When all seems lost: management of refractory constipation-Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more.

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited.

The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference.

BACKGROUND: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. AIM: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders. METHODS: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. RESULTS: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. CONCLUSIONS: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.

Surgery for constipation: systematic review and practice recommendations: Graded practice and future research recommendations.

AIM: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). METHODS: Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. RESULTS: The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. CONCLUSION: While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.

Surgery for constipation: systematic review and practice recommendations: Results V: Sacral Nerve Stimulation.

AIM: To assess the outcomes of sacral nerve stimulation in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Seven articles were identified, providing data on outcomes in 375 patients. Length of procedures and length of stay was not reported. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 13 and 34%, with overall device removal rate between 8 and 23%. Although inconsistently reported, pooled treatment success was typically 57-87% for patients receiving permanent implants, although there was significant variation between studies. Patient selection was inconsistently documented. No conclusions could be drawn regarding particular phenotypes that responded favourably or unfavourably to sacral nerve stimulation. CONCLUSION: Evidence supporting sacral nerve stimulation is derived from poor quality studies. Three methodologically robust trials are have reported since this review and all have all urged greater caution.

A prospective trial of temporary sacral nerve stimulation for constipation associated with neurological disease.

AIM: This study assessed the effectiveness of temporary sacral nerve stimulation (SNS) in patients with constipation associated with neurological disease using an off-on-off design, and evaluated the long-term response in patients undergoing permanent SNS. METHOD: Patients with chronic constipation associated with neurological disease receiving specialist clinic care at the University Hospital North Durham over a 2-year period were recruited to a trial of SNS. Recordings of bowel function were made for 6 weeks (baseline) and a temporary electrode was then inserted and recordings were made for the next 3 weeks (stimulation). The electrodes were then removed and assessment was continued for a further 3 weeks (posttreatment). Patient-completed questionnaires were used to determine the severity of constipation (Global Assessment of Symptoms, Constipation, GA Constipation), symptoms (Patient Assessment of Constipation Symptoms score, PAC-SYM) and quality-of-life (Patient Assessment of Constipation-Quality Of Life score, PAC-QOL; European Quality of Life-Five-Domain score; European Quality of Life-Visual Analogue Score). Information was obtained on bowel function and medication. Physiological data were also available for transit and laser Doppler flow cytometry to measure mucosal blood flow. RESULTS: Twenty-two patients were recruited, of whom 18 completed the trial. GA Constipation reduced significantly during temporary SNS: -1.09 (95% CI -1.59 to -0.59; P = 0.0003). PAC-SYM and PAC-QOL scores showed similar improvements. There was also a significant fall in the time spent in the toilet (P = 0.04) and a decrease in laxative use (P = 0.03). Twelve (67%) patients responded to temporary SNS and received a permanent implant with long-term success in 50%. CONCLUSION: Sacral nerve stimulation can be effective in treating some patients with refractory severe neuroconstipation. A response to temporary SNS may predict long-term benefit in only half the patients undergoing permanent SNS.

Blinded comparison of faecal loading on plain radiography versus radio-opaque marker transit studies in the assessment of constipation.

AIM: To compare faecal loading on plain radiography versus radio-opaque marker transit studies in the assessment of constipation. METHODS: The study group was a convenience sample of patients attending the Durham Constipation Clinic. All patients underwent transit studies according to an established protocol, and severity of constipation was assessed contemporaneously using a validated questionnaire (PAC-SYM). Transit studies were performed using radio-opaque markers that were ingested over 3 consecutive days, with a radiograph taken on the fourth day. Digital images of the radiograph were digitally altered to remove all traces of the transit markers without affecting the underlying pattern of faecal loading. Four observers assessed faecal loading independently; two clinicians (C1 and C2) and two radiologists (R1 and R2). C1 and R1 used a previously described formal scoring method of assessing faecal loading, whereas C2 and R2 assessed the images as if they were in a clinic or reporting session, grading the faecal loading as mild, moderate, or severe. RESULTS: One hundred patients were recruited out of 186 presenting in a 2-year period. All patients completed assessments. The correlation between observers was only fair to moderate (r ranging from 0.34-0.51). There were some surprisingly marked disagreements in 10-18% of assessments. The correlation between faecal loading and transit was weak for all observers (r ranging from 0.261-0.311). Symptom severity did not correlate with faecal loading. CONCLUSION: These results suggest that there is considerable inter-observer variation in the radiological assessment of faecal loading, irrespective of the training or method used by the observer, and that there is very poor correlation with colonic transit. The diagnosis of constipation, and the assessment of severity, is best performed clinically.

How good is zoom endoscopy for assessment of villous atrophy in coeliac disease?

BACKGROUND AND STUDY AIMS: The advent of magnification endoscopy may allow the macroscopic detection of unrecognised villous atrophy in patients with unsuspected coeliac disease. In addition, it may also be possible to use this method to assess the degree of villous atrophy. The aim of this study was to determine the accuracy of zoom endoscopy for the macroscopic evaluation of villous atrophy, in comparison with histological evaluation. PATIENTS AND METHODS: The zoom endoscope provided a magnification capability of x 115. A scoring system (Z score) was devised for grading the appearances of villous atrophy: "Z1" for normal mucosa, "Z2" for stunted villi, "Z3" for markedly stunted villi (with ridges and pits) and "Z4" for a flat mucosa. A total of 53 consecutive patients with treated coeliac disease were followed up over almost 2 years using the Olympus GIF-Q240Z zoom endoscope; a total of 80 procedures were carried out. Four biopsies from the second part of the duodenum were taken from each patient for histological assessment. Histological assessment of villous atrophy was made by a pathologist blinded to the Z score. The correlation between the Z score and the histological score was assessed using the weighted kappa method. RESULTS: The kappa score for the correlation between the macroscopic assessment of villous atrophy and the histology was 0.631, indicating fair to good reproducibility. Agresti's method revealed a very strong baseline association between the two methods ( P < 0.001). Zoom endoscopy had a positive predictive value of 83 % and a negative predictive value of 77 % in detecting villous atrophy. CONCLUSIONS: Our findings suggest that zoom endoscopy may be valuable in assessing the degree of villous atrophy. However, further studies are needed to assess its efficacy in routine practice as a screening or case-finding tool.