The Promise of Single-Cell RNA Sequencing to Redefine the Understanding of Crohn's Disease Fibrosis Mechanisms.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a high prevalence throughout the world. The development of Crohn's-related fibrosis, which leads to strictures in the gastrointestinal tract, presents a particular challenge and is associated with significant morbidity. There are currently no specific anti-fibrotic therapies available, and so treatment is aimed at managing the stricturing complications of fibrosis once it is established. This often requires invasive and repeated endoscopic or surgical intervention. The advent of single-cell sequencing has led to significant advances in our understanding of CD at a cellular level, and this has presented opportunities to develop new therapeutic agents with the aim of preventing or reversing fibrosis. In this paper, we discuss the current understanding of CD fibrosis pathogenesis, summarise current management strategies, and present the promise of single-cell sequencing as a tool for the development of effective anti-fibrotic therapies.

Day case laparoscopic cholecystectomy at Kilimanjaro Christian Medical Centre, Tanzania.

INTRODUCTION: The Lancet Commission on Global Surgery has promoted the case for safe, affordable surgical care in low- and middle-income countries (LMICs). In 2017, Kilimanjaro Christian Medical Centre (KCMC) in Tanzania introduced a day case laparoscopic cholecystectomy (DCLC) service, the first of its kind in Sub-Saharan Africa (SSA). We aimed to evaluate this novel service in terms of safety, feasibility and acceptability by patients and staff. METHODS: This study used mixed methods and was split into two stages. In stage 1, we reviewed records of all laparoscopic cholecystectomies (LCs) comparing day cases and admissions. These patients were followed up with a telephone questionnaire to investigate complication rates and receive service feedback. Stage 2 consisted of semi-structured interviews with staff exploring the challenges KCMC faced in implementing DCLC. RESULTS: 147 laparoscopic cholecystectomies were completed: 109 were planned for DCLC, 82 (75.2%) of which were successful, whilst 27 (24.8%) patients were admitted. No variables significantly predicted unplanned admission, the commonest causes for which were pain and nausea. In the DCLC group there was 1 readmission. 62 patients answered the follow up questionnaire, 60 (97%) of which were satisfied with the service. Stage 2 interviews suggested staff to be motivated for DCLC but revealed poor organisation of the day case pathway. CONCLUSION: High rates of DCLC combined with low rates of complications and readmission suggests DCLC is feasible at KCMC. However, staff interviews alluded to administrative problems preventing KCMC from reaching its full DCLC potential. A dedicated day case surgery unit would address most of these problems.

Perforated sigmoid diverticulitis: Hartmann's procedure or resection with primary anastomosis-a systematic review and meta-analysis of randomised control trials.

INTRODUCTION: The surgical management of perforated sigmoid diverticulitis and generalised peritonitis is challenging. Surgical resection is the established standard of care. However, there is debate as to whether a primary anastomosis (PA) or a Hartmann's procedure (HP) should be performed. The aim of the present study was to perform a review of the literature comparing HP to PA for the treatment of perforated sigmoid diverticulitis with generalised peritonitis. METHODS: A systematic literature search was performed for articles published up to March 2018. We considered only randomised control trials (RCTs) comparing the outcomes of sigmoidectomy with PA versus HP in adults with perforated sigmoid diverticulitis and generalised peritonitis (Hinchey III or IV). Primary outcomes were mortality and permanent stoma rate. Outcomes were pooled using a random-effects model to estimate the risk ratio and 95% confidence intervals. RESULTS: Of the 1,204 potentially relevant articles, 3 RCTs were included in the meta-analysis with 254 patients in total (116 and 138 in the PA and HP groups, respectively). All three RCTs had significant limitations including small size, lack of blinding and possible selection bias. There was no statistically significant difference in mortality or overall morbidity. Although 2 out of the 3 trials reported a lower permanent stoma rate in the PA arm, the difference in permanent stoma rates was not statistically significant (RR = 0.40, 95% CI 0.14-1.16). The incidence of anastomotic leaks, including leaks after stoma reversal, was not statistically different between PA and HP (RR = 1.42, 95% CI 0.41-4.87, p = 0.58) while risk of a postoperative intra-abdominal abscess was lower after PA than after HP (RR = 0.34, 95% CI 0.12-0.96, p = 0.04). CONCLUSIONS: PA and HP appear to be equivalent in terms of most outcomes of interest, except for a lower intra-abdominal abscess risk after PA. The latter finding needs further investigation as it was not reported in any of the individual trials. However, given the limitations of the included RCTs, no firm conclusion can be drawn on which is the best surgical option in patients with generalised peritonitis due to diverticular perforation.

Protocol for a multicentre, prospective, observational cohort study of variation in practice in perioperative analgesic strategies in elective laparoscopic colorectal surgery: the LapCoGesic Study.

INTRODUCTION: Laparoscopic surgery combined with enhanced recovery programmes has become the gold standard in the elective management of colorectal disease. However, there is no consensus with regard to the optimal perioperative analgesic regime in this cohort of patients, with a number of options available, including thoracic epidural spinal analgesia, patient-controlled analgesia, subcutaneous and/or intraperitoneal local anaesthetics, local anaesthetic wound infiltration catheters and transversus abdominis plane blocks. This study aims to explore any differences in analgesic strategies employed across the North East of England and to assess whether any variation in practice has an impact on clinical outcomes. METHODS AND ANALYSIS: All North East Colorectal units will be recruited for participation by the Northern Surgical Trainees Research Association (NoSTRA). Data will be collected over a consecutive 2-month period. Outcome measures will include postoperative pain score, postoperative opioid analgesic use and side effects, length of stay, 30-day complication rates, 30-day reoperative rates and 30-day readmission rates. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the National Research Ethics Service. The protocol will be disseminated through NoSTRA. Individual unit data will be presented at local meetings. Overall collective data will be published in peer-reviewed journals and presented at relevant surgical meetings.

A case of syphilitic anal condylomata lata mimicking malignancy.

INTRODUCTION: Condylata lata in secondary syphilis is well known presentation and needs to be considered in differential diagnosis of perianal lesions. In England between 2013 and 2014 the overall incidence of infectious syphilis increased by 33% and is mainly seen in men who have sex with men. PRESENTATION OF CASE: We report the management of a 49-years-old Caucasian homosexual man with perianal lesions that were suspicious of malignancy. After biopsies, colonoscopy, staging with computed tomography, magnetic resonance imaging and syphilis serology anal cancer was excluded and a diagnosis of syphilis was confirmed. He was referred to the sexual health clinic for the appropriate investigations and treatment. DISCUSSION: This case highlights the consideration of treatable infectious syphilis pathology. The main differential diagnosis of perianal growths to consider is condylomata acuminata (warts caused by human papillomavirus), anal cancer, syphilis, chancroid, haemorrhoids, tuberculosis and lymphogranuloma venereum. To differentiate a biopsy is needed for histopathological examination. A dense plasma cell infiltrate and numerous spirochetes visualised by immunostaining confirms condylomata lata. CONCLUSION: In UK, it is important for colorectal surgeons to be aware of syphilitic condylomata lata and consider this when dealing with perianal lesions. It is advisable to refer patients suspected of or diagnosed with syphilis to sexual health clinics to help improve outcome. In sexual health clinics additional investigations and treatment are available in addition to partner notification and follow-up can be offered.

Does mixing acute medical admissions with burn patients increase infective complications from paediatric thermal injuries?

In the winter of 2005-2006, the management at our children's hospital elected to admit 'overspill' acute medical admissions to the ward used for plastic surgery and burns for logistical reasons. This study was conducted to assess the effects of that change on the incidence of infective complications in thermally-injured patients. Seventy-three patients were studied, 23 in the sample winter and 50 in the two preceding control winters. The data gathered included days on IV fluids and antibiotics, transfer to the Paediatric Intensive Care Unit (PICU), microbiology and a 'septic signs score' - based on pyrexia, irritability, diarrhoea/vomiting, wound colonization, bacteraemia. The outcomes studied were: the maximum 'septic signs score'; patients with a score ≥3; wound colonization; PICU admission; days on antibiotics and IV fluids. A statistically significant increase in patients with septic episodes was demonstrated by an increase in the mean septic signs score (0.66-1.48, P = 0.044) and the number of patients with a score ≥3 (4-22%, P = 0.017). Other analysed variables did not reach statistical significance although the raw data suggested a trend. It was concluded that there is an association between mixing acute medical admissions with thermally-injured patients and an increase in the incidence of infective complications in the latter group.