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Perivascular epithelioid cell tumours (PEComa) are rare tumours of mesenchymal origin. We report a 39-year-old patient who presented with painful defecation secondary to an anorectal mass. The diagnosis of anorectal PEComa was confirmed following excision and histopathological examination. We review the literature and discuss the management of this uncommon entity.

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.

Objectives This study aimed to provide an in-depth exploration of follow-up care experiences and supportive care needs in long-term colorectal cancer (CRC) survivors within multiethnic Asian communities. Methods Semi-structured in-depth interviews were conducted on a purposive sample of 30 long-term CRC survivors who had completed all treatment without recurrence ranging 2-17 years in Singapore. Interviews were audio-recorded, and transcribed verbatim. Thematic analysis was conducted following grounded theory approach. Results Four themes represented the experience of the Asian long-term CRC survivors: (1) living with long-term consequences, (2) dealing with unceasing adaptation demands, (3) navigating a healthcare journey with limited direction, (4) regaining mastery through adversity. CRC and its treatment had profound physical impacts on some long-term survivors and these effected their psychological well-being. A sense of abandonment and vulnerability following the cessation of a 5-year follow-up care was repeatedly expressed. Participants defined recovery from CRC as not merely surviving but also having high physical function and full independence. They often sought less conventional remedies and medicine based on cultural beliefs rather than current evidence. Participants noted pervasive social stigma associated with CRC that impeded their inclusion in the workforce. Conclusions Asian long-term CRC survivors experienced multiple challenges and needs relating to the care experience, information provision and workforce stigmatization, several of which were unique to the Asian context. Future work will need to consider the implementation of culturally tailored cancer survivorship care plans that incorporate the specific needs of Asian CRC survivors. This article is protected by copyright. All rights reserved.

Worldwide, colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality. Metastasis to distal organ is the major cause of cancer mortality. However, chemotherapeutic treatment of metastatic CRC has a dismayed success rate of less than 30%. Patients who are resistant to chemotherapy and who are KRAS wildtype are sometimes offered anti-EGFR as a second line therapy. Nevertheless, only about ½ of these patients respond and those who do inevitably develop resistance within months due to selection for downstream KRAS mutations. Moreover, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. Hence, there is an unmet need to identify novel therapeutics for CRC. KRAS is a gatekeeper gene in colorectal tumorigenesis but is ‘undruggable’ due to its structure not being easily amenable to inhibitor docking. Focus has been diverted to develop small molecule inhibitors for its downstream effectors such as ERK/MAPK and AKT. Despite intense research efforts for the past few decades, however, no small molecule inhibitor has been in clinical use for CRC. Recently developed Sotorasib inhibitor specific for KRAS G12C mutations (rare in CRC) is not effective for CRC. Antibodies have high affinity to their target proteins without having to bind to specific pocket and are fully human in nature and hence less toxic. Antibody targeting KRAS itself is thus an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live matched mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its trafficking to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. In the present study, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells suggesting down-regulation of KRAS signaling. Our results demonstrated that anti-KRAS antibody can be internalized and specifically inhibits KRAS function in live tumor cells. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers. Citation Format: Peh Yean Cheah, Kuen Kuen Lam, Yee Syuen Low, Michelle Lo, Michelle Wong, Choong Leong Tang, Emile Tan, Aik Yong Chok, Issac Seow En, Siew Heng Wong. Anti-KRAS antibody aggregates KRAS in the cytoplasm of live ex vivo cultured human colorectal adenocarcinoma cells and prevents its trafficking to the plasma membrane. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4119.

Colorectal cancer (CRC) is the third highest incident cancer worldwide and a major cause of cancer death. KRAS protein gain-of-function point mutations play major roles in colorectal tumorigenesis. However, direct inhibition of KRAS is challenging as its protein structure is inadmissible to inhibitor docking. Efforts have been diverted to inhibit downstream RAF/MEK/ERK and PI3K/Akt signaling. Nevertheless, none of these inhibitors has progressed to clinical use in CRC despite extensive trials over the past few decades. We examined levels of phospho-ERK1/2(T202/Y204) and phospho-Akt1/2/3(S473) in human colorectal tumor and matched mucosa at least 10 cm away with quantitative near infrared western blot and immunofluorescence imaging. Surprisingly, 75.5% (25/33) of tumors has lower or equivalent phospho-ERK1/2 and 96.9% (31/32) of tumors has lower phospho-AKT1/2/3 compared to matched mucosa, irrespective of KRAS mutation status and tumor stage. In contrast, we discovered KRAS-dependent SOX9 upregulation in 28 of the 31 (90.3%) tumors. CPTAC phosphoproteomics data similarly showed significantly lower phospho-ERK1/2 levels in tumor compared to matched mucosa. Analysis of transcriptome data from TCGA and GEO series GSE95132 also showed no activation of RAF/MEK/ERK signaling in CRC tumors. These data indicate that the pursue of targeted therapy inhibiting RAF/MEK/ERK and PI3K/Akt signaling is unlikely to be effective in sporadic CRC and possibly harmful as phospho-ERK1/2 are highly expressed in the matched mucosa suggesting a role in normal colonic homeostasis. The widespread use of RAF/MEK/ERK or PI3K/Akt signaling downregulation as a biomarker in drug testing on CRC cell lines needs to be re-evaluated. The data suggest further that SOX9 could be an alternative effector and biomarker of KRAS signaling. Citation Format: Peh Yean Cheah, Kuen Kuen Lam, Choong Leong Tang, Emile Tan, Siew Heng Wong. ERK/AKT pathways may be the wrong effectors for KRAS signaling inhibition in colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6192.

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

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.

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.

Percutaneous tibial nerve stimulation (PTNS) and sacral nerve stimulation (SNS) are both second-line treatments for faecal incontinence (FI). To compare the clinical outcomes and effectiveness of SNS versus PTNS for treating FI in adults. A literature search of MEDLINE, Embase, Science Citation Index Expanded and Cochrane was performed in order to identify studies comparing SNS and PTNS for treating FI. A risk of bias assessment was performed using The Cochrane Collaboration’s risk of bias tool. A random effects model was used for the meta-analysis. Four studies (one randomised controlled trial and three nonrandomised prospective studies) reported on 302 patients: 109 underwent SNS and 193 underwent PTNS. All included studies noted an improvement in symptoms after treatment, without any significant difference in efficacy between SNS and PTNS. Meta-analysis demonstrated that the Wexner score improved significantly with SNS compared to PTNS (weighted mean difference 2.27; 95% confidence interval 3.42, 1.12; P

Adequate oncological outcomes have been demonstrated with rectal resection and handsewn coloanal anastomosis (CAA) in tumours in close proximity to the internal anal sphincter. Our aim was to assess functional differences between handsewn CAA and ultralow stapled anastomosis. Participants were identified from a single-surgeon series. Included participants underwent anorectal physiology testing of anal sphincter function, in addition to completion of several questionnaires: Wexner Incontinence Score (WIS); Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ); Low Anterior Resection Syndrome (LARS) Score; SF36. Non-parametric data compared using the Mann-Whitney U test. 20 participants were included; 11 stapled and 9 handsewn. Mean follow-up was 2.95 ± 1.97 years. The mean LARS score was 21.9 ± 1.97 years in the stapled group versus 29.4 ± 9.57 in the handsewn group (p = 0.133). The Wexner incontinence score was significantly higher in the handsewn group (p = 0.0076), with a mean score of 4.6 ± 3.69 versus 10.9 ± 4.76. The incontinence domain of the BBUSQ was also significantly worse in patients with a handsewn anastomosis (p = 0.001). With the exception of general health (p = 0.035) and social functioning (p = 0.035), which were worse in the handsewn groups, the other six domains of the SF-36 showed no statistical difference between groups. Anorectal physiology scores were not significantly different. Handsewn CAA anastomosis is known to be safe and oncologically feasible. Patient selection should be vigorous, with preoperative counseling regarding the likelihood of incontinence to manage patients' expectations and promote comparable quality of life in the long-term.

Introduction This study aimed to ascertain whether missed obstetric anal sphincter injury at delivery had worse functional and quality of life outcomes than primary repair immediately following delivery. Materials and methods Two to one propensity matching was undertaken of patients presenting to a tertiary pelvic floor unit with ultrasound evidence of missed obstetric anal sphincter injury within 24 months of delivery with patients who underwent primary repair at the time of delivery by parity, grade of injury and time to assessment. Outcomes compared included Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ), Wexner Incontinence Score, Short Form-36, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire and anorectal physiology results. Results Thirty-two missed anal sphincter injuries were matched two to one with sixty-two patients who underwent primary repair of an anal sphincter defect. Mean time to follow-up was 9.31 ± 6.79 months. Patients with a missed anal sphincter injury had suffered more incontinence, as seen in higher the Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ; 30.56% ± 14.41% vs. 19.75% ± 15.65%, P = 0.002) and Wexner scores (6.00 ± 3.76 vs. 3.67 ± 4.06, P = 0.009). They also had a worse BBUSQ urinary domain score (28.25% ± 14.9% vs. 17.01 ± 13.87%, P = 0.001) and worse physical functioning as measured by the Short Form-36 questionnaire (P = 0.045). There were no differences in other outcomes compared, including anorectal physiology and sexual function. Discussion In the short-term, patients with a missed obstetric anal sphincter injury had significantly worse faecal incontinence and urinary function scores, however quality of life and sexual function were largely comparable between groups. Conclusions Longer-term follow-up is needed to assess the effects of missed obstetric anal sphincter injury over time.

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.

Summary Introduction Home parenteral nutrition (HPN) is an expensive therapy. Restoring bowel continuity has been shown to wean patients off HPN. The aims of this study were to estimate the economic impact and QALY gained after restoring bowel continuity in adult patients with short bowel and intestinal failure due to mesenteric infarction. Method A Markov cohort model was constructed to simulate patients undergoing bowel restoration following mesenteric infarction. Probabilities associated with restoration of bowel continuity were determined using published data. Costs were estimated using the National Health Service (NHS) reference costs (2013–14). Utilities were determined from literature and opinion of experts. Results The expected QALY at 1 year following restoring bowel was 0.47. This increased to 3.29 at 5 years. The marginal cost per QALY gained calculated for the first year following restoration of bowel continuity was £95959.72 and this decreases to £10797.63 at 5 years. Conclusion Restoring bowel continuity reduces the overall costs associated with HPN and it results in increased QALY over time.

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.

Purpose This study aims to establish the ability of patient-reported outcome measures (PROMs) and anorectal manometry (ARM) in predicting the need for surgery in patients with fecal incontinence (FI). Methods Between 2008 and 2015, PROMs data, including the Birmingham Bowel and Urinary Symptoms Questionnaire (BBUSQ), Short Form 36 (SF-36), Wexner Incontinence Score and ARM results, were prospectively collected from 276 patients presenting with FI. Spearman rank was used to assess correlations between specific PROMs questions and ARM assessments of sphincter motor function. Binomial regression analyses were performed to identify factors predictive of the need for surgery. Finally, receiver operating characteristic (ROC) curve analyses were performed to establish the utility of individual ARM and PROMs variables in predicting the need for surgical intervention in patients with FI. Results Two hundred twenty-eight patients (82.60%) were treated conservatively while 48 (17.39%) underwent surgery. On univariate analyses, all 4 domains of the BBUSQ, all 8 domains of the SF-36, and the Wexner Incontinence Score were significant predictors of surgery. Additionally, maximum resting pressure, 5-second squeeze endurance, threshold volume, and urge volume were significant. On ROC curve analyses, the only significant ARM measurement was the 5-second squeeze endurance. PROMs, such as the incontinence domain of the BBUSQ and five of the SF-36 domains, were identified as fair discriminators of the need for surgery. Conclusion PROMs are reliable predictors of maximal treatment in patients with FI and can be readily used in primary care to aid surgical referrals and can be applied in hospital settings as an aid to guide surgical treatment decisions.

Surgical site infection (SSI) is a well-known complication of colorectal surgery associated with increased morbidity and hospital stay. Antimicrobial prophylaxis can reduce the risk of SSI by as much as 75%. Extended-spectrum β-lactamase (ESBL)-producing pathogens make the successful use of such prophylaxis a challenge and are a real threat to patient care following colorectal surgery.The aim of this study is to report the common characteristics of SSIs after colorectal surgery and to highlight the prevalence, risk factors, and clinical relevance of ESBL infections among these patients in a tertiary center.All patients who underwent bowel resection operation (ie, laparoscopy, laparotomy, or laparoscopic-assisted colectomy) for benign or malignant colorectal disease were identified retrospectively from the prospective database of the colorectal department in the authors' tertiary center from March 2015 to March 2016.There were 123 patients included in this study, of which 21% (n = 26) had a SSI. The microorganisms isolated in the surgical sites included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, Morganella morganii, and Enterobacter cloacae. Thirty-eight percent of the wound infections grew ESBL-producing pathogens in their wound cultures and 62% grew non-ESBL microbes.More than one-third of the wound infections were due to ESBL-producing pathogens, which were resistant to the antibiotic prophylaxis given. Inappropriate antibiotic usage can delay postoperative recovery. High-risk patients for ESBL colonization may benefit from preoperative screening based on an established protocol. The cost effectiveness of an ESBL screening program needs to be further studied.

AIM Chronic constipation is difficult to treat when symptoms are intractable. Colonic propulsion may be altered by distal neuromodulation but this is conventionally delivered percutaneously. Transcutaneous tibial nerve stimulation is noninvasive and cheap: this study aimed to assess its efficacy in chronic constipation. METHOD Eighteen patients (median age 46 years, 12 female) with chronic constipation were recruited consecutively. Conservative and behavioural therapy had failed to improve symptoms in all 18. Thirty minutes of daily bilateral transcutaneous tibial nerve stimulation was administered by each patient at home for 6 weeks. The primary outcome measure was a change in the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. Change in Patient Assessment of Constipation Symptoms (PAC-SYM), weekly bowel frequency and visual analogue scale (VAS) score were also measured. RESULTS Fifteen patients (12 female) completed the trial. The PAC-QoL score improved significantly with treatment [pretreatment, median 2.95, interquartile range (IQR) 1.18; posttreatment, median 2.50, IQR 0.70; P = 0.047]. There was no change in PAC-SYM score (pretreatment, median 2.36, IQR 1.59; posttreatment, median 2.08, IQR 0.92; P = 0.53). Weekly stool frequency improved as did VAS score, but these did not reach statistical significance (P = 0.229 and 0.161). The PAC-QoL and PAC-SYM scores both improved in four (26%) patients. Two patients reported complete cure. There were no adverse events reported. CONCLUSION Bilateral transcutaneous tibial nerve stimulation appears to be effective in a quarter of patients with chronic constipation. Carefully selected patients with less severe disease may benefit more. This requires further study.

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.

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 types

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.

Purpose: Female patients with pelvic floor diseases may suffer from several sexual disorders and sexual life impairments. The aim of this manuscript was to evaluate sexual dysfunction in female patients presenting with faecal incontinence (FI) and defecation disorder (DD). Methods: A retrospective review was performed of a prospectively collected database of sexually active women referred to the pelvic floor clinic, who completed the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-12 (PISQ-12) at first visit. Statistical analysis was performed to evaluate and compare sexual dysfunction between patients with FI and DD and with published data on the general population. Regression analysis was used to identify predictors of sexual dysfunction and surgery. Results: Three hundred thirteen patients were included, 192 (61%) with FI and 121 (39%) with DD. The patients with DD received more non-gynaecological surgical procedures (p = 0.023). More patients with DD received surgery for their current pelvic floor disease (p

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.

The levator ani is the main muscular support of the pelvic floor organs and damage caused by childbirth can affect its function. The full functionality of this muscle group is still unknown but it is essential for effective surgical planning. To elucidate its functional significance, a physical-based statistical shape model was built from the levator ani surfaces of 15 subjects scanned in an open access scanner. Simulation of dynamic exercises was performed on the resulting surfaces with finite element analysis. Statistical shape modeling was performed on the training set consisting of the original and simulated shapes along with thickness and strain distributions. Simulation results are presented on 15 subjects. The statistical shape model shows good correspondence to inter- and intra-subject shape variability, with the modes of variation highlighting movement in the posterior of the levator ani as well as in the levator arms. Strain distribution plots and the modes of variation show results that correspond to clinical findings. Further validation of the technique and a repeatability test were performed on four subjects with internal global pressure readings taken from a perineometer and five patients suffering from minor pelvic floor disorders due to obstructed defaecation. A Mann-Whitney nonparametric test was used to compare the normal model fitting to the two subject groups.

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.

Objective Anal-sphincter injury may result in faecal incontinence. Sphincteroplasty is usually performed as a primary (immediate) procedure. Delayed sphincteroplasty (DS) can be performed if there is significant trauma or soiling, if the primary procedure has failed, and if the injury was not recognized initially. This study aimed to determine the cost to patient and health service in the event a DS is performed. Method Patients with anal-sphincter-injury who underwent primary sphincteroplasty (PS)/DS were identified from the published literature (primary, n = 103; delayed, n = 777) using Medline, Embase, Ovid and Cochrane databases for studies published between 1976 and 2006. Studies included described at least one of the measured outcomes--probability of functional success/failure and quality of life (QOL). An economic model was constructed and decision analysis performed using a decision tree based on a Markov process. Main outcomes were quality-adjusted-life-years (QALYs) gained from each strategy, costs incurred and incremental cost-effectiveness ratio (ICER) over a 10- and 15-year time horizon. Results Over 10 years, primary sphincteroplasty (PS) produced a gain of 5.72 QALYs for an estimated 2750 pounds, giving an ICER of 487 pounds per QALY. DS produced a gain of 3.73 QALYs for a cost of 2667 pounds, giving an ICER of 719 pounds per QALY. Both procedures fell below the 10,000 pounds per QALY willingness-to-pay threshold, but PS produced the highest QALYs. Both procedures performed poorly beyond the 10-year mark. Conclusion If DS has to be performed, the resultant cost is greater with concurrently lower QALYs gained. Successful PS substantially improves QOL and reduces overall cost-of-treatment.

Background Artificial bowel sphincter (ABS) and dynamic graciloplasty (DG) are surgical treatments for faecal incontinence (FI). FI may affect quality of life (QOL) so severely that patients are often willing to consider a permanent end stoma (ES). It is unclear which is the more cost-effective strategy. Method Probability estimates for patients with FI were obtained from published data (ABS, n = 319; DG, n = 301), supplemented by expert opinion. The primary outcome was quality-adjusted life years (QALYs) gained from each strategy. Factors considered were the risk of failure of the primary and redo operation and the consequent risk of permanent stoma. Results were assessed as incremental cost-effectiveness ratio (ICER). Results Over the 5-year time horizon, ES gave a QALY gain of 3.45 for 16,280 pounds sterling, giving an ICER of 4719 pounds sterling/QALY. ABS produced a gain of 4.38 QALYs for 23,569 pounds sterling, giving an ICER of 5387 pounds sterling/QALY. DG produced a gain of 4.00 QALYs for 25,035 pounds sterling, giving an ICER of 6257 pounds sterling/QALY. With the willingness-to-pay threshold set at 30,000 pounds sterling/QALY, ES was the most cost-effective intervention. The ABS was most cost-effective after 10 years. Conclusion All three procedures were found to be cost-effective. The ES was most cost-effective over 5 years, while the ABS was most cost-effective in excess of 10. DG maybe considered as an alternative in specialist centres.

This study aims to evaluate the diagnostic precision of endoanal magnetic resonance imaging in identifying anal sphincter injury and/or atrophy when compared with either endoanal ultrasound or surgical diagnosis. Quantitative meta-analysis was performed on nine studies, comparing endoanal MRI with endoanal ultrasound or surgical diagnosis in 157 patients. Sensitivity, specificity, and diagnostic odds ratio were calculated for each study. Summary receiver operating characteristic curves (SROC) and subgroup analysis were undertaken. The overall sensitivity and specificity of endoanal MRI for external sphincter injury was 0.78 (95%CI: 0.66–0.84) and 0.66 (95%CI: 0.51–0.79), respectively. For internal sphincter injury detection, this was 0.63 (95%CI: 0.50–0.74) and 0.71 (95%CI: 0.60–0.81), respectively. For detection of atrophy, this was 0.86 (95%CI: 0.71–0.95) and 0.82 (95%CI: 0.65–0.93), respectively. The area under the SROC curve and diagnostic odds ratio were 0.84 (SE = 0.07) and 6.14 (95%CI: 2.17–17.4) for external sphincter injury, 0.79 (SE = 0.07) and 4.60 (95%CI: 1.75–12.15) for internal sphincter injury, and 0.92 (SE = 0.08) and 21.49 (95%CI: 2.87–160.64) for sphincter atrophy. Endoanal MRI was sensitive and specific for the detection of external sphincter injury and especially sphincter atrophy. It may be useful as an alternative to endoanal ultrasound in patients presenting with fecal incontinence, although further clinical studies are needed to identify its best application in clinical practice.

Summary Background Narrow band imaging is a new endoscopic technology that highlights mucosal surface structures and microcapillaries, which may be indicative of neoplastic change. Aim To assess the diagnostic precision of narrow band imaging for the diagnosis of epithelial neoplasia compared to conventional histology both overall and in specific organs. Methods We performed a meta-analysis of studies which compared narow band imaging-based diagnosis of neoplasia with histopathology as the gold standard. Search terms: ‘endoscopy’ and ‘narrow band imaging’. Results Five hundred and eighty-two patients and 1108 lesions in 11 studies were included. Overall, sensitivity was 0.94 (95% confidence interval 0.92–0.95), specificity 0.83 (0.80–0.86); weighted area under the curve was 0.96 (standard error 0.02), diagnostic odds ratio (DOR) 72.74 (34.11–155.15). DORs were 66.65 (25.84–171.90), 61.19 (7.09–527.97), 69.74 (8.04–605.24) for colon, oesophagus and lung respectively. Studies with more than 50 patients had higher diagnostic precision, relative DOR 4.96 (1.28–19.27), P = 0.022. There was no difference in accuracy between microvessel and mucosal (pit) pattern based measures, relative DOR 1.29 (0.05–35.16), P = 0.87. There was significant heterogeneity overall between studies, Q = 31.2, P = 0.003. Conclusion Narrow band imaging is accurate with high diagnostic precision for in vivo diagnosis of neoplasia across a range of organs, using simple microvessel-based measures.

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.