Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK.
BACKGROUND: High-quality rectal cancer surgery is known to improve patient outcome. We aimed to assess the quality of colon cancer surgery by studying the extent of variation in the plane of surgical resection, the amount of tissue removed, and its association with survival. METHODS: All resections for primary colon adenocarcinoma done at Leeds General Infirmary (Leeds, UK) between Jan 1, 1997, and June 30, 2002, were identified. The specimens were photographed and graded according to the plane of mesocolic dissection. Tissue morphometry was done on 253 tumours. Univariate and multivariate models were used to ascertain whether there was an association with 5-year survival. The primary outcome measure was overall survival defined as death from any cause. FINDINGS: 521 cancers were identified, 122 were excluded because of either no photographic images or insufficient images to allow retrospective grading, leaving 399 specimens for analysis. There was marked variation in the proportion of each plane of surgery: muscularis propria in 95 of 399 (24%) specimens, intramesocolic in 177 of 399 (44%) specimens, and mesocolic in 127 of 399 (32%) specimens. Mean cross-sectional tissue area outside the muscularis propria was significantly higher with mesocolic plane surgery (mean 2181 [SD 895] mm(2)) compared with intramesocolic (mean 2109 [1273] mm(2)) and muscularis propria plane (mean 1447 [913] mm(2)) surgery (p=0.0003). There was also a significant increase in the distance from the muscularis propria to the mesocolic resection margin with mesocolic plane surgery (mean 44 [21] mm) compared with intramesocolic (mean 30 [16] mm) and muscularis propria plane (mean 21 [12] mm) surgery, which was independent of tumour site (all excisions p<0.0001). We noted a 15%(95% CI) overall survival advantage at 5 years with mesocolic plane surgery compared with surgery in the muscularis propria plane (HR 0.57 [0.38-0.85], p=0.006) in univariate analysis. However, this association was no longer significant in the multivariate model (HR 0.86 [95% CI 0.56-1.31], p=0.472), but was especially noted in patients with stage III cancers (HR 0.45 [95% CI 0.24-0.85], p=0.014; multivariate analysis). The plane of surgery and amount of mesocolon removed varied between the different sites with better planes in left-sided resections than right-sided ones, which were better than transverse resection (p<0.0001). INTERPRETATION: As previously shown in the rectum, we have now shown there is marked variability in the plane of surgery achieved in colon cancer. Improving the plane of dissection might improve survival, especially in patients with stage III disease. If confirmed by clinical trial data, such as from the ongoing National Cancer Research Institute Fluoropyrimidine, Oxaliplatin and Targeted Receptor pre-Operative Therapy for colon cancer (FOxTROT) trial of neoadjuvant chemotherapy in advanced resectable colon cancer, improvement of the plane of dissection might be a new cost-effective method of decreasing morbidity and mortality in patients with colon cancer. FUNDING: National Institute for Health Research Academic Clinical Fellowship Programme, Experimental Cancer Medicine Centre programme (both Department of Health, London, UK), Yorkshire Cancer Research (Harrogate, UK), and the Pelican Trust (Basingstoke, UK).
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Phil Quirke,
Robert Steele,
John Monson,
Robert Grieve,
Subhash Khanna,
Jean Couture,
Chris O'Callaghan,
Arthur Sun Myint,
Eric Bessell,
Lindsay C Thompson,
Mahesh Parmar,
Richard J Stephens,
David Sebag-Montefiore
Leeds University, Leeds, UK; St James's University Hospital, Leeds, UK.
BACKGROUND: Local recurrence rates in operable rectal cancer are improved by radiotherapy (with or without chemotherapy) and surgical techniques such as total mesorectal excision. However, the contributions of surgery and radiotherapy to outcomes are unclear. We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved. METHODS: In this prospective study, the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists, using a standard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial, which compared short-course (5 days) preoperative radiotherapy and selective postoperative chemoradiotherapy, between March, 1998, and August, 2005. All analyses were by intention to treat. This trial is registered, number ISRCTN 28785842. FINDINGS: 128 patients (11%) had involvement of the circumferential resection margin, and the plane of surgery achieved was classified as good (mesorectal) in 604 (52%), intermediate (intramesorectal) in 398 (34%), and poor (muscularis propria plane) in 154 (13%). We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates. Hazard ratio (HR) was 0.32 (95% CI 0.16-0.63, p=0.0011) with 3-year local recurrence rates of 6%(5-8%) and 17%(10-26%) for patients who were negative and positive for circumferential resection margin, respectively. For plane of surgery achieved, HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0.32 (0.16-0.64) and 0.48 (0.25-0.93), respectively. At 3 years, the estimated local recurrence rates were 4%(3-6%) for mesorectal, 7%(5-11%) for intramesorectal, and 13%(8-21%) for muscularis propria groups. The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups (p=0.30 for trend). Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1%. INTERPRETATION: In rectal cancer, the plane of surgery achieved is an important prognostic factor for local recurrence. Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups, almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane. The plane of surgery achieved should therefore be assessed and reported routinely. FUNDING: Medical Research Council (UK) and the National Cancer Institute of Canada.
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Pathology & Tumour Biology, Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds; John Goligher Colorectal Unit, Leeds General Infirmary, Leeds, United Kingdom; and the Department of Surgery, University Hospital of Erlangen, Erlangen, Germany.
PURPOSE: The plane of surgery in colonic cancer has been linked to patient outcome although the optimal extent of mesenteric resection is still unclear. Surgeons in Erlangen, Germany, routinely perform complete mesocolic excision (CME) with central vascular ligation (CVL) and report 5-year survivals of higher than 89%. We aimed to further investigate the importance of CME and CVL surgery for colonic cancer by comparison with a series of standard specimens. METHODS: The fresh photographs of 49 CME and CVL specimens from Erlangen and 40 standard specimens from Leeds, United Kingdom, for primary colonic adenocarcinoma were collected. Precise tissue morphometry and grading of the plane of surgery were performed before comparison to histopathologic variables. RESULTS: CME and CVL surgery removed more tissue compared with standard surgery in terms of the distance between the tumor and the high vascular tie (median, 131 v 90 mm; P <.0001), the length of large bowel (median, 314 v 206 mm; P <.0001), and ileum removed (median, 83 v 63 mm; P =.003), and the area of mesentery (19,657 v 11,829 mm(2); P <.0001). In addition, CME and CVL surgery was associated with more mesocolic plane resections (92% v 40%; P <.0001) and a greater lymph node yield (median, 30 v 18; P <.0001). CONCLUSION: Surgeons in Erlangen routinely practicing CME and CVL surgery remove more mesocolon and are more likely to resect in the mesocolic plane when compared with standard excisions. This, along with the associated greater lymph node yield, may partially explain the high 5-year survival rates reported in Erlangen.
Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds; and Department of Colorectal Surgery, Leeds General Infirmary, Leeds, United Kingdom; and Department of Coloproctology; and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
PURPOSE: Abdominoperineal excision (APE) of the rectum and anus for rectal cancer continues to have greater local recurrence and poorer survival than that seen following anterior resection. Changing to an extended prone perineal dissection results in a more cylindrical specimen and should improve outcomes. PATIENTS AND METHODS: One hundred twenty-eight specimens from patients who underwent APE that was performed for potentially curable primary rectal adenocarcinoma were dissected according to standard protocol in Leeds and Stockholm between 1997 and 2007 and were studied. Tissue morphometry was performed on the cross sectional photographs of 93 patient cases. RESULTS: The cylindrical technique removed more tissue in the distal rectum and in all slices that contained tumor compared with the standard operation (both P <.0001). Greater distance was observed from the muscularis propria or internal sphincter to the anterior, posterior, and lateral resection margins (all P <.0001). This was associated with lower circumferential resection margin (CRM) involvement (14.8% v 40.6%; P =.013) and intraoperative perforations (3.7% v 22.8%; P =.0255). An increase in the amount of tissue removed in the distal rectum (P <.0001) was demonstrated by a single surgeon who changed from the standard to the cylindrical technique during the study period; the change was associated with a reduction in CRM positivity (from 36.2% to 12.5%) and in perforations (from 12.8% to 0.0%). CONCLUSION: Cylindrical APE performed in the prone position for low rectal cancer removes more tissue around the tumor that leads to a reduction in CRM involvement and intraoperative perforations, which should reduce local disease recurrence. The cylindrical technique has the potential to improve patient outcomes substantially if appropriate surgical education programs are developed.
Kevin F Birbeck,
Christopher P Macklin,
Nicholas J Tiffin,
Wendy Parsons,
Michael F Dixon,
Nicholas P Mapstone,
Cedric R Abbott,
Nigel Scott,
Paul J Finan,
David Johnston,
Philip Quirke
Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
OBJECTIVE: To analyze the potential variability in rates of circumferential resection margin (CRM) involvement between different surgeons and time periods and to determine the suitability of using CRM status as an immediate predictor of outcome after rectal cancer surgery. SUMMARY BACKGROUND DATA: After disease stage has been taken into account, survival in rectal cancer has been shown to be very variable between surgeons and institutions. One of the major factors influencing survival is local recurrence, and this in turn is strongly related to inadequate tumor excision, particularly at the CRM. METHODS: In a study involving 608 patients who underwent surgery for rectal cancer in Leeds during the 12-year period 1986 to 1997, the authors examined the role of CRM status as an immediate predictor of likely outcome, paying particular attention to its relationships with different surgeons and time periods. RESULTS: Of 586 patients on whom full clinical follow-up was obtained, 165 (28.2%) had CRM involvement by carcinoma on pathologic examination. Up to the end of 1998, 105 (17.9%) patients had developed local recurrence. A significantly higher proportion (38.2%) of CRM-positive patients developed local recurrence than CRM-negative ones (10.0%). Kaplan-Meier survival analysis showed significant improvements in survival for CRM-negative patients over CRM-positive patients. Survival analysis in relation to two gastrointestinal surgeons and a group of other surgeons showed survival improvements that paralleled a reduction in the rates of CRM involvement for the two gastrointestinal surgeons during the period of the study. No improvement in survival or reduction in rates of CRM involvement was seen in the group of other surgeons. CONCLUSIONS: These results show that CRM status may be used as an immediate predictor of survival after rectal cancer surgery and serves as a useful indicator of the quality of surgery. The frequency of CRM involvement can be used both for overall surgical audit and for monitoring the value of training programs in improving rectal surgery by individual surgeons. Its use in the current MRC CR07 study is valid and the best indicator of a requirement for further local therapy.
Colorectal Research, Pelican Cancer Foundation, Basingstoke, Hampshire, United Kingdom.
PURPOSE: Patients with low rectal cancer have worse outcomes compared to those with upper rectal cancer. Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. We looked at a recent series of patients with low rectal cancer to explore some of the issues. METHODS: We analyzed 153 patients from the MERCURY study with low rectal cancer (<or=6 cm from the anal verge). The median tumor height, percentage undergoing neoadjuvant therapy, involved margin rates, and degree of local invasion were compared for abdominoperineal excision vs low anterior resection. RESULTS: The mean tumor height from the anal verge was 2.9 cm for the patients with abdominoperineal excision vs 4.6 cm in the patients with low anterior resection. The involved margin rate was 20% overall, but was 31.9% for abdominoperineal excision vs 12% for low anterior resection. More patients who had abdominoperineal excision had neoadjuvant therapy (64% vs 41%) and a higher proportion had more locally advanced (T4) tumors. CONCLUSION: Patients undergoing abdominoperineal excision have higher involved margin rates; however, they had lower and more locally extensive tumors despite a greater proportion undergoing neoadjuvant therapy. Patients with low rectal cancer pose difficulties with regard to optimal management. Targeted strategies are needed to improve outcome in this complex and common cancer.
Oliver C Shihab,
Richard J Heald,
Eric Rullier,
Gina Brown,
Torbjorn Holm,
Philip Quirke,
Brendan J Moran
Colorectal Research, Pelican Cancer Foundation, Basingstoke, Hampshire, UK.
Cancer of the low rectum provides a challenge for both preoperative staging and optimum operative management. Current outcomes for patients with low rectal cancer are poor, particularly for those treated by abdominoperineal excision. It has been suggested that this poor outcome is due to an inherent oncological inferiority of the traditional abdominoperineal excision procedure, which might be explained by the unique anatomical features of the low rectum and the lack of clearly defined anatomical excision planes. In this Personal View, we discuss the anatomical and surgical planes available for the management of low rectal cancer, and describe the two-plane approach to low rectal cancer using the mesorectal plane and the extralevator plane.
Associate Professor, Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University Faculty of Dentistry, Ile-Ife, Nigeria.
Mycobacterial Research Program, Centenary Institute, New South Wales, Australia.
Infection with Mycobacterium tuberculosis continues to be a leading cause of death in many regions of the world, and control of this disease is hampered by the lack of a safe and effective vaccine. Secreted proteins of M. tuberculosis are an important group of antigens for subunit vaccines which target this infection. We have tested three secreted members of the cutinase-like protein (CULP) family of M. tuberculosis for their potential as protein vaccine antigens. Culp6 elicited a strong T lymphocyte response in M. tuberculosis infected mice, and importantly, in tuberculosis (TB) patients tested. Culp1, Culp2 and Culp6 when delivered as protein vaccines to mice, induced potent IFN-gamma responses which in turn translated into a significant level of protection against aerosol M. tuberculosis infection. A Culp1-6 fusion protein provided an increased level of protection against infection compared to Culp1 or Culp6 alone. The data presented here may indicate that Culp6, as a cell wall-associated, putatively essential protein shown here for the first time to be recognised in TB patients, as an attractive candidate for inclusion in future subunit vaccines.
Susan D Richman,
Matthew T Seymour,
Philip Chambers,
Faye Elliott,
Catherine L Daly,
Angela M Meade,
Graham Taylor,
Jennifer H Barrett,
Philip Quirke
Leeds Institute of Molecular Medicine, St. James's Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds; and the Medical Research Council Clinical Trials Unit, London, United Kingdom.
PURPOSE: Activating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies. PATIENTS AND METHODS: The Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry. RESULTS: Three hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P <.0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P =.05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P =.012). CONCLUSION: KRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.
Michael S Braun,
Susan D Richman,
Lindsay Thompson,
Catherine L Daly,
Angela M Meade,
Julian W Adlard,
James M Allan,
Mahesh K B Parmar,
Philip Quirke,
Matthew T Seymour
Oncology & Clinical Research and Pathology & Tumour Biology Sections, Leeds Institute of Molecular Medicine, University of Leeds, Leeds; Medical Research Council Clinical Trials Unit; Colorectal Cancer Clinical Studies Group, National Cancer Research Institute, London; and University of Newcastle, Newcastle, United Kingdom.
PURPOSE: Predicting efficacy and toxicity could potentially allow individualization of cancer therapy. We investigated putative pharmacogenetic markers of chemotherapy toxicity in a large randomized trial. Patients, Materials, and METHODS: Patients were randomly assigned to different sequences of chemotherapy for advanced colorectal cancer. First-line therapy was fluorouracil (FU), irinotecan/FU (IrFU) or oxaliplatin/FU (OxFU). Patients allocated first-line FU had planned second-line irinotecan alone, IrFU, or OxFU. The primary toxicity outcome measure was toxicity-induced delay or dose reduction; the secondary outcome was Common Terminology Criteria of Adverse Events grade >/= 3 toxicity. DNA was analyzed in 1,188 patients; 1,036 were assessable for the primary outcome, including 688 treated with FU, 270 with IrFU (first or second line), 280 with OxFU (first or second line), 184 with irinotecan alone, and 454 with any irinotecan-containing regimen. Ten polymorphisms were assessed: thymidylate synthase-enhancer region (TYMS-ER), thymidylate synthase 1494 (TYMS-1494), dihydropyrimidine dehydrogenase (DPYD), methylenetetrahydrofolate reductase (MTHFR), mutL homolog 1 (MLH1), UDP glucuronyltransferase (UGT1A1), ATP-binding cassette group B gene 1 (ABCB1), x-ray cross-complementing group 1 (XRCC1), glutathione-S-transferase P1 (GSTP1), and excision repair cross-complementing gene 2 (ERCC2). RESULTS: Using the primary outcome measure, no polymorphism was significantly associated (P <.01) with the toxicity of any regimen or with the difference in toxicity of IrFU or OxFU versus FU alone. Trends (of doubtful significance) were seen for associations of XRCC1, ERCC2, and GSTP1 with toxicity during irinotecan regimens: XRCC1, primary end point, any irinotecan-containing regimen (P =.045); ERCC2, secondary end point, irinotecan alone (P =.003); GSTP1, secondary end point; IrFU (P =.039); and irinotecan alone (P =.05). There was no evidence of association of UGT1A1*28 with irinotecan toxicity. CONCLUSION: These results do not support the routine clinical use of the evaluated polymorphisms, including UGT1A1*28. Further investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan toxicity is warranted.
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Department of Surgery, St. John's Queens Hospital, Queens, New York, NY, USA.
BACKGROUND: Colonoscopy findings compared with findings at time of surgery have a discrepancy rate of 3-21%. The objective of our study was to investigate this discrepancy and provide potential resolutions. METHODS: In this retrospective study, we identified 400 patients who underwent colonoscopy followed by colon resection at our community hospitals in 1999-2006. Discrepancies between colonoscopy and intraoperative findings were noted. Each discrepancy was classified as major if the surgical procedure had to be altered, the lesion was missed, an unnecessary segment was removed, or the incision was extended. A discrepancy was classified as minor if there was no alteration in planned surgery. RESULTS: Of the 400 cases, 160 (40%) were located in the right colon, 13 (3%) were in the transverse colon, 185 (46%) were in the left colon, and 42 (11%) were in the rectum. A total of 48 (12%) discrepancies between colonoscopy and intraoperative findings were identified: 26 (54%) were major and 22 (46%) were minor. Thirteen (27%) were in the proximal colon (3 major and 10 minor discrepancies), 3 (6.3%) were in the transverse colon (all major), 22 (46%) were in the distal colon (17 major and 5 minor), and 10 (21%) were in the rectum (3 major, 7 minor). Major discrepancies were significantly higher in the left colon (17 of the 185 left-sided lesions; 9.1%) than in the right colon (3/160; 1.9%; P = 0.045). CONCLUSIONS: In our study, colonoscopy has an error rate of 12% when used to localize tumors; more than half of these patients require significant unanticipated changes in their surgery. The discrepancies are significantly higher in left side of colon.
Experimental study of hyperthermal methods usage in spleen-saving surgery are presented. Means of plasmic and thermal flow spleen resection, which were proven to be effective and reliable were developed. Comparative analysis of different method application has shown equatable results for hyperthermal methods and their advantage over sutural and gluing methods.
Marko Simunovic,
Eddy Rempel,
Marc-Erick Thériault,
Nancy N Baxter,
Beth A Virnig,
Neal J Meropol,
Mark N Levine
Departments of Surgery.
BACKGROUND: There has been minimal research on the influence of delays for cancer treatments on patient outcomes. We measured the influence of delays to nonemergent colon cancer surgery on operative mortality, disease-specific survival and overall survival. METHODS: We used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare databases (1993-1996) to identify patients who underwent nonemergent colon cancer surgery. We assessed 2 time intervals: surgeon consult to hospital admission for surgery and first diagnostic test for colon cancer to hospital admission. Follow-up data were available to the end of 2003. We selected the time intervals to create patient groups with clinical relevance and they did not extend past 120 days. RESULTS: We identified 7989 patients who underwent nonemergent colon cancer surgery. Median delays from surgeon consult to admission and from first diagnostic test to admission were 7 and 17 days, respectively. The odds of operative mortality were similar if the consult-to-admission interval was 22 days or more versus 1-7 days (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.6-1.8, p = 0.91) or if the test-to-admission interval was 43 days or more versus 1-14 days (OR 0.8, 95% CI 0.4-1.5, p = 0.51), respectively. For these same respective interval comparisons, disease-specific survival was not influenced by the consult-to-admission wait (hazard ratio [HR] 1.0, 95% CI 0.9-1.2, p = 0.91) or the test-to-admission wait (HR 1.0, 95% CI 0.8-1.1, p = 0.63). The risk of death was slightly greater if the consult-to-admission interval was 22 or more days versus 1-7 days (HR 1.1, 95% CI 1.0-1.2, p = 0.013) and if the test-to-admission interval was 43 days or more versus 1-14 days (HR 1.2, 95% CI 1.1-1.3, p = 0.003). CONCLUSION: It is unlikely that delays to nonemergent colon cancer surgery longer than 3 weeks from initial surgical consult or longer than 6 weeks from first diagnostic test negatively impact operative mortality, disease-specific survival or overall survival.
Donauspital-SMZ Ost, Sebészeti és Orvostudományi Egyetem Sebészeti Klinika Bécs.
Robert B Hines,
Chakrapani Chatla,
Harvey L Bumpers,
John W Waterbor,
Gerald McGwin Jr,
Ellen Funkhouser,
Christopher S Coffey,
James Posey,
Upender Manne
Departments of Epidemiology, Pathology, Preventive Medicine, Biostatistics, and Medicine, University of Alabama at Birmingham, Birmingham, AL; and the Department of Surgery, Morehouse School of Medicine, Atlanta, GA.
PURPOSE: Although, for patients with cancer, comorbidity can affect the timing of cancer detection, treatment, and prognosis, there is little information relating to the question of whether the choice of comorbidity index affects the results of studies. Therefore, to compare the association of comorbidity with mortality after surgery for colon cancer, this study evaluated the Adult Comorbidity Evaluation-27 (ACE-27), the National Institute on Aging (NIA) and National Cancer Institute (NCI) Comorbidity Index, and the Charlson Comorbidity Index (CCI). PATIENTS AND METHODS: The study population consisted of colon cancer patients (N = 496) who underwent surgery at the University of Alabama at Birmingham Hospital from 1981 to 2002. Hazard ratios (HRs) with 95% CIs were obtained using the method of Cox proportional hazards for the three comorbidity indices in predicting overall and colon cancer-specific mortality. The point estimates obtained for comorbidity and other risk factors across the three models were compared. RESULTS: For each index, the highest comorbidity burden was significantly associated with poorer overall survival (ACE-27: HR = 1.63; 95% CI, 1.24 to 2.15; NIA/NCI: HR = 1.83; 95% CI, 1.29 to 2.61; CCI: HR = 1.46; 95% CI, 1.14 to 1.88) as well as colon cancer-specific survival. For the other risk factors, there was little variation in the point estimates across the three models. CONCLUSION: The results obtained from these three indices were strikingly similar. For patients with severe comorbidity, all three indices were statistically significant in predicting shorter survival after surgery for colon cancer.
Asim Jamal Shaikh,
Sajjad Raza,
Altaf Ahmed Shaikh,
Romana Idress,
Shiyam Kumar,
Yasmin Abdul Rasheed,
Amar Lal,
Nehal Masood
Department of Medicine, The Aga Khan University Hospital, Karachi, Pakistan. Asim.jshaikh@aku.edu
BACKGROUND: Colon cancer is a common malignancy with its incidence reportedly rising in Asian countries, including Pakistan. There are no comprehensive data available from Pakistan which focus on associations of various factors with long-term survival of colon cancer. We therefore present an analysis of findings from our centre. METHODOLOGY: In this retrospective study adult patients with colon cancer diagnosed through 2000-2003 were included. A comprehensive questionnaire was filled for each individual through review medical and pathology reports. Long term survival data was collected from contactable patients or their relatives. RESULTS: A total of 93 patients were assessed, 57 males and 36 females (M: F= 1.58: 1). Mean age of diagnosis was 54 years. Of the total, 49.5% of the patients had right sided (mortality rate 51.6%), 10.8% had transverse colon,(mortality rate 37.5%), 7.5% had descending colon (mortality rate 66.7%) and 32.2% had sigmoid colon (mortality rate 40.9%) cancers. Stage I disease on diagnosis was found in 16%, stage II in 42.7 (mortality 40 %) and stage III in 41.3%(mortality 70 %). Tumors were well differentiated in 20.2%(mortality 42.9%), moderately differentiated in 61.9%(mortality 43%) and poorly differentiated in 17.9%(mortality 70%). In 36.3% of the patients less than 12 lymph nodes were removed (mortality 55% Vs 43% in patients with <12 lymph nodes removed). Margins were free in most patients but a radial margin was reported in only 44%. Most patients had pure adenocarcinoma while a mucinous type differentiation was seen in 19.7%, 3% had signet ring morphology, 1.5% adeno-squamous carcinoma and similar number with neuroendocrine differentiation. Overall 5 year all cause mortality for all stages combined was 46.9%. CONCLUSION: Colon cancer in Pakistan commonly presents at an advanced stage, there is a male preponderance, and relatively mean younger age at presentation for males is seen. Advanced stage and lymph node involvement along with poorly differentiated pathology, signet ring or mucinous morphology, location in descending colon, positive surgical margins and removal of less than twelve lymph nodes are factors associated with poor long term survival. There is a need to reinforce information about colon cancer and larger studies from the region are needed to confirm the factors analyzed here.
Pathology & Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds, UK.
Institute for Clinical Outcomes Research and Education (iCORE), St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
*Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, USA daggerDepartment of Pediatric Surgery, USA double daggerDepartment of Pathology, Division of Anatomic Pathology, Nationwide Children's Hospital, Ohio State University, Columbus, USA.