National differences in implementation of minimally invasive surgery for colorectal cancer and the influence on short-term outcomes.

BACKGROUND: The timing and degree of implementation of minimally invasive surgery (MIS) for colorectal cancer vary among countries. Insights in national differences regarding implementation of new surgical techniques and the effect on postoperative outcomes are important for quality assurance, can show potential areas for country-specific improvement, and might be illustrative and supportive for similar implementation programs in other countries. Therefore, this study aimed to evaluate differences in patient selection, applied techniques, and results of minimal invasive surgery for colorectal cancer between the Netherlands and Sweden. METHODS: Patients who underwent elective minimally invasive surgery for T1-3 colon or rectal cancer (2012-2018) registered in the Dutch ColoRectal Audit or Swedish ColoRectal Cancer Registry were included. Time trends in the application of MIS were determined. Outcomes were compared for time periods with a similar level of MIS implementation (Netherlands 2012-2013 versus Sweden 2017-2018). Multilevel analyses were performed to identify factors associated with adverse short-term outcomes. RESULTS: A total of 46,095 Dutch and 8,819 Swedish patients undergoing MIS for colorectal cancer were included. In Sweden, MIS implementation was approximately 5 years later than in the Netherlands, with more robotic surgery and lower volumes per hospital. Although conversion rates were higher in Sweden, oncological and surgical outcomes were comparable. MIS in the Netherlands for the years 2012-2013 resulted in a higher reoperation rate for colon cancer and a higher readmission rate but lower non-surgical complication rates for rectal cancer if compared with MIS in Sweden during 2017-2018. CONCLUSION: This study showed that the implementation of MIS for colorectal cancer occurred later in Sweden than the Netherlands, with comparable outcomes despite lower volumes. Our study demonstrates that new surgical techniques can be implemented at a national level in a controlled and safe way, with thorough quality assurance.

Permanent stoma rates after anterior resection for rectal cancer: risk prediction scoring using preoperative variables.

BACKGROUND: A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling. METHODS: Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk. RESULTS: Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive. CONCLUSION: Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.

Usually, the goal of rectal cancer surgery is to remove the tumour and construct a bowel join. Sometimes, it is necessary to construct a stoma, which may become permanent. Swedish registry data were used to develop and test a statistical model to forecast the risk of a stoma 2 years after surgery. In addition, an online calculator was developed. The model performed reasonably well, and can be used to inform the patient and surgeon before surgery of the risk of a permanent stoma.

What is the risk of permanent stoma beyond 5 years after low anterior resection for rectal cancer? A 15-year follow-up of a randomized trial.

AIM: Low anterior resection of the rectum for cancer (LAR) entails a risk of symptomatic anastomotic leakage as well as impaired anorectal function, both of which may eventually result in the need for a permanent stoma (PS). The aim was to investigate the incidence of and risk factors for PS beyond 5 years following LAR. METHODS: Patients undergoing LAR and included in a multicentre trial with randomization to defunctioning stoma or not were followed for a median of 15 years. The reasons for a PS up to 5 years (PS ≤ 5 years) and beyond 5 years (PS > 5 years) were identified and compared. Risk factors for PS were analysed. RESULTS: Of all patients, 25% (57/232) had a PS. PS ≤ 5 years occurred in 19% (44/232) at a median of 12.5 months and PS > 5 years in 6% (13/232) at a median of 118 months following LAR. The main reason for PS ≤ 5 years was impaired anorectal function in 55% (24/44) and the main reason for PS > 5 years was pelvic sepsis related to the colorectal anastomosis in 46% (6/13). The major risk factor for PS was symptomatic anastomotic leakage, which occurred in 56% (32/57) of patients with PS and 10% (17/175) of patients without PS (P < 0.001). CONCLUSION: One-fourth of the patients who ended up with a PS had it fashioned beyond 5 years at a median of 10 years following LAR. Symptomatic anastomotic leakage was the major risk factor for PS, and impaired anorectal function was the main overall reason for a PS.

Self-reported sexual dysfunction in patients with rectal cancer.

AIM: Patients with rectal cancer often experience sexual dysfunction after treatment. The aim of this study was to evaluate sexual function in a prospective cohort of patients regardless of treatment and tumour stage and explore what factors might affect sexual activity 1 year after diagnosis. METHOD: The QoLiRECT study (Quality of Life in RECTal cancer) is a prospective study on the health-related quality of life in patients with rectal cancer in Denmark and Sweden. Questionnaires were completed at diagnosis and 1 year. Clinical data were retrieved from national quality registries. RESULTS: Questionnaire data were available from 1085 patients at diagnosis and 920 patients at 1 year. Median age was 69 years (range 25-100). At diagnosis, 29% of the women and 41% of the men were sexually active, which was lower than an age-matched reference population. This was further reduced to 25% and 34% at 1 year. Risk factors for sexual inactivity were absence of sexual activity prior to the diagnosis and the presence of a stoma. Women experienced reduced lubrication and more dyspareunia at 1 year compared with the time of diagnosis. In men, erectile dysfunction increased from 46% to 55% at 1 year. CONCLUSION: Sexual activity in patients with rectal cancer is lower at diagnosis compared with the population norm and is further reduced at 1 year. The presence of a stoma contributed to reduced sexual activity after operation. Sexual dysfunction was difficult to evaluate due to low sexual activity in the cohort. In men, erectile dysfunction is common.

Low anterior resection syndrome in a Scandinavian population of patients with rectal cancer: a longitudinal follow-up within the QoLiRECT study.

AIM: Low anterior resection syndrome (LARS) is common after low anterior resection. Our aim was to evaluate the prevalence and 'bother' (subjective, symptom-associated distress) of major LARS after 1 and 2 years, identify possible risk factors and relate the bowel function to a reference population. METHOD: The QoLiRECT (Quality of Life in RECTal cancer) study is a Scandinavian prospective multicentre study including 1248 patients with rectal cancer, of whom 552 had an anterior resection. Patient questionnaires were distributed at diagnosis and after 1, 2 and 5 years. Data from the baseline and at 1- and 2-year follow-up were included in this study. RESULTS: The LARS score was calculated for 309 patients at 1 year and 334 patients at 2 years. Prevalence was assessed by a generalized linear mixed effects model. Major LARS was found in 63% at 1 year and 56% at 2 years. Bother was evident in 55% at 1 year, decreasing to 46% at 2 years. Major LARS was most common among younger women (69%). Among younger patients, only marginal improvement was seen over time (63-59%), for older patients there was more improvement (62-52%). In the reference population, the highest prevalence of major LARS-like symptoms was noted in older women (12%). Preoperative radiotherapy, defunctioning stoma and tumour height were found to be associated with major LARS. CONCLUSION: Major LARS is common and possibly persistent over time. Younger patients, especially women, are more affected, and perhaps these patients should be prioritized for early stoma closure to improve the chance of a more normal bowel function.

Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery.

BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery. METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis. RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin. CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

A nationwide study on the incidence of mesenteric ischaemia after surgery for rectal cancer demonstrates an association with high arterial ligation.

AIM: The incidence of mesenteric ischaemia after resection for rectal cancer has not been investigated in a population-based setting. The use of high ligation of the inferior mesenteric artery might cause such ischaemia, as the bowel left in situ depends on collateral blood supply after a high tie. METHOD: The Swedish Colorectal Cancer Registry was used to identify all patients subjected to an abdominal resection for rectal cancer during the years 2007-2017 inclusive. Mesenteric ischaemia within the first 30 postoperative days was recorded, classified as either stoma necrosis or colonic necrosis. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for mesenteric ischaemia in relation to high tie, with adjustment for confounding. RESULTS: Some 14 657 patients were included, of whom 59 (0.40%) had a reoperation for any type of mesenteric ischaemia, divided into 34 and 25 cases of stoma necrosis and colonic necrosis, respectively. Compared with patients who did not require reoperation for mesenteric ischaemia following rectal cancer surgery, the proportion having high tie was greater (54.2% vs 38.5%; P = 0.032). The adjusted OR for reoperation due to any mesenteric ischaemia with high tie was 2.26 (95% CI 1.34-3.79), while the corresponding estimates for stoma and colonic necrosis, respectively, were 1.60 (95% CI 0.81-3.17) and 3.69 (95% CI 1.57-8.66). CONCLUSION: The incidence of reoperation for mesenteric ischaemia after abdominal resection for rectal cancer is low, but the use of a high tie might increase the risk of colonic necrosis demanding surgery.

High stoma prevalence and stoma reversal complications following anterior resection for rectal cancer: a population-based multicentre study.

AIM: Fashioning a defunctioning stoma is common when performing an anterior resection for rectal cancer in order to avoid and mitigate the consequences of an anastomotic leakage. We investigated the permanent stoma prevalence, factors influencing stoma outcome and complication rates following stoma reversal surgery. METHOD: Patients who had undergone an anterior resection for rectal cancer between 2007 and 2013 in the northern healthcare region were identified using the Swedish Colorectal Cancer Registry and were followed until the end of 2014 regarding stoma outcome. Data were retrieved by a review of medical records. Multiple logistic regression was used to evaluate predefined risk factors for stoma permanence. Risk factors for non-reversal of a defunctioning stoma were also analysed, using Cox proportional-hazards regression. RESULTS: A total of 316 patients who underwent anterior resection were included, of whom 274 (87%) were defunctioned primarily. At the end of the follow-up period 24% had a permanent stoma, and 9% of patients who underwent reversal of a stoma experienced major complications requiring a return to theatre, need for intensive care or mortality. Anastomotic leakage and tumour Stage IV were significant risk factors for stoma permanence. In this series, partial mesorectal excision correlated with a stoma-free outcome. Non-reversal was considerably more prevalent among patients with leakage and Stage IV; Stage III patients at first had a decreased reversal rate, which increased after the initial year of surgery. CONCLUSION: Stoma permanence is common after anterior resection, while anastomotic leakage and advanced tumour stage decrease the chances of a stoma-free outcome. Stoma reversal surgery entails a significant risk of major complications.

Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery: a prospective, randomized study.

AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery. METHODS: Ninety-six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient-controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1ß (IL-1ß), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1-6 h postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers. RESULTS: >There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL-10 which was 87% higher in group P [median and range 4.1 (2.3-9.2) pg/ml] compared to group E [2.6 (1.3-4.7) pg/ml] (P = 0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6, IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2. CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.

Level of vascular tie and its effect on functional outcome 2 years after anterior resection for rectal cancer.

AIM: Previous research indicates that high tie of the inferior mesenteric artery during anterior resection for rectal cancer might be associated with an increased risk of postoperative functional disturbances. The goal of this population-based retrospective cohort study was to further investigate that association. METHOD: Patients who underwent anterior resection for rectal cancer from April 2011 to September 2012 were identified through the Swedish Colorectal Cancer Registry. Bowel and urogenital function were assessed by a postal questionnaire 2 years after surgery. Information on the level of mesenteric tie and clinical variables was retrieved from the registry. The outcome was defined as any defaecatory, urinary or sexual dysfunction as reported by the patient. The association between high tie and the outcome was evaluated with multivariable logistic and linear regression with adjustment for confounders, such as sex, body mass index, comorbidity and preoperative radiation. RESULTS: With a response rate of 86%, 805 patients were included in the study. Of these, 46% were operated with high tie. After adjustment for confounders, high tie did not affect the risk of faecal incontinence (OR 0.85; 95% CI 0.59-1.22), urinary incontinence (OR 0.94; 95% CI 0.63-1.41) or various aspects of sexual dysfunction (erectile dysfunction, anejaculation, dyspareunia and coital vaginal dryness). However, an association between high tie and defaecation at night was detected (OR 1.44; 95% CI 1.02-2.03). CONCLUSION: This study does not support that the level of vascular tie influences the risk of major defaecatory, urinary or sexual disturbances 2 years after anterior resection for rectal cancer.

Laparoscopic and open right-sided colonic resection in daily routine practice. A prospective multicentre study within an Enhanced Recovery After Surgery (ERAS) protocol.

AIM: The study compared the outcome of laparoscopic and open surgery in daily practice when performed in a strict Enhanced Recovery After Surgery (ERAS) environment. METHOD: Two-hundred and ninety-two consecutive patients who received elective surgery, in three Swedish ERAS centres, for cancer or adenoma in the right colon in the period 1 January 2011 to 31 December 2012, were prospectively registered in a Web-based ERAS database. Peri-operative data were collected from the database and patient charts. The primary end-points included postoperative recovery and morbidity. The secondary objective was to identify preoperative variables that influenced the selection of patients for laparoscopic or open surgery. RESULTS: One-hundred and twenty-three (42%) patients were selected for laparoscopic surgery. The overall preoperative ERAS-compliance rate was 87% and no significant difference was seen between the surgical techniques. In multivariate analysis, patients treated with laparoscopy had significantly earlier pain control (2.4 ± 3.2 days vs 4.2 ± 5.9 days; P = 0.016) and a shorter length of hospital stay (LOS) (4 days vs 6 days; P = 0.002) compared with open surgery. There was no significant difference in the complication rate [18.7% vs 21.3%; OR = 1.0 (95% CI: 0.5-2.0)], the number of lymph nodes removed or the rate of R0 resection between laparoscopic and open surgery. Tumours selected for laparoscopy were generally smaller, had a lower T-stage and were predominantly situated in the caecum and the ascending colon compared with those of patients selected for open surgery. CONCLUSION: The use of laparoscopy in routine right-sided colectomy in an ERAS environment, with data on outcome corrected for selection bias, may result in faster recovery compared with open surgery.

High arterial ligation and risk of anastomotic leakage in anterior resection for rectal cancer in patients with increased cardiovascular risk.

AIM: Controversy still exists as to whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage after anterior resection for rectal cancer. This population-based study was carried out to evaluate the independent association between high arterial ligation and anastomotic leakage in patients with increased cardiovascular risk. METHOD: All 2673 cases of registered anterior resection for rectal cancer from 2007 to 2010 were identified from the Swedish Colorectal Cancer Registry and cross-referenced with the Prescribed Drugs Registry, rendering a cohort of all patients with increased cardiovascular risk. Operative charts and registered data were reviewed for 722 patients. The association between high tie and anastomotic leakage, as quantified by ORs and 95% CIs, was evaluated in a logistic regression model, with adjustment for confounding, including assessment of interaction. RESULTS: Symptomatic anastomotic leakage occurred in 12.3% (41/334) of patients in the high tie group and in 10.6% (41/388) in the low tie group. The use of high tie was not independently associated with a higher risk of anastomotic leakage (OR = 1.05; 95% CI: 0.61-1.84). In a post-hoc analysis, patients with a history of manifest cardiovascular disease and American Society of Anesthesiologists (ASA) score III-IV seemed to be at greater risk (OR = 3.66; 95% CI: 1.04-12.85). CONCLUSION: In the present population-based, observational setting, high tie was not independently associated with an increased risk of symptomatic anastomotic leakage after anterior resection for rectal cancer. However, this conclusion may not hold for patients with severe cardiovascular disease.

Early postoperative mortality after surgery for rectal cancer in Sweden, 2000-2011.

AIM: Postoperative mortality has traditionally been defined as death within 30 days of surgery. Such mortality after rectal cancer resection has declined significantly during the last decades. However, it is possible that this decline can be explained merely by a shift towards an increase in 90-day mortality. METHOD: A nationwide cohort study was based on data from the Swedish Colorectal Cancer Registry and the Swedish Patient Registry concerning patients who had undergone surgical resection for rectal cancer in 2000-2011. Unconditional logistic regression was used to calculate ORs with 95% CIs regarding mortality in different calendar periods (2000-2003, 2004-2007 and 2008-2011) in two different postoperative time periods (0-30 days and 31-90 days). RESULTS: Some 15,437 patients were included in this surgical cohort. Mortality within 30 days of surgery decreased from 2.1% in 2000-2003 to 1.6% in 2008-2011, whilst the corresponding mortality within the 31- to 90-day time window decreased from 2.1% to 1.4%. The adjusted risk of 30-day mortality in 2008-2011 was statistically significantly decreased compared with that in 2000-2003 (OR = 0.67; 95% CI: 0.48-0.93) and mortality in the 31- to 90-day time window was also reduced for 2008-2011 compared with 2000-2003 (OR = 0.71; 95% CI: 0.51-0.99). CONCLUSION: This population-based, nationwide Swedish study indicates that postoperative mortality, as measured within 30 days and 31-90 days after surgery, has decreased with time. However, no relevant shift from earlier to later postoperative mortality was discerned.

Early and late symptomatic anastomotic leakage following low anterior resection of the rectum for cancer: are they different entities?

AIM: The aim of the study was to compare patients with symptomatic anastomotic leakage following low anterior resection of the rectum (LAR) for cancer diagnosed during the initial hospital stay with those in whom leakage was diagnosed after hospital discharge. METHOD: Forty-five patients undergoing LAR (n = 234) entered into a randomized multicentre trial (NCT 00636948), who developed symptomatic anastomotic leakage, were identified. A comparison was made between patients diagnosed during the initial hospital stay on median postoperative day 8 (early leakage, EL; n = 27) and patients diagnosed after hospital discharge at median postoperative day 22 (late leakage, LL; n = 18). Patient characteristics, operative details, postoperative course and anatomical localization of the leakage were analysed. RESULTS: Leakage from the circular stapler line of an end-to-end anastomosis was more common in EL, while leakage from the stapler line of the efferent limb of the J-pouch or side-to-end anastomosis tended to be more frequent in LL (P = 0.057). Intra-operative blood loss (P = 0.006) and operation time (P = 0.071) were increased in EL compared with LL. On postoperative day 5, EL performed worse than LL with regard to temperature (P = 0.021), oral intake (P = 0.006) and recovery of bowel activity (P = 0.054). Anastomotic leakage was diagnosed most often by a rectal contrast study in EL and by CT scan in LL. The median initial hospital stay was 28 days for EL and 10 days for LL (P < 0.001). CONCLUSION: The present study has demonstrated that symptomatic anastomotic leakage can present before and after hospital discharge and raises the question of whether early and late leakage after LAR may be different entities.

Degree of specialisation of the surgeon influences lymph node yield after right-sided hemicolectomy.

AIM: To investigate the degree to which specialisation or case-load of the surgeon is associated with the number of lymph nodes isolated from pathology specimens after right-sided hemicolectomy. METHOD: Data from 6 hospitals with well-defined catchment areas included in the Uppsala/Örebro Regional Oncology Centre Colon Cancer Register 1997-2006 were used to assess 821 patients undergoing right-sided hemicolectomy for stages I-III colon cancer. Factors influencing the lymph node yield were evaluated. RESULTS: A surgeon with colorectal accreditation and a university pathology department were both associated with a significantly higher proportion of patients having 12 or more lymph nodes isolated from surgical specimens after right-sided hemicolectomy in both unadjusted and multivariate analyses. Emergency surgery did not affect the lymph node yield. CONCLUSION: The degree of specialisation of the surgeon influences the number of lymph nodes isolated from specimens obtained during routine right-sided colon cancer surgery.

High tie in anterior resection for rectal cancer confers no increased risk of anastomotic leakage.

BACKGROUND: It is controversial whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage, especially in the elderly and unfit. This population-based study was carried out to evaluate the independent association between a high arterial ligation and anastomotic leakage in anterior resection for rectal cancer. METHODS: All patients who had anterior resection for rectal cancer from 2007 to 2009 inclusive were identified in the Swedish Colorectal Cancer Registry. The association between high tie and anastomotic leakage was evaluated in a logistic regression model, with adjustment for confounders. Stratification was performed for co-morbidity as judged by the American Society of Anesthesiologists (ASA) classification. RESULTS: Symptomatic anastomotic leakage occurred in 81 (9·9 per cent) of 818 patients with a high tie and 108 (9·8 per cent) of 1101 without. Overall, the use of a high tie was not associated with a higher risk of anastomotic leakage (odds ratio (OR) 1·00, 95 per cent confidence interval 0·72 to 1·39). There was no increased risk in patients classifed as ASA grade I or II (OR 0·97, 0·69 to 1·35), or in those graded ASA III or IV (OR 1·26, 0·58 to 2·75). CONCLUSION: In the present population-based setting, use of a high tie was not associated with an increased rate of symptomatic anastomotic leakage.

Surgeon and hospital-related risk factors in colorectal cancer surgery.

AIM: The aim of this study was to identify surgeon and hospital-related factors in a well-defined population-based cohort; the results of this study could possibly be used to improve outcome in colorectal cancer. METHOD: Data from the colonic (1997-2006) and rectal (1995-2006) cancer registers of the Uppsala/Örebro Regional Oncology Centre were used to assess 1697 patients with rectal and 2692 with colonic cancer. Putative risk factors and their impact on long-term survival were evaluated using the Cox proportional hazard model. RESULTS: The degree of specialization of the operating surgeon had no significant effect on long-term survival. When comparing the surgeons with the highest degree of specialization, noncolorectal surgeons demonstrated a slightly lower long-term survival for rectal cancer stage I and II (HR, 2.03; 95% CI, 1.05-3.92). Surgeons with a high case-load were not associated with better survival in any analysis model. Regional hospitals had a lower survival rate for rectal cancer stage III surgery (HR, 1.47; 95% CI, 1.08-2.00). CONCLUSION: Degree of specialization, surgeon case-load and hospital category could not be identified as important factors when determining outcome in colorectal cancer surgery in this study.

Indices of stress in three-spined sticklebacks Gasterosteus aculeatus in relation to extreme weather events and exposure to wastewater effluent.

Whole-body concentrations of cortisol and glucose were measured in three-spined sticklebacks Gasterosteus aculeatus from two rivers (Rivers Ray and Ock) in southern England during a 30 month period in order to assess effects on the stress axis of (1) remediation of a wastewater treatment works (WWTW) effluent (River Ray) and (2) episodic changes in flow rate arising from periods of high rainfall (Rivers Ray and Ock). The postcapture concentrations of cortisol and glucose in fish from both rivers did not exhibit a seasonal periodicity but did show significant between-sample, between-site and between-river variation, superimposed upon a consistent downward trend for each analyte during the monitoring period. Corticosteroid and glucose concentrations following capture were inversely linked with a progressive increase in condition of the fish during this period. Site-dependent trends possibly related to exposure to the WWTW effluent were detected for both analytes in fish from the River Ray. For fish in the River Ray, a significant proportion of variation in both corticosteroid and glucose concentrations, additional to the downward trend with time, was accounted for by temporal proximity of the sample to exceptional flow events arising from episodes of high rainfall and high turbidity. This relationship was not statistically significant for fish from the River Ock. These data suggest that the responsiveness of the stress axis in free-living G. aculeatus may be altered by exposure to WWTW effluent and by exposure to physical changes in the aquatic environment such as those arising from extreme weather events. The magnitude of these effects may be increased by exposure to both stressors concurrently.