Martin Rutegård

The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk

Background: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer. Methods: A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1:1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status. Results: Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82–1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.57–1.22; OR for rectal cancer, 1.90; 95% CI, 1.14–3.19; Pheterogeneity = 0.14). Conclusions: In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer. Impact: Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 24(12); 1855–63. ©2015 AACR.

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

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.

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

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.

Anastomotic leakage in rectal cancer surgery: The role of blood perfusion

Anastomotic leakage after anterior resection for rectal cancer remains a common and often devastating complication. Preoperative risk factors for anastomotic leakage have been studied extensively and are used for patient selection, especially whether to perform a diverting stoma or not. From the current literature, data suggest that perfusion in the rectal stump rather than in the colonic limb may be more important for the integrity of the colorectal anastomosis. Moreover, available research suggests that the mid and upper rectum is considerably more vascularized than the lower part, in which the posterior compartment seems most vulnerable. These data fit neatly with the observation that anastomotic leaks are far more frequent in patients undergoing total compared to partial mesorectal excision, and also that most leaks occur dorsally. Clinical judgment has been shown to ineffectively assess anastomotic viability, while promising methods to measure blood perfusion are evolving. Much interest has recently been turned to near-infrared light technology, enhanced with fluorescent agents, which enables intraoperative perfusion assessment. Preliminary data are promising, but large-scale controlled trials are lacking. With maturation of such technology, perfusion measurements may in the future inform the surgeon whether anastomoses are at risk. In high colorectal anastomoses, anastomotic revision might be feasible, while a diverting stoma could be fashioned selectively instead of routinely for low anastomoses.

Time Shift in Early Postoperative Mortality After Oesophagectomy for Cancer

BackgroundPostoperative mortality is traditionally defined as death within 30xa0days of surgery. We hypothesised that the declining 30-day mortality after oesophageal cancer resection is, at least partly, explained by a shift towards increased 90-day mortality.MethodsThis population-based cohort study included 95xa0% of all patients who underwent surgical resection for oesophageal cancer in Sweden in 1987–2010. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) with 95xa0% confidence intervals (CIs) of 30-day and 31–90xa0days postoperative mortality in three calendar periods (1987–1994, 1995–2002, and 2003–2010). Adjustments were made for age, sex, comorbidity, tumour stage, tumour histology, surgical radicality, neoadjuvant therapy, and hospital volume of oesophagectomy.ResultsAmong 1,822 patients, the 30-day postoperative mortality decreased from 9.3xa0% in 1987–1994 to 3.0xa0% in 2003–2010, while the corresponding 31–90xa0days mortality decreased from 8.4 to 4.6xa0%. The adjusted HR of 30-day mortality in the earliest period was markedly increased compared to the latest period (HR 3.26; 95xa0% CI 1.96–5.45), whereas the corresponding HR of 31–90 days mortality was weaker (HR 2.16; 95xa0% CI 1.34–3.46). Among patients who died within 90xa0days of surgery, the proportion of 31–90xa0days mortality increased from 47 to 61xa0% during the study period.ConclusionsThis population-based study indicates a shift of postoperative mortality following surgery for oesophageal cancer from 30xa0days to 31–90xa0days with more recent calendar periods. Reporting of 90-day mortality rates might replace 30-day mortality rates in assessing early postoperative mortality in oesophageal cancer patients.Postoperative mortality is traditionally defined as death within 30xa0days of surgery. We hypothesised that the declining 30-day mortality after oesophageal cancer resection is, at least partly, explained by a shift towards increased 90-day mortality. This population-based cohort study included 95xa0% of all patients who underwent surgical resection for oesophageal cancer in Sweden in 1987–2010. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) with 95xa0% confidence intervals (CIs) of 30-day and 31–90xa0days postoperative mortality in three calendar periods (1987–1994, 1995–2002, and 2003–2010). Adjustments were made for age, sex, comorbidity, tumour stage, tumour histology, surgical radicality, neoadjuvant therapy, and hospital volume of oesophagectomy. Among 1,822 patients, the 30-day postoperative mortality decreased from 9.3xa0% in 1987–1994 to 3.0xa0% in 2003–2010, while the corresponding 31–90xa0days mortality decreased from 8.4 to 4.6xa0%. The adjusted HR of 30-day mortality in the earliest period was markedly increased compared to the latest period (HR 3.26; 95xa0% CI 1.96–5.45), whereas the corresponding HR of 31–90 days mortality was weaker (HR 2.16; 95xa0% CI 1.34–3.46). Among patients who died within 90xa0days of surgery, the proportion of 31–90xa0days mortality increased from 47 to 61xa0% during the study period. This population-based study indicates a shift of postoperative mortality following surgery for oesophageal cancer from 30xa0days to 31–90xa0days with more recent calendar periods. Reporting of 90-day mortality rates might replace 30-day mortality rates in assessing early postoperative mortality in oesophageal cancer patients.

Efficiency of Colorectal Cancer Surveillance in Patients with Ulcerative Colitis: 38 Years’ Experience in a Patient Cohort from a Defined Population Area

Background and Aims: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program. Material and Methods: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10u2009years. Results: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10u2009years, 2.0% at 20u2009years, 3.0% at 30u2009years, and 9.4% at 40u2009years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42–5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients. Conclusion: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.

Substantial underreporting of anastomotic leakage after anterior resection for rectal cancer in the Swedish Colorectal Cancer Registry

Abstract Background: The causes and effects of anastomotic leakage after anterior resection are difficult to study in small samples and have thus been evaluated using large population-based national registries. To assess the accuracy of such research, registries should be validated continuously. Material and methods: Patients who underwent anterior resection for rectal cancer during 2007–2013 in 15 different hospitals in three healthcare regions in Sweden were included in the study. Registry data and information from patient records were retrieved. Registered anastomotic leakage within 30 postoperative days was evaluated, using all available registry data and using only the main variable anastomotic insufficiency. With the consensus definition of anastomotic leakage developed by the International Study Group on Rectal Cancer as reference, validity measures were calculated. Results: Some 1507 patients were included in the study. The negative and positive predictive values for registered anastomotic leakage were 96 and 88%, respectively, while the κ-value amounted to 0.76. The false-negative rate was 29%, whereas the false-positive rate reached 1.3% (the vast majority consisting of actual leaks, but occurring after postoperative day 30). Using the main variable anastomotic insufficiency only, the false-negative rate rose to 41%. Conclusions: There is considerable underreporting of anastomotic leakage after anterior resection for rectal cancer in the Swedish Colorectal Cancer Registry. It is probable that this causes an underestimation of the true effects of leakage on patient outcomes, and further quality control is needed.

Anterior Resection for Rectal Cancer and Visceral Blood Flow: An Explorative Study

Background and Aims: Impaired blood perfusion may be implicated in anastomotic leakage after anterior resection for rectal cancer. We investigated whether high ligation of the inferior mesenteric artery or total mesorectal excision compromises visceral blood flow in the colonic limb and the rectal stump, respectively. Material and Methods: A prospective cohort study was conducted in a university hospital setting. We used Laser Doppler flowmetry to evaluate the impact of level of tie on colonic limb perfusion and the extent of the mesorectal excision on the rectal blood flow. In the rectum, different quadrants were also assessed. The Mann–Whitney U test was used to compare mean blood flow ratios between groups. Results: Some 23 patients were recruited in a convenience sample during a period in 2012–2013. The mean blood flow ratio was not decreased after high tie compared to low tie surgery (1.71 vs 1.19; pu2009=u20090.28). Total mesorectal excision reduced the mean blood flow ratio in the rectum, as compared with partial mesorectal excision (0.76 vs 1.28; pu2009=u20090.14). This was especially pronounced in the posterior aspect of the rectum (0.66 vs 1.68; pu2009=u20090.02). Conclusion: High tie ligation did not seem to decrease colonic limb perfusion, while total mesorectal excision may decrease rectal blood flow. The posterior quadrant of the rectum might be particularly vulnerable to the dissection involved in total mesorectal excision.

Current use of diverting stoma in anterior resection for cancer: population-based cohort study of total and partial mesorectal excision

PurposeA diverting stoma is commonly used to reduce the risk of anastomotic leakage when performing total mesorectal excision (TME) in anterior resection for rectal cancer. The purpose of this study was to evaluate the impact of fecal diversion in relation to partial mesorectal excision (PME).MethodsA retrospective analysis was undertaken on a national cohort, originally created to study the impact of central arterial ligation on patients with increased cardiovascular risk. Some 741 patients operated with anterior resection for rectal cancer during the years 2007 through 2010 were followed up for 53xa0months. Multivariate logistic regression was used to evaluate the impact of diverting stoma on the risk of anastomotic leakage and permanent stoma, expressed as odds ratios (ORs) and 95xa0% confidence intervals (CIs).ResultsThe risk of anastomotic leakage was increased in TME surgery when not using a diverting stoma (OR 5.1; 95xa0% CI 2.2–11.6), while the corresponding risk increase in PME patients was modest (OR 1.8; 95xa0% CI 0.8–4.0). At study completion or death, 26 and 13xa0% of TME and PME patients, respectively, had a permanent stoma. A diverting stoma was a statistically significant risk factor for a permanent stoma in PME patients (OR 4.7; 95xa0% CI 2.5–9.0), while less important in TME patients (OR 1.8; 95xa0% CI 0.6–5.5).ConclusionThe benefit of a diverting stoma concerning anastomotic leakage in this patient group seems doubtful. Moreover, the diverting stoma itself may contribute to the high rate of permanent stomas.

A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log2‐transformed multivariable models, equol (odds ratio [OR] per log2‐value, 0.86, 95% confidence interval [95% CI]u2009=u20090.79–0.93; qvalueu2009=u20090.01) and homovanillic acid (OR per log2‐value, 1.46, 95% CIu2009=u20091.16–1.84; qvalueu2009=u20090.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (ORu2009=u20090.61, 95% CIu2009=u20090.41–0.91, ptrendu2009=u20090.003), while homovanillic acid concentrations were positively associated with colon cancer development (ORu2009=u20091.72, 95% CIu2009=u20091.17–2.53, ptrendu2009<u20090.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.