Better survival for patients with colon cancer operated on by specialized colorectal surgeons - a nationwide population-based study in Sweden 2007-2010.

AIM: Mortality and complication rates after surgery for colon cancer are high, especially after emergency procedures. The aim of the present study was to evaluate the importance of the formal competence of surgeons for survival and morbidity. METHOD: The Swedish Colorectal Cancer Registry prospectively records data on patients diagnosed with cancer within the colon and rectum. A cohort of patients operated on for colon cancer between 2007 and 2010 were followed 5 years after surgery. Data on postoperative morbidity, mortality and long-term survival were compared with regard to formal competency of the most senior surgeon attending the procedure. RESULTS: This analysis includes 13 365 patients operated on for colon cancer, including 10 434 elective procedures and 2931 emergency cases. The overall 5-year survival was higher for those operated on by subspecialist colorectal surgeons compared with general surgeons (60% vs 48%; P < 0.001). Five-year survival after elective surgery was 63% vs 55% (P < 0.001) and 35% vs 31% (P < 0.05) after emergency procedures when performed by colorectal surgeons compared with general surgeons. Postoperative 30-day mortality was 3% after surgery performed by colorectal surgeons compared with 7% when performed by general surgeons. Mortality at 90 days was 6% after surgery performed by colorectal surgeons compared with 11% for patients operated on by general surgeons (P < 0.001). CONCLUSION: Subspecialization in colorectal surgery is associated with better outcome for patients operated on for colon cancer, and effort should be made to increase the availability of colorectal surgeons for both acute and elective colon cancer surgery.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

Population-based data from the Swedish Colon Cancer Registry.

BACKGROUND: Evaluating the external validity of clinical trials requires knowledge not only of the study population but also of a relevant reference population. The main aim of this study was to present data from a large, contemporary, population-based cohort of patients with colonic cancer. METHODS: Data on patients diagnosed between 2007 and 2011 were extracted from the Swedish Colon Cancer Registry. The data, registered prospectively in a national population of almost 10 million, included over 99 per cent of all diagnosed adenocarcinomas of the colon. RESULTS: This analysis included 18,889 patients with 19,526 tumours (3·0 per cent had synchronous tumours). The sex distribution was fairly equal, and the median age was 74·1 (interquartile range 65-81) years. The overall and relative (cancer-specific) survival rates after 3 years were 62·7 and 71·4 per cent respectively. Some 88·0 per cent of the patients were operated on, and 83·8 per cent had tumours resected. Median blood loss during bowel resection was 200 (mean 311) ml, and the median operating time was 160 min; 5·6 per cent of the procedures were laparoscopic. Preoperative chemotherapy was administered to 2·1 per cent of patients; postoperative chemotherapy was planned in 90·1 per cent of fit patients aged less than 75 years with stage III disease. In patients operated on in an emergency setting (21·5 per cent), the preoperative evaluation was less extensive, the proportion of R0 resections was lower, and the outcomes were poorer, in both the short and long term. CONCLUSION: These population-based data represent good-quality reference points.

Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure.

Several factors determine overall outcome and possible local recurrence after curative surgery for rectal carcinoma. Surgical performance is usually believed to be the most pertinent factor, followed by adjuvant oncological treatment and tumor histopathology. However, chromosomal instability is common in colorectal cancer and tumor clones are assumed to differ in aggressiveness and potential of causing local recurrence. The aim of this study was, therefore, to evaluate if genetic alterations in primary rectal carcinoma are predictive of local recurrences. A large clinical database with linked bio-bank allowed for careful matching of two patient groups (R0) resected for rectal carcinoma. One group had developed early, isolated local recurrences and the other group seemed cured after 93 months follow-up. DNA from the primary tumors was analysed with array-CGH (comparative genomic hybridization) including 55,000 genomic probes. DNA from all primary tumors in both groups displayed previously reported and well-recognised DNA aberrations in colorectal carcinoma. Significant copy number gains were confirmed in the 4q31.1-31.22 region in DNA from tumors with subsequent local recurrence. Twenty-two affected genes in this region code for products with high relevance in tumor biology (p53 regulation, cell cycle activity, transcription). DNA from rectal carcinoma displayed well-known aberrations as described for colon carcinoma with no obvious prediction of local rectal recurrence. Gains in the 4q31.1-31.22 DNA region are highly potential for local recurrence despite R0 resection to be confirmed in larger patient materials.

Local recurrence of rectal cancer: a population-based cohort study of diagnosis, treatment and outcome.

AIM: Local recurrence is an important endpoint of rectal cancer treatment, but details of this form of treatment failure are less well described. The aim of this study was to acquire deeper knowledge of local recurrence regarding symptoms, diagnostic work-up, clinical management, health-care utilization and outcome. METHOD: Of 671 patients with rectal cancer, 57 were diagnosed with local recurrence within 5 years after surgery. Their records were analysed. RESULTS: At diagnosis of local recurrence 49 (86%) of 57 patients were symptomatic and 40 (70%) were diagnosed between scheduled follow-up visits. The predominant symptom was pain. Forty-five of the 57 (79%) had a palpable tumour. Most were deemed incurable at presentation and 10 (18%) were operated on with curative intent. Five years after the initial rectal cancer surgery, two patients were alive, with one free of disease. Despite the need for multiple interventions, including surgery, only four out of 40 patients were classified as being well-palliated in the terminal stage. CONCLUSION: Follow-up after rectal cancer surgery by annual clinical examination is not sufficient to detect local recurrence when it is asymptomatic. Local recurrence of rectal cancer is often associated with intractable symptoms. These patients require frequent interventions and can rarely be cured if diagnosed at an advanced stage. Strategies for early detection of local recurrence and the management thereof require improvement.

A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer.

AIM: The aim was to assess the feasibility of preoperative chemotherapy and possible tumour response using Pemetrexed (Alimta) in rectal cancer. METHOD: The study was a prospective, non-randomized, single-centre phase I/II feasibility trial. 37 patients with resectable rectal cancer were recruited and given three 3-week cycles of preoperative Pemetrexed therapy. Tumour size and stage were assessed by MRI scans before and after chemotherapy. Treatment tolerability and response such as changes in tumour size and symptoms were assessed. RESULTS: All patients completed the chemotherapy. Whilst mild side effects were frequent (grade 1, 34/37), the risk of severe effects was limited (grade 3 or 4, 4/37). Overall, there was a significant reduction in tumour size (p < 0.001). By RECIST criteria, one patient had tumour progression, 23/36 had stable disease and 12 patients had a response of up to 65%. There was also a significant decrease in the number of pre-treatment symptoms (p < 0.018) including reduction of bleeding and diarrhoea/constipation. CONCLUSION: Preoperative (Neoadjuvant) treatment with Pemetrexed was feasible in studied patients. Serious side effects were limited and a radiological tumour response or stable disease was seen in a majority of patients.

Rectal washout and local recurrence of cancer after anterior resection.

BACKGROUND: Adenocarcinomas of the rectum shed viable cells, which have the ability to implant. Intraoperative rectal washout decreases the amount and viability of these cells, but there is no conclusive evidence of the effect of rectal washout on local recurrence after rectal cancer surgery. METHODS: Data were analysed from a population-based registry of patients who had anterior resection from 1995 to 2002 and were followed for 5 years. Rectal washout was performed at the discretion of the surgeon. National inclusion of patients with rectal cancer and follow-up was near complete (approximately 97 and 98 per cent respectively). RESULTS: A total of 4677 patients were analysed (3749 who had washout, 851 no washout and 77 with information missing); 52.0 per cent of patients in the washout group and 41.4 per cent in the no-washout group had preoperative radiotherapy (P < 0.001). Local recurrence rates were 6.0 and 10.2 per cent respectively (P < 0.001). Univariable and multivariable logistic regression analyses produced odds ratios that favoured washout: 0.56 (95 per cent confidence interval (c.i.) 0.43 to 0.72) and 0.61 (0.46 to 0.80) respectively (both P < 0.001). In multivariable analysis restricted to patients who had curative surgery, the odds ratio was 0.59 (95 per cent c.i. 0.44 to 0.78; P < 0.001). CONCLUSION: There was a more favourable outcome in patients after rectal washout than without.

Regional differences in local recurrence rates after rectal cancer surgery.

AIM: To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management. METHOD: National, population-based, prospective registry data were used, including comprehensive 5-year follow up of 3783 patients operated on in the period 1998-2000. Local recurrence rates were compared using crude rate, Kaplan-Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed. RESULTS: The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed. CONCLUSIONS: We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.