The long-term survival characteristics of a cohort of colorectal cancer patients and baseline variables associated with survival outcomes with or without time-varying effects.

BACKGROUND: Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. METHODS: The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. RESULTS: During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. CONCLUSIONS: This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.

Management of primary rectal cancer by surgeons in Atlantic Canada: results of a regional survey.

BACKGROUND: We sought to determine the current practice patterns of general surgeons in Atlantic Canada in the management of primary rectal cancer in relation to surgeon-specific variables. METHODS: We sent mail-out surveys to all practising general surgeons (n = 183) in Atlantic Canada to determine screening preferences, preoperative assessment, the use of neoadjuvant and adjuvant therapy, surgical therapy for rectal cancer and surgeon demographics. We analyzed the responses using χ(2) tests. RESULTS: The response rate was 98 (54%) after 2 mail-outs; there were 82 (49%) eligible responses. Surgeons in practice for 21 years or more were more likely than those with fewer than 21 years of practice to order preoperative ultrasonography of the liver and were less likely to order preoperative computed tomography. Endorectal ultrasonography was ordered routinely by 23% of surgeons, whereas 71% of surgeons would order it if time and resources were available. Surgeons who were not certified by the Royal College of Physicians and Surgeons of Canada were significantly more likely than those who were certified to use neoadjuvant therapy in all patients with rectal cancer (43% v. 12%; p = 0.031). Surgeons who performed more than 10 rectal cancer surgeries per year were significantly more likely than those who performed 10 or fewer surgeries per year to use neoadjuvant treatment for T3 tumours (94% v. 61%; p = 0.007). Surgeons with medical or radiation oncology services in their communities were significantly more likely than those without such services to recommend neoadjuvant treatment in T3 rectal tumours and rectal tumours with pathologic lymph nodes. CONCLUSION: We found significant variation in the management of rectal cancer depending on surgeon-specific variables. The implications of these differences on the outcomes of patients with rectal cancer are unknown.

Canadian Association of University Surgeons' Annual Symposium: W(h)ither generalism(?).

This 2008 Symposium of the Canadian Association of University Surgeons (CAUS) brought together surgeons from a number of jurisdictions to discuss generalism in general surgery and its future. Dr. John Birkmeyer, the 2008 Charles Tator lecturer, started the symposium by framing the problem: the need to improve surgical outcomes, selective referral, centres of excellence, process compliance and performance feedback. Dr. John Bohnen, chair of the Royal College of Physicians and Surgeons of Canada's (RCPSC) General Surgical Specialty Committee, underscored the mismatch between the provision of care and regional Canadian patient needs. By measuring structure and process and maintaining a national dialogue, solutions to potential care inequities will be found. Dr. Bill Fitzgerald, president of the RCPSC and past president of the Canadian Association of General Surgeons (CAGS), defined the enormous breadth in the scope of practice that is available to general surgeons across Canada. He highlighted the importance of the community surgeon not only in his or her specialty but also as a vital trainer of students, residents and international medical graduates. He identified the importance of general surgery in the country's military mission. He called for a thorough re-examination of the compensation model to ensure equity and recognition of diversity. Dr. Bill Pollett, president of CAUS, identified the alternative types of practice encountered in communities of 50 000 or less. Surveys of members and trainees of the CAGS showed how much postfellowship training is done, and that whereas the perception is one of diminished quality of life and less remuneration, the nature of community general surgery makes it a highly desirable career choice. He called for focused community general surgical training to recognize the unique demands compared with urban and large city practices.

Concordance with clinical practice guidelines for adjuvant chemotherapy in patients with stage I-III colon cancer: experience in 2 Canadian provinces.

BACKGROUND: Clinical practice guidelines (CPGs) for the adjuvant treatment of colorectal cancer were published by the National Institutes of Health in 1991. The American Society of Clinical Oncology and Cancer Care Ontario have recommended adjuvant chemotherapy for patients with high-risk stage II colon cancer. We evaluated differences in concordance with guidelines in the treatment of patients with stage I-III colon cancer in the Canadian provinces of Newfoundland and Labrador and Ontario. METHODS: We assessed clinical data and treatment from January 1999 to December 2000 for 130 patients from Newfoundland and Labrador and 315 patients from Ontario who had stage I-III colon cancer. The primary outcome was concordance with guidelines for adjuvant treatment. We evaluated factors affecting the use of chemotherapy in patients with stage II disease. RESULTS: No patients received adjuvant therapy for stage I disease. Forty-five of 52 patients (87%) in Newfoundland and Labrador and 108 of 115 patients (94%) in Ontario received adjuvant chemotherapy for stage III colon cancer. Twenty of 55 patients (36%) in Newfoundland and Labrador and 44 of 116 patients (38%) in Ontario received adjuvant therapy for stage II disease. Eighteen of 41 patients (44%) in Newfoundland and Labrador and 30 of 53 patients (57%) in Ontario with high-risk features received adjuvant treatment, which was significantly higher than patients without high-risk features. There was a strong trend toward using chemotherapy in patients with stage II disease who were 50 years or younger, independent of high-risk status. CONCLUSION: Concordance with CPGs for adjuvant chemotherapy in patients with stage II colon cancer was not optimal. This may reflect selection bias among referring surgeons, a paucity of level-I evidence and the belief that other factors such as age may play a role in predicting outcome.

Utilization rates for surgical procedures in rural and urban Canada.

OBJECTIVE: To investigate whether utilization rates of common surgical procedures are different between urban and rural Canadians in 2 provinces and to examine whether these rates are influenced by the presence and scope of local surgical programs and by the availability of different physician providers. METHODS: Utilization rates for 8 common surgical procedures (appendectomy, carpal tunnel release, closed hip fracture repair, rectal cancer surgery, joint replacement, thyroidectomy, unilateral or bilateral inguinal herniorrhaphy, and cholecystectomy) were identified in rural Alberta and rural Northern Ontario from hospital discharge records. Rural populations were characterized by 3 types of communities, based on availability of local physician and diagnostic resources. Travel time for consultations and surgery were estimated. Age-sex-adjusted rates, their standard errors, and 95% confidence intervals (CIs) were calculated for the purpose of comparisons among residents' locations using the method of direct standardization. To test a possible association between travel times and utilization rates, hierarchical linear and nonlinear modelling was used to analyze a 2-level model, with patients nested within rural hospital catchment areas in the province of Alberta. RESULTS: Utilization rates for appendectomy, cholecystectomy and carpal tunnel release are significantly greater for rural populations compared with urban in both Alberta and Northern Ontario. Rural Northern Ontario had higher rates of utilization than rural Alberta for carpal tunnel release and cholecystectomy (p < 0.01) and closed hip fracture repair (p < 0.05). No statistical differences between the provinces were noted for the remaining procedures. No difference in utilization rates was found between the 3 types of rural centres. The modelling found a significant association between travel time and use for only one procedure--carpal tunnel release. Patients who had to travel < or =1 hour had a 13% higher surgery rate. CONCLUSION: Rates of utilization were higher in rural areas for procedures where greater surgical variability is known to exist. These higher rural rates were not influenced by either the presence or scope of local surgical programs nor by the differences in providers. There was no difference in rates for procedures where previous research has shown little variability.

Rural surgical services in two Canadian provinces.

OBJECTIVE: Contrast alternative health delivery systems and the use of differently trained physician providers in the supply of surgical services to rural residents in 2 Canadian provinces. METHODS: Four surgical procedures (carpal tunnel release, inguinal herniorrhaphy, appendectomy and cholecystectomy) provided to rural residents of Alberta and Northern Ontario were identified between 1997/98 and 2001/02. Surgical staff were identified as specialists or non-specialists. Rural populations were mapped into the catchment areas of rural acute care facilities. Rural surgical programs were characterized by the level of surgical service available locally. RESULTS: Alberta and Northern Ontario have a similar number of rural surgical programs staffed by Canadian-certified general surgeons (10 and 12, respectively). However, Alberta has 27 smaller rural surgical programs staffed by non-specialist surgeons and Northern Ontario has only 4. These non-specialist surgeons play a significant role in Alberta, often in collaboration with specialist surgeons. In Northern Ontario the non-specialist surgeons play a minor role. The small rural surgical programs in Northern Ontario that are staffed by specialist surgeons are significantly more successful in retaining the local surgical caseload compared with similar programs in Alberta. CONCLUSIONS: The principal differences between Alberta and Northern Ontario in the delivery of rural surgical services are the greater number of small rural surgical programs in Alberta, and the substantial role of non-specialist surgical staff in these programs.

Outcomes in the surgical treatment of low rectal cancer: does neoadjuvant treatment equalize results?

BACKGROUND: The choice of operation for potentially curable cancer of the low rectum (≤6 cm from the anal verge) is usually between ultra low anterior resection (ULAR) or abdominal perineal excision (APE). Numerous studies have suggested improved results with ULAR. METHODS: This study was a retrospective review of prospectively collected data for a series of patients undergoing surgical treatment for low rectal cancer at three Melbourne hospitals. The patient details and outcomes were compared between those undergoing APE and ULAR. RESULTS: One hundred and ninety-eight of 213 patients with potentially curable low rectal cancer were treated by either ULAR (n = 82) or APE (n = 116). Overall survival and local recurrence rates were similar, although there was a trend towards improved results for ULAR. Preoperative radiation was received by 89 (76.7%) of APE patients and 44 (53.7%) of ULAR patients (P < 0.0005). CONCLUSION: In this study there was no statistical difference in the oncological results between APE and ULAR. However, there was a trend to improved result for ULAR in spite of a strikingly higher rate of neoadjuvant radiation in the APE group. It is possible that enhanced use of preoperative radiation has a beneficial role in the management of low rectal cancer treated by conventional APE.

Quality of life after surgery in individuals with familial colorectal cancer: does extended surgery have an adverse impact?

BACKGROUND: There is controversy regarding the optimum surgical treatment of patients presenting with colorectal cancer with known or suspected genetic cancer syndromes. Although standard segmental resection may be curative, a high risk of metachronous malignancy leads many to advocate extended surgery. The current study was designed to assess whether or not extended surgery adversely impacts quality of life compared to segmental surgery. METHODS: Records at The Royal Melbourne Hospital Family Cancer Clinic were searched in order to identify patients with suspected high risk familial colon cancer. Patients who underwent surgery were identified and mailed two Standardized Quality of Life Questionnaires (EORTC QLQ-C30 and EORTC QLQ-CR38). RESULTS: Fifty respondents met the inclusion criteria. None of the 15 patients whose primary operation was an extended procedure developed a metachronous cancer. Seventeen of the 35 (48.67%) who had an initial segmental resection had subsequent surgery for metachronous cancer. At the time of the questionnaire, 27 had extended surgery and 23 had segmental operations. The overall global health status and quality of life was very similar between the two groups. CONCLUSION: This study confirms that there is a high rate of metachronous cancer for patients undergoing segmental resection for hereditary colon cancer. Quality of life following either segmental or extended resection is not significantly different. Consequently, it is reasonable to recommend extended surgery for most patients with high risk hereditary colon cancer.

MTHFR Glu429Ala and ERCC5 His46His polymorphisms are associated with prognosis in colorectal cancer patients: analysis of two independent cohorts from Newfoundland.

INTRODUCTION: In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland. METHODS: The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort. RESULTS: When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04-2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15-2.76, p = 0.01), SERPINE1 -675indelG (HR: 0.52, 95%CI: 0.32-0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03-1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18-2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04-2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11-2.94, p = 0.018). CONCLUSIONS: In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.

Postgraduate surgical education and training in Canada and Australia: each may benefit from the other's experiences.

Canada and Australia share similar cultural origins and current multicultural societies and demographics but there are differences in climate and sporting pursuits. Surgeons and surgeon teachers similarly share many of the same challenges, but the health care and health-care education systems differ in significant ways. The objective of this review is to detail the different postgraduate surgical training programs with a focus on general surgery and how the programs of each country may benefit from appreciating the experiences of the other. The major differences relate to entry requirements, the role of universities in governance of training, mandatory skills courses in early training, the accreditation process, remuneration for surgical teachers and the impact of private practice. Many of the differences are culturally entrenched in their respective medical systems and unlikely to change substantially. Direct entry into specialty training without an internship per se is now firmly established in Canada just as delayed entry after internship is mandated by the Australian Medical Board. Both recognize the importance of establishing goals and objectives, modular curricular and the emerging role of online educational resources and how these may impact on assessments. The Royal Australasian College of Surgeons is unlikely to cede much responsibility to the universities but alternative academic models are emerging. Private health care in the two countries differs, but there are increasing opportunities for training in the private sector in Australia. In spite of the differences, both provide excellent health care and surgical training opportunities in an environment with significant fiscal, technological and societal challenges.

Training of Canadian general surgeons: are they really prepared? CAGS questionnaire on surgical training.

BACKGROUND: General surgery in Canada varies from single system subspecialty practice in large centres to multisystem broad-based practice in smaller communities. We have attempted to determine whether Canadian training programs in general surgery are appropriate for these varied practices. METHODS: A questionnaire was circulated to members of the Canadian Association of General Surgeons to collect demographic data and information about community size and patterns of practice. We also sought the source of training for general surgical subspecialties and other surgical specialties if applicable. RESULTS: Surgeons in smaller communities performed significantly more subspecialty and other specialty surgical practice than do surgeons in larger communities. Much of the training for this practice comes not from the primary fellowship but from senior colleagues in the community. Surgeons in smaller communities feel less well prepared than their colleagues in larger communities and are less likely to take additional fellowship training. CONCLUSION: These results have important implications for surgical educators and manpower planners.