Identification of diverticular disease in Swedish healthcare registers: a validation study.

PURPOSE: The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied. METHODS: From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated. RESULTS: The overall PPV for all diagnoses and both years was 95% (95% CI: 93-96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95-99) than in the year 2002, 91% (95% CI: (87-94) which may be due to the increasing use of computed tomography (CT). CONCLUSION: The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD.

The impact of hospital volume on survival in patients with locally advanced colonic cancer.

BACKGROUND: High hospital volume has been shown associated with improved survival in patients with several cancers. The aim of this nationwide cohort study was to investigate whether hospital volume affects survival in patients with locally advanced colonic cancer. METHODS: All patients with non-metastatic locally advanced colonic cancer diagnosed between 2007 and 2017 in Sweden were included. Tertiles of annual hospital volume of locally advanced colonic cancer were analysed and 5-year overall and colonic cancer-specific survival were calculated with the Kaplan-Meier method. HRs comparing all-cause and colonic cancer-specific mortality rates were estimated using Cox models adjusted for potential confounders (age, sex, year of diagnosis, co-morbidity, elective/emergency resection, and university hospital) and mediators (preoperative multidisciplinary team assessment, neoadjuvant chemotherapy, radical resection, and surgical experience). RESULTS: A total of 5241 patients were included with a mean follow-up of 2.7-2.8 years for low- and high-volume hospitals. The number of patients older than 79 years were 569 (32.3 per cent), 495 (29.9 per cent), and 482 (26.4 per cent) for low-, medium- and high-volume hospitals respectively. The 3-year overall survival was 68 per cent, 60 per cent and 58 per cent for high-, medium- and low-volume hospitals, respectively (P < 0.001 from log rank test). High volume hospitals were associated with reduced all-cause and colon cancer-specific mortality after adjustments for potential confounders (HR 0.76, 95 per cent CI 0.62 to 0.93 and HR 0.73, 95 per cent CI 0.59 to 0.91, respectively). The effect remained after inclusion of potential mediators. CONCLUSIONS: High hospital volume is associated with reduced mortality in patients with locally advanced colonic cancer.

Emergency resection or diverting stoma followed by elective resection in patients with colonic obstruction due to locally advanced cancer: a national cohort study.

AIM: The aim was to assess long-term prognosis after emergency resection versus primary diverting stoma followed by elective tumour resection. METHOD: A national-register-based cohort study with retrospective analysis of prospectively collected data was performed. All Swedish patients with non-metastatic obstructive locally advanced colon cancer treated with emergency resection or diverting stoma, followed by an elective resection, between 2007 and 2017 were included. The Kaplan-Meier method and Cox proportional hazards model were used to compare all-cause mortality between patients with emergency resection and elective right- and left-sided resection. The multivariable model was adjusted for year of diagnosis, age at diagnosis, sex, Charlson Comorbidity Index, American Society of Anesthesiologists class, tumour location and pN stage. RESULTS: In all, 751 patients with a tumour in the right colon and 700 patients with a tumour in the left colon were included. Emergency resection was more common in patients with right-sided colon tumours (681/751) than in patients with left-sided colon tumours (483/700). The 5-year overall survival in patients with right-sided tumours was 25% after emergency resection and 46% after diverting stoma followed by elective resection (log-rank test P = 0.001). The corresponding numbers for patients with left-sided colon tumours were 40% and 64% (P < 0.001). Emergency resection was independently associated with increased all-cause mortality in patients with left-sided tumour (hazard ratio 1.63, 95% CI 1.21-2.19) but not in patients with right-sided tumour (hazard ratio 1.21, 95% CI 0.80-1.81). CONCLUSION: Diverting stoma followed by elective resection is associated with improved survival compared with emergency resection in patients with left-sided colonic obstruction due to locally advanced tumours.

Morphological predictors for lymph node metastases on computed tomography in colon cancer.

INTRODUCTION/BACKGROUND: The aim of the study was to assess morphological predictors for lymph node metastases (Stage III disease) in colon cancer on computed tomography. METHODS AND MATERIALS: Ninety-four patients with histology-proven colon cancer (adenocarcinoma) who underwent elective primary curative resection between the years 2012 and 2014 were included. Contrast-enhanced CT examinations were independently reviewed by two blinded observers regarding tumor location, depth of tumor invasion, and presence of lymph node metastases. Ocular presence of internal heterogeneity and presence of irregular outer border were used as morphological criteria for lymph node involvement. Protocol-based histopathology after curative surgery served as reference standard. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy for each morphological criterion for prediction of stage III disease were calculated. Inter-observer agreement was compared using Kappa statistics. RESULTS: According to histopathology, 59 patients were staged as I-II disease and 35 patients were staged as stage III disease. The presence of internal heterogeneity in a lymph node on CT resulted in moderate sensitivity (66-77%) but high specificity (95-95%) for prediction of Stage III disease by both observers. The presence of irregular outer border also resulted in poor sensitivity (49-54%) but high specificity (97-97%). The combination of either internal heterogeneity and/or irregular outer border per patient resulted in a moderate sensitivity (67-77%) and high specificity (95-95%), PPV (89-96%), and NPV (84-88%). Inter-observer agreement (Cohens Kappa) was 0.72. Consensus reading for the combined criteria resulted in sensitivity and specificity of 69% and 100%, respectively. CONCLUSION: Using morphological criteria for lymph node metastases on CT examination in patients with colon cancer results in high specificity but moderate sensitivity in predicting stage III disease.

High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease.

BACKGROUNDS AND AIMS: High intake of dietary fibres has been associated with a reduced risk of DD. However, reports on which type of dietary fibre intake that is most beneficial have been conflicting. The aim of this study was to investigate the association between different dietary fibres and hospitalisation due to diverticular disease (DD) of the colon. METHODS: This was a major cohort study. The Swedish Mammography Cohort and the Cohort of Swedish Men were linked to the Swedish Inpatient Register and the Causes of Death Register. Data on the intake of dietary fibre were collected through questionnaires. The effect of intake (in quartiles) of different types of dietary fibre on the incidence of hospitalisation due to DD was investigated using multivariable Cox regression. Estimates were adjusted according to age, BMI, physical activity, co-morbidity, intake of corticosteroids, smoking, alcohol intake and education level. RESULTS: Women with intake of fruit and vegetable fibres in the highest quartile (median 12.6 g/day) had a 30% decreased risk of hospitalisation compared to those with the lowest intake (4.1 g/day). Men within the highest quartile (10.3 g/day) had a 32% decreased risk compared to those with a low intake (2.9 g/day). High intake of fibres from cereals did not affect the risk. CONCLUSION: A high intake of fruits and vegetables may reduce the risk of hospitalisation due to DD. Intake of cereals did not influence the risk.

Management and Outcome After Multivisceral Resections in Patients with Locally Advanced Primary Colon Cancer.

BACKGROUND: Locally advanced colon cancer invading surrounding organs or structures is challenging to surgeons and oncologists. Multivisceral resections with tumor removal en bloc with invaded tissues provide the best chance for cure. OBJECTIVE: We aimed to assess the management and outcomes after multivisceral resections in patients with clinically infiltrative, locally advanced primary colon cancer. DESIGN: This is a descriptive retrospective cohort study. SETTINGS: A total of 121 consecutive patients with locally advanced primary colon cancer underwent en bloc multivisceral resections at a tertiary referral unit for colorectal cancer between 2007 and 2014. MAIN OUTCOME MEASURES: Patient demographics, surgical details, histopathological findings, and outcomes were analyzed through registry data and reviews of patient files. RESULTS: An R0 resection was achieved in 112 patients (92.6%), and an R1 resection was achieved in 9 patients (7.4%). Actual tumor cell infiltration in resected tissues was found in 77 patients (63.6%), and inflammation was found in 44 patients (36.4%). The estimated 5-year overall survival was 60.8% and 86.9%. Survival was significantly better after R0 than after R1 resections. After a median follow-up of 28 months, recurrent disease was diagnosed in 25 patients (20.7%). Female sex, low tumor stage, and adjuvant chemotherapy, but not tumor infiltration per se, were independently associated with better overall survival in a multivariate analysis. LIMITATIONS: The main limitations of the study are the retrospective design and the fact that all patients were operated on at 1 institution by a small number of surgeons. CONCLUSIONS: Patients with locally advanced colon cancer can be cured with an R0 resection. All involved surrounding tissues should be removed en bloc with the primary tumor. See Video Abstract at http://links.lww.com/DCR/A548.

Management and prognosis of locally recurrent rectal cancer - A national population-based study.

BACKGROUND: The rate of local recurrence of rectal cancer (LRRC) has decreased but the condition remains a therapeutic challenge. This study aimed to examine treatment and prognosis in patients with LRRC in Sweden. Special focus was directed towards potential differences between geographical regions and time periods. METHOD: All patients with LRRC as first event, following primary surgery for rectal cancer performed during the period 1995-2002, were included in this national population-based cohort-study. Data were collected from the Swedish Colorectal Cancer Registry and from medical records. The cohort was divided into three time periods, based on the date of diagnosis of the LRRC. RESULTS: In total, 426 patients fulfilled the inclusion criteria. Treatment with curative intent was performed in 149 patients (35%), including 121 patients who had a surgical resection of the LRRC. R0-resection was achieved in 64 patients (53%). Patients with a non-centrally located tumour were more likely to have positive resection margins (R1/R2) (OR 5.02, 95% CI:2.25-11.21). Five-year survival for patients resected with curative intent was 43% after R0-resection and 14% after R1-resection. There were no significant differences in treatment intention or R0-resection rate between time periods or regions. The risk of any failure was significantly higher in R1-resected patients compared with R0-resected patients (HR 2.04, 95% CI:1.22-3.40). CONCLUSION: A complete resection of the LRRC is essential for potentially curative treatment. Time period and region had no influence on either margin status or prognosis.

The value of preoperative computed tomography combined with ultrasound in the investigation of small indeterminate liver lesions in patients with colorectal cancer.

Background Computed tomography (CT) is used routinely for the preoperative detection of colorectal cancer (CRC) metastases. When small indeterminate focal liver lesions are detected that are too small to characterize (TSTC) on CT, additional imaging is usually needed, resulting in a potential delay in obtaining a complete diagnostic work-up. Purpose To determine the diagnostic accuracy of ultrasound (US) of the liver performed in direct conjunction to CT in the preoperative investigation among patients with newly diagnosed CRC when indeterminate liver lesions were found on CT. Material and Methods Preoperative investigations with CT and consecutive US where CT had shown at least one focal liver lesion in 74 patients diagnosed with CRC between June 2009 and February 2012 were retrospectively reviewed. Either histopathological findings or a combination of imaging and clinical follow-up one to three years after surgery was used as the reference. Results Liver metastases were diagnosed with CT/US in 13 out of 74 patients (17.6%). In one patient, a liver cyst was preoperatively regarded as liver metastasis by a combined CT/US. The sensitivity and specificity for the CT with consecutive US procedure was 100% (13/13) and 98.4% (60/61). Conclusion US performed in conjunction with CT in patients with indeterminate focal liver lesions on CT is an accurate work-up for detection of liver metastases in patients with newly diagnosed CRC. Although our results are promising, they cannot be considered safely generalizable to all hospitals.

Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial.

BACKGROUND: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. METHODS: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 × 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 × 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1·7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. FINDINGS: Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33·4 months (range 18·2-62·2) in the short-course radiotherapy group and 19·3 months (8·5-39·5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33·3 months (range 17·8-114·3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1·44 [95% CI 0·41-5·11]; long-course radiotherapy with delay 2·24 [0·71-7·10]; p=0·48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (<1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0·59 [95% CI 0·36-0·97], long-course radiotherapy with delay 0·63 [0·38-1·04], p=0·075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0·61 [95% CI 0·45-0·83] p=0·001). INTERPRETATION: Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery. FUNDING: Swedish Research Council, Swedish Cancer Society, Stockholm Cancer Society, and the Regional Agreement on Medical Training and Clinical Research in Stockholm.

Emergency management with resection versus proximal stoma or stent treatment and planned resection in malignant left-sided colon obstruction.

BACKGROUND: Emergency surgery for colon cancer, as a result of obstruction, has been vitiated by a high frequency of complications and poor survival. The concept of "bridge to surgery" includes either placement of self-expanding metallic stents (SEMS) or diverting stoma of an obstructing tumour and subsequent planned resection. The aim of this study was to compare acute resection with stoma or stent and later resection regarding surgical and oncological outcomes and total hospital stay. METHODS: This is a retrospective cohort study. All 2424 patients diagnosed with colorectal cancer during 1997-2013 were reviewed. All whom underwent acute surgery with curative intention for left-sided malignant obstruction were included in the study. RESULTS: One hundred patients fulfilled the inclusion criteria. Among them, 57 patients were treated with acute resection and 43 with planned resection after either acute diverting colostomy (n = 23) or stent placement (n = 20). The number of harvested lymph nodes in the resected specimen was higher in the planned resection group compared with acute resection group (21 vs. 8.7; p = 0.001). Fewer patients were treated with adjuvant chemotherapy in the acute resection group than in the stoma group (14 % (8/57 patients) vs. 43 %, (10/23 patients; p = 0.024)). Patients operated with acute resection had a higher 30-day mortality rate and were more frequently left with a permanent stoma. CONCLUSIONS: Decompression of emergency obstructive left colon cancer with stent or stoma and subsequent curative resection appears safer and results in a higher yield of lymph node harvest, and fewer patients are left with a permanent stoma.

Transanal submucosal polyacrylamide gel injection treatment of anal incontinence: a randomized controlled trial.

INTRODUCTION: The efficacious and safe use of transurethral injections of polyacrylamide hydrogel (Bulkamid(®)) in women with stress urinary incontinence suggests that it may be suitable also for treatment of anal incontinence. We aimed to determine the effectiveness and safety of polyacrylamide hydrogel when used as a transanal submucosal bulking agent in women with anal incontinence. MATERIALS AND METHODS: Thirty women with a diagnosis of anal incontinence and a Cleveland Clinic Incontinence Score (CCIS) >10 were randomized to three different techniques of transanal submucosal injections using polyacrylamide hydrogel. Follow up was performed at 2, 6 and 12 months using CCIS and the Fecal Incontinence Quality of Life scale (FIQL). RESULTS: In all, 29 of the 30 women completed the follow up. Approximately half of the women requested a re-injection at the 6-month visit. The overall CCIS improved significantly from baseline (14.7. SD 2.5) to 1 year (12.4. SD 3.1) (p = 0.003). There was a significant improvement with regard to the occurrence of loose fecal incontinence (p = 0.014) but not for solid fecal incontinence (p = 0.28). At 1 year the FIQL domains of coping-behavior, depression, and embarrassment showed significant improvements (p = 0.012, p = 0.007 and p = 0.007, respectively). We recorded no adverse events related either to the injection technique or the biomaterial. There were no significant differences between the treatment groups in either CCIS or FIQL scores. CONCLUSION: Transanal submucosal injection of polyacrylamide hydrogel resulted in a modest although significant overall improvement in anal incontinence symptom scores with corresponding improvements in several domains of quality of life, regardless of injection volume.

A population-based case-control study on statin exposure and risk of acute diverticular disease.

OBJECTIVE: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. MATERIAL AND METHODS: A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed ≤ 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. RESULTS: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). CONCLUSIONS: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.

Cancer and diverticulitis of the sigmoid colon. Differentiation with computed tomography versus magnetic resonance imaging: preliminary experiences.

BACKGROUND: Both colon cancer and diverticular disease are common in the Western world. A challenge when patients present with clinical findings is that both diseases can present with symptoms that may mimic the other. PURPOSE: To determine whether magnetic resonance imaging (MRI) could be helpful to differentiate between diverticulitis and cancer of the sigmoid colon compared to the differentiation offered by evaluation of multidetector computed tomography (CT) in a clinical situation. MATERIAL AND METHODS: Thirty patients were consecutively included. Fifteen patients were under work-up for a recently diagnosed sigmoid cancer and 15 patients had recently been treated in hospital due to first-time acute sigmoid diverticulitis. All patients underwent CT, T2- weighted MRI and diffusion-weighted MRI. Anonymized examinations were retrospectively presented in random order to one experienced radiologist. RESULTS: With contrast-enhanced CT, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 66.7% (10/15) and 93.3% (14/15), respectively. Using T2-weighted and diffusion-weighted MR images, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 100% (14/14) and 100% (14/14), respectively. CONCLUSION: MRI provides information that may contribute to improve the differentiation between sigmoid cancer and diverticulitis that is offered by CT. These encouraging results need to be confirmed in a larger study.

Obesity, physical inactivity, and colonic diverticular disease requiring hospitalization in women: a prospective cohort study.

OBJECTIVES: Lifestyle factors other than dietary fiber intake and risk for colonic diverticular disease have only been examined in few studies. The objective of this study was to investigate the association between obesity and physical inactivity and diverticular disease in a population-based cohort of women. METHODS: This was a prospective population-based cohort study. In all, 36,592 women, born 1914-1948, in the Swedish Mammography Cohort were followed 1997-2009. Body mass index (BMI; kg/m(2)), physical activity, diet, smoking, and other lifestyle factors were collected at baseline through questionnaires. Cases of diverticular disease were identified from the Swedish Patient and Death Registers. Relative risks (RRs) of diverticular disease requiring hospitalization (or being the cause of death) according to BMI and physical activity were estimated using Cox proportional hazards models. The multivariable models were adjusted for age; intake of dietary fiber; diabetes; hypertension; use of acetylsalicylate acid, non-steroid anti-inflammatory drug, or steroid medication; alcohol consumption; smoking; and educational level. RESULTS: During 12 years, 626 cases of incident diverticular disease requiring hospitalization were found. Two women were registered in the National Death Register only. In multivariable analysis, women with BMI 25-29.99 had 29% increased risk (RR=1.29; 95% confidence interval (CI): 1.08, 1.54) and obese women (BMI≥30) had 33% (1.33; 95% CI: 1.03-1.72) increased risk of diverticular disease compared to women with BMI 20-24.99. Exercise ≤30 min/day increased the risk for disease with 42% (1.42; 95% CI: 1.18-1.69) compared with exercise >30 min/day in multivariable analysis. Ninety-eight subjects were hospitalized due to complications; perforation or abscess. Women with BMI≥30 had a twofold (RR=2.00; 95% CI: 1.08-3.73; P=0.028) increased risk for complicated disease. CONCLUSIONS: Overweight, obesity, and physical inactivity among women increase diverticular disease requiring hospitalization.

Common variants in human CRC genes as low-risk alleles.

The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.

Lack of an association between the TGFBR1*6A variant and colorectal cancer risk.

PURPOSE: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies. EXPERIMENTAL DESIGN: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted. RESULTS: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A. CONCLUSION: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.

Conservative treatment of acute colonic diverticulitis: are antibiotics always mandatory?

OBJECTIVE: Most patients admitted for acute colonic diverticulitis (AD) are managed conservatively and receive antibiotics, although it is uncertain whether all patients with AD benefit from this treatment. The aim of this study was to evaluate the influence of antibiotic treatment on outcome in the conservative management of patients with mild AD. MATERIAL AND METHODS: A retrospective audit of 311 patients (64% F, mean age 60 years) hospitalized for AD was carried out. All patients were initially treated conservatively with observation and restriction of oral intake. Patients receiving antibiotics (n=118) were compared with patients treated with observation and restriction of oral intake only (n=193). Mean follow-up time (FU) was 30 months. RESULTS: Inflammation in patients treated with antibiotics was more pronounced (laboratory parameters (C-reactive protein, white blood cell count) were higher (p<0.01), fever was more common (p<0.01) and CT grading of inflammation was classified as severe in a higher proportion (p<0.01)) compared with patients treated without antibiotics. When initially treated with antibiotics, 3 patients (3%) failed to respond to treatment and had to undergo surgery. There were 7 (4%) failures in patients initially treated without antibiotics, and antibiotics were then added. During FU, 29% of patients treated with antibiotics had further events (recurrent AD and/or subsequent surgery) compared with 28% (NS) among those treated without antibiotics. In a multivariate analysis, the risk of a further event was not influenced by antibiotic treatment (OR 1.03, CI 95% 0.61-1.74). CONCLUSIONS: Our results indicate that antibiotics are not mandatory in mild AD. Treatment without antibiotics appears to be safe and seems not to change the rate of further events. These results warrant further randomized prospective studies.

The CHEK2 1100delC variant in Swedish colorectal cancer.

BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.

Functional and anatomic outcome after transvaginal rectocele repair using collagen mesh: a prospective study.

PURPOSE: This study was designed to evaluate rectocele repair using collagen mesh. METHODS: 32 female patients underwent surgical repair using collagen mesh. Outcome was assessed in 29 patients and preoperative assessment included standardized questionnaire, clinical examination, and defecography. At the six-month follow-up, patients answered a standardized questionnaire and underwent clinical examination. At the 12-month follow-up, patients answered a standardized questionnaire, underwent clinical examination, and defecography. RESULTS: Preoperatively, 26 patients had a Stage II and 3 patients had a Stage III rectocele. At the 6-month follow-up, five patients had rectocele > or = Stage II (P < 0.001) and at the 12-month follow-up, seven patients had rectocele > or = Stage II (P < 0.001) at clinical examination. At the preoperative defecography, all patients presented a rectocele. At the 12-month defecography, 14 patients had no rectocele (P < 0.001) and 15 had a rectocele. At the six-month follow-up, there was a significant decrease in rectal emptying difficulties, need of digital support of the posterior vaginal wall at defecation, and defecation frequency. At the 12-month follow-up, symptom improvement remained, but was less pronounced. CONCLUSIONS: Rectocele repair using collagen mesh improved anatomic support, but there is a substantial risk for recurrence with unsatisfactory anatomic and functional outcome one year after surgery. Rectocele repair using mesh was not associated with an increased risk of dyspareunia. Rectocele repair using biomaterial mesh reinforcement needs further evaluation before adopted into clinical practice.