An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease.

BACKGROUND: The ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriCol™), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery. METHODS: Using National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020-May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol™ test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory. Samples were processed using QIAamp® DNA Blood Midi kit to extract DNA and Quant-iT™ PicoGreen® dsDNA Reagent to quantify the retrieved DNA. DNA integrity was measured by Agilent TapeStation system. 25 ng of human amplifiable DNA was prepared for Next Generation Sequencing (NGS), which was performed on an Illumina NextSeq550 sequencer using the 300-cycle high output kit v2.5. RESULTS: This study assessed the first 300 patients enrolled to the ORI-EGI-02 Study (n = 800). 290/300 (96.67%) were eligible to undergo OriCol™ sampling procedure and 285/290 (98.27%) had a successful OriCol™ sample taken. After transportation, extraction and quantification of DNA, 96.20% (279/290) of the samples had NGS successfully performed for bioinformatic analysis. CONCLUSIONS: Our internal pilot study demonstrated that the OriCol™ sampling device can capture rectal mucus from unprepared bowel in subjects who could undergo a digital rectal examination. The technique could be applied irrespective of age, frailty, or co-morbidity. Completion of the study to 800 patients and analysis of NGS data for colorectal cancer mutations will now proceed.

Clinical management of high-output stoma: a systematic literature review and meta-analysis.

PURPOSE: High output is a common complication after stoma formation. Although the management of high output is described in the literature, there is a lack of consensus on definitions and treatment. Our aim was to review and summarise the current best evidence. METHODS: MEDLINE, Cochrane Library, BNI, CINAHL, EMBASE, EMCARE, and ClinicalTrials.gov were searched from 1 Jan 2000 to 31 Dec 2021 for relevant articles on adult patients with a high-output stoma. Patients with enteroatmospheric fistulas and case series/reports were excluded. Risk of bias was assessed using RoB2 and MINORS. The review was registered in PROSPERO (CRD42021226621). RESULTS: The search strategy identified 1095 articles, of which 32 studies with 768 patients met the inclusion criteria. These studies comprised 15 randomised controlled trials, 13 non-randomised prospective trials, and 4 retrospective cohort studies. Eighteen different interventions were assessed. In the meta-analysis, there was no difference in stoma output between controls and somatostatin analogues (g - 1.72, 95% CI - 4.09 to 0.65, p = 0.11, I2 = 88%, t2 = 3.09), loperamide (g - 0.34, 95% CI - 0.69 to 0.01, p = 0.05, I2 = 0%, t2 = 0) and omeprazole (g - 0.31, 95% CI  - 2.46 to 1.84, p = 0.32, I2 = 0%, t2 = 0). Thirteen randomised trials showed high concern of bias, one some concern, and one low concern. The non-randomised/retrospective trials had a median MINORS score of 12 out of 24 (range 7-17). CONCLUSION: There is limited high-quality evidence favouring any specific widely used drug over the others in the management of high-output stoma. Evidence, however, is weak due to inconsistent definitions, risk of bias and poor methodology in the existing studies. We recommend the development of validated core descriptor and outcomes sets, as well as patient-reported outcome measures.

Single centre experience of bilateral gracilis flap perineal reconstruction following extra-levator abdominoperineal excision.

AIM: A variety of tissue flaps have been described for the closure of perineal wounds following abdominoperineal excision of the rectum (APE) or exenteration for locally advanced/recurrent rectal cancer and salvage surgery for anal cancer. The aim of this study was to demonstrate the utility of the bilateral pedicled gracilis muscle flaps (BPGMFs) as a reconstruction option in these patients. This is of particular benefit when using a laparoscopic approach for the abdominal component of the operation, avoiding disruption of the abdominal wall and risk of herniation with other reconstruction options, e.g. vertical rectus abdominis myocutaneous flaps. METHOD: This is a retrospective single centre case series of patients who underwent reconstruction of perineal defects using BPGMFs using a novel weave technique, from January 2008 to August 2017. RESULTS: There were 25 patients (16 female), with a median follow-up of 19 months (3-102). The indications for BPGMFs were cancer resection (21) and perineal hernia (4). The median length of stay was 14 days (6-60). All-cause mortality was 36% within the follow-up period. A healed perineal wound was achieved in 72% of patients within 30 days (84% of patients received neoadjuvant chemoradiotherapy). The overall donor site complication rate was 20% (including infection, dehiscence, numbness, haematoma and seroma) and 28% for the perineal site (including infection, dehiscence and prolapse). CONCLUSIONS: BPGMFs provide an important option for reconstruction of the perineum particularly with a minimally invasive approach or with two stomas.

Incisional hernia following closure of loop ileostomy: The main predictor is the patient, not the surgeon.

BACKGROUND: Incisional hernia at the ileostomy site occurs in 0-48% of patients undergoing loop ileostomy closure. Risk factors for ileostomy-site hernia are not currently well understood. We explored the predictive value of patient and clinical factors for ileostomy-site hernias. METHOD: Loop ileostomy reversals undertaken between 1st January 2009 and 31st December 2013 were retrospectively evaluated. Preoperative patient data (BMI, age, gender, blood pressure, diabetes), surgical variables (preoperative ileostomy marking, intraoperative management (suture type, closure method), postoperative complications (≤30 days), approach, urgency, and chemotherapy, hospital stay, stoma closure interval, follow-up duration) were collected. Patients were followed up by clinical examination and postoperative imaging. RESULTS: 193 loop ileostomy reversals were identified. Operative indications included: colorectal cancer (n = 102, 52.8%); inflammatory bowel disease (n = 47, 24.3%); diverticulosis (n = 20, 10.4%); assorted indications (n = 19, 9.8%); and inflammatory fistulae (n = 5, 2.6%). Median duration of clinical follow-up was 20.5 months (0-69). Hernia occurred in 26 patients (13.5%), detected at a median of eight months post-reversal. Radiological follow-up occurred in 72% of patients and, as a reference standard, in 100% of patients diagnosed with a hernia. Concordance between clinical and radiological findings was 88.5%. Postoperative complications predicted higher hernia risk. BMI and preoperative blood pressure were significant hernia predictors. Differences in the type of suture material to close the defect (absorbable vs. non-absorbable) and stoma skin closure method (primary vs. secondary intention healing) were non-predictive of hernia. CONCLUSION: Whilst BMI and patient comorbidity are the major hernia predictors, variability in surgical practice does not constitute a significant risk factor for ileostomy-site incisional hernia.

Systematic review and meta-analysis of the role of metronidazole in post-haemorrhoidectomy pain relief.

AIM: Conventional haemorrhoidectomy is still considered the reference standard for the management of severe or recurrent haemorrhoids. Pain is reported by patients to be the most common postoperative complication. Although the literature lacks a consensus on its effectiveness, metronidazole is often used to reduce postoperative pain. We have performed a meta-analysis of all randomized controlled trials (RCTs) that investigated the use of metronidazole for pain relief after haemorrhoidectomy. METHOD: A systematic review was undertaken in accordance with the PRISMA protocol using the MESH headings 'haemorrhoidectomy', 'hemorhoidectomy', 'hemorrhoidectomy', 'haemorrhoid', 'metronidazole', 'Flagyl® ' 'antibiotic' and 'pain'. The search returned 421 articles of which eight were RCTs suitable for inclusion in the review with a total population of 437 patients. The outcomes of interest were postoperative pain intensity on days 1, 2 and 7 and on first defaecation as measured using a visual analogue scale. RESULTS: The meta-analysis demonstrated a significant reduction in postoperative pain for patients treated with metronidazole with a reduced mean difference for the metronidazole group on day 1 of -1.42 (95% CI: -2.14 to -0.69, P = 0.0001), on day 2 of -1.43 (95% CI: -2.45 to -0.40, P = 0.006) and on day 7 of -2.40 (95% CI: -3.10 to -1.71, P < 0.00001). Pain on first defaecation was likewise reduced with a mean difference of -1.38 (95% CI: -2.15 to -0.60, P = 0.0005). Limitations of this study include variation in the grade of haemorrhoids treated and variability in the quality of included studies. CONCLUSION: Metronidazole is a cheap, safe and effective intervention for reducing postoperative pain following conventional haemorrhoidectomy.

Meta-analysis of closure of the fascial defect during laparoscopic incisional and ventral hernia repair.

BACKGROUND: Laparoscopic incisional and ventral hernia repair (LIVHR) is being used increasingly, with reported outcomes equivalent to those of open hernia repair. Closure of the fascial defect (CFD) is a technique that may reduce seroma formation and bulging after LIVHR. Non-closure of the fascial defect makes the repair of larger defects easier and reduces postoperative pain. The aim of this systematic review was to determine whether CFD affects the rate of adverse outcomes, such as recurrence, pseudo-recurrence, mesh eventration or bulging, and the rate of seroma formation. METHODS: A systematic search was performed of PubMed, Ovid, the Cochrane Library, Google Scholar and Scopus to identify RCTs that analysed CFD with regard to rates of adverse outcomes. A meta-analysis was done using fixed-effect methods. The primary outcome of interest was adverse events. Secondary outcomes were seroma, postoperative pain, mean hospital stay, mean duration of operation and surgical techniques employed. RESULTS: A total of 16 studies were identified involving 3638 patients, 2963 in the CFD group and 675 in the non-closure of facial defect group. Significantly fewer adverse events were noted following CFD than non-closure (4·9 per cent (79 of 1613) versus 22·3 per cent (114 of 511)), with a combined risk ratio (RR) of 0·25 (95 per cent c.i. 0·18 to 0·33; P < 0·001). CFD resulted in a significantly lower rate of seroma (2·5 per cent (39 of 1546) versus 12·2 per cent (47 of 385)), with a combined RR of 0·37 (0·23 to 0·57; P < 0·001), and shorter duration of hospital stay. No significant difference was noted in postoperative pain. CONCLUSION: CFD during LIVHR reduces the rate of seroma formation and adverse hernia-site events.

The impact of cardiopulmonary exercise testing on patients over the age of 80 undergoing elective colorectal cancer surgery.

AIM: Advanced age and occult cardiorespiratory disease are associated with increased morbidity and mortality following surgery. Cardiopulmonary exercise testing (CPET) may allow the identification of high-risk patients and facilitate planned postoperative critical care support. The aim of this study was to determine whether preoperative CPET in patients aged over 80 undergoing elective colorectal cancer resection was associated with improved outcome. METHOD: All patients aged 80 years and above undergoing elective colorectal cancer resection between 1 March 2011 and 1 September 2013 were retrospectively analysed. Referral for CPET testing was at the discretion of the operating surgeon. Postoperative critical care unit (CCU) admission was based upon the CPET results. RESULTS: Ninety-four patients were identified, of whom 48 underwent CPET testing. The CPET group were significantly older than the non-CPET group (85 vs 83 years, P = 0.04) and were more likely to have a planned admission to CCU postoperatively (P < 0.0001). Despite the increased use of CCU resources, the overall CCU length of stay (LOS) in the CPET group did not differ from the non-CPET group, but the non-CPET group had a higher proportion of Level-3 care. There were no differences in the incidence of unplanned CCU admission between the CPET and the non-CPET group (P = 0.23). There were no differences in overall LOS between the two groups (P = 0.42). There was no difference in mortality (P = 0.11), overall complications (P = 0.53) or severe complications (P = 0.3). CONCLUSION: Preoperative CPET testing in patients aged over 80 undergoing elective colorectal cancer resection allows identification of higher-risk patients and mitigation of risk by preemptive admission to a CCU. This stratification allows equivalent results to be achieved in high- and low-risk elderly patients undergoing colorectal surgery.

Delayed absorbable synthetic plug (GORE® BIO-A®) for the treatment of fistula-in-ano: a systematic review.

AIM: Recent advances in the treatment of fistula-in-ano have focused on surgical techniques that preserve sphincter integrity. Plugs that obliterate the lumen of the fistula track have been proposed as one such method, and may be derived from biological or delayed absorbable synthetic materials. Biological plugs have highly variable results and have not been widely adopted. The aim of this systematic review was to assess the effectiveness and safety of a delayed absorbable synthetic plug (GORE® BIO-A®) for treatment of anal fistula. METHOD: A systematic review of all literature in the English language relevant to the use of a plug to treat anal fistula and published between 1 January 2008 and 15 February 2015 was carried out by searching MEDLINE, EMBASE and the Cochrane Library of Systematic Reviews/Controlled Trials for relevant literature. Relevant articles were identified, quality assessed using the methodological index for nonrandomized studies criteria and data were extracted by two independent researchers (SKN and NNA). The identified articles were assessed with regard to fistula healing rate, duration of follow-up and complication rates related to the use of delayed absorbable synthetic fistula plugs. RESULTS: Twenty six potential articles were identified from the literature search. Using the predefined inclusion and exclusion criteria, six were included in the final analysis, data extraction and data synthesis. Of these included in the review only three were prospective in design. Complete data were available for 187 of the 221 patients who underwent this treatment. The age of the participants ranged from 19 to 82 years. The fistula healing rates were reported to be between 15.8% and 72.7% at a follow-up ranging between 2 and 19 months. Early or delayed plug extrusion occurred in 16 (8.5%) of the 187 patients. Deterioration in continence was reported in 11 (5.8%) of 187 patients. CONCLUSION: There are insufficient high-quality data on the delayed absorbable synthetic (GORE® BIO-A®) fistula plug to draw meaningful conclusions regarding its effectiveness. It does, however, appear to be a simple and safe technique associated with low complication rates and a minor deterioration in continence in a few cases.

Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

AIM: There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. METHOD: An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. RESULTS: The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6-monthly physical examination to annual anoscopy ± biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old. CONCLUSION: Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s.

The use of an acellular porcine dermal collagen implant in the repair of complex abdominal wall defects: a European multicentre retrospective study.

BACKGROUND: The use of biological materials for the repair of complex abdominal wall defects has increased over the years; however, the role of these materials in routine practice remains unclear. The aim of the study was to evaluate clinical outcomes following the use of Permacol™ porcine collagen surgical implant in complex abdominal wall repair. METHODS: This subset analysis of seven European sites from a multicentre retrospective study included patients undergoing open or laparoscopic surgery and treated with Permacol™ surgical implant. Inguinal, parastomal, diaphragmatic, perineal, and hiatal repairs were excluded. Only patients with at least 12 months of follow-up after surgery were included. RESULTS: A total of 109 patients (56 males and 53 females) were included. Patients had a median of two comorbidities (range 0-6). Thirty-three per cent of patients were treated for recurrent hernia. All but one case used an open approach. Sixty-six per cent were Center for Disease Control wound class II-IV at the time of surgery. Fascial closure was achieved in 69%. Median follow-up length was 720 days (range 368-2857). Recurrence rates at 1 and 2 years were 9.2 and 18.3 %, respectively, and were higher in cases without fascial closure. One-year recurrence was higher following use of an onlay technique (P = 0.025). In a multivariate analysis, among 16 comorbidities examined only fascial closure significantly impacted 1-year recurrence (P = 0.049). CONCLUSIONS: Data from this large retrospective multicentre European study strongly suggest the use of Permacol™ porcine collagen surgical implant to be safe and effective for complex abdominal wall repair. The recurrence rate was impacted by fascial closure.

Is C-reactive protein useful in prognostication for colorectal cancer? A systematic review.

AIM: With the advent of several different therapeutic strategies to manage the different stages of colorectal cancer, it would be beneficial to allow substratification of patients into groups who are most likely to benefit from costly interventions. The purpose of this review is to analyse the evidence from several retrospective studies examining the prognostic significance of C-reactive protein (CRP). METHOD: A literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google Scholar databases to identify studies that analysed CRP and its prognostic significance in all stages of operable colorectal cancer. The primary end-points of interest were overall survival and disease-free survival. RESULTS: In all, 205 studies were identified by the search. Twelve involving 1705 patients fulfilled the inclusion criteria and were included. Three of the included studies including 305 patients considered Stage IV colorectal cancer and the impact of CRP on survival. Overall survival and disease-free survival were shorter in the presence of an elevated preoperative CRP in local and advanced colorectal cancer. CONCLUSION: CRP may be useful for prognosis in patients with primary and metastatic colorectal cancer, but currently there is insufficient evidence to justify its routine use. Further well-designed prospective studies are needed to validate its role in substratification of patients for consideration of (neo)adjuvant therapies.

Synthetic or biological mesh use in laparoscopic ventral mesh rectopexy--a systematic review.

AIM: Laparoscopic ventral mesh rectopexy (VMR) is a surgical option for internal and external rectal prolapse with low perioperative morbidity and low recurrence rates. Use of synthetic mesh in the pelvis may be associated with complications such as fistulation, erosion and dyspareunia. Biological meshes may avoid these complications, but the long-term outcome is uncertain. Debate continues as to which type of mesh is optimal for laparoscopic VMR. METHOD: A literature search was performed of electronic databases including MEDLINE, Embase and Scopus (2000-12). Studies describing outcomes relating to the mesh were included for review. Only English language studies were included. RESULTS: Thirteen observational studies reported the outcome of 866 patients following laparoscopic VMR. Eleven reported the outcome using synthetic mesh with a median follow-up ranging from 7 to 74 months. Two studies reported the outcome with biological mesh with a median follow-up of 12 months. Pooled analysis of the studies demonstrated that 767 patients had a repair with synthetic mesh and 99 with a biological implant. There was no difference in recurrence (3.7 vs 4.0%, P = 0.78) or mesh complications (0.7 vs 0%, P = 1.0%) between synthetic and biological mesh repair. CONCLUSION: Biological meshes appear to be as effective as synthetic meshes in the short term for laparoscopic VMR. Mesh complication rates are low in both groups. Long-term follow-up is required to ascertain if these findings persist.

Long-term follow-up of bilateral gracilis reconstruction following extra-levator abdominoperineal excision.

INTRODUCTION: Colorectal operations such as an extra-levator abdominoperineal (elAPE) excision for locally advanced or recurrent cancer create a significant perineal tissue deficit. Options for perineal reconstruction include bilateral pedicled gracilis muscle flaps (BPGMF). Fashioning the gracili into a 'weave' creates a muscular sling that supports pelvic contents and is a novel technique. Our series reports the outcomes of the BPGMF in 50 patients undergoing surgery for pelvic cancer. METHOD: This is a retrospective, single-centre study of patients undergoing reconstruction of perineal defects using BPGMF. All surgeries took place between January 2008 and February 2021. The primary outcome measured was perineal wound healing. The secondary outcomes measured were complications of surgical sites and length of hospital stay (short term), flap integrity on follow-up imaging and functional outcomes (long term). RESULTS: Fifty patients underwent perineal reconstruction using BPGMF (26 males). The median age was 62 years. The 30-day mortality was 2% (n = 1). The average follow-up period was 2 years. Complete perineal wound healing was 86% (42/49) at outpatient follow-up. Complication rates for the donor site and reconstructed site were 14% and 22%, respectively. Complications included infection (2% donor site, 12% perineum), haematoma (4% donor site), dehiscence (2% donor site, 4% perineum) and seroma (3% donor site, 2% perineum). CONCLUSION: BPGMF offers a reliable and technically simple muscle flap to reconstruct large perineal defects. The muscle flap integrity appears maintained on follow-up imaging despite a lack of flap monitoring tools. This cohort had minimal functional impairment following BPGMF.

The role of biologic meshes in abdominal wall reconstruction.

There are unacceptably high rates of recurrence following surgery for incision hernia repair using suture repair techniques in isolation. As the reconstruction of abdominal walls has expanded with complex surgery, the materials used as adjuncts to support the repair have changed. In the article we review the current use of biologic meshes in abdominal wall reconstruction and the techniques used.

Biologic meshes in perineal reconstruction following extra-levator abdominoperineal excision (elAPE).

Recent improvements in the outcome for low rectal cancer have focused on the reconstruction of the perineal defect following greater acceptance of the need for a wider perineal excision encompassing the levator ani complex. In this article we look at the use of biologic materials to close the perineal defect and compare this with the use of other techniques.

A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management?

AIM: The aim of the study was to assess the outcome of patients who received chemoradiotherapy (CRT) for locally advanced rectal cancer, specifically those with complete clinical response (CCR) and who were then managed nonoperatively with a 'Watch and Wait' follow-up protocol. METHOD: A retrospective study was carried out of patients undergoing preoperative CRT for rectal cancer, conducted in a district general hospital managing rectal cancer through the multidisciplinary team process. RESULTS: Forty-nine patients received preoperative CRT over a 5-year period (2004-2009). Twelve (24%) were considered potentially to have had a complete response on MRI. Of these, six subsequently had clinical evidence of residual disease, leading to surgery (mean time to surgery, 24 weeks; range, 12-36 weeks). The remaining six had CCR, avoiding surgery (mean follow up, 26 months; range, 12-45 months), with all six patients disease free to date. A further six patients had complete pathological response (CPR) following surgery after comprehensive histopathological assessment of the specimen. CONCLUSION: In this consecutive series of patients with locally advanced rectal cancer treated with CRT, 12% demonstrated a CCR and have been actively managed conservatively, thereby avoiding surgery. With further improvements in diagnostic assessment of response to CRT, this figure may rise.