Circular RNA as a source of neoantigens for cancer vaccines.

BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8+ T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids. RESULTS: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC. CONCLUSIONS: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities.

Pan-cancer pervasive upregulation of 3' UTR splicing drives tumourigenesis.

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3' UTR splicing and present this in SpUR ( http://www.cbrc.kaust.edu.sa/spur/home/ ). 3' UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3' UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB1 3' UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3' UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3' UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.

Academy of Medicine, Singapore clinical guideline on the use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting.

INTRODUCTION: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. METHODS: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. RESULTS: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. CONCLUSION: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting.

MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers.

3'UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers. MYC overexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of the MYC 3'UTR in cancer, and identify miR-138 as a potent regulator of the heterogenous MYC transcript population.

Multimodal prehabilitation before major abdominal surgery: A retrospective study.

INTRODUCTION: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme. METHODS: Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation. RESULTS: There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (P=0.150) or major complications (P=0.690) were noted. Patients in the prehabilitation group were observed to ambulate a longer distance and participate more actively with their physiotherapists from postoperative day 1 until 4. In the subgroup of patients with cancer, more patients had undergone neoadjuvant therapy in the prehabilitation group compared to the control group (21.7% versus 12.6%, P=0.009). Prehabilitation patients were more likely to proceed to adjuvant chemotherapy (prehabilitation 87.2% vs control 65.6%, P<0.001) if it had been recommended. CONCLUSION: The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.

Successful use of tissue expander and pelvic sling to exclude small bowel for high-dose pelvic irradiation.

OBJECTIVE: Our study seeks to describe our surgical technique of the use of a tissue expander and a pelvic sling in order to perform high-dose pelvic irradiation without incurring radiation toxicity to the small bowel. High-dose radiation therapy for pelvic tumours comes at a risk of radiation toxicity to the small bowel. Our study discusses our novel surgical technique of compartmentalising the abdomen and the pelvis through the use of a tissue expander and pelvic sling to avoid small bowel radiation toxicity. METHODS: We present a patient with an unresectable sacral chordoma. We describe our surgical technique incorporating both a tissue expander and an absorbable pelvic mesh sling to successfully compartmentalise the abdomen from the pelvis. RESULTS: The patient underwent an uneventful surgical procedure to place the tissue expander within the pelvis and deploy the pelvic mesh sling. Following surgery, a separation of at least 8 cm was achieved between bowel loops and the tumour. A dose of 70 Gy delivered over 35 fractions using intensity modulated radiotherapy (IMRT) was administered to the sacral chordoma, whilst managing to constrain the maximum bowel dose to 35.7 Gy. Surgery to remove the tissue expander was uneventful. The patient has not suffered any small bowel irradiation toxicity. CONCLUSIONS: Our technique to exclude small bowel from the pelvis is effective and safe. This technique not only can be applied in the setting of unresectable sacral chordomas but also may be applicable to other pelvic cancers which require radiation therapy.

Longitudinal monitoring reveals dynamic changes in circulating tumor cells (CTCs) and CTC-associated miRNAs in response to chemotherapy in metastatic colorectal cancer patients.

We evaluated the changes in CTC count and CTC-associated miRNAs during the course of chemotherapy in patients with metastatic colorectal cancer. Blood samples were collected from 9 metastatic colorectal cancer patients prior to chemotherapy and at every other chemotherapy session during the course of treatment. CTCs were isolated and enumerated using a size-exclusion method (CellSievo, Singapore). CTC-associated miRNAs were isolated using a paper-based, partitioning method, and analyzed using reverse transcription quantitative real-time PCR (MiRXES, Singapore). CTC count trends generally correlated with disease progression defined by radiological measurements and trends in carcinoembryonic antigen (CEA) levels; hence CTC counts may be useful in cases where CEA is not elevated. CTC-associated miRNAs identified were miR-15b, miR-16, miR-19a, miR-21, miR-25, miR-30d, miR-126, miR-185, miR-221, miR-222, and miR-324-5p. The expression of CTC-associated miRNAs did not appear to correlate with CTC count and exhibited inter-individual heterogeneity. This pilot study suggests that analysis of CTC changes during the course of treatment may be useful in monitoring response to therapy in metastatic colorectal cancer.

Outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery for locally advanced rectal cancer: a single-institution experience.

INTRODUCTION: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) surgery for locally advanced rectal cancer has been shown to improve local control and reduce toxicity, as compared to adjuvant CRT. We reported the outcomes of our patients with locally advanced rectal cancer treated at National University Hospital, Singapore. METHODS: From April 2002 to December 2014, 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT followed by TME surgery. The treatment regimen comprised a total radiotherapy dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil or capecitabine chemotherapy over 5.5 weeks. All patients were planned for TME surgery. Local control, disease-free survival, overall survival and treatment toxicities were analysed. RESULTS: Median follow-up was 34 (range 2-122) months. 11.5% (13/113) of patients achieved a pathological complete response (pCR) and 72.6% (85/117) had either tumour or nodal downstaging following neoadjuvant CRT. 5.2% (5/96) of patients had Grade 3 acute toxicities (dermatitis and diarrhoea) and 3.1% (3/96) had Grade 3 late toxicities (fistula and stricture). There was no Grade 4 toxicity noted. The five-year local recurrence, disease-free survival and overall survival rates were 4.5%, 65.7% and 80.6%, respectively. Multivariate analysis showed that nodal positivity was a predictor of poor disease-free survival and poor overall survival. Tumour downstaging and pCR did not improve outcomes. CONCLUSION: Our outcomes were comparable to internationally published data, and this treatment regimen remains the standard of care for locally advanced rectal cancer in our local population.

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer.

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

Analysis of colorectal cancer glyco-secretome identifies laminin ß-1 (LAMB1) as a potential serological biomarker for colorectal cancer.

The high mortality rate in colorectal cancer is mostly ascribed to metastasis, but the only clinical biomarker available for disease monitoring and prognosis is the carcinoembryonic antigen (CEA). However, the prognostic utility of CEA remains controversial. In an effort to identify novel biomarkers that could be potentially translated for clinical use, we collected the secretomes from the colon adenocarcinoma cell line HCT-116 and its metastatic derivative, E1, using the hollow fiber culture system, and utilized the multilectin affinity chromatography approach to enrich for the secreted glycoproteins (glyco-secretome). The HCT-116 and E1 glyco-secretomes were compared using the label-free quantitative SWATH-MS technology, and a total of 149 glycoproteins were differentially secreted in E1 cells. Among these glycoproteins, laminin ß-1 (LAMB1), a glycoprotein not previously known to be secreted in colorectal cancer cells, was observed to be oversecreted in E1 cells. In addition, we showed that LAMB1 levels were significantly higher in colorectal cancer patient serum samples as compared to healthy controls when measured using ELISA. ROC analyses indicated that LAMB1 performed better than CEA at discriminating between colorectal cancer patients from controls. Moreover, the diagnostic performance was further improved when LAMB1 was used in combination with CEA.

Laparoscopic colorectal surgery is safe and benefits octogenarian patients with malignant disease: a matched case-control study comparing laparoscopic and open colorectal surgery.

PURPOSE: Increased physiological stress from laparoscopic surgery and the lower physiological reserves in the elderly are causes for concern. This study aims to compare the outcomes between laparoscopic and open colorectal surgery in octogenarians. METHODS: Octogenarians who underwent elective colorectal resections from 2000 to 2011 were reviewed. Patients who underwent laparoscopic surgery were matched for comorbidities, T-staging and type of resection performed to patients with open surgery. RESULTS: Each group had 36 patients. Both groups were comparable for median age (85 vs 83, p = 0.43), gender (21 vs 18 males, p = 0.64) and the American Society of Anaesthesiologists (ASA) score (p = 0.486). Both groups had comparable median maximal tumour dimensions (4.75 vs 4.25 cm, p = 0.38) and median number of lymph nodes harvested (15 vs 14, p = 0.94). The laparoscopic group had, however, a longer median operative time (167.5 vs 124.5 min, p < 0.001). Both groups had comparable median length of hospitalisation (8 vs 7, p = 0.83), number of complications with a grade of complication (GOC) of ≥3 (5 vs 7, p = 0.75) and 30-day mortality rates (8.3 vs 5.6%, p = 1.00). One-year survival rate for the open group was lower (75.0 vs 94.4%, p = 0.09). CONCLUSIONS: Despite a longer operating time, laparoscopic surgery had comparable short-term outcomes and might have a long-term survival benefit.

Long-term outcome following advancement flaps for high anal fistulas in an Asian population: a single institution's experience.

BACKGROUND: The management of high anal fistula is often complicated and challenging. In spite of numerous new techniques, the advancement flap technique remained an integral procedure in its management. The purpose of this study was to determine the long-term outcome of advancement flap procedures for high anal fistulas. METHODS: A retrospective review of patients who have undergone an advancement flap procedure for high anal fistula of cryptoglandular origin from June 2003 to April 2012 was performed. Patients were contacted via telephone to evaluate their continence status using the Wexner score. RESULTS: Sixty-one patients with a median age of 48 (range, 19-74) years and a median follow-up of 6.5 (range, 1-59) months were evaluated. Fifty-three (86.9 %) patients had successful surgery while 8 (13.1 %) failed the procedure. Four of them underwent subsequent surgery. Of the 53 patients who had a successful procedure, 27 were successfully contacted for a telephone interview. Twenty-one (77.8 %) of them reported a Wexner score of '0'. Two (7.4 %) patients had a Wexner score of <4, another 2 had a score of '4' and '10', while the last 2 patients had a score of >10. CONCLUSION: Advancement flap procedure is effective in the management of high anal fistulas with an acceptable success rate. The majority of the patients experienced good anal continence.

Does the timing of an invasive mesenteric angiography following a positive CT mesenteric angiography make a difference?

BACKGROUND: Computed tomographic mesenteric angiography (CTMA) is integral in the management of patients with acute lower gastrointestinal tract bleeding (LGIB). An invasive mesenteric angiography (MA) with a view to embolize the site of bleeding is usually performed if active contrast extravasation was seen on the CTMA scans. However, the bleeding may have ceased by the time the invasive MA is performed. This study aims to identify predictors for active extravasation in invasive MA following a positive CTMA in patients with massive LGIB. METHODOLOGY: A single-center retrospective study of all patients who underwent an invasive MA following a positive CTMA for LGIB from August 2007 to October 2013 was performed. Comparison was performed between patients who had positive and negative invasive MA after a positive CTMA. RESULTS: Forty-eight invasive MA scans were performed in patients with LGIB following a positive CTMA scan. Twenty-three (47.9%) were due to diverticular disease while 20 (41.7%) bled from the small bowel. The median delay from a positive CTMA to invasive MA was 144 (32-587) min. Of the 48 invasive MA, 25 demonstrated active extravasation. Invasive MA scans that was performed within 90 min after a positive CTMA scan were 8.56 (95% CI 0.96-76.1, p = 0.05) times more likely to detect a positive extravasation. CONCLUSION: Invasive MA should be executed promptly after a positive CTMA to increase the probability of detecting the site of bleed to allow superselective embolization.

Caecal pneumatosis is not an absolute contraindication for endoluminal stenting in patients with acute malignant large bowel obstruction.

BACKGROUND: The computed tomographic (CT) finding of caecal pneumatosis in patients with malignant large bowel obstruction has been associated with ischaemia and impending perforation. Emergency surgery is then usually performed without consideration of endoluminal stenting. The aim of our study was to correlate caecal viability to the CT finding of caecal pneumatosis in patients with acute malignant large bowel obstruction. METHODS: A retrospective review of the CT scans of all patients presenting with acute malignant large bowel obstruction was performed. Patients with CT evidence of caecal pneumatosis were identified and this was correlated with intraoperative and histopathological findings. RESULTS: There were 10 patients who had caecal pneumatosis on their CT scans between 2007 and 2010. Five underwent immediate surgery while the other five had emergency endoluminal stenting performed. One failed the stenting procedure and proceeded to emergency surgery. The other four were stented successfully and underwent interval surgery in an elective setting. In the six patients who underwent emergency surgery, four were found to have a viable caecum intra-operatively and underwent a segmental resection. The remaining two had an ischaemic caecum--one had curvilinear pneumatosis and the other had a predominantly bubbly pattern of pneumatosis on their CT scans. CONCLUSION: Caecal pneumatosis alone is not a reliable predictor of caecal viability in patients with acute malignant large bowel obstruction. Such a finding on CT scan should be correlated clinically before excluding the role of endoluminal stenting.

Surgical pitfalls in patients with Ehlers-Danlos type IV: a case of spontaneous sigmoid perforation in a 17-year-old male.

Ehlers-Danlos syndrome (EDS) is a group of well described connective tissue disorders in which collagen production is impaired. The surgical management of affected individuals remains challenging, with no general consensus. We report a case of spontaneous sigmoid perforation in a 17-year-old Eurasian male, in whom we subsequently established the diagnosis of EDS type IV (EDS-IV). We review the literature to discuss the clinical features and diagnosis, and the recommended therapeutic management.

Artificial bowel sphincter implantation for faecal incontinence in Asian patients.

BACKGROUND: To evaluate the outcomes with the American Medical Systems artificial bowel sphincter (ABS) implantation for the treatment of intractable faecal incontinence in an Asian population. METHODS: Six Asian patients who underwent ABS implantation between March 2004 and December 2007 for the treatment of faecal incontinence were reviewed. RESULTS: The ABS was successfully implanted in six patients [mean age 50 (20-73) years; 4 males]. The most common causes of incontinence were congenital anomaly of the anus (imperforate anus status post a pull-through procedure) and status-post ultralow anterior resection. Two patients required device explantation due to postoperative infection. One eventually required a colostomy. After a mean follow-up of 22 (4-36) months, four patients continued to have a functional artificial bowel sphincter. Faecal incontinence severity scores improved from a mean of 13 (12-14) to 6 (0-9) postactivation. Anal manometry showed an increase in mean resting pressures (19.2 +/- 7.5 mmHg vs. postimplantation with cuff inflated 45.0 +/- 12.0 mmHg). The comparative preoperative and postactivation faecal incontinence quality of life scores showed improvement in all aspects. CONCLUSIONS: Patients with successful ABS implantation benefited from improved outcomes in function and quality of life. Infection was the most common cause of failure in our patients.