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Colorectal cancer (CRC) is a high incidence cancer and major cause of cancer mortality. Though disease-causing tumor suppressors for major syndromes are well characterized, about 10% of CRC is familial but without mutations in known tumor suppressors. We exhaustively screened 100 polyposis families for APC germline mutations and identified 13, which are APC mutation-negative, microsatellite-stable (MSS), and with undetectable mutation in known tumor suppressors. Whole exome sequencing in three probands uncovered two with germline frameshift NR0B2 mutations, c.293_301delTTGGGTTGGinsAC and c.227delT. Sanger Sequencing identified a third proband with NR0B2 c.157_166delCATCGCACCT frameshift mutation. All three mutations deleted the C-terminus activation/repression domain of NR0B2, thus are loss-of-function mutations. Real-time RT-PCR performed on tumor and matched mucosa of one patient revealed that NR0B2 downstream targets, SMAD3 was derepressed while GLI1 was downregulated in the colonic mucosa compared to healthy controls. Truncated NR0B2 molecule was predicted to have weakened binding with interacting partners SMAD3, GLI1, BCL2, and RXRα, implying perturbation of TGF-β, Hedgehog, anti-apoptotic and nuclear hormone receptor signaling pathways. Immunostaining also revealed nuclear retention of the most severely truncated NR0B2 molecule compared to the wildtype. Microsatellite and sequencing analysis did not detect loss of wildtype allele in probands' tumors. The patient who acquired somatic KRAS mutation progressed rapidly whist the other two patients manifested with late-onset obesity and diabetes. We propose that haploinsufficiency of NR0B2 is associated with a novel CRC syndrome with metabolic phenotypes.

After almost three decades since the first description of colonic stents, the controversies of its safe application continue to impede the readiness of adoption by clinicians for malignant left bowel obstruction. This review seeks to address some of the controversial aspects of stenting and its impact on surgical and oncological outcomes. Medline, Embase, and CNKI were searched for articles employing SEMS for left colonic obstruction. Outcomes analyzed include success rates, complications, and long-term survival. Pooled risk ratio (RR) and 95% confidence interval (CI) were estimated. 36 studies were included with 2002 patients across seven randomized controlled trials and 29 observational studies. High technical (92%) and clinical (82%) success rates, and low rates of complications, including perforation (5%), were found. Those with > 8% perforation rates had poorer technical success rates than those with ≤ 8%, but there were no significant differences in 90-day in-hospital mortality and three and 5-year overall and disease-free survival. A significant increase was found in technical (RR = 1.094; CI, 1.041–1.149; p

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1–4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7–10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein–Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39− CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells. Human lung and colorectal tumours contain a population of tumour-infiltrating lymphocytes that are specific for tumour-unrelated antigens and, unlike tumour-antigen-specific tumour-infiltrating lymphocytes, do not express CD39.

Magnetic resonance defecography (MRD) allows for dynamic visualisation of the pelvic floor compartments when assessing for pelvic floor dysfunction. Additional benefits over traditional techniques are largely unknown. The aim of this study was to compare detection and miss rates of pelvic floor abnormalities with MRD versus clinical examination and traditional fluoroscopic techniques.A systematic review and meta-analysis was conducted in accordance with recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were accessed. Studies were included if they reported detection rates of at least one outcome of interest with MRD versus EITHER clinical examination AND/OR fluoroscopic techniques within the same cohort of patients.Twenty-eight studies were included: 14 studies compared clinical examination to MRD, and 16 compared fluoroscopic techniques to MRD. Detection and miss rates with MRD were not significantly different from clinical examination findings for any outcome except enterocele, where MRD had a higher detection rate (37.16% with MRD vs 25.08%; OR 2.23, 95% CI 1.21-4.11, p = 0.010) and lower miss rates (1.20 vs 37.35%; OR 0.05, 95% CI 0.01-0.20, p = 0.0001) compared to clinical examination. However, compared to fluoroscopy, MRD had a lower detection rate for rectoceles (61.84 vs 73.68%; OR 0.48 95% CI 0.30-0.76, p = 0.002) rectoanal intussusception (37.91 vs 57.14%; OR 0.32, 95% CI 0.16-0.66, p = 0.002) and perineal descent (52.29 vs 74.51%; OR 0.36, 95% CI 0.17-0.74, p = 0.006). Miss rates of MRD were also higher compared to fluoroscopy for rectoceles (15.96 vs 0%; OR 15.74, 95% CI 5.34-46.40, p 0.00001), intussusception (36.11 vs 3.70%; OR 10.52, 95% CI 3.25-34.03, p = 0.0001) and perineal descent (32.11 vs 0.92%; OR 12.30, 95% CI 3.38-44.76, p = 0.0001).MRD has a role in the assessment of pelvic floor dysfunction. However, clinicians need to be mindful of the risk of underdiagnosis and consider the use of additional imaging.

Colorectal carcinoma (CRC) is the third highest incidence cancer and leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. This trend is expected to be exacerbated by an aging population in the developed world. Genetic predisposition plays a greater role in disease progression than disease etiology in sporadic CRC. However, the underlying genetic factors for metastasis are currently unclear. We identified germline single nucleotide polymorphism (SNP) variants contributing to metastasis risk from a case-case (metastasis-positive vs metastasis-negative) genome-wide association study (GWAS) comprising 3,000 sporadic Chinese CRC cases with definitive metastasis status. Metastasis-positive case is defined as one with distal-organ involvement attributable to primary CRC; metastasis-negative case is defined as metastasis-free with 5 years or more follow-up. By interrogating summarized SNP statistics from the case-case GWAS using the Functional Mapping and Annotation (FUMA) software, we identified 5 genomic risk loci and 74 disease-relevant genes based on gene set enrichment analysis and the Molecular Signatures Database. These genes are in various pathways implicated in different metastasis steps, from epithelial-mesenchymal transition (EMT) to implantation at distal organs. They are different from the risk variants identified by case-control GWAS for disease occurrence. We will expression-profile 250 metastasis-positive vs metastasis negative cases from the GWAS panel to validate the bioinformatics analysis by quantitative real-time PCR. We will focus first on the five genes implicated in glycolysis as this is a biochemical fingerprint of malignant cells that represents one of the ‘hallmarks of cancer'. Expression profile of these genes will be validated in a second independent panel. Kaplan Meier survival analysis as function of the median expression value will be performed to assess prognostic value of these genes. The ultimate goal is to improve metastasis risk assessment for secondary prevention to reduce cancer mortality and morbidity for individual patient as well as reducing public health expenditure. Citation Format: PehYean Cheah, Lai Fun Thean, Michelle Wong, Michelle Lo, Emile Tan, Choong Leong Tang. Identifying germline variants for metastatic risk assessment in sporadic colorectal carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2829.

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer mortality in the developed world including Singapore. Despite an aging populace which is now more compliant to having a baseline colonoscopy at age 50 or earlier, interval cancer (cancer that develops in between colonoscopies) is an unmet critical problem. The identification of early driver genes that can serve as biomarkers for CRC risk will aid in clinical management decision to counter cancer-associated mortality and morbidity. We profiled the genome-wide expression of matched mucosa (M), mucosa next to tumor (MT) and tumor (T) samples of a series of 23 patients using Affymetrix Gene Array. M samples are at least 20 cm away from the tumor and MT samples are adjoining the T samples but maintained the normal colonic crypt architecture of M. We discovered that thirty-nine dysregulated genes in MT samples compared to M samples persists until tumor formation. These early driver genes comprise not only tumor suppressors or oncogenes but included metabolic and transporter genes indicating that transformation towards malignancy requires the disruption of many pathways. Majority of these genes were down-regulated; the top three most drastically down-regulated genes include AQP8 (a water transporter), CA7 (a metabolic gene) and PHLPP2 (a tumor suppressor). Further analysis indicates that the three genes were already down-regulated in the normal appearing mucosa of a ‘healthy' individual compared to age-, gender-, ethnicity-matched (AGE-) controls seven years before recto-sigmoid cancer was diagnosed. This suggests that the dysregulation can occur several years before tumor formation and hence could possibly be used as early or pre-cancer biomarker. We have validated the down-regulation of the 3 genes in an independent series of 135 CRC samples from the same center using real-time RT-PCR assays. Correlation of the expression with clinicopathological features of the patients (gender, tumor site, age-group) and molecular subtypes (CMS 1-4) of the tumors will be ascertained to assess whether the signature is applicable to all CRC subtypes. Furthermore, the expression in matched blood samples will also be determined to explore feasibility of using these samples for assessing interval colorectal carcinoma risk. Citation Format: Peh Yean Cheah, Lai Fun Thean, Kuen Kuen Lam, Soo Chin Liew, Michelle Wong, Nicholas Koh, Michelle Lo, Emile Tan, Choong Leong Tang. Developing an early expression-based signature to assess interval colorectal carcinoma risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1134.

Aim Laparoscopic ventral rectopexy (VR) with the use of prosthesis has been advocated for both overt rectal prolapse (ORP) and obstructed defaecation syndrome (ODS). The present study reviews the short-term and functional results of laparoscopic VR. Method A search was performed of MEDLINE, EMBASE, Ovid and Cochrane databases on all studies reporting on VR for ORP, ODS and other anatomical abnormalities of the pelvic floor from 2004 until February 2013. No language restrictions were made. All studies on VR were reviewed systematically. The main outcomes were intra-operative complications, conversion, procedure duration, short-term mortality and morbidity, length of stay, recurrence of ORP, recurrence of anatomical disorder, faecal incontinence and constipation, quality of life (QoL) score and patient satisfaction. Quality assessment and data extraction were performed independently by three observers. Results Twenty-three studies including 1460 patients were eligible for analysis. The conversion rate ranged from 0 to 14.3%. No mortality was reported. The immediate postoperative morbidity rate was 8.6%. Length of stay ranged from 1 to 7 days. A significant improvement in constipation and incontinence symptoms was observed in the postoperative period for both ORP and ODS (chi-square test, P

MR defecography (MRD) is an alternative to conventional defecography (CD) which allows for dynamic visualisation of the pelvic floor. The aim of this study was to assess whether MRI features indicative of pelvic floor dysfunction correlated with patient-reported symptom severity. MR proctograms were matched to a prospectively-maintained functional database. Univariate and multivariate analyses were performed using pre-treatment questionnaire responses to the Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ), Wexner Incontinence Score (WIS), and modified Obstructed Defecation Symptom (ODS) Score. 302 MRI proctograms were performed between January 2012 and April 2015. 170 patients were included. Patients with a rectocele > 2 cm (p = 0.003; OR 5.756) or MRD features suggestive of puborectalis syndrome (p = 0.025; OR 8.602) were more likely to report a higher ODS score on multivariate analysis. Lack of rectal evacuation was negatively associated with an abnormal WIS (p = 0.007; OR 0.228). Age > 50 (p = 0.027, OR 2.204) and a history of pelvic floor surgery (p = 0.042, OR 0.359) were correlated with an abnormal BBUSQ incontinence score. Lack of rectal evacuation (p = 0.027, OR 3.602) was associated with an abnormal BBUSQ constipation score. Age > 50 (p = 0.07, OR 0.156) and the presence of rectoanal intussusception (p = 0.010, OR 0.138) were associated with an abnormal BBUSQ evacuation score. Whilst MRD is a useful tool in aiding multidisciplinary decision making, overall, it is poorly correlated with patient-reported symptom severity, and treatment decisions should not rest solely on results.

e14178 Background: Colorectal Cancer (CRC) is the third most commonly diagnosed cancer in the world. Yet, CRC has been difficult to treat with immunotherapy, as majority (85%) of CRC are Microsatellite stable (MSS), lowly immunogenic and do not respond well. To investigate immuno-cytotoxicity in MSS cancers, we set up an ex vivo co-culture model using patient-derived tumor epithelial cells and autologous tumor-infiltrating lymphocytes (TILs). Aims: To perform phenotypic and functional characterisation of the model, and show we are able to modulate immuno-cytotoxicity. Methods: Fresh tumor, adjacent normal and/or liver metastasis samples were collected and freshly dissociated from 29 colorectal cancer patients undergoing surgery. TILs and tumor epithelial cells were grown in culture. Weekly immunophenotyping of TILs was performed via flow cytometry and data was analysed to identify temporal changes in proportions of cell types. To modulate cytotoxicity, epithelial cell lines were co-cultured with autologous and allogeneic TILs at various effector:target ratios with and without anti-PD1 (Pembrolizumab). Caspase dye was used to detect apoptosis and measure cell death. Results: TILs from most patients were successfully expanded, with a theoretical potential of up to 10,000 times. CD4+ T cells were selectively expanded, while CD8+ T cells decreased in proportion over time. A select group of patients showed an opposite trend. Cell type proportions in metastases mirrored those of the primary tumour while NK cells expanded more in tumour samples than normal samples. Selection proceeded up to 3 weeks then decreased. In the cytotoxicity experiment, we show that cell death is increased at higher effector:target ratios in the presence of autologous TILs. Addition of Pembrolizumab further modulates cytotoxicity in vitro. Conclusions: We have developed and characterised an autologous T cell and epithelial cell co-culture system to evaluate immuno-cytotoxicity in colorectal cancer. This will allow screening of perturbations for improved immuno-cytotoxicity in colorectal cancer.

Aim There is wide disparity in the care of patients with multi-visceral involvement of rectal cancer. The results of treatment of advanced and recurrent colorectal cancer are presented from a centre where a dedicated Multidisciplinary Team (MDT) is central to the management. Method All consecutive MDT referrals between 2010 and 2014 were examined. Analysis was undertaken of the referral pathway, site, selection process, management decision, R0 resection rate, mortality / morbidity / Clavien-Dindo (CD) classification of morbidity, length of stay (LOS), and improvement of quality of life. Results There were 954 referrals. These included locally advanced primary rectal cancer (LAPRC b-TME) [39.0%], rectal recurrence (RR) [22.0%], locally advanced primary colon cancer (LAPCC T3c/d-T4) [21.1%], colon cancer recurrence (CR) 12.4%, locally advanced primary anal cancer (LAPAC-failure of CRT/ T3c/d-T4) [3.0%] and anal cancer recurrence (AR) [2.2%]. Among these patients 271 operations were performed, 212 primary and 59 for recurrence. These included 16 sacrectomies, 134 total pelvic exenterations) and 121 other multi-visceral exenterative procedures. An R0 resection (no microscopic margin involvement) was achieved in 94.4% and R1 (microscopic margin involvement) in 5.1%. In LAPRC b-TME the R0 rate was 96.1% and for RR it was 79%. The length of stay (LOS) varied from 13.3-19.9 days. RR operations had the highest morbidity (Clavien–Dindo [CD] 1-2 33.3%) and LAPRC operations had the highest rate of CD 3-4 complications (18.4%). Most (39.6%) of the referred patients were from other UK hospitals Conclusion Advanced colorectal cancer can be successfully treated in a dedicated referral centre, achieving R0 resection in over 90% with low morbidity and mortality. Implementation of a standardised referral pathway is encouraged. This article is protected by copyright. All rights reserved.

Aim Females of child-bearing age have been reported to have a two to three-fold increase in infertility after restorative proctocolectomy (RPC). This study aimed to assess aspects of infertility and pregnancy. Method A postal questionnaire was sent to 790 females who had undergone primary RPC in two tertiary centres. Infertility, the number and outcome of pregnancies, delivery method and the use of fertility treatments were determined. Results Three hundred and six (38.5%) females responded (median age 47.9 years at follow up; 35.3 years at the time of RPC). Eighty-two per cent (n = 250) had ulcerative colitis. Forty-five per cent (n = 138) had conceived prior to RPC, 5.2% (n = 16) conceived both before and after RPC, 5.5% (n = 17) conceived after RPC only and 44.1% (n = 135) had never conceived. Females delivering before RPC had significantly more vaginal deliveries than those conceiving after (pre-RPC 69.6%, n = 96 vs post-RPC 35.3%, n = 6; P = 0.001). Fifty-seven patients stated they had attempted to conceive after RPC, with 25 (45.5%) being successful. Eighteen females had been referred to a fertility specialist, of whom 16 received in vitro fertilization (IVF). Four (30.7%) females conceived using IVF. Conclusion While RPC is known to be associated with infertility, only a small proportion of patients are referred for fertility management. IVF outcomes and success rates after RPC are similar to the general population. Patients are more likely to have a Caesarean section following RPC.

Known collectively as serrated polyps, hyperplastic polyps (HP), sessile serrated adenomas (SSA/SSP) and traditional serrated adenoma (TSA) may represent a spectrum of increasing malignant potential with characteristic immunological markers. There is increasing evidence that HP, SSA/SSP and TSA are biologically different and are likely to represent a spectrum along the serrated polyp pathway. Although there is general consensus about the diagnostic features of serrated polyps, the morphological differences between the categories are often subtle. This study compares the expression of p53 and P504S among serrated polyps. Sixty seven randomly selected biopsies (n = 59) and resection specimens (n = 8) histologically diagnosed for SSA/SSP, TSA and HP (19, 30 and 18 specimens, respectively) were obtained. There was a significant difference in p53 (P

3612Background: Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event as patients survive longer. While human epidermal growth factor receptor 2 (HER2) gene amplificati...

Lateral pelvic lymph-node metastases occur in 10-25% of patients with rectal cancer, and are associated with higher local recurrence and reduced survival rates. A meta-analysis was undertaken to assess the value of extended lateral pelvic lymphadenectomy in the operative management of rectal cancer.We searched Medline, Embase, Ovid, Cochrane Library, and Google Scholar for studies published between 1965 and 2009 that compared extended lymphadenectomy (EL) with standard rectal resection. 20 studies, which included 5502 patients from one randomised, three prospective non-randomised, and 14 retrospective case-control studies published between 1984 and 2009, met our search criteria and were assessed. 2577 patients underwent EL and 2925 underwent non-EL for rectal cancer. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. End-points evaluated included peri-operative outcomes, 5-year survival and recurrence rates.Operating time was significantly longer in the EL group by 76.7 min (95% CI 18.77-134.68; p=0.0096). Intra-operative blood loss was greater in the EL group by 536.5 mL (95% CI 353.7-719.2; p0.0001). Peri-operative mortality (OR 0.81, 95% CI 0.34-1.93; p=0.63) and morbidity (OR 1.45, 95% CI 0.89-2.35; p=0.13) were similar between the two groups. Data from individual studies showed that male sexual dysfunction and urinary dysfunction (three studies: OR 3.70, 95% CI 1.66-8.23; p=0.0012) were more prevalent in the EL group. There were no significant differences in 5-year survival (hazard ratio [HR] 1.09, 95% CI 0.78-1.50; p=0.62), 5-year disease-free survival (HR 1.23, 95% CI 0.75-2.03, p=0.41), and local (OR 0.83, 95% CI 0.61-1.13; p=0.23) or distant recurrence (OR 0.93, 95% CI 0.72-1.21; p=0.60).Extended lymphadenectomy does not seem to confer a significant overall cancer-specific advantage, but does seem to be associated with increased urinary and sexual dysfunction.

Introduction The aim of the study was to evaluate the diagnostic precision of serum carcinoembryonic antigen (CEA) in the detection of local or distant recurrence following resectional surgery for colon and rectal cancer. Methods Quantitative meta-analysis was performed on 20 studies, comparing serum CEA with radiological imaging and/or pathology in detecting colorectal cancer (CRC) recurrence in 4285 patients. The cut-off for a ‘positive’ CEA ranged from 3 to 15 ng/ml between the various studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver operating characteristic curves (SROC) and sub-group analysis were undertaken. Results The overall sensitivity and specificity of CEA for detecting CRC recurrence was 0.64 (95% CI: 0.61–0.67) and 0.90 (95% CI: 0.89–0.91), respectively. The area under the SROC curve was 0.75 (SE = 0.04) and the diagnostic odds ratio was 18.44 (95% CI: 11.94–28.49). A CEA cut-off of 5 ng/ml yielded a higher diagnostic odds ratio than a cut-off of 3 ng/ml (15.5 vs. 11.1). Using meta-regression analysis the optimum CEA cut-off point for the best combination of sensitivity and specificity was 2.2 ng/ml. On sub-group analysis high quality studies, and those involving ≥100 patients yielded a marginal improvement in the sensitivity and specificity with minimal change to the SROC. Conclusion Serum CEA is a test with high specificity but insufficient sensitivity for detecting CRC recurrence in isolation. A cut-off of 2.2 ng/ml may provide an ideal balance of sensitivity and specificity. It may be useful as a first-line surveillance investigation in patients during surgical follow-up based on serial CEA measurements using temporal trends in conjunction with clinical, radiological and/or histological confirmation.

Transcutaneous sacral nerve stimulation is reported to improve symptoms of fecal incontinence. Chronic constipation may also respond to stimulation, but this is poorly reported in the literature.The study assessed the efficacy of transcutaneous electrical stimulation directly over the sacral nerve roots in chronic constipation.Chronic functional constipation was established in all patients using the Rome III criteria.The therapy was self-administered at home.A pilot study was conducted of transcutaneous sacral stimulation given over a 4-week period for 12 hours a day.Patients were assessed using the Patient Assessment of Constipation Symptoms, the Patient Assessment of Constipation Quality of Life, and the Cleveland constipation tool. A Global Rating of Change measure and a 1-week bowel diary was kept for the final week and compared with baseline.Of the 20 patients recruited (16 female, median age 38.5 years), 80% (16) completed the trial. Five (31%) patients reported at least a point reduction in the Patient Assessment of Constipation Symptoms score, 4 (25%) deteriorated, and 7 (44%) improved by less than one point. Median (interquartile range) Patient Assessment of Constipation Symptoms scores were 2.33 (2.34) at baseline and 2.08 (2.58) at follow-up (p = 0.074). Median scores for the Patient Assessment of Constipation Quality of Life and Cleveland systems were 3.00 (1.64) and 17.15 (18) at baseline and 2.22 (3.04) and 15.31 (12) at follow-up (p = 0.096 and 0.111). One-third of patients reported a positive Global Rating of Change measure, although 68% required concurrent laxatives during the trial.This is a pilot study and is limited by its small sample size.Continuous transcutaneous sacral stimulation in the short term appears to be ineffective for chronic constipation. Larger well-powered studies with intermittent stimulation regimens are required to investigate this further.

This study was designed to evaluate the effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy, and delivery in patients with ulcerative colitis. A systematic literature search was performed of articles published between 1980 and 2005 on patients undergoing restorative proctocolectomy for ulcerative colitis reporting data on the outcomes of interest. A random-effect, meta-analytical model was used for pooled estimates and 95 percent confidence intervals. A total of 22 studies, with 1,852 females, were included. Infertility rate was 12 percent before restorative proctocolectomy and 26 percent after, among 945 patients in seven studies. The incidence of sexual dysfunction was 8 percent preoperatively and 25 percent postoperatively (7 studies, n = 419). Two studies (n = 62) reported no urinary dysfunction in patients undergoing restorative proctocolectomy. There was an increased incidence of cesarean section after restorative proctocolectomy. During the third trimester of pregnancy, there was an increase in stool frequency by 1.15 stools per day compared with before pregnancy frequency (n = 49 95 percent confidence interval, 0.28–2.03 P = 0.01 chi-squared statistic, 0.04 P = 0.84). No significant differences were seen in pouch function after vaginal delivery (n = 456; weighted mean difference, 0.23; 95 percent confidence interval, 0.43–0.88; P = 0.49; chi-squared statistic, 1.29; P = 0.26). The incidence of dyspareunia increases after restorative proctocolectomy. There was a decrease in fertility after restorative proctocolectomy. Pregnancy after restorative proctocolectomy was not associated with an increase in complications. There was an increase in stool frequency and pad usage during the third trimester. Vaginal delivery is safe after restorative proctocolectomy. Pouch function after delivery returns to pregestational function within six months.

Aim Ileal pouch-anal anastomosis (IPAA) is performed in ulcerative colitis or familial adenomatous polyposis with a view to restoration of GI continuity and prevention of permanent faecal diversion. Debate exists as to its safety in older patients. This review aims to assess functional outcomes and safety of restorative proctocolectomy (RPC) in older compared to younger patients. Methods Literature search was performed for age-stratified studies which assessed functional outcomes of IPAA. Twelve papers were included overall. Patients were categorized into ‘older’ and ‘younger’ groups. Analysis was split into three separate parts: 1. Age cut-off of 50 ± 5 years (with sensitivity analysis); 2. Age cut-off of 65 ± years; 3. Long-term outcomes (>10 years). Results With an age cut-off of 50 years (4327 versus 513 patients), complication rates were comparable with the exception of an increased rate of small-bowel obstruction in the younger patients (p = 0.034). At 1 year, 24-h stool frequency was significantly higher in the older patient group (p

Aim Several sphincter-preserving techniques have been described with extremely encouraging initial reports. However, more recent studies have failed to confirm the positive early results. We evaluate the adoption and success rates of advancement flap procedures (AFP), fibrin glue sealant (FGS), anal collagen plug (ACP) and ligation of intersphincteric fistula tract (LIFT) procedures based on their evolution in time for the management of anal fistula. Method A PubMed search from 1992 to 2015. An assessment of adoption, duration of study and success rate was undertaken. Results We found 133 studies (5604 patients): AFP (40 studies, 2333 patients), FGS (31 studies, 871 patients), LIFT (19 studies, 759 patients), ACP (43 studies, 1641 patients). Success rates ranged from 0% to 100%. Study duration was significantly associated with success rates in AFP (P = 0.01) and FGS (P = 0.02) but not in LIFT or ACP. The duration of use of individual procedures since first publication was associated with success rate only in AFP (P = 0.027). There were no statistically significant differences in success rates relative to the number of the patients included in each study. Conclusion Success and adoption rates tend to decrease with time. Differences in patient selection, duration of follow-up, length of availability of the individual procedure and heterogeneity of treatment protocols contribute to the diverse results in the literature. Differences in success rates over time were evident, suggesting that both international trials and global best practice consensus are desirable. Further prospective randomized controlled trials with homogeneity and clear objective parameters would be needed to substantiate these findings.

Aim This study compared the operative outcome and long-term survival of three types of hand-sewn coloanal anastomosis (CAA) for low rectal cancer. Method Patients presenting with low rectal cancer at a single centre between 2006 and 2014 were classified into three types of hand-sewn CAA: type 1 (supra-anal tumours undergoing transabdominal division of the rectum with transanal mucosectomy); type 2 (juxta-anal tumours, undergoing partial intersphincteric resection); and type 3 (intra-anal tumours, undergoing near-total intersphincteric resection with transanal mesorectal excision). Results Seventy-one patients with low rectal cancer underwent CAA: 17 type 1; 39 type 2; and 15 type 3. The median age of patients was 61.6years, with a male/female ratio of 2:1. Neoadjuvant therapy was given to 56 (79%) patients. R0 resection was achieved in 69 (97.2%) patients. Adverse events occurred in 25 (35.2%) of the 71 patients with a higher complication rate in type 1 vs type 2 vs type 3 (47.1% vs 38.5% vs 13.3%, respectively; P=0.035). Anastomotic separation was identified in six (8.5%) patients and pelvic haematoma/seroma in five (7%); two (8.3%) female patients developed a recto-vaginal fistula. Ten (14.1%) patients were indefinitely diverted, with a trend towards higher long-term anastomotic failure in type 1 vs type 2 vs type 3 (17.6% vs 15.5% vs 6.7%). The type of anastomosis did not influence the overall or disease-free survival. Conclusion CAA is a safe technique in which anorectal continuity can be preserved either as a primary restorative option in elective cases of low rectal cancer or as a salvage procedure following a failed stapled anastomosis with a less successful outcome in the latter. CAA has acceptable morbidity with good long-term survival in carefully selected patients.

A 55 -year-old Asian man was seen in the emergency department with bleeding per rectum. He was a teetotaller and had no previous abdominal surgery. He did, however, report a change in bowel habit towards constipation. He underwent colonoscopy which revealed a lesion, highly suspicious of malignancy, in the caecum. On review by two consultants, a decision to completely resect this lesion was made. Histological analysis of the polypoidal growth showed it to be a consequence of chronic infection with the helminth Enterobius vermicularis. Importantly, there was no evidence of dysplastic or malignant cells. The patient was subsequently discharged with a 3-day course of antihelminthic mebendazole and reassured that his per rectal bleeding was most likely due to haemorrhoids discovered at rectal examination.

Background: The aim was to investigate quality of life, sexual, fecal, and urinary function in females undergoing restorative proctocolectomy (RPC). Methods: A prospective case–control study was performed in two tertiary centers. Controls were females with ulcerative colitis, without a stoma or RPC. Validated questionnaires (SF-36, Female sexual function index, King's questionnaire, and the Wexner scale) were administered in the outpatient setting. Pearson chi2, t-test, and Mann–Whitney U-tests were used to assess significance. Results: A total of 255 females were identified and 49% (n = 124) recruited. In all, 109 patients fulfilled the inclusion criteria: 55 (50.5%) inflammatory bowel disease (IBD); 54 (49.5%) RPC. The mean age of RPC patients was 41.8 years (± 12.7 SD) vs. 43.8 years (± 15.8) for IBD (P = 0.491). RPC females with urinary symptoms (urgency, frequency, or incontinence) were 10 years younger than IBD (RPC mean age 37.6 ± 7.3 years vs. IBD 47.4 ± 13.5; P = 0.044). Urgency in fecal function was experienced by more IBD patients (IBD 75.0% vs. RPC 47.9%; P = 0.006), although RPC patients had increased day (P < 0.001) and night bowel frequency (P < 0.001) and were more likely to experience night seepage (P = 0.001). RPC females who had a vaginal delivery (VD) were more likely to have day seepage (P = 0.046) and require pads (P = 0.026) than RPC females who had not undergone VD. There was no significant difference in sexual function. Conclusions: RPC may adversely impact urinary function in female patients over time. Bowel frequency, seepage, and pad usage are increased following RPC and function may be worse following VD. RPC does not adversely affect overall sexual function. (Inflamm Bowel Dis 2012;)

The National Bowel Cancer Audit Project (NBOCAP) collects data from hospitals in the UK and aims to improve surgical outcomes and quality of care for patients. The aims of this study were to understand why trusts were/were not participating in the NBOCAP and how to improve the quality of data collected and feedback. This was a prospective e-survey on colorectal surgeons’ attitudes towards and opinions of the NBOCAP, within trusts in the UK. A questionnaire was emailed to members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI). Of the 171 trusts contacted by email, 66% of trusts (n = 117) had at least 1 consultant respond. Of the 117 trusts that responded, 60 (51.2%) had submitted data to the NBOCAP. A total of 549 consultants received the questionnaire, and 159 (29.0%) consultants responded. Fifty-one per cent (n = 60) of the trusts had submitted data to the NBOCAP. Reasons for data submission included the following: comparison of a units’ data with national data (56.8%), a national audit improves outcomes (45.9%) and generation of information for use at a local level (42.6%). The main reasons for non-submission were as follows: lack of technical support (23.6%), lack of funding (19.6%) and lack of dedicated audit time (18.9%). Ninety-six (60.4%) consultants felt that the audit report should identify individual trust results. Fifty-three per cent of consultants (n = 87) rated their trusts’ resources for audit as being very poor or poor. Consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) within hospital trusts in the UK feel participation in the National Bowel Cancer Audit improves patients’ quality of care and surgical outcomes. Increased awareness of the benefits of the NBOCAP and improved allocation of resources from hospital trusts could improve participation.

PURPOSE: The aim of this study was to evaluate clinical outcomes, quality-adjusted life-years, and the cost-effectiveness gained from percutaneous drainage followed by elective surgery vs. initial surgery for abdominopelvic abscesses related to Crohn's disease. METHODS: All consecutive patients with spontaneous Crohn's disease-related abdominopelvic abscess from 1997 to 2007 were reviewed. The authors excluded postoperative and perirectal abscesses. Decision analysis during one year of patient life was used to calculate quality-adjusted life-years and the cost-effectiveness of each strategy. RESULTS: Of 94 patients, 48 (51 percent) were initially approached with percutaneous drainage. Thirty-one (65 percent) had successful percutaneous drainage and delayed elective surgery. The factors significantly associated with percutaneous drainage failure were steroid use, colonic phenotype, and multiple or multilocular abscesses. The initial treatment was surgery in the remaining 46 (49 percent) patients. The initial approach with percutaneous drainage gave higher quality-adjusted life-years and was more cost-effective than initial surgery. Percutaneous drainage was the optimal strategy in spite of the risk of failure and septic complications within the plausible range. CONCLUSIONS: Percutaneous drainage failure is associated with steroid use, colonic phenotype, and multiple or multilocular abscesses. When feasible, percutaneous drainage is the most effective strategy from the perspective of patients and third-party payers.

Several environmental and genetic factors have been implicated to date in the development of Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to provide a quantification of the risk of oral contraceptive pill (OCP) use in the etiology of inflammatory bowel disease.A literature search was performed to identify comparative studies reporting on the association of oral contraceptive use in the etiology of UC and CD between 1983 and 2007. A random-effect meta-analysis was used to compare the incidence of UC or CD between the patients exposed to the OCP and nonexposed patients. The results were adjusted for smoking.A total of 75,815 patients were reported on by 14 studies, with 36,797 exposed to OCP and 39,018 nonexposed women. The pooled relative risk (RR) for CD for women currently taking the OCP was 1.51 (95% confidence interval [CI] 1.17-1.96, P= 0.002), and 1.46 (95% CI 1.26-1.70, P0.001), adjusted for smoking. The RR for UC in women currently taking the OCP was 1.53 (95% CI 1.21-1.94, P= 0.001), and 1.28 (95% CI 1.06-1.54, P= 0.011), adjusted for smoking. The RR for CD increased with the length of exposure to OCP. Moreover, although the RR did not reduce once the OCP was stopped, it was no longer significant once the OCP was stopped (CI contains 1), both for CD and for UC.This study provides evidence of an association between the use of oral contraceptive agents and development of IBD, in particular CD. The study also suggests that the risk for patients who stop using the OCP reverts to that of the nonexposed population.

To evaluate the epidemiology and risk of surgery in the treatment of colorectal cancer in the elderly.Patients undergoing colorectal cancer surgery were identified from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) bowel cancer database, comprising 47,455 patients treated over a 5-year period. Demographic characteristics and outcomes were compared between patients aged75 and those 75 or above. The primary endpoint was 30-day mortality. Secondary endpoints were the length of hospital stay, abdominoperineal excision (APER) rates and lymph node harvest.Elderly patients were likely to be female and have higher American Society of Anaesthesiology (ASA) grade, while Dukes' stage was lower. They underwent surgery less often (81% versus 88%, p0.001), but more frequently needed urgent or emergency procedures (p0.001) and non-excisional surgery (7.7% versus 6.6%, p0.001). Operative mortality was significantly higher for the older age group (10.6% versus 3.8%, p0.001), and their median length-of-stay was 2 days longer (p0.001). Mortality has improved over time for elderly patients with ASA grade III, and Dukes' stage A and D disease, but not for other subgroups.Significant differences in the demographic characteristics and operative risk-factors between under-75s, and those aged 75 or above exist. These variations are reflected in the inferior outcomes experienced by elderly patients.

Summary Background Alvimopan is a selective, competitive μ-opioid receptor antagonist with limited oral bioavailability which may be used to reduce length of post-operative ileus. Aim The study compared alvimopan with placebo following bowel resection or total abdominal hysterectomy. Methods A meta-analysis of randomized–controlled trials published between 2001 and 2006 of alvimopan vs. placebo was performed. The primary efficacy end-points were composite measures of passage of flatus, stool, and tolerance of solid food (GI-3) and passage of stool and tolerance of solid food (GI-2). The incidence of treatment emergent adverse events was assessed. Results Five trials matched the selection criteria, reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%) placebo. GI-3 significantly improved (hazard ratio 1.30; 95% confidence intervals 1.16, 1.45, P

Aim The efficacy of sacral nerve stimulation (SNS) in low anterior resection syndrome (LARS) is largely undocumented. A review of the literature was carried out to study this question. Method Pubmed, Medline and Cochrane databases were searched for relevant articles up to August 2014. Studies were included if they evaluated the use of SNS following rectal resection and assessed at least one of the following end-points: bowel function, quality of life and ano-neorectal physiology. No restrictions on language or study size were made. Results Seven papers were identified including one case report and six prospective case series. These included 43 patients with a median follow-up of 15 months. After peripheral nerve evaluation definitive implantation was carried out in 34 (79.1%) patients. Overall, 32 (94.1%) of the 34 patients experienced improvement of symptoms which, based on intention to treat, was 32/43 (74.4%). Conclusion The review suggests that SNS for faecal incontinence in LARS has success rates comparable to its use for other forms of faecal incontinence.

To investigate the relationship between organisational structure, process and surgical outcomes for bowel cancer surgery.An e-survey was sent to the members of the Association of Coloproctology of Great Britain and Ireland to determine the organisational structure of their Trusts. Responses were combined with the National Bowel Cancer Audit (NBOCAP) data. Items investigated included; number of consultants, nurse specialists, volume of cases and intensive care facilities. Main outcome measures included: 30-day risk-adjusted mortality, length of stay (LOS), lymph node yield and circumferential margin involvement (CRM).One hundred and seventeen Trusts responded (65.8%), matched to 7666 patient episodes (NBOCAP data) from 54 (62.8%)Trusts who submitted data to the audit. Trusts treating190 cases/annum (p0.001),4 colorectal consultants (p0.001),4 HDU beds (p0001) and8 ITU beds (p0001) were more likely to have a 30-day-risk-adjusted mortality twice that of the national mean. Sixty five percent (n = 1603) of Trusts treating ≥ 190 cases/annum harvested ≥ 12 lymph nodes vs. 58.3% (n = 1435) in Trusts190 cases/annum (p0.001). Trusts with ≥ 2 pathologists with an interest in bowel cancer harvested ≥ 12 lymph nodes more frequently (p=0.001) and were more likely to identify extramural vascular invasion in the specimen (p = 0.015). Negative CRM was achieved in 81.4% (n = 81.4) of patients in Trusts treating ≥ 190 cases vs. 66.5% (n = 569) in Trusts190 cases/annum (p0.001). Trusts offering fast track discharge were more likely to have a LOS15 days (p = 0.006). Surgeons treating ≤ 35 cases/annum had increased major post-operative complications (35 cases = 70.2% vs. ≥ 35 cases = 21.9%; p0.001), however 30 day risk adjusted mortality was not increased in surgeons treating35 cases/annum.This study shows that the organisational infrastructure of hospitals appears to have as great an impact on patient outcomes as the volume of cases performed by hospital Trusts.