Surgery remains the only radical treatment for colorectal cancer. However, with introduction of multidisciplinary teams and availability and advancement in all modes of treatments (surgical technique, technology and perioperative care, sistemic therapy and radiotherapy protocols), in more advanced stages the better disease control is achieved. In this article
we outline primarily indications and considerations in surgical treatment modeKirurško liječenje je jedini kurativni pristup liječenju kolorektalnog karcinoma. Ipak, uvođenjem multidisciplinarnih timova i napretkom i dostupnošću svih načina liječenja (kirurška tehnika i tehnologija kao i perioperativna skrb za pacijenta, te napredak u sistemskoj i radioterapiji) u poodmaklim stadijima, su omogućili uspješniju kontrolu bolesti. U ovom
članku izosimo primarno indikacije i dileme kirurškog načina liječenj

Borna Vrdoljak

Elizabet Glavan

Ilija Guteša

Iva Kirac

Marko Doko

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15REVIEW Libri Oncol., Vol. 41 (2013), No 1-3, 15 – 19SURGICAL TREATMENT OF COLORECTAL CARCINOMAELZIABET GLAVAN1, ILIJA GUTEŠA2, IVA KIRAC2, BORNA VRDOLJAK3 and MARKO DOKO11Department of surgery, University Hospital Center Sestre milosrdnice, Zagreb, Croatia2Department of Surgical Oncology, University Hospital for Tumors, University Hospital Center Sestre milosrdnice, Ilica 197, Zagreb, Croatia3School of Medicine, University of Zagreb, Zagreb, CroatiaSummarySurgery remains the only radical treatment for colorectal cancer. However, with introduction of multidisciplinary teams and availability and advancement in all modes of treatments (surgical technique, technology and perioperative care, sistemic therapy and radiotherapy protocols), in more advanced stages the better disease control is achieved. In this article we outline primarily indications and considerations in surgical treatment mode.KEYWORDS: surgery, colorectal cancer, multidisciplinary approachKIRUR[KO LIJE^ENJE KOLOREKTALNOG KARCINOMASa`etakKirur{ko lije~enje je jedini kurativni pristup lije~enju kolorektalnog karcinoma. Ipak, uvo|enjem multidisciplinarnih timova i napretkom i dostupno{}u svih na~ina lije~enja (kirur{ka tehnika i tehnologija kao i perioperativna skrb za paci-jenta, te napredak u sistemskoj i radioterapiji) u poodmaklim stadijima, su omogu}ili uspje{niju kontrolu bolesti. U ovom ~lanku izosimo primarno indikacije i dileme kirur{kog na~ina lije~enja.KLU^NE RIJE^I: kirurgija, kolorektalni karcinom, multidisciplinarni pristupPRINCIPALS OF ONCOLOGIC SURGERYRadical surgery with curative intent is the treatment of choice in colorectal cancer. The basic surgical principles are to remove the major tumor feeding vascular pedicle along with adjucent lym-phatics while obtaining tumor-free margina, and en bloc resection of structures or organs invaded by the tumor.In tumors in the cecum, ascending colon, he-patic flexure, and proximal transverse colon, the right branch of the middle colic artery is ligated along with the right colic and the ileocolic arteries. If the middle colic artery is ligated at its origin, the extent of the resection of the bowel should be per-formed to the distal third of the transverse colon. Tumors in the transverse colon may be resected by transverse colectomy or an extended right col-ectomy incorporating cecum, ascending colon, he-patic flexure, transverse colon, splenic flexure, and upper descending colon into the specimen. Descending and upper sigmoid colon cancers are resected with left hemicolectomy with ligation of the IMA at its origin from the aorta or by segmen-tal resections. The continuity of colon is restored by either hand-sewn or stapled anastomosis. Good vascularization and no tension at the anastomosis are required to reduce leak and sepsis. The recom-Libri Oncol., Vol. 41 (2013), No 1–3, 15 – 1916mended margin for colon cancer is at least a 5-cm margin of normal bowel on oral and aboral side of the tumor. Rectal cancer requires the distal surgi-cal margin of at least 2 cm in the fresh specimen, since it rarely has distal submucosal spread. In pa-tients with low rectal adenocarcinomas (less than 5 cm from the anal verge) at least a 1-cm margin of resection is required. Margins of less than 1 cm in patients who received neoadjuvant chemoradia-tion and underwent sphincter-saving procedures may be obtained without compromising either re-currence or disease-free survival (1). A set mini-mum of 12 examined lymph nodes is required for accurate staging of node negative disease. How-ever, smaller number of lymph nodes is often identified in rectal cancer after neoadjuvant treat-ment and its significance is being discussed (1).OBSTRUCTION AND PERFORATIONObstruction or perforation and rectal bleed-ing in colorectal cancer has a negative effect on survival (2). Moreover, emmergency setting and socioeconomic parameters also influence the out-come (3). In case of obstruction (with or without) in colorectal cacner patients, two or three staged procedures are performed. On one hand, resection of the obstructing tumor and proximal ostomy may be performed. On the other hand, a diverting stoma (the first stage), then a colorectal cancer re-section (second stage), and the occlusion of the os-tomy (the third stage) may be performed. Finally, resection and continuity formation may be per-formed in obstructing right-sided, distal transverse or splenic flexure carcinoma or when considering subtotal colectomy. The procedure must be tai-lored based on the the patient performance status, the surgeon’s skills and the comorbidities (4).CONTIGUOUS ORGAN INVOLVEMENTAdherence to adjacent organs is often found in colorectal cancer patients. This may be to local tumor growth or secondary to perforation or fis-tula formation. Mostly the colon cancer is adher-ent to abdominal wall, stomach, duodenum, small bowel, ureters, urinary bladder, uterus, and ova-ries, while rectal cancers invades uterus and vagi-na, urinary bladder, sacrum or coccyx. The princi-pal is to surgically remove the tumors en bloc without disturbing the adhesions. These adhe-sions are malignant in nature in over 40% of the cases (5).PERITONEAL DISEASEPeritoneal carcinomatosis is encountered in a number of patients at diagnosis and it carries a poor prognosis. For these, after careful selection, some benefit may be derived from cytoreductive surgery combined with intraperitoneal chemo-therapy (6,7).RECTAL CANCERDue to its anatomical specificities and loca-tion within confined pelvic space and mostly ex-traperitoneal locaclisation rectal cancer has a dif-ferent treatment strategies than the rest of the co-lon. Presently, combined-modality therapy greatly reduced, the risk of local and distant recurrence and improved overall survival. However, surgical resection remains the most important treatment mode. The rectum is divided in three parts by curves and distance form the anal verge. Tumors in proximal two thirds are resected by low anteri-or resection. The lower rectum, however, could be resected with ultralow resection with/without di-verting ileostomy or abdominoperineal extirpa-tion. Only in emmergency setting or occationally after neoadjuvant treatment and in line with pa-tient’s preferences Hartmann procedure is war-ranted. Inoperable cases or obstructed cases planned for neoadjuvant treament receive a di-verting ostomy. For all the procedures and their choice, multiple reports in the surgical literature correlate better stage-adjusted results in expert hands (8). The availability of adjuvant therapy en-courages surgeons to be more aggressive in treat-ment, including treatment of metastatic disease. As the local recurrence rate decreased to the teens with total mesorectal excision (TME), the practice of neo/adjuvant use of chemoradiation has been selectively decreased (9).TOTAL MESORECTAL EXCISION (TME)Total Mesorectal excision consists of sharp dissection of the space between the endopelvic fascia and the mesorectum. The mesorectum 17Libri Oncol., Vol. 41 (2013), No 1–3, 15 – 19should be removed with intact fascia propria and with preservation of the pelvic fascia and the au-tonomic nerve plexus. This ensures the control of distal extramural spread and gaines free circum-ferential margins. Discontiguous spread in the mesorectum varies from 5% to 64% for which lymph nodes are most responsible. Circumferen-tial or radial margin involvement by tumor is a prognostic factor for both local and distant dis-ease. The radial margin of excision can also serve as an indicator of the quality of the surgery, evalu-ated by the pathologist after the resection (9).EXTENDED LATERAL PELVIC NODE DISSECTIONInternal iliac node dissection is no longer rec-ommended in rectal cancer surgery. Metastases to these lymph nodes occur in approximately 10% of patients and imply a poor prognosis. If clinically indicated, an attempt to remove these lymph nodes at the time of surgery is warranted(10).RECURRENCESRectal salvage surgery for recurrences in-cludes re-resection with a low anterior resection, abdominoperineal resection, pelvic exenterations (or its modifications), and, occasionally, extended sacral resections. If chemoradiation was not used during the management of the primary tumor, preoperative chemoradiation may be warranted prior to re-resection. It must be mentioned that these procedures are generally performed in con-junction with urology, neurosurgery, and plastic surgery. If available, intraoperative radiotherapy should be strongly considered. After re-resection of isolated pelvic recurrences, there is a 15% 5-year survival (11). It cannot be overemphasized that these procedures carry a significant morbidity and mortality and should be performed by experi-enced surgeons. Other forms of palliation should be considered prior to undertaking an aggressive surgical approach in a patient in whom cure will not be attainable.SURGICAL PROGNOSISAdvanced periopeative management greatly reduced perioperative morbidity and mortality (12). Despite the complementary sistemic and lo-cal treatment, surgical results also depend on tu-mor stage and its biologic behavior. Early colorec-tal cancers (T1-2N0M0) can be cured with surgery alone. The 5-year survival for patients with stage II colorectal cancer is approximately 70%. Surgery alone in stages II and III rectal cancer carries a high failure rate; postoperative chemoradiation is war-ranted if the patients were not treated with neoad-juvant chemoradiation. Because the 5-year surviv-al in stage II (T3N0M0) colon cancer patients is approximately 77% with surgery alone, adjuvant therapy is not widely recommended for these pa-tients. As previously discussed, molecular mark-ers may help in deciding adjuvant therapy for a subgroup of these patients. T4N0M0 colon cancer patients are at high risk of both local and distant recurrence and should be considered for adjuvant chemoradiation. Stage III colorectal cancer pa-tients (any T N1-2 M0) have a 20% to 50% 5-year survival rate after surgery alone (13). It is in stage III colon cancer patients that adjuvant therapy has proven to be effective. Again, due to complemen-tary mode of treatments many stage III and IV pa-tients are downstaged and become elligable for surgical treatment, therefore multidisciplinary meetings after treatment evaluation are highly recommended.FOLLOWUP AFTER PRIMARY THERAPY FOR COLORECTAL CANCERSixty percent to 80% of recurrences after cu-rative intent surgery for colorectal cancer occurer within the first 2-years of therapy which requires an intensive follow up during that period. Con-trols are usually scheduled every 3-6 months, and every six months after second year, yearly after five years. Follow up diagnostics at our Institution consists of CEA levels, imaging (abdominal US or chest X ray, and MR/CT abdomen and chest CT when indicated). Colorectal tumor recurrence is most common when the nodal involvement and tumor penetration beyond the bowel wall (T3 and T4 disease) are present. Differentiation and sub-types of tumors are also prognostic factors for therapy failure (14,15). Moreover, resection of lower rectal cancers is technically more demand-ing and wide negative margins due to physical anatomic restrictions may be difficult to obtain Libri Oncol., Vol. 41 (2013), No 1–3, 15 – 1918which leads to a higher recurrence risk with lower tumors (16). In fact, there is an association with number of resected lymphnodes and favorable prognosis (17). Survival is also influenced by re-gression rate after neoadjuvant terapy in rectal cancer (18). Finally, type of institution where the patient is treated- availability of multidisciplinary team- is important for the outcome(19).The role of adjuvant chemoradiotherapy in colorectal cancer is well established by landmark Phase III trials that showed that concurrent chemo-radiation improved survival in resected stages II and III rectal cancer() The recognition that 5-FU-based alone or in combinations reduces distant failure risk led to the current standard of postop-erative chemoradiation integrated with four cycles of adjuvant chemotherapy (with 5-FU and leucov-orin). Adjuvant chemotherapy has traditionally been given for two months both before or six months after surgery, but this standard was em-pirically established. Neoadjuvant radio/chemo-radiation became the standard in rectal cancer af-ter initial clinical staging on MRI. Its role in colon cancer is still a matter of debate.CONCLUSIONThe primary surgical resection of colorectal cancer is the only mode of treatment considered curative. However, for patients who had an inad-equate surgical resection of the primary tumor or who had been downstaged and then resected, multimodal treatment including combination of surgery, sistemic and radiotherapy in various se-quences, seem to be a good way to obtain disease control (21).REFERENCES 1. Scottish Intercollegiate Guidelines Network, Diagno-sis and management of colorectal cancer, A national clinical guideline, 2011. http://sign.ac.uk/pdf/sign126.pdf. Accsessed on 14th December 2014. 2. Steinberg SM, Barkin JS, Kaplan RS, Stablein DM. Prognostic indicators of colon tumors. The Gastroin-testinal Tumor Study Group experience. Cancer. 1986 May 1;57(9):1866-70. 3. Pruitt SL, Davidson NO, Gupta S, Yan Y, Schootman M.Missed opportunities: racial and neighborhood so-cioeconomic disparities in emergency colorectal can-cer diagnosis and surgery. BMC Cancer. 2014 Dec 9;14(1):927. 4. Hildebrandt U. [Rectal carcinoma. Optimizing the procedures in an emergency]. Zentralbl Chir. 1999;124(5):446-50. [Article in German], Chen HS, Sheen-Chen SM. Obstruction and perforation in colorectal adenocarcinoma: an analysis of prognosis and current trends. Surgery. 2000 Apr;127(4):370-6. 5. Govindarajan A, Fraser N, Cranford V, Wirtzfeld D, Gallinger S, Law CH, Smith AJ, Gagliardi AR. Predic-tors of multivisceral resection in patients with locally advanced colorectal cancer. Ann Surg Oncol. 2008 Jul;15(7):1923-30. doi: 10.1245/s10434-008-9930-1. Epub 2008 May 13. 6. Teo M. Peritoneal based malignancies and their treat-ment. Ann Acad Med Singapore. 2010;39:545–772. 7. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperito-neal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal car-cinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–3743. 8. Oliphant R, Nicholson GA, Horgan PG, McMillan DC, Morrison DS; West of Scotland Colorectal Cancer Man-aged Clinical Network. The impact of surgical spe-cialisation on survival following elective colon cancer surgery. Int J Colorectal Dis. 2014 Sep;29(9):1143-50. 9. Kapiteijn E, Kranenbarg EK, Steup WH, Taat CW, Rut-ten HJ, Wiggers T, van Krieken JH, Hermans J, Leer JW, van de Velde CJ.Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective ran-domised trial with standard operative and histopatho-logical techniques. Dutch ColoRectal Cancer Group. Eur J Surg. 1999 May;165(5):410-20.10. Yu YY, Wang C, Xu D, Shen XG, Ding SQ, Zhou ZG.Mesorectal and lateral node metastasis and micro-metastasis in lower rectal cancer. Hepatogastroenter-ology. 2011 May-Jun;58(107-108):745-8.11. Krivokapic Z, Dimtrijevic I, Markovic V, Barisic G, Antic S, Jovanovic D, Petrovic J. Acta Chir Iugosl. Sal-vage rectal surgery--overview.2006;53(2):125-32.12. Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaven-ture A, Marcos-Gragera R, Stiller C, Azevedo E Silva G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP; the CONCORD Working Group.Global surveillance of cancer survival 1995-2009: analysis of individual data for 25?676?887 patients from 279 popu-lation-based registries in 67 countries (CONCORD-2). Lancet. 2014 Nov 26. pii: S0140-6736(14)62038-9.13. Ciga Lozano MA, Codina Cazador A, Ortiz Hurtado H; en representación de los centros participantes en el Proyecto del Cáncer de Recto de la Asociación Espa-ñola de Cirujanos. Cir Esp. Oncological results accord-ing to type of resection for rectal cancer. 2014 Nov 22. pii: S0009-739X(14)00241-3. doi: 10.1016/j.ciresp.2014.06.014.19Libri Oncol., Vol. 41 (2013), No 1–3, 15 – 1914. Deliu IC, Georgescu EF, Bezna MC. Analysis of prog-nostic factors in colorectal carcinoma. Rev Med Chir Soc Med Nat Iasi. 2014 Jul-Sep;118(3):808-16.15. Wanebo HJ, LeGolvan M, Paty PB, Saha S, Zuber M, D’Angelica MI, Kemeny NE.Meeting the biologic chal-lenge of colorectal metastases. Clin Exp Metastasis. 2012 Oct;29(7):821-39.16. Ortiz H, Wibe A, Ciga MA, Kreisler E, Garcia-Granero E, Roig JV, Biondo S; Spanish Rectal Cancer Project. Multicenter study of outcome in relation to the type of resection in rectal cancer. Dis Colon Rectum. 2014 Jul;57(7):811-22.17. Deliu IC, Georgescu EF, Bezna MC. Analysis of prog-nostic factors in colorectal carcinoma. Rev Med Chir Soc Med Nat Iasi. 2014 Jul-Sep;118(3):808-16.18. Mace AG, Pai RK, Stocchi L, Kalady MF. American joint committee on cancer and college of american pa-thologists regression grade: a new prognostic factor in rectal cancer. Dis Colon Rectum. 2015 Jan;58(1):32-44.19. Etzioni DA, Young-Fadok TM, Cima RR, Wasif N, Madoff RD, Naessens JM, Habermann EB. Cancer. Pa-tient survival after surgical treatment of rectal cancer: impact of surgeon and hospital characteristics. 2014 Aug 15;120(16):2472-81.20. Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR. Improved survival in metastatic colorectal cancer is associated with adoption of he-patic resection and improved chemotherapy. J Clin Oncol. 2009 Aug 1;27(22):3677-83.21. Dahl O, Fluge Ø, Carlsen E, Wiig JN, Myrvold HE, Vonen B, Podhorny N, Bjerkeset O, Eide TJ, Halvorsen TB, Tveit KM; Norwegian Gastrointestinal Cancer Group. Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Nor-wegian Gastrointestinal Cancer Group. Acta Oncol. 2009;48(3):368-76.Author’s address: Elziabet Glavan, Department of sur-gery, University Hospital Center Sestre milosrdnice,  Vinogradska 29, Zagreb, Croatia. E-mail: elizabet.gla-vanºgmail.com

Kirurško liječenje kolorektalnog karcinoma

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