Documente Academic
Documente Profesional
Documente Cultură
CHEMOTHERAPY,
Coresponden: Dr. Lili-Gabriela Lozneanu, medic primar chirurgie general, doctorand Universitatea de
Medicin i Farmacie Gr.T.Popa Iasi, Clinica I Chirurgie, Sp. Sf. Spiridon, str. Independenei, nr. 1,
700111, e-mail: lili_lozneanu@yahoo.com*.
511
Articole de sintez
INTENIA TRATAMENTULUI
Exist dou modaliti de tratament: cu intenie curativ sau paliativ.
Ocazional, intenia curativ poate fi deliberat compromis, fie datorit comorbiditilor
asociate, prea severe pentru a permite o rezecie standard n deplin siguran, fie
datorit refuzului pacientului de a accepta protocolul standard cu intenie curativ.
Intenia curativ, n tratamentul cancerului rectal, impune rezecia i/sau ablaia
esutului neoplazic n ntregime, fiind asigurat de o rezecie R0, de obicei sub forma
unei rezecii radicale standard (rezecie anterioar-AR sau rezecie abdomino-perineal
APR). n trecut, stadiul IV al cancerului rectal excludea intenia potenial curativ, dar
aceast dogm a fost pus sub semnul ntrebrii cnd s-a dovedit c metastazele(MTS)
izolate, hepatice sau pulmonare, pot fi rezecate, fie sincron cu tumora primar, fie prin
operaii secveniale, cu o rat de supravieuire la 5 ani de 25-40% din pacieni [3].
n prezent, cazurile care erau odat o indicaie clar pentru ngrijire doar
paliativ, sunt adesea abordate printr-o terapie agresiv multimodal, cu intenia de a
ameliora stadiul bolii, pn la punctul n care poate fi aplicat o chirurgie cu viz
curativ.
OPIUNI ALE TRATAMENTULUI MULTIMODAL
Chirurgia rmne principala modalitate de tratament n cancerul rectal, dei
asistm la o extindere a rolul radioterapiei, chimioterapiei i a noilor ageni biologici
I. OPIUNILE CHIRURGICALE
Decizia de a apela la o rezecie radical standard, la o excizie local sau o
operaie extins sau la o intervenie paliativ, se bazeaz n principal pe evaluarea
preterapeutic. Chirurgului i revine rolul critic de a alege, printr-o judecat matur,
abordarea optimal, i el devine, astfel, determinantul primar al rezultatului pentru
pacientul cu cancer de rect. Ca membru al echipei multidisciplinare, dup evaluarea
datelor preliminare, chirurgul cu experien poate identifica potenialele provocri
tehnice i estima, n limite rezonabile, necesitatea efecturii unei anastomoze primare,
cu sau fr diversie fecal proximal temporar, comparativ cu o colostomie
permanent. n majoritatea cazurilor se impune o rezecie radical standard (AR sau
APR), dar uneori sunt indicate proceduri locale de tratament. Informaiile obinute pot
alerta chirurgul asupra necesitii de a modifica tehnicile standard pentru a rspunde mai
bine particularitilor cancerului rectal; de exemplu, tipul histologic cu celule n inel cu
pecete va impune coborrea limitei de excizie distal, iar patologia colonic sincron
poate impune o colectomie extins.Un aspect important, care trebuie considerat cu
obiectivitate i discutat onest cu pacientul, este impactul anticipat al tratamentului
chirurgical prefigurat, asupra continenei fecale i asupra funciilor urinare i sexuale.Un
pacient cu incontinen fecal sau afectare preexistent a sfincterului poate beneficia
mai degrab de o APR i colostomie, dect de un efort bine intenionat, dar eroic in
concepie, de a salva sfincterul printr-o RA joas sau ultrajoas (LAR/uLAR). n
corelaie cu extensia locoregional, pot fi indicate rezecii multiviscerale. n raport cu
magnitudinea acestora, chirurgul poate solicita expertize suplimentare colegilor
specialiti n chirurgie hepatic, plastic, urologie, ginecologie, chirurgie toracic sau
altele.
512
Articole de sintez
II.CONTROVERSE
n prezent, principalele controverse privind tratamentul multimodal al cancerului
rectal sunt:
1. Criteriile de selecie a tumorilor (cnd va crete terapia multimodal posibilitatea
de a realiza o rezecie R0 sau va mbunti rezultatele oncologice, funcionale
sau calitatea vieii pacientului?);
2. Timing-ul tratamentului (ar trebui s fie preoperator, postoperator sau ambele?);
3. Dozele i cursul radioterapiei (continu sau de scurt durat);
4. Alegerea chimioterapiei i agenilor biologici;
5. Utilizarea chimioterapiei n conjuncie cu tratamentul chirurgical local;
6. Dac marginea de siguran chirurgical distal ar trebui s aib la baz
evaluarea preterapeutic sau pe cea post-radio-chimioterapie neoadjuvant;
7. Dac un rspuns complet la radio-chimioterapie neoadjuvant, este suficient
pentru urmrirea pacientului, fr a mai aplica un tratament chirurgical radical.
III. ROLUL RADIOTERAPIEI N OPTIMIZAREA REZULTATELOR
CHIRURGIEI RADICALE
Recidiva local i/sau metastazele la distan survin la 50% din pacienii cu
cancer rectal.Invazia profund n peretele rectal, precum i prezena adenopatiilor
metastatice sunt factori de prognostic negativ.n absena adenopatiilor, rata de recidiv
pelvin este de 5-19% n stadiul I, de 15-30% n stadiul II, iar n stadiul III, incidena
crete la peste 50% [4-6]. Radioterapia (RT) este utilizat pentru a steriliza focarele
neoplazice microscopice i a reduce riscul de recidiv local.Rezecia chirurgical a
reprezentat mult timp singura modalitate terapeutic n carcinoamele rectale.Adugarea
RT a demonstrat, la pacienii cu boal avansat loco-regional, o ameliorare
semnificativ a controlului local, dar fr rsunet asupra supravieuirii globale [6].
Cercetarea rolului asocierii RT preoperatorii la chirurgia radical cu excizia
totala a mezorectului (TME) a artat reducerea ratei recurenelor locale de la 10,9% n
grupul tratat doar prin chirurgie la 5,6% n grupul cu RT asociat,dar nu s-au semnalat
diferene n ratele de supravieuire a pacienilor [7].
Rata complicaiilor acute i tardive postoperatorii a fost mai mare fa de
pacienii tratai chirurgical per-primam (48% vs. 41%, p=0,008). Majoritatea
complicaiilor nregistrate au constat n ntrzierea vindecrii plgii perineale (29
vs.18%), tulburri ale funciei sexuale la ambele sexe, precum i tulburri ale defecaiei
[8]. Ocluzia intestinal a fost una din cele mai frecvente complicaii [9].
Asocierea RT a artat beneficii mai mari la pacienii cu CR in stadiul III
comparativ cu stadiul lI (scderea ratelor de recidiv de la 20, 6% la 1,7%), i pentru
localizrile n poriunea mijlocie a rectului (intre 5 si 10 cm de marginea anal),
(scderea ratelor de recidiv de la 13,7% la 3,7%). Avantajele conferite de RT
preoperatorie sunt mai consistente n condiiile unui tratament chirurgical standard (cu
TME) [5].
Radioterapia ar putea fi omis dac examenul patologic al piesei de exerez
relev un mezorect intact, cu margini de rezecie radiale adecvate (>2mm), o penetrare
tumoral minim n grsimea perirectal, un numr adecvat de ganglioni limfatici
regionali negativi (>12), situaia unor tumori moderat i bine difereniate [6].
513
Articole de sintez
514
Articole de sintez
515
Articole de sintez
timp de 4 sptmni, rata de recidiv local la 5 ani fiind redus la jumatate (6%
vs.13%) [11].
Incidena toxicitii pe termen lung, n special cea gastro-intestinal, este mai
mic n favoarea grupului tratat preoperator.
CHT- RT preoperatorie este mai bine tolerat, asigur un control local mai bun,
dar nu pare s influeneze frecvena apariiei metastazelor la distan [11]. Dei ratele de
supravieuire fr boal la 5 ani i de supravieuire global sunt echivalente cu ale CHTRT postoperatorii, este recomandat n prezent de majoritatea autorilor la toi pacienii
cu cancere rectale T3 sau T4 i tinde s devin un nou standard in cancerul rectal [2].
VII. CONSIMMNTUL INFORMAT
Odat stabilit un protocol terapeutic de urmat, acesta trebuie explicat
pacientului, in vederea obinerii consimmntului. Chirurgul conduce de obicei
discuia, trecnd n revist informaiile despre stadiul clinic, n contextul situaiilor
tactice i tehnice operatorii anticipate, a rezultatelor funcionale scontate, riscului
operator, comorbidittilor, tratamentelor anterioare i situaiei particulare a pacientului.
Uneori teama sau morbiditatea legat de tratament,precum i rezultatele funcionale
nesatisfctoare sau lipsa de nelegere a ceea ce trebuie fcut i a alternativelor
posibile, stau la baza refuzului pacientului de a accepta protocolul terapeutic
recomandat. Aceasta se ntmpl mai ales n situaiile n care tratamentul recomandat
pacientului implic, pentru a obine un control optim al cancerului rectal, o colostomie
permanent. Un plan terapeutic de compromis este totui necesar, chiar dac alegerea
are un impact negativ asupra rezultatului oncologic. Indiferent de protocolul selectat n
final, chirurgul cu experien n chirurgia colorectal, este probabil cel mai nimerit a
consilia pacientul n ceea ce privete opiunile terapeutice i ateptrile realistice privind
rezultatul funcional i prognosticul.
VIII. CATEGORII I STRATEGII TERAPEUTICE
Acestea sunt precizate n detaliu n cadrul ghidului de tratament al
carcinoamelor colorectale aflat n vigoare n ara noastr [20].
A. TUMOR RECTAL LOCALIZAT, OPERABIL - cuprinde stadiul
I TNM (T1-2NoMo) - stadializat preoperator cu ecografie endorectal i CT/RMN
abdomino-pelvin.
Chirurgia radical reprezint tratamentul de electie. Standardul este reprezentat
de rezecia transabdominal, cu tehnica adaptat limitei inferioare a tumorii:
-rezecie anterioara (AR) cu rezecie total de mezorect si anastomoz colorectal joas sau anastomoz colo-anal cu/fr rezervor;
-rezecie abdomino-perineal (APR) cu rezecie total de mezorect.
Postoperator, conduita difer, n funcie de examenul histopatologic i
stadializarea pTNM: urmrire(n cazurile pT1-2N0M0) sau chimio-radioterapie
adjuvanta(n situaia pT3 sau pN1-2).
Rezecia total de mezorect (TME) este obligatorie pentru a realiza un tratament
chirurgical optimal n cancerul rectal. Aceast tehnic impune disecie instrumental
sub viziune direct, cu mobilizarea n totalitate a rectului, ceea ce permite obinerea de
margini de rezecie negative distal i lateral, permind astfel reducerea ratei de recidiv
local la sub 10%. Se recomand excizia a minimum 4 ganglioni (ggl) pentru a afirma
statusul pN0. Noile achiziii n ceea ce privete sutura mecanic au permis coborrea
limitei inferioare a tumorii la care se practic APR la 4 cm.
516
Articole de sintez
517
Articole de sintez
518
Articole de sintez
519
Articole de sintez
Chimioterapia linia I
FOLFOX+/-bevazucimab
FOLFIRI+/-bevazucimab
FU-FOL bolus(Mayo)+/bevazucimab
FU-FOL infuzional (De
Gramont)+/-bevazucimab
Capecitabina
UFT+Leucovorin
Tabel 1
Chimioterapia de salvare
Chimioterapia linia II
Irinotecan/FOLFIRI
FOLFOX
Irinotecan+Cetuximab
FOLFOX
Irinotecan/FOLFIRI
Cetuximab
520
Articole de sintez
521
Articole de sintez
522
Articole de sintez
CONCLUZII
Tratamentul multimodal i-a demonstrat rolul n reducerea morbiditii i
mortalitii n cancerul rectal, dar i n mbuntirea supravieuirii la distan.
Abordarea multidisciplinar este de importan major, att pre ct i postoperator.
Tratamentul chirurgical a rmas principala modalitate de tratament i este standardizat,
dar sunt nc controverse n tipul i timingulcelorlalte mijloace terapeutice. Trialuri
viitoare vor rafina strategiile pentru a identifica protocoalele optime de tratament.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
BIBLIOGRAFIE:
American Society of Colon and Rectal Surgeons.Practice parameters for the treatment of rectal
cancer (revised). Dis Colon Rectum 2005; 48: 411-23.
National Comprehensive cancer Network. Rectal cancer clinical practice guidelines in
Oncology. J Natl Compr Can Netw 2005; 3:492-508.
DAngelica M, Idrees K, Paty PB, Blumgart LH. Colorectal Cancer: Metastatic (Palliation). In:
Wolff BG, Fleshman JW, Beck DE, Pemberton JH, Wexner SD eds. The ASCRS textbook of
colon and rectal surgery. New York, Springer. 2007; p.471-472.
Libutti SK, Tepper JE, Salz LB. Rectal Cancer. In: DeVita VT, Lawrence TS, Rosenberg SA,
eds. De Vita Hellman, and Rosenbergs Cancer : Principles and Practice of Oncology. 8-th ed.
Philadelphia, Wolter Kluivert/Lippincott Williams and Wilkins 2008; p.1285-1301.
Cohen AM, Garofalo MC, De Simone PA, Hanna NN, Regine WF. Cancer of the rectum. In:
Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, Mc Kenna WG. eds. Abeloffs Clinical
Oncology. 4-th ed. Philadelphia, Churchill Livingstone Elsevier 2008; p.2353-2370.
Deutsch E, Ezra P, Mangoni M, Ducreux M. Radiotherapy for localized rectal cancer. Ann
Oncol. 2007; 18(suppl.9): ix105-ix113.
Kapitejin E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman
L, Glimelius B,van Krieken JH, Leer JW, van de Velde CJ. For the Dutch Colorectal Cancer
Group (2001). Preoperative Radiotherapy combined with total mesorectal Excision for resectable
rectal cancer. N Engl J Med. 2001; 345: 638-646.
Marijnen CA, Kapitejin E, van der Velde CJ, Martijn H, Steup WH, Wiggers T, Kranenbarg EK,
Leer JW. Acute side effects and complications after short-term preoperative radiotherapy
combined with total mesorectal excision in primary rectal cancer: report of a multicenter
randomized trial. JClinOncol. 2002; 20: 817-825.
Birgisson H, Pahlman L, Gunnarson U, Glimelius B; Swedish Rectal Cancer Trial Group.
Adverse effects of preoperative radiation therapy for rectal cancer : long term follow-up of the
Swedish Rectal Cancer Trial. J Clin Oncol. 2005; 23(24): 8697-8705.
Enker WE, Thaler HT, Cranor ML,Polyak T. Total mesorectal excision in the operative
treatment of carcinoma of the rectum. J Am Coll Surg. 1995; 181(4): 335-346.
.Sauer R, Becker H, Hohenberger W, Rodel C, Witterkind C, Fietkau R, Martus P, Tschmelisch
J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. Preoperative versus
postoperative Chemoradiotherapy for Rectal Cancer. N Engl J Med. 2004; 351: 1731-1740.
Glimelius B. Rectal cancer: ESMO Clinical Recommendations for diagnosis, treatment and
follow-up. Ann Oncol. 2007; 18(suppl.2):ii23-ii24.
Peeters K, Marijnen C, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman
L, Glimelius B, Leer JW, van de Velde C, for the Dutch Colorectal Cancer Group: The
Randomised controlled TME trial after a median follow-up of 6 years: increased local control
but no survival benefit in irradiated patients with resectable rectal carcinoma.A report from the
TME trial. Ann Surg. 2007; 246: 693-700.
Bosset J, Colette L,Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny
A, Ollier JC. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med.
2006; 355(11): 1114-1123.
Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Pudelko M, Kryi
M, Oledzki J, Szmeja J, Sluszniak J, Serkies K, Kladny J, Pamucka M, Kukowicz P. Sphincter
preservation following preoperative radiotherapy for rectal cancer : report of a randomised trial
comparing short-term radiotherapy vs. conventional fractionated radiotherapy. Radiother Oncol.
2004; 72: 15-24.
523
Articole de sintez
16. Marijnen CAM, Nagtegaal ID, Klein-Kranenbarg E, Hermans J, van de Velde CJ, Leer JW. No
downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol.
2001; 19: 1976-1984.
17. Gunderson LL, Nelson H, Martenson JA, Cha S, Haddock M, Devine R, Fieck JM, Wolff B,
Dozois R, O Connell MJ. Locally advanced primary colorectal cancer: intraoperative electron
and external beam irradiation +/- 5-FU. Int J Radiat Oncol Biol Phys. 1997; 37(3): 601-614.
18. Gerad JP, Conoroy T, Bonnentain F,et al. Preoperative radiotherapy with or without concurrent
fluorouracil and leucovorin in T3-4 rectal tumors; results of FFCD 9203. J Clin Oncol. 2006; 24:
4620-4629.
19. Skibber JM, Eng C. Colon, rectal and anal cancer management. In: Chang AE, Ganz PA, Hayes
DF. eds. Oncology - an evidence based approach. New York: Springer 2006; p.704-732.
20. Ciuleanu TE, Curca R, Popescu I, Anghel Rodica, Croitoru Adina, Dediu M. Ghid de tratament
al carcinoamelor colorectale. Radioter Oncol Med. 2006; 4: 251-262.
21. Baik SH, Kim NK, Lee KY, Sohn SK, Cho CH. Hand-sewn coloanal anastomosis for distal
rectal cancer: long-term clinical outcomes. J Gastrointest Surg 2005; 9(6): 775-780.
22. Leo E, Belli F, Andreola S, Baldini MT, Gallino GF, Giovanazzi R, Mascheroni L, Patuzzo R,
Vitellaro M, Lavarino C, Bufalino R. Total rectal resection, mesorectum excision, and
coloendoanal anastomosis: a therapeutic option for the treatment of low rectal cancer. Ann Surg
Oncol 1996;3(4):336-343.
23. Tytherleigh MG, McC Mortensen NJ. Options for sphincter preservation in surgery for low
rectal cancer. Br J Surg 2003; 90(8): 922-933.
24. Liang JT, Lai HS, Lee PH. Laparoscopic pelvic autonomic nerve-preservation surgery for
patients with lower rectal cancer after chemoradiotherapy. Ann Surg Oncol 2007; 14(4):
1285-1287.
25. Ptok H, Meyer F, Marusch F, Steinert R, Gastinger I, Lippert H, Meyer L. Palliative stent
implantation in the treatment of malignant colorectal obstruction. Surg Endosc 2006; 20(6):
909-914.
26. Leitman IM, Sullivan JD, Brams D, De Cosse JJ. Multivariate analysis of morbidity and
mortality from the initial surgical management of obstructing carcinoma of the colon. Surg
Gynecol Obstet 1992; 174(6): 513-518.
27. Sebastian S, Johnston S, Geoghegan T, Torreggiani W, Buckley M. Pooled analysis of the
efficacy and safety of self-expanding metal stenting in malignant colorectal obstruction. Am J
gastroenterol 2004; 99(10): 2051-2057.
28. Simmons DT, Baron TH. Technological insight: enteral stenting and new technology. Nat Clin
Pract Gastroenterol Hepatol 2005; 2: 365-374.
29. Suzuki N, Saunders BP, Thomas-Gibson S, Akle C, Marshall M, Halligan S. Colorectal stenting
for malignant and benign disease:outcomes in colorectal stenting. Dis Colon Rectum 2004;
47(7): 1201-1207.
30. Hunerbein M, Krause M, Moesta KT, Rau B, Schlag PM. Palliation of malignant rectal
obstruction with self-expanding metal stents. Surgery 2005; 137(1): 42-47.
31. 31.Yoo PS, Lopez-Soler RI, Longo WE,Cha CH. Liver resection for metastatic colorectal cancer
in the age of neoadjuvant therapy and bevazucimab. Clin Colorectal Cancer 2006; 6(3):
202-207.
32. Van Cutsem E, Nordlinger B, Adam R. Towards a pan-European consensus on the treatment
ofpatients with colorectal liver metastasis. Eur J Cancer 2006; 42: 2212-2221.
33. Choti MA, Sitzmann JV, Tiburi MF. Trends in long-term survival following liver resection for
hepatic colorectal metastasis. Ann Surg 2002; 235: 759-766.
34. Tsai M, Su Y, Ho M. Clinicopathological features and prognosis in resectable syncronous and
metachronous colorectal metastasis. Ann Surg Oncol 2007; 14: 786-794.
35. Nordlinger B, Van Cutsem E, Rougier P, Kohne CH, Ychou M, Sobrero A, Adam R, Arvidsson
D, Carrato A, Georgoulias V, Giuliante F, Glimelius B, Golling M, Gruenberger T, Tabernero J,
Wasan H, Poston G. Does chemotherapy prior to liver resection increase the potential for cure in
patients with metastatic colorectal cancer? A report from the European Colorectal Metastases
Treatment Group. Eur J Cancer 2007; 43(14): 2037-2045.
36. Hewes J, Dighe S. Morris R, Hutchins R, Bhattacharya S, Davidson B. Preoperative
chemotherapy and the outcome of liver resection for colorectal metastases. World J Surg 2007;
31(2): 353-364.
524
Articole de sintez
37. Weish FK, Tilney HS, Tekkis PP, John TG, Rees M. Safe liver resection following
chemotherapy for colorectal metastases is a matter of timing. Br J Cancer 2007; 96(7):
1037-1042.
38. Aschele C, Lonardi S. Multidisciplinary treatment of rectal cancer: medical oncology. Ann
Oncol. 2007; 18(9): 114-121.
39. Glynne-Jones R, Grainger J, Harrison M. Neoadjuvant chemotherapy prior to preoperative
chemoradiation or radiation in rectal cancer: should we be more cautious? Br J Cancer 2006; 94:
363-371.
40. NCCN Clinical Practice Guidelines in Oncology. Rectal Cancer 2008; 3: 1-69.
41. Fernandez FG, Ritter J Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM. Effect of
steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic
colorectal metastases. J Am Coll Surg 2005; 200(6): 845-853.
42. Merchant NB, Guillem JG, Paty PB, Enker WE, Minsky BD, Quan SH, Wong D, Cohen AM.
T3N0M0 rectal cancer : results following sharp mesorectal excision and no adjuvant therapy. J
Gastrointestinal Surg 1999; 3(6): 642-647.
43. Guillem JG, Diaz-Gonzales JA, Minsky BD, Valentini V, Jeong SY, Rodriguez-Bigas MA,
Coco C, Leon R, Hernandez- Lizoain JL, Aristu JJ, Riedel ER, Nitti D, Wong WD, Pucciarelli S.
cT3N0M0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is
warranted. J Clin Oncol 2008; 26(3): 368-373.
44. Heintz A, Morschel M, Juninger T. comparison of results after transanal endoscopic
microsurgery and radical resection for T1 carcinoma of the rectum. Surg Endosc 1998; 12(9):
1145-1148.
45. Palma P, Freudenberg S, Samel S, Post S. Transanal endoscopic microsurgery indications and
results after 100 cases. Colorectal Dis 2004; 6(5): 350-355.
46. Garcia-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee S-H, Madoff RD, Rothenberger DA.
A pathologic complete response to preoperative chemoradiation is associated with lower local
recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis
Colon Rectum 2003; 46(3): 298-304.
47. Willett CG, Hagan M, Daley W, Warland G, Shellito PC, Compton PC.Changes in tumor
proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation. Dis Colon
Rectum 1998; 41(1): 62-67.
48. Nair RM, Siegel EM, Chen DT, Fulp WJ, Yeatman TJ, Malafa MP, Marcet J, Shibata D. Longterm results of transanal excision after neoadjuvant chemoradiation for T2 and T3
adenocarcinoma of the rectum. J Gastrointest Surg 2008; 12(10): 1797-1805.
525