS was developed with the technical support of SICE to provide a national informatics tool useful for performing both retrospective and prospective multicenter studies investigating spleen laparoscopic surgery.8 As an ofcial member of the European Association for Endoscopic Surgery since 1996, SICE is the leading Italian scientic society for endoscopic surgery, representing more than 500 surgeons involved in the practice and diffusion of new technologies in this eld. Although adherence to the IRLSS is on a voluntary basis, most of the Italian laparoscopic centers have participated with data entry, making IRLSS highly representative of LS activity in Italy. The initial number of participating centers was 13, whereas 8 centers have adhered in the last 2 years of data collection. Furthermore, only 90 cases operated on prior to Registry Institution (December 2000) and for whom a complete set of data was available, were entered in the IRLSS. Thus, in the evaluation of the number of both participating centers and entered cases, these statements should be considered. In this study analyzing IRLSS data, a cohort of patients with splenic pathologies was retrospectively investigated for potentially predictive parameters that could affect intraoperative or immediate postoperative LS outcome. Attempts have been made to dene the perfect candidate to undergo a safe LS on the basis of splenic dimensions and 290 | www.annalsofsurgery.com

weight. Besides these, further clinical parameters must be taken into account when assessing the risks connected to LS. In fact, the type of hematologic pathology can play a fundamental role in risk modication. Notwithstanding the excellent outcome for non-HM patients according to elective LS reports,1,2,11 the role of the laparoscopic approach in HM is more complex. Malignant spleens are frequently seen in older, more physiologically frail patients; they are usually larger in size and can often be associated with coagulopathies, signicant anemia, thrombocytopenia and perisplenitis. In fact, in the IRLSS study, signicant differences were present between HM and non-HM patients not only for SLD and spleen weight but also for age, ASA score, and BMI. The operative time in the current study was similar to that reported in single-center studies.57 In particular, a direct correlation between surgery time and spleen size of the HM patients was observed. This may be explained by the fact that during LS for splenomegaly, the space available in the abdominal cavity is diminished after the creation of the pneumoperitoneum, making organ manipulation more difcult. In addition, extra time must be added for extraction of a large spleen. The operative time was also correlated with BMI. The impact of obesity on the outcomes of many laparoscopic procedures has been well documented. Our nding of longer operative times for LS on obese patients is consistent with the ndings reported in previous studies.12,13 In the IRLSS dataset, the overall conversion rate reached 5.8%, consistent with previous LS studies.14 16 In the multivariate analysis, BMI was an independent factor related to surgery conversion, conrming that obesity may increase the technical difculty of laparoscopic procedures due to reduced abdominal working space and worse visualization.12,13 A BMI 30 was found in 13.6% of the patients who experienced a conversion from LS to open splenectomy, as compared with 5.7% of the patients who underwent completed laparoscopic procedures (P 0.05). The impact of BMI on surgical conversion in LS is controversial. Berindoague et al17 showed that BMI was not related to the conversion rate. In contrast to this, Delaitre et al18 reported a signicantly higher conversion rate (37.9%) for obese patients. Dominguez et al13 analyzed the data for 112 patients classied into groups by BMI before they underwent LS. The complication and conversion rates were higher in the group with a BMI greater than 40, but the differences between this group and that for BMI 40 were not statistically signicant. In the rst study performed on the IRLSS dataset, BMI had a low impact on intraoperative and immediate postoperative LS outcome.10 Interestingly, in the present study, with a nearly doubled number of patients, BMI played a major role in affecting the LS intraoperative outcome. In our series of results, aside from the BMI value, the most powerful predictor of conversion to open splenectomy was the type of underlying pathology, reected by the conversion rate for HM patients reaching 11.7%. Higher conversion rates in HM patients when compared with patients with benign pathologies have already been documented.19,20 In any case, this result seems to represent a good outcome, on comparison with other series, in which only data for HM patients were taken into account.14,20,21 In the IRLSS data series, a mortality rate of 0.4% and a morbidity rate of 17.2% was reported, making these results comparable with those of the latest series of LS.20,22,23 In the multivariate analysis performed on the IRLSS dataset, surgical conversion was a strong predictor for the occurrence of postoperative complications. In patients who had conversion to open surgery, the 2010 Lippincott Williams & Wilkins

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frequency of morbidity was almost 3-fold that of patients without surgical conversion. Another parameter independently associated to postoperative morbidity was SLD. This nding correlates with the results of a previous study by Targarona et al24 in which the predictive factors for postoperative complications were explored in a series of 130 nonselected patients undergoing LS and found that spleen size, age, malignancy, and surgical experience were independent factors for the risk of complications. In previous studies, a higher complication rate was observed in splenectomy performed for malignancy.16,22,23 Similarly, in our analysis, morbidity occurred more frequently for patients with a diagnosis of HM than for those with a benign pathology (24.7% vs. 13.9%, respectively; P 0.001), even if at multivariate analysis, HM did not turn out to be an independent predictor for the occurrence of postoperative complications. This study analyzing the IRLSS data represents one of the largest multicenter analysis concerning LS for patients with hematologic diseases. The IRLSS conrms that LS may be considered the gold standard treatment for benign hematologic diseases, and proposes that it can also be exercised successfully for HM with associated splenomegaly. A laparoscopic approach may provide the greatest benet in this subgroup of patients at greatest risk of complications. With the advent of advanced bariatric laparoscopic procedures, obesity is not a contraindication to LS. Following a careful preoperative clinical evaluation, LS can be deemed to be an attractive therapeutic approach because the potential benets are greater also for obese patients. The present study illustrates the clinical relevance of important clinical variables in providing information that allows us to predict LS outcome prior to surgery. This valuable tool demonstrates that the anatomy of the spleen and its pathologic characteristics together with patients habitus play a key role in assessing the feasibility of laparoscopic surgery and also in predicting the immediate outcome. ACKNOWLEDGMENTS IRLSS Centers: M. Casaccia, U. Valente (Dipartimento di Chirurgia Generale e Trapianti, Ospedale San Martino, Universita ` di Genova); G. Spinoglio (Azienda Ospedaliera Santi Antonio e Biagio, Alessandria); F. Prete (Universita ` di Bari); G. Logrieco (Ospedale Generale Regionale F. Miulli, Acquaviva delle Fonti [Bari]); F. Buccoliero, R. Berta (Ospedale Bufalini, Cesena); I. Donini, A. Donini (Ospedale S. Anna, Universita ` di Ferrara); A. Valeri, P. Prosperi (Ospedale Careggi, Firenze); M. Saviano, R. Gelmini (Policlinico di Modena, Universita ` di Modena); F. Uggeri, R. Caprotti, F. Romano (Ospedale S. Gerardo, Monza [Milano], II Universita ` di Milano); G. Colecchia, E. Monteferrante (Ospedale Civ. Spirito Santo, Pescara); C. Pedrazzoli, L. Bigi, I. M. Barbieri (Arcispedale Maria Nuova, Reggio Emilia); A. Moraldi, A. Dallatorre (Ospedale S. Giacomo, Roma); N. Basso, G. Silecchia (U.O.C. Patologia Chirurgica VII, Universita ` degli Studi La Sapienza, Roma); R. Rosati, S. Bona (U.O.di Chirurgia Generale e Mini-Invasiva, Istituto Clinico Humanitas. Rozzano [Milano]); P. Cavaliere (Ospedale S. Paolo, Savona); F. Bresadola, G. Terrosu (Policlinico Universitario Pugo, Udine); F. Mosca, A. Pietrabissa (Chir. Gen. e Trapianti, Ospedale Cisanello, Universita ` degli Studi di Pisa); V. Memeo, F. Puglisi (Chir. Trapianti Fegato, Universita ` di Bari); R. Dionigi, A. Benevento, L. Boni (Chirurgia Generale Dipartimento di Scienze Chirurgiche, Universita ` degli Studi dellInsubria, Varese); A. Liboni, C. Feo (Sezione di Chirurgia Generale, Dipartimento di Scienze Chirurgiche, Anestesiologiche e Radiologiche, Universita ` di Ferrara); F. Borghi, P. Geretto (S.C. Chirurgia Generale, ASO S. Croce e Carle, Cuneo); P. Torelli 2010 Lippincott Williams & Wilkins

(Chirurgia Generale ad Indirizzo Mininvasivo, Ospedale di Sanremo); R. Moroni, M. Sorrentino (U.O.S. Chirurgia Laparoscopica e dellObesita ` , Ospedale Marino, Cagliari); P. di Sebastiano, A. Ambrosio (UOC Chirurgia I Addominale, Ospedale Casa Sollievo della SofferenzaIRCCS San Giovanni Rotondo [Foggia]); and G. M. Verdecchia, D. Cavaliere (U.O. Chirurgia e Terapie Oncologiche Avanzate, Ospedale G.B. MorgagniL. Pierantoni, Forl). REFERENCES
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