Purpose: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. Methods: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. Results: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. Conclusion: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Introduction: Training and quality assurance in oesophagogastroduodenoscopy (OGD) is important to ensure competent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for OGD training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted with stakeholder representation from British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on OGD training and certification were formulated following literature review and appraised using Grading of Recommendations Assessment, Development and Evaluation. These were subjected to electronic voting to achieve consensus. Accepted statements were incorporated into the updated certification pathway. Results: In total, 32 recommendation statements were generated for the following domains: definition of competence (4 statements), acquisition of competence (12 statements), assessment of competence (10 statements) and post-certification support (6 statements). The consensus process led to following certification criteria: (1) performing ≥250 hands-on procedures; (2) attending a JAG-accredited basic skills course; (3) attainment of relevant minimal performance standards defined by British Society of Gastroenterology/Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, (4) achieving physically unassisted D2 intubation and J-manoeuvre in ≥95% of recent procedures, (5) satisfactory performance in formative and summative direct observation of procedural skills assessments. Conclusion: The JAG standards for diagnostic OGD have been updated following evidence-based consensus. These standards are intended to support training, improve competency assessment to uphold standards of practice and provide support to the newly-independent practitioner.

Background: Superior patient outcomes rely on surgical training being optimized. Accordingly, we conducted an international, prospective, cross-sectional study determining relative impacts of COVID-19, gender, race, specialty and seniority on mental health of surgical trainees. Method: Trainees across Australia, New Zealand and UK enrolled in surgical training accredited by the Royal Australasian College of Surgeons or Royal College of Surgeons were included. Outcomes included the short version of the Perceived Stress Scale, Oxford Happiness Questionnaire short scale, Patient Health Questionnaire-2 and the effect on individual stress levels of training experiences affected by COVID-19. Predictors included trainee characteristics and local COVID-19 prevalence. Multivariable linear regression analyses were conducted to assess association between outcomes and predictors. Results: Two hundred and five surgical trainees were included. Increased stress was associated with number of COVID-19 patients treated (P = 0.0127), female gender (P = 0.0293), minority race (P = 0.0012), less seniority (P = 0.001), and greater COVID-19 prevalence (P = 0.0122). Lower happiness was associated with training country (P = 0.0026), minority race (P = 0.0258) and more seniority (P < 0.0001). Greater depression was associated with more seniority (P < 0.0001). Greater COVID-19 prevalence was associated with greater reported loss of training opportunities (P = 0.0038), poor working conditions (P = 0.0079), personal protective equipment availability (P = 0.0008), relocation to areas of little experience (P < 0.0001), difficulties with career progression (P = 0.0172), loss of supervision (P = 0.0211), difficulties with pay (P = 0.0034), and difficulties with leave (P = 0.0002). Conclusion: This is the first study to specifically describe the relative impacts of COVID-19 community prevalence, gender, race, surgical specialty and level of seniority on stress, happiness and depression of surgical trainees on an international scale.

Background: Severe community-acquired pneumococcal pneumonia is commonly associated with bacteraemia. Although it is assumed that the bacteraemia solely derives from pneumococci entering the blood from the lungs it is unknown if other organs are important in the pathogenesis of bacteraemia. Using three models, we tested the relevance of the spleen in pneumonia-associated bacteraemia. Methods: We used human spleens perfused ex vivo to explore permissiveness to bacterial replication, a non-human primate model to check for splenic involvement during pneumonia and a mouse pneumonia-bacteraemia model to demonstrate that splenic involvement correlates with invasive disease. Findings: Here we present evidence that the spleen is the reservoir of bacteraemia during pneumonia. We found that in the human spleen infected with pneumococci, clusters with increasing number of bacteria were detectable within macrophages. These clusters also were detected in non-human primates. When intranasally infected mice were treated with a non-therapeutic dose of azithromycin, which had no effect on pneumonia but concentrated inside splenic macrophages, bacteria were absent from the spleen and blood and importantly mice had no signs of disease. Interpretation: We conclude that the bacterial load in the spleen, and not lung, correlates with the occurrence of bacteraemia. This supports the hypothesis that the spleen, and not the lungs, is the major source of bacteria during systemic infection associated with pneumococcal pneumonia; a finding that provides a mechanistic basis for using combination therapies including macrolides in the treatment of severe community-acquired pneumococcal pneumonia. Funding: Oxford University, Wolfson Foundation, MRC, NIH, NIHR, and MRC and BBSRC studentships supported the work.

Background: The service capacity for colonoscopy remains constrained, and while efforts are being made to recover elective services, polyp surveillance remains a challenge. (2) Methods: This is a multi-centre study recruiting patients already on polyp surveillance. Stool and urine samples were collected for the faecal immunochemical test (FIT) and volatile organic compounds (VOC) analysis, and all participants then underwent surveillance colonoscopy. (3) Results: The sensitivity and specificity of VOC for the detection of a high-risk finding ((≥2 premalignant polyps including ≥1 advanced polyp or ≥5 premalignant polyps) were 0.94 (95% CI, 0.88 to 0.98) and 0.69 (95% CI, 0.64 to 0.75) respectively. For FIT, the sensitivity was (≥10 µg of haemoglobin (Hb) / g faeces) 0.54 (95% CI, 0.43 to 0.65) and the specificity was 0.79 (95% CI, 0.73 to 0.84). The probability reduction for having a high-risk finding following both negative VOC and FIT will be 24% if both tests are applied sequentially. (4) Conclusion: The diagnostic performance of VOC is superior to FIT for the detection of a high-risk finding. The performance further improves when VOC is applied together with FIT sequentially (VOC first and then FIT). VOC alone or the combination of VOC and FIT can be used as a triage tool for patients awaiting colonoscopy within a polyp surveillance population, especially in resource-constrained healthcare systems.

Objective: To determine long-term outcomes of a randomized trial (BIOPEX) comparing biological mesh and primary perineal closure in rectal cancer patients after extralevator abdominoperineal resection and preoperative radiotherapy, with a primary focus on symptomatic perineal hernia. Summary background data: BIOPEX is the only randomized trial in this field, which was negative on its primary endpoint (30-day wound healing). Methods: This was a posthoc secondary analysis of patients randomized in the BIOPEX trial to either biological mesh closure (n = 50; 2 dropouts) or primary perineal closure (n = 54; 1 dropout). Patients were followed for 5 years. Actuarial 5-year probabilities were determined by the Kaplan-Meier statistic. Results: Actuarial 5-year symptomatic perineal hernia rates were 7% (95% CI, 0-30) after biological mesh closure versus 30% (95% CI, 10-49) after primary closure (P = 0.006). One patient (2%) in the biomesh group underwent elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P = 0.062). Reoperations for small bowel obstruction were necessary in 1/48 patients (2%) and 5/53 patients (9%), respectively (P = 0.208). No significant differences were found for chronic perineal wound problems, locoregional recurrence, overall survival, and main domains of quality of life and functional outcome. Conclusions: Symptomatic perineal hernia rate at 5-year follow-up after abdominoperineal resection for rectal cancer was significantly lower after biological mesh closure. Biological mesh closure did not improve quality of life or functional outcomes.

Introduction: Recurrence after surgery for pilonidal sinus disease is a recognised problem and patients often re-present months after discharge. We routinely treat primary and recurrent pilonidal sinus disease with Pilonidal sinus Laser-Assisted Closure (PiLAC). Long-term outcomes following PiLAC surgery was examined following clinical and telephone review. Methods: All patients undergoing PiLAC as a day-case between April 2016 and July 2019 were included. Patients were followed up in a nurse-led clinic until complete healing or recurrence. A prospective database and retrospective audit of notes combined with longer-term follow-up by telephone were used. Results: A total of 35 patients underwent PiLAC, median age 28 (18-53 years), 28 males:7 females. A total of 28 patients had long-term (>60 days) follow-up, mean 407 days (range 67-887 days); 25/28 patients (89.3%) had healed with no recurrence on long-term follow-up. Of these 28 patients, 11 were first presentation of pilonidal disease and underwent PiLAC as their first treatment, with a 91% heal rate long term. A total of 15 patients had seton drainage prior to PiLAC, with a 93% heal rate versus no seton (83%). Fisher's exact test showed no significant difference between sex, new/recurrent pilonidal disease and seton placement (p>0.05). Conclusions: Healing after PiLAC for the treatment of primary and recurrent pilonidal sinus disease is preserved with excellent long-term outcomes. We recommend it as an alternative to surgical excision.

Understanding patient concerns regarding skin surgery during the COVID-19 pandemic is a vital way of learning from individual experiences. A shift towards using superficial absorbable sutures (AS) has been anecdotally observed. We explored patient attitudes to the use of AS, and their experiences and perceptions of attending for skin surgery during the pandemic. In total, 35 participants were interviewed (74% men, 100% white British; mean age 72.5 years, range 43-95 years). Participants reported that they were reassured by precautions taken to minimize exposure and risk from COVID-19. The majority (86%) did not feel that personal protective equipment worn by staff impaired their experience, and 29% reported that their experience of attending for skin surgery during the lockdown period was more efficient and organized than on prepandemic visits. The vast majority (94%) of participants would opt to have AS again or had no strong preference for either suture type. Based on their experiences, most participants would have no concerns about attending for further skin surgery during the pandemic and would opt to have AS.

Background: Ulceration is a recognized risk factor for surgical site infection (SSI); however, the proportion of patients developing SSI after excision of an ulcerated skin cancer is unknown. Aim: To determine the proportion of participants with SSI after surgical excision of an ulcerated skin cancer. A secondary aim was to assess feasibility outcomes to inform the design of a randomized controlled trial to investigate the benefits and harms of perioperative antibiotics following excision of ulcerated tumours. Methods: This was a multicentre, prospective, observational study of patients undergoing excision of an ulcerated skin cancer between March 2019 and March 2020. Prior to surgical excision, surface swabs of the ulcerated tumours of participants recruited from one centre were undertaken to determine organism growth. At 4 weeks after surgery, all participants were e-mailed or posted the Wound Healing Questionnaire (WHQ) to determine whether they had developed SSI. Results: In total, 148 participants were recruited 105 (70.9%) males; mean ± SD age 77.1 ± 12.3 years. Primary outcome data were available for 116 (78.4%) participants, of whom 35 (30.2%) were identified as having an SSI using the WHQ with a cutoff score of 8, and 47 (40.5%) were identified with a cutoff score of 6. Using the modified WHQ in participants with wounds left to heal by secondary intention, 33 (28.4%) and 43 (37.1%) were identified to have SSI respectively. Conclusion: This prospective evaluation of SSI identified with the WHQ following excision of ulcerated skin cancers demonstrated a high proportion with SSI. The WHQ was acceptable to patients; however, further evaluation is required to ensure validity in assessing skin wounds.

Background: Angiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). According to previous studies, miR-378a participates in tumorigenesis and tumor metastasis, but its exact role in HCC angiogenesis remains poorly understood. Methods: qRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by Cell Counting Kit-8 (CCK-8), Transwell, tube formation and Matrigel plug assays, RNA sequencing, bioinformatics, luciferase reporter, immunofluorescence and chromatin immunoprecipitation (ChIP) assays were used to detect the molecular mechanism by which miR-378a-3p inhibits angiogenesis. Results: We confirmed that miR-378a-3p expression was significantly downregulated and associated with higher microvascular density (MVD) in HCC; miR-378a-3p downregulation indicated a short survival time in HCC patients. miR-378a-3p knockdown led to a significant increase in angiogenesis in vitro and in vivo. We found that miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then downregulated secreted vascular endothelial growth factor. DNA methyltransferase 1 (DNMT1)-mediated hypermethylation of miR-378a-3p was responsible for downregulating miR-378a-3p. Moreover, a series of investigations indicated that p65 initiated a positive feedback loop that could upregulate DNMT1 to promote hypermethylation of the miR-378a-3p promoter. Conclusion: Our study indicates a novel DNMT1/miR-378a-3p/TRAF1/NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.