70 ISSN East Cent. Afr. J. surg

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1 70 ISSN Eat Cent. Afr. J. urg Favourable Outcome After Reection for Contained Malignant Colorectal Perforation T E Madiba Colorectal Unit, Department of Surgery, Univerity of KwaZulu-Natal and Inkoi Albert Luthuli Central Hopital, Durban. Preented at the World Surgical Congre of the International Surgical Society in Helinki, Finland on Augut Correpondence to: Profeor T E Madiba, madiba@ukzn.ac.za Background: Perforation in colorectal cancer occur due todirect perforation from or from proximal colon rupture. Thi tudy wa aimed at documenting our experience with malignant colorectal perforation and to etablih trend in preentation. Analyi of ongoing databae of all patient with colorectal cancer in the KwaZulu-Natal State Hopital etablihed ince 2000 wa undertaken. The Setting wa the Colorectal Unit in a tertiary centre Patient: All patient with malignant perforation were extracted from the databae and analyzed. Data collected included demographic, preentation, treatment, outcome, and follow-up. The main outcome meaure wa the In-hopital mortality Reult: By the end of 2012, the databae wa then compried 1425 patient, of whom 48 (3.4%) were found to have malignant perforation. The Male-to-female ex ratio wa 1:1, and age (mean + SD) wa year. Perforation occurred in 3%, 2%, 4%, and 5% of African, Indian, Coloured, and White repectively. The dieae ditribution wa right colon (15), decending colon (5), hepatic flexure (1), igmoid (21), and rectum (6). Twelve patient with intetinal obtruction required emergency reection (25%). The ret underwent elective reection with the perforation dicovered either at operation or at hitopathologic analyi. One, 19, 23, 5 patient had Stage I, II, III, and IV repectively. There wa no potoperative mortality. Only 6 patient had early dieae and were deemed not to require adjunctive or palliative therapy. Patient were followed up for (range 1-94) month. Seven patient were lot to follow up, and two are confirmed dead. Up to now four of the 39 evaluable patient have developed metatae. Limitation: Inadequate follow-up data Concluion: Malignant perforation occur in about 3% of colorectal cancer in our geographical area of Southern Africa. The ex ditribution and prevalence i the ame in all population group. Dieae ditribution follow general norm. Interetingly the perforation rarely lead to peritoniti. There wa no potoperative mortality in thi cohort. Keyword: colorectal cancer, malignant perforation, Hartmann procedure, emergency colectomy, South Africa. Introduction Carcinoma of the colon and rectum account for about 1.2 million new cae worldwide 1, and it i the third mot common cancer in men and econd mot common in women.colorectal cancer rank econd in term of both incidence and mortality in more developed countrie uch a the USA 2. While thi cancer i etimated to account for 9.4% of all cancer worldwide, it appear to account for only 2.5% of all cancer in Africa 3. Up to 30% of patient with colorectal carcinoma preent with complication, the mot common being obtruction and perforation 4-8, of which 2-10% are due to perforated colorectal cancer Perforation in colorectal cancer occur due to either direct perforation from tumour necroi or from proximal colon rupture or blow-out from an obtructed tumour and a competent ileo-caecal valve producing a cloed-loop obtruction Greater morbidity and COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

2 71 ISSN Eat Cent. Afr. J. urg mortalityhave been reported for perforated colorectal cancer 5, 6, 10, 13. The criticim of thee previou tudie i that they did not clearly decribe the mechanim of perforation namely free v contained or perforation at the tumour ite v proximal perforation 10. There are few, if any, tudie pecifically dedicated to contained colorectal perforation. The author hypotheized that, when conidered in iolation, contained perforation of colorectal cancer ha a favourable outcome and that the previouly quoted high mortality may have been due to the failure to differentiate between contained and free perforation. The aim of thi tudy wa to etablih clinicopathological trend in patient with contained malignant perforation of colorectal carcinoma and to document outcome in our geographic etting. The main outcome meaure wa in-hopital mortality. Patient and Method The colorectal cancer databae in the KwaZulu-Natal Province wa etablihed in 2000 and i till on-going 14. All patient with colorectal carcinoma attending all KwaZulu-Natal Hopital are referred to the Colorectal Unit at Inkoi Albert Luthuli Central Hopital where they areeenin the Multidiciplinary Clinic. All patient with pathologically proven malignant perforation were extracted from the databae at the end of 13 year and analyzed. Data collected included demographic, preentation, taging, treatment, outcome, and follow-up.for the purpoe of thi tudy, the UICC taging wa ued. Diagnoi of perforation wa made either on the bai of gro operative finding and confirmed by hitology or entirely on pathologic review and hitopathology. A free perforation wa defined a a perforation into the peritoneum with localized or generalized peritoniti. A contained perforation occurred into a confined pace localized by peritoneum, omentum, or bowel. Data were collected on a dedicated proforma. Data were analyzed uing M-Excel, in which different ethnic group were compared. Continuou data are preented either a mean and tandard deviation or median value (range). One way analyi of variance (ANOVA) wa ued to compare age of the different population group. Ethical approval wa obtained from the Biomedical Reearch Ethic Committee of the Univerity of KwaZulu-Natal. Reult At the end of 2012,thedatabae compried 1425 patient (495 African, 569 Indian, 64, Coloured and 297 White).Of thee 48 were found to have malignant perforation (3.4%) compriing patient of African (16), Indian (15), Coloured (2), and White (15).There were 24male and 24 female. Mean age at preentation wa year. The median age(range) wa 40.5 (19-68), 56 (38-73), 56.5 (54-59), and 66 (39-82) year for African, Indian, Coloured and White repectively. The age of preentation tended to be le in patient of African decent (African v White, p<0.0001, Indian v Coloured v White, p = NS).Clinical manifetation included abdominal pain (19),abdominal ditenion (12),change in bowel habit (12),lo of weight (7), abdominal ma (6),rectal bleeding (5), vomiting (5), and lo of appetite (5). Procedure undertaken are hown in Table I. The perforation occurred at the ite of the tumour and wa contained in all; none of the patient preented with localized or generalized peritoniti. The mot common ite of perforation wa the igmoid colon (21) followed by the right colon (15), rectum (6) decending colon (5), and hepatic flexure (1). Twelve patient (25%) preented with colonic obtruction and the perforation wa dicovered at the time of emergency reection. The ret of the patient underwent elective urgery with the perforation dicovered either at operation or on pathologic analyi. COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

3 72 ISSN Eat Cent. Afr. J. urg The majority preented a tage II (19, 40%) and III (23, 48%). Only 5 preented a tage IV (10%) and one a tage I (2%). Figure 1 how the comparion of taging for the perforated tumour and the entire cohort of 1425 patient. Of the perforated cancer, 45 patient had moderately differentiated carcinoma, while one each had mucinou, poor, and undifferentiated carcinoma. No patient had peritoneal carcinomatoi or peritoneal metatae.three patient had a reection with reidual microcopic dieae (R-1 reection)at the circumferential margin (6.4%). All proximal and dital margin were free of tumour. There wa no potoperative mortality. Six patient did not preent for treatment at the Oncology Clinic and have been lot to follow-up. Six other patient were deemed not to require adjunctive or palliative therapy becaue of good prognotic feature. The ret received adjuvant chemotherapy. Patient were followed for month. Two patient have been confirmed dead due to dieae progreion. Four of the other 34 patient have developed metatae to date. Table 1. Procedure Undertaken in 47 Patient with Colorectal Cancer Perforation. Procedure No % Sigmoid colectomy Right hemicolectomy Left hemicolectomy 4 9 Anterior reection 4 9 Subtotal colectomy 3 6 Abdomino-perineal reection 2 4 Extended right hemicolectomy 1 2 Extended left hemicolectomy 1 2 Figure 1. Comparing the age ditribution of patient with contained perforation compared to all patient with colorectal cancer. Dicuion Thi tudy demontrated that contained neoplatic perforation occurred in 3% of patient with colorectal cancer with no peritoniti confirmed at the time of urgery and no in-hopital mortality. Thi rate fall within the % reported in the literature 5, 9-12, 15.Only 27% required emergency operationbecaue of aociated malignant large bowel obtruction. COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

4 73 ISSN Eat Cent. Afr. J. urg The mean age of 55 year noted in thi erie i coniderably le than the year reported in the world literature 9, 11, 16. Interetingly, the age at preentation for African wa the younget, being about two decade younger than the world literature, while White patient were the oldet at preentation, again in agreement with the world literature. Thee population difference in age ditribution mimic that een in the general population of patient with colorectal cancer in KwaZulu-Natal, where African were a decade younger than the other population group 14. A een in mot erie 10, 16 the igmoid colon wa the mot common ite of the primary leion; thi incidence differ the general dieae ditribution of colorectal cancer in the world literature and in outh Africa 14, where the rectum i the mot common ite. The greater tendency for perforation in the igmoid colon compared to other region i unknown but may be related in part to the narrower diameter of the lumen. There wa no difference in ex ditribution, and moderate differentiation wa a finding in all except three patient; imilar obervation have been made by other 10. In contrat to obtructing colorectal cancer which ha been repeatedly hown to be aociated with advanced dieae 9, 13, 17,report on perforated colorectal cancer have yielded conflicting reult. Some tudie have uggeted a greater incidence of metatatic dieae, moreadvanced dieae tage, and greater reidual tumour burden at the time of preentation for perforated colorectal cancer 6, 8-12, 15, 16, 18, 19.Other tudie have hown perforated cancer to be le advanced compared to obtructing cancer 9, 10.The reaon for thi difference may be related to a preumed longer time required to caue obtruction, reulting advanced tage at diagnoi, compared to the horter time needed for tumour necroi which appear to be the bai for perforation 10. The operative treatment of colorectal cancer with or without a contained perforation or obtruction depend primarily on the location of the leion and the ability of a given patient to tolerate the procedure 20, 21. Circumtance which may lead to the modification of the urgical procedure are the preence of free perforation with peritoniti or the preence of obtruction in addition to perforation which may lead to change on the calibre of the proximal bowel thereby potentially affecting the afety of an anatomoi. A egmental colectomy following oncologic principle uffice in the majority of cae with contained perforation. Subtotal colectomy with primary anatomoi may be conidered for patient with left-ided perforation aociated with obtruction which may lead to ditenion and ichaemia of the proximal colon; thi approach relieve the obtruction (and it occult or obviou perforation) a well a the proximal ditended colon or ichemia Otherwie reection of the neoplam with proximal colonic diverion and a Hartmann procedure may be indicated if there i local peritoniti. All patient in thi erie, however, were able to be managed by colectomy and primary anatomoi. The clinical coure of patient with malignant colorectal perforation depend on the onet of ymptom, a well a the patient nutritional tatu, age, and co-morbiditie 23. Wherea patient with free perforation generally preent in extremi, thoe with contained perforation tend to preent in a more elective fahion, albeit with ign of infection, uch a fever and leucocytoi 8. The predominant ymptom in thi erie were abdominal pain, abdominal ditenion, and change in bowel habit. The zero mortality rate in thi tudy i triking compared to the reported 5-40% in-hopital mortality for perforated colorectal cancer in other erie 5-7, 10-13, 15, 19, Thi dicrepancy may be explained by the fact that contained perforation doe not lead to peritoniti with it equelae. Thi finding i upported by the oberved greater mortality rate for free neoplatic perforation or perforation proximal to the obtructed tumour compared to contained perforation, uggeting that free perforation lead to peritoniti and poibly later carcinomato i both of which lead to ubequent death 8, 10, 11, 15, 28. A free perforation i aociated with greater COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

5 74 ISSN Eat Cent. Afr. J. urg mortality whether it i aociated with generalized peritoniti or localized abce 27. The rik factor predictive of poor outcome are patient age, degree of peritoniti and epi, tumour tage, cardiopulmonary co-morbiditie, ASA grade, and the preence or abence of ditant metatai at preentation 5, 8, 10-12, 15, 17, 19, 25. Furthermore, patient in thi tudy did not undergo emergency laparotomy except when there wa aociated obtruction and, even under thee circumtance; the reaon for the emergency procedure wa the preence of colonic obtruction. Another poible explanation for the extremely low operative mortality may be that all thee patient needed to be able to arrive at their local hopital and were thu not phyiologically compromied. It i poible that patient with free perforation and thu with evere phyiologic compromie may have been elected out and demied before arrival at the local hopital. Thi very low mortality i upported by finding in the only other tudy reporting on contained perforation 8. Our 93% rate of an R-0 reection compare favourably with other tudie in which R-0 reection i reported in 62 68% of patient with perforated colorectal cancer 8. Whether or not the malignant proce extend to the circumferential margin i dependent not on the perforation itelf but rather on the extent to which the malignant proce ha permeated through the bowel wall along with the necroi a it caue the perforation. The prognoi of patient with neoplatic perforation ha not been entirely clear in the literature with ome tudie documenting a negative effect on patient outcome 10, 29, while other tudie have aociated perforation with poitive outcome 10, 12, 30, 31. Two tudie have aociated a poorer urvival and recurrence rate with perforation proximal to the tumour compared to non-perforated tumour, uggeting that pillage of tumour cell from the perforation into the peritoneal cavity reult in tumour pread by peritoneal diemination and a negative influence on urvival 8, 10. Other erie have uggeted that once immediate pot-operative morbiditie have been corrected and if radical oncologic treatment ha been performed, long term outcome are imilar to thoe of non-perforated control. Therefore, an aggreive urgical approach baed on oncologic criteria i indicated, and thi further ugget that perforation with pillage of tumour cell into the contained area of perforation, if it indeed occur, doe not reach a degree that augment tumour implantation and i not necearily an indicator of poor prognoi 8, 10, 12, 16, 27. Thee conflicting data tem from the tendency of previou tudie to not clearly differentiate between free and contained perforation or between neoplatic and proximal perforation. Prognoi eem to be related to the nature of the perforation and the ite of perforation in relation to the tumour itelf, with conenu dictating that thee patient hould receive aggreive urgical intervention and appropriate adjuvant oncologic therapy 10. The limitation of thi tudy are that the duration of follow-up wa very poor. Follow-up i a major problem in our geographic ociety, with ocio-economic tatu and difficultie with tranport for face-to-face follow-up being major driver of the poor follow-up.alo, it i likely that other patient with a perforated colorectal cancer were managed locally and might have been too ill to be ent to our regional unit. The trength of the tudy i that it pecifically addree contained perforation of colorectal cancer a oppoed to free perforation and it differentiate direct neoplatic perforation from proximal perforation. Thi i an improvement on previou tudie, whoe weakne wa failure to differentiate between free and contained perforation a well a neoplatic and proximal perforation. Moreover, thi work i the firt report to addre thi condition in South Africa and in Africa. Concluion Malignant perforation in our etting i imilar to that reported in the literature. The prevalence i the ame in all population group, and the ex incidence i imilar, but the age at preentation COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

6 75 ISSN Eat Cent. Afr. J. urg i younger in native African. The dieae ditribution follow general norm with minor variation. Contained perforation rarely led to peritoniti in our patient cohort which probably explain the zero potoperative mortality. The long term outcome depend on other factor and not on the perforation tatu. Therefore, provided thee patient receive the ame radical, oncologic reection a non-perforated colorectal cancer, the hort and long term outcome hould be quite imilar. Acknowledgement The author would like to thank Dr Michael Sarr, Mayo Clinic, for critique of the final verion of the manucript. Reference 1. Jemal A BF, Center MM. et al. Global Cancer Statitic. CA Cancer J Clin 2011; 61(2): Stewart BW KP. Colorectal cancer. In: Stewart BW KP, ed. WHO World Cancer Report. Lyon: IARC Pre; 2003: Parkin DM BF, Ferlay J, et al. Global Cancer Statitic, CA Cancer J Clin 2005; 55: Gunnaron H, Holm T, Ekholm A, Olon LI. Emergency preentation of colon cancer i mot frequent during ummer. Colorectal Di 2011; 13(6): Kelley WE, Jr., Brown PW, Lawrence W, Jr., Terz JJ. Penetrating, obtructing, and perforating carcinoma of the colon and rectum. Arch Surg 1981; 116(4): Runkel NS, Hinz U, Lehnert T, Buhr HJ, Herfarth C. Improved outcome after emergency urgery for cancer of the large intetine. Br J Surg 1998; 85(9): Smother L, Hynan L, Fleming J, Turnage R, Simmang C, Anthony T. Emergency urgery for colon carcinoma. Di Colon Rectum 2003; 46(1): Zielinki MD, Merchea A, Heller SF, You YN. Emergency management of perforated colon cancer: how aggreive hould we be? J Gatrointet Surg 2011; 15(12): Alvarez JA, Baldonedo RF, Bear IG, Truán N, Pire G, Alvarez P. Preentation, treatment, and multivariate analyi of rik factor for obtructive and perforative colorectal carcinoma. Am J Surg 2005; 190(3): Chen HS, Sheen-Chen SM. Obtruction and perforation in colorectal adenocarcinoma: an analyi of prognoi and current trend. Surgery 2000; 127(4): Anwar MA, D'Souza F, Coulter R, Memon B, Khan IM, Memon MA. Outcome of acutely perforated colorectal cancer: experience of a ingle ditrict general hopital. Surg Oncol 2006; 15(2): Mandava N, Kumar S, Pizzi WF, Jopeh Aprile I. Perforated colorectal carcinoma. Am J Surg 1996; 172(3): Phillip RK, Hittinger R, Fry JS, Fielding LP. Malignant large bowel obtruction. Br J Surg 1985; 72(4): Zulu B MT. Colorectal cancer in the KwaZulu-Natal Province: An etablihed dieae with a variable clinicopathological pectrum. S Afr J Surg 2011; 49: Kriwanek S, Armbruter C, Dittrich K, Beckerhinn P. Perforated colorectal cancer. Di Colon Rectum 1996; 39(12): Biondo S, Kreiler E, Millan M, et al. Difference in patient potoperative and long-term outcome between obtructive and perforated colonic cancer. Am J Surg 2008; 195(4): Garcia-Valdecaa JC, Llovera JM, delacy AM, et al. Obtructing colorectal carcinoma. Propective tudy. Di Colon Rectum 1991; 34(9): Khan S, Pawlak SE, Eggenberger JC, Lee CS, Szilagy EJ, Margolin DA. Acute colonic perforation aociated with colorectal cancer. Am Surg 2001; 67(3): COSECSA/ASEA Publication -Eat & Central African Journal of Surgery. Nov/Dec 2014 Vol. 19 (3)

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