Protocol for the UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study).

AIM: Abdominal surgery sometimes necessitates the creation of a stoma, which can cause future complications including parastomal hernia (PSH), an incisional hernia adjacent to and related to the stoma. PSH affects approximately 40% of patients within 2 years of stoma formation. Complications of PSH reduce a patient's quality of life and can be severe (e.g. bowel obstruction). PSHs are difficult to manage and can recur after surgical repair. Therefore, it is very important to prevent a PSH. Surgeons create stomas in different ways and both patient and surgical factors are believed to influence the development of PSH. The aim of the CIPHER study is to investigate the influence of different surgical techniques on the development of PSH. METHOD: The UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study) aims to recruit 4000 patients undergoing elective or expedited surgery with the intention of forming an ileostomy or colostomy, irrespective of the primary indication for the planned surgery. For each patient, surgeons will describe their methods of trephine formation, mesh reinforcement of the stoma trephine, use of the stoma as a specimen extraction site and wound closure. The primary outcome will be incident PSH during follow-up, defined as symptoms of PSH (custom-designed questionnaire) and anatomical PSH, ascertained by independent reading of usual care CT scans. Secondary outcomes will include surgical site infection, the Comprehensive Complication Index, quality of life (EQ-5D-5L and SF-12), PSH repair and use of NHS resources. RESULTS: Results of the study will be submitted for publication in peer-reviewed journals. All publications relating to the results of CIPHER will use a corporate authorship, 'The CIPHER Study Investigators' with named writing committee members. CONCLUSION: The CIPHER study will be the first to investigate detailed surgical methods of stoma formation in a large, representative cohort of patients with a range of primary indications, both cancer and noncancer.

A systematic review of new treatments for cryptoglandular fistula in ano.

AIM: In 2007 the ACPGBI published a position statement on the management of cryptoglandular fistula in ano. Over the last seven years a number of new treatments have been developed and the aim of this systematic review was to assess their effectiveness. METHOD: A systematic review of all English language literature relevant to novel treatment strategies for cryptoglandular fistula in ano, published between 1 January 2007 and 31 Dec 2014 was carried out using MEDLINE (PubMed and Ovid), EMBASE (Ovid) and the Cochrane Library of Systematic Reviews/Controlled Trials for relevant literature. Technical notes, commentaries, letters and meeting abstracts were excluded. The different treatments were assessed with regards to fistula closure rate in relation to length of follow up and reported complications. RESULTS: Seventy potential articles published between 1 January 2007 and 31 December 2014 were identified from the initial literature search. Twenty-one articles were included for final analysis although only two were randomized controlled trials, the remainder being retrospective or prospective series. CONCLUSION: This systematic review has demonstrated that whilst there have been technological advances to treat complex cryptoglandular fistula in ano, these are in an early stage of evolution and although early results were promising they are difficult to reproduce. Longer follow up data is not currently available and these treatments should not be introduced without further evidence.

Genetic, epigenetic and environmental factors in diverticular disease: systematic review.

BACKGROUND: Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop diverticulitis in their lifetime. Many patients present emergently, suffer high morbidity rates and require substantial healthcare resources. Diverticulosis is the most common finding at colonoscopy and has the potential for causing a significant morbidity rate and burden on healthcare. There is a need to better understand the aetiology and pathogenesis of diverticular disease. Research suggests a genetic susceptibility of 40-50% in the formation of diverticular disease. The aim of this review is to present the hypothesized functional effects of the identified gene loci and environmental factors. METHODS: A systematic literature review was performed using PubMed, MEDLINE and Embase. Medical subject headings terms used were: 'diverticular disease, diverticulosis, diverticulitis, genomics, genetics and epigenetics'. A review of grey literature identified environmental factors. RESULTS: Of 995 articles identified, 59 articles met the inclusion criteria. Age, obesity and smoking are strongly associated environmental risk factors. Intrinsic factors of the colonic wall are associated with the presence of diverticula. Genetic pathways of interest and environmental risk factors were identified. The COLQ, FAM155A, PHGR1, ARHGAP15, S100A10, and TNFSF15 genes are the strongest candidates for further research. CONCLUSION: There is increasing evidence to support the role of genomics in the spectrum of diverticular disease. Genomic, epigenetic and omic research with demographic context will help improve the understanding and management of this complex disease.

Did the 'Be Clear on Bowel Cancer' public awareness campaign pilot result in a higher rate of cancer detection?

OBJECTIVES: To assess the impact of a 7-week public bowel cancer awareness campaign pilot by reviewing the number of 2-week referrals from general practitioners (GPs) to hospital, endoscopic procedures and new cancers diagnosed throughout the five acute hospitals in The Peninsular Cancer Network, UK. DESIGN: A retrospective before and after study. SETTING: The Peninsula Cancer Network in the South West of England, UK. MAIN OUTCOME MEASURES: For the period July 2010-July 2011, data were collected on the number of 2-week referrals, number of endoscopic procedures performed and number of new cancers diagnosed. The average for the 6 months before the campaign was compared with the immediate 3 months and then the fourth to sixth months following the campaign. Student's t test was used to compare the means of the three groups. RESULTS: There was a statistically significant increase in the number of 2-week referrals from GPs to hospital in the 3 months following the campaign but this effect disappeared after that. There was no statistical increase in the number of endoscopic procedures or new cancers diagnosed following the awareness campaign. CONCLUSIONS: The pilot 'Be Clear on Cancer' awareness campaign had a significant effect on the number of patients being referred from GPs to hospital; however, the effect was short lived and had returned to baseline by 3 months. The campaign had no effect on the number of new cancers diagnosed, which was the stated underlying aim of the pilot.

Exfoliated colonocyte DNA levels and clinical features in the diagnosis of colorectal cancer: a cohort study in patients referred for investigation.

AIM: Selection of patients for investigation of suspected colorectal cancer is difficult. One possible improvement may be to measure DNA isolated from exfoliated cells collected from the rectum. METHOD: This was a cohort study in a surgical clinic. Participants were aged ≥40 years and referred for investigation of suspected colorectal cancer. Exclusion criteria were inflammatory bowel disease, previous gastrointestinal malignancy, or recent investigation. A sample of the mucocellular layer of the rectum was taken with an adapted proctoscope (the Colonix system). Haemoglobin, mean cell volume, ferritin, carcino-embryonic antigen and faecal occult bloods were tested. Analysis was by logistic regression. RESULTS: Participation was offered to 828 patients, of whom 717 completed the investigations. Three were lost to follow up. Seventy-two (10%) had colorectal cancer. Exfoliated cell DNA was higher (P<0.001) in cancer (median 5.4 µg/ml [inter-quartile range 1.8,12]) compared with those without cancer (2.0 µg/ml [IQR 0.78,5.5]). Seven variables were independently associated with cancer, including age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02,1.08; P<0.001) DNA (OR, 1.05; CI, 1.01,3.6; P=0.01), mean cell volume (OR, 0.93; CI, 0.89,0.97; P=0.001), carcino-embryonic antigen 1.02 per µg/l (CI, 1.00,1.04; P=0.02), male sex (OR, 2.0; CI, 1.1,3.6; P=0.02), rectal bleeding (OR, 2.4; CI, 1.3,4.5; P=0.007) and positive faecal occult blood (OR, 6.7; CI, 3.4, 13; P<0.001). The area under the receiver-operating characteristic curve for the DNA score was 0.65 (0.58-0.72) and for the seven variable model 0.88 (CI, 0.84-0.92). CONCLUSION: Quantification of exfoliated DNA from rectal cellular material has promise in the diagnosis of colorectal cancer, but this requires confirmation in a larger study.

Biological meshes: a review of their use in abdominal wall hernia repairs.

PURPOSE: Biological meshes are mostly used in infected fields within complex abdominal wall hernia repairs. There is no consensus, however, on the most appropriate material to be used in a given situation. METHODS: A literature review of published articles reporting the utilization of biological meshes in ventral/incisional hernia repair was conducted. Data were analyzed to compare the recurrence rates obtained with biological meshes. MAIN FINDINGS: Only a few prospective comparative studies were identified. Most publications relate to AlloDerm®, Permacol™ and Surgisis™ with data from other meshes insufficient to draw conclusions. AlloDerm has a 0-100% recurrence rate among studies. It compares poorly with Surgisis and results in an unfavorable outcome when used as a 'bridge prosthesis'. Permacol has consistent recurrence rates of 0-15%, whatever the patients' profiles or the context of infected fields, when considering the most relevant studies. The Surgisis results are more conflicting: the mesh exhibits low recurrence rates in clean fields, but in infected fields the recurrence rate is up to 39%. CONCLUSION: Taken together, these studies suggest that the cross-linked mesh, Permacol has the lowest failure rate and the longest time to failure, particularly in contaminated or infected fields. However, this data should be confirmed by large prospective randomized studies.

Quality of life in restorative versus non-restorative resections for rectal cancer: systematic review.

BACKGROUND: Low rectal cancers could be treated using restorative (anterior resection, AR) or non-restorative procedures with an end/permanent stoma (Hartmann's, HE; or abdominoperineal excision, APE). Although the surgical choice is determined by tumour and patient factors, quality of life (QoL) will also influence the patient's future beyond cancer. This systematic review of the literature compared postoperative QoL between the restorative and non-restorative techniques using validated measurement tools. METHODS: The review was registered on PROSPERO (CRD42020131492). Embase and MEDLINE, along with grey literature and trials websites, were searched comprehensively for papers published since 2012. Inclusion criteria were original research in an adult population with rectal cancer that reported QoL using a validated tool, including the European Organization for Research and Treatment of Cancer QLQ-CR30, QLQ-CR29, and QLQ-CR38. Studies were included if they compared AR with APE (or HE), independent of study design. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Outcomes of interest were: QoL, pain, gastrointestinal (GI) symptoms (stool frequency, flatulence, diarrhoea and constipation), and body image. RESULTS: Nineteen studies met the inclusion criteria with a total of 6453 patients; all papers were observational and just four included preoperative evaluations. There was no identifiable difference in global QoL and pain between the two surgical techniques. Reported results regarding GI symptoms and body image documented similar findings. The ROBINS-I tool highlighted a significant risk of bias across the studies. CONCLUSION: Currently, it is not possible to draw a firm conclusion on postoperative QoL, pain, GI symptoms, and body image following restorative or non-restorative surgery. The included studies were generally of poor quality, lacked preoperative evaluations, and showed considerable bias in the data.

Root-cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice. AIM: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC. We matched patients with IBD-associated CRC to patients with CRC in the general population to identify differences in staging at diagnosis and clinical outcomes. RESULTS: Compared with the general population, patients with IBD were at increased risk of developing CRC (odds ratio 2.7 [95% CI 1.6-3.9], P < 0.001). The mean incidence of IBD-associated CRC between 1998 and 2019 was 165.4 (IQR 130.4-199.4) per 100 000 patients and has not changed over the last 20 years. Seventy-eight patients had IBD-associated CRC. Forty-two (54%) patients were eligible for CRC surveillance: 12% (5/42) and 10% (4/42) patients were diagnosed with CRC at an appropriately timed or overdue surveillance colonoscopy, respectively. Interval cancers occurred in 14% (6/42) of patients; 64% (27/42) of patients had a missed opportunity for colonoscopic surveillance where root-cause analyses demonstrated that 10/27 (37%) patients known to secondary care had not been offered surveillance. Four (15%) patients had a delayed diagnosis of CRC due to failure to account for previous colonoscopic findings. Seventeen (63%) patients were managed by primary care including seven patients discharged from secondary care without a surveillance plan. Matched case-control analysis did not show significant differences in cancer staging or 10-year survival outcomes. CONCLUSION: The incidence of IBD-associated CRC has remained static. Two-thirds of patients eligible for colonoscopic surveillance had missed opportunities to diagnose CRC. Surveillance programmes without comprehensive and fully integrated recall systems across primary and secondary care are set to fail.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Patients with low rectal cancer treated by abdominoperineal excision have worse tumors and higher involved margin rates compared with patients treated by anterior resection.

PURPOSE: Patients with low rectal cancer have worse outcomes compared to those with upper rectal cancer. Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. We looked at a recent series of patients with low rectal cancer to explore some of the issues. METHODS: We analyzed 153 patients from the MERCURY study with low rectal cancer (

Major surgery induces acute changes in measured DNA methylation associated with immune response pathways.

Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

Magnetic resonance imaging prediction of an involved surgical resection margin in low rectal cancer.

PURPOSE: Low rectal cancers (<5 cm from the anal verge), compared with all others, have greater positive resection margin rates, attributed to mesorectal tapering and higher perforation risk. The aim of this study was to assess positive resection margin prediction by using magnetic resonance imaging staging. METHODS: The following features were analyzed by using preoperative magnetic resonance imaging from 101 consecutive patients with low rectal tumors: tumor location (posterior/anterior) and magnetic resonance stage (Stage 1-2, tumor within the intersphincteric plane; Stage 3-4 tumor extending into the intersphincteric plane). Magnetic resonance imaging tumor regression grade was measured where posttreatment magnetic resonance imaging was available and compared with histopathologic findings. RESULTS: Seventy of 101 patients had abdominoperineal excisions, and 31 of 101 had low anterior resections. Using logistic regression, positive resection margin odds were higher for magnetic resonance Stages 3 to 4 than Stages 1 to 2 by a factor of 17.7 (P < 0.001), and positive resection margin odds were higher by a factor of 2.8 for anterior vs. posterior tumors (P = 0.026). Magnetic resonance imaging tumor regression grade strongly predicted for positive resection margins; 11 of 15 patients with little treatment response had positive resection margins, compared with 2 of 15 with >50 percent complete treatment response on magnetic resonance imaging (P < 0.001). CONCLUSION: Significant magnetic resonance imaging positive resection margin predictors are tumor into or beyond the intersphincteric plane and magnetic resonance imaging tumor regression grade.

A case report of squamous cell carcinoma in a suprapubic urinary catheter tract: surgical excision and simultaneous colostomy formation.

Squamous cell carcinoma (SCC) arising from a suprapubic cystostomy tract is a rare complication of long-term suprapubic catheterization (SPC). A 53-year-old man with paraplegia secondary to spina bifida presented with a painful granulomatous lesion around his SPC site that was being treated with silver nitrate cauterization in the community. Consequently, he developed a sacral pressure sore due to reduced mobility from the pain. He also had increasing difficulties with defaecation secondary to his spina bifida. His sacral pressure sore was secondary to a cryptoglandular fistula with coccygeal osteomylelitis. Post-operative pathology revealed infiltrative SCC involving full thickness of the specimen from skin to the bladder wall with clear surgical margins. We describe the first case requiring a simultaneous suprapubic tract SCC excision and colostomy formation. We recommend early investigation of lesions arising from a long-term suprapubic tract especially in patients with spinal cord injuries or congenital defects.

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer.

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.

Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.

BACKGROUND: In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth. METHODS: We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1, 2016, to May 5, 2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to São Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean θ as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934. FINDINGS: We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11, 1990, and Feb 13, 2017, with a median follow-up of 37·6 months (IQR 25·0-58·7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21·4% (random-effects 95% CI 15·3-27·6), with high levels of between-study heterogeneity (I2=61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1·40, 95% CI 1·00-1·94; ptrend=0·048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1·50, random-effects 95% CI 1·03-2·17; ptrend=0·0330). We estimated that measured factors contributed 4·8-45·3% of observed between-centre heterogeneity. INTERPRETATION: In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response. FUNDING: None.

Retro-rectus repair of complex incisional hernia leads to low recurrence rate.

BACKGROUND: To assess the outcome of retro-rectus repair of complex abdominal wall repair (CAWR) in a single institution in relation to the use of biologic and synthetic mesh. METHOD: A retrospective review was undertaken of complex abdominal wall repairs performed by a single surgical team, assessing the outcome of the retro-rectus repair and factors affecting the outcome. RESULTS: Between 2007 and 2013, 57 (33 male) patients underwent CAWR retro-rectus repair. The material used was assessed as either synthetic or biologic (cross-linked porcine dermal collagen). The Ventral Hernia Working Group grades were similar between groups of patients having a repair with synthetic and biologic mesh. Median follow-up in the synthetic group was 18 months (1-80.5) and 18.4 months (0.5-70.7) in the biologic group. There was no statistical difference in seroma, wound infection or haematoma rates. No fistulae occurred in either group. Overall recurrence was 3.4% and there was no statistical difference between groups. CONCLUSION: The retro-rectus repair technique is associated with a low rate of recurrence and is now the technique of choice. The choice of material, biologic or synthetic, in Ventral Hernia Working Group grades 1-3 remains controversial.