The PanSurg-PREDICT Study: Endocrine Surgery During the COVID-19 Pandemic.

BACKGROUND: In the midst of the COVID-19 pandemic, patients have continued to present with endocrine (surgical) pathology in an environment depleted of resources. This study investigated how the pandemic affected endocrine surgery practice. METHODS: PanSurg-PREDICT is an international, multicentre, prospective, observational cohort study of emergency and elective surgical patients in secondary/tertiary care during the pandemic. PREDICT-Endocrine collected endocrine-specific data alongside demographics, COVID-19 and outcome data from 11-3-2020 to 13-9-2020. RESULTS: A total of 380 endocrine surgery patients (19 centres, 12 countries) were analysed (224 thyroidectomies, 116 parathyroidectomies, 40 adrenalectomies). Ninety-seven percent were elective, and 63% needed surgery within 4 weeks. Eight percent were initially deferred but had surgery during the pandemic; less than 1% percent was deferred for more than 6 months. Decision-making was affected by capacity, COVID-19 status or the pandemic in 17%, 5% and 7% of cases. Indication was cancer/worrying lesion in 61% of thyroidectomies and 73% of adrenalectomies and calcium 2.80 mmol/l or greater in 50% of parathyroidectomies. COVID-19 status was unknown at presentation in 92% and remained unknown before surgery in 30%. Two-thirds were asked to self-isolate before surgery. There was one COVID-19-related ICU admission and no mortalities. Consultant-delivered care occurred in a majority (anaesthetist 96%, primary surgeon 76%). Post-operative vocal cord check was reported in only 14% of neck endocrine operations. Both of these observations are likely to reflect modification of practice due to the pandemic. CONCLUSION: The COVID-19 pandemic has affected endocrine surgical decision-making, case mix and personnel delivering care. Significant variation was seen in COVID-19 risk mitigation measures. COVID-19-related complications were uncommon. This analysis demonstrates the safety of endocrine surgery during this pandemic.

Factors associated with burnout syndrome in surgeons: a systematic review.

INTRODUCTION: To date, studies have shown a high prevalence of burnout in surgeons. Various factors have been found to be associated with burnout, and it has significant consequences personally and systemically. Junior doctors are increasingly placing their own health and wellbeing as the most important factor in their decisions about training. Finding ways to reduce and prevent burnout is imperative to promote surgical specialties as attractive training pathways. METHODS: The MEDLINE, PsychInfo and EMBASE databases were searched using the subject headings related to surgery and burnout. All full text articles that reported data related to burnout were eligible for inclusion. Articles which did not use the Maslach Burnout Inventory or included non-surgical groups were excluded; 62 articles fulfilled the criteria for inclusion. FINDINGS: Younger age and female sex tended to be associated with higher levels of burnout. Those further in training had lower levels of burnout, while residents suffered more than their seniors. Burnout is associated with a lower personal quality of life, depression and alcohol misuse. Academic work and emotional intelligence may be protective of burnout. Certain personality types are less likely to be burnt out. Mentorship may reduce levels of burnout. CONCLUSIONS: Workload and work environment are areas that could be looked at to reduce job demands that lead to burnout. Intervening in certain psychological factors such as emotional intelligence, resilience and mindfulness may help to reduce burnout. Promoting physical and mental health is important in alleviating burnout, and these factors likely have a complex interplay.

The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review.

BACKGROUND: Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities, such as diabetes. The metabolic improvements occur through both weight-dependent and weight-independent mechanisms. Bile acids (BAs) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery. This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery. METHODS: We conducted a systematic search of Medline and Embase databases to identify all articles investigating the role of BAs in mediating the metabolic changes observed following bariatric surgery in both animal and human studies. Boolean logic was used with relevant search terms, including the following MeSH terms: 'bile acids and salts', 'bariatric surgery', 'metabolic surgery', 'gastrointestinal tract/surgery' and 'obesity/surgery'. RESULTS: Following database searches (n=1197), inclusion from bibliography searches (n=2) and de-duplication (n=197), 1002 search results were returned. Of these, 132 articles were selected for full-text review, of which 38 articles were deemed relevant and included in the review. The findings support the effects of BAs on satiety, lipid and cholesterol metabolism, incretins and glucose homoeostasis, energy metabolism, gut microbiota and endoplasmic reticulum stress following bariatric surgery. Many of these metabolic effects are modulated through the BA receptors FXR and TGR5. We also explore a possible link between BAs and carcinogenesis following bariatric surgery. CONCLUSIONS: Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms. BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities.

Hand-sewn coloanal anastomosis for low rectal cancer: technique and long-term outcome.

AIM: This study compared the operative outcome and long-term survival of three types of hand-sewn coloanal anastomosis (CAA) for low rectal cancer. METHOD: Patients presenting with low rectal cancer at a single centre between 2006 and 2014 were classified into three types of hand-sewn CAA: type 1 (supra-anal tumours undergoing transabdominal division of the rectum with transanal mucosectomy); type 2 (juxta-anal tumours, undergoing partial intersphincteric resection); and type 3 (intra-anal tumours, undergoing near-total intersphincteric resection with transanal mesorectal excision). RESULTS: Seventy-one patients with low rectal cancer underwent CAA: 17 type 1; 39 type 2; and 15 type 3. The median age of patients was 61.6 years, with a male/female ratio of 2:1. Neoadjuvant therapy was given to 56 (79%) patients. R0 resection was achieved in 69 (97.2%) patients. Adverse events occurred in 25 (35.2%) of the 71 patients with a higher complication rate in type 1 vs type 2 vs type 3 (47.1% vs 38.5% vs 13.3%, respectively; P = 0.035). Anastomotic separation was identified in six (8.5%) patients and pelvic haematoma/seroma in five (7%); two (8.3%) female patients developed a recto-vaginal fistula. Ten (14.1%) patients were indefinitely diverted, with a trend towards higher long-term anastomotic failure in type 1 vs type 2 vs type 3 (17.6% vs 15.5% vs 6.7%). The type of anastomosis did not influence the overall or disease-free survival. CONCLUSION: CAA is a safe technique in which anorectal continuity can be preserved either as a primary restorative option in elective cases of low rectal cancer or as a salvage procedure following a failed stapled anastomosis with a less successful outcome in the latter. CAA has acceptable morbidity with good long-term survival in carefully selected patients.

Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis.

BACKGROUND: Current management of suspected appendicitis is hampered by the overadmission of patients with non-specific abdominal pain and a significant negative exploration rate. The potential benefits of risk stratification by the Appendicitis Inflammatory Response (AIR) score to guide clinical decision-making were assessed. METHODS: During this 50-week prospective observational study at one institution, the AIR score was calculated for all patients admitted with suspected appendicitis. Appendicitis was diagnosed by histological examination, and patients were classified as having non-appendicitis pain if histological findings were negative or surgery was not performed. The diagnostic performance of the AIR score and the potential for risk stratification to reduce admissions, optimize imaging and prevent unnecessary explorations were quantified. RESULTS: A total of 464 patients were included, of whom 210 (63·3 per cent) with non-appendicitis pain were correctly classified as low risk. However, 13 low-risk patients had appendicitis. Low-risk patients accounted for 48·1 per cent of admissions (223 of 464), 57 per cent of negative explorations (48 of 84) and 50·7 per cent of imaging requests (149 of 294). An AIR score of 5 or more (intermediate and high risk) had high sensitivity for all severities of appendicitis (90 per cent) and also for advanced appendicitis (98 per cent). An AIR score of 9 or more (high risk) was very specific (97 per cent) for appendicitis, and the majority of patients with appendicitis in the high-risk group (21 of 30, 70 per cent) had perforation or gangrene. Ultrasound imaging could not exclude appendicitis in low-risk patients (negative likelihood ratio (LR) 1·0) but could rule-in the diagnosis in intermediate-risk patients (positive LR 10·2). CT could exclude appendicitis in low-risk patients (negative LR 0·0) and rule-in appendicitis in the intermediate group (positive LR 10·9). CONCLUSION: Risk stratification of patients with suspected appendicitis by the AIR score could guide decision-making to reduce admissions, optimize utility of diagnostic imaging and prevent negative explorations.

Complete mesocolic excision in colorectal cancer: a systematic review.

AIM: Several studies have suggested an increased lymph node yield, reduced locoregional recurrence and increased disease-free survival after complete mesocolic excision (CME) for colorectal cancer. This review was undertaken to assess the use of CME for colon cancer by evaluating the technique and its clinical outcome. METHOD: A literature search of publications was performed using PubMed and Medline. Only studies published in English were included. Studies assessed for quality and data were extracted by two independent reviewers. End-points included number of lymph nodes per patient, quality of the plane of mesocolic excision, postoperative mortality and morbidity, 5-year locoregional recurrence and 5-year cancer-specific survival. RESULTS: There were 34 articles comprising 12 retrospective studies, nine prospective studies and 13 original articles including case series, observational studies and editorials. Of the prospective studies, four reported an increased lymph node harvest and a survival benefit. The others reported an improvement in the quality of the specimen as assessed by histopathological examination. Laparoscopic CME has the same oncological outcome as open surgery but completeness of excision during laparoscopy may be compromised for tumours in the transverse colon. CONCLUSION: Studies demonstrate that CME removes significantly more tissue around the tumour including maximal lymph node clearance. There is little information on serious adverse events after CME and a long-term survival benefit has not been proved.

Modified right colon inversion technique as a salvage procedure for colorectal or coloanal anastomosis.

AIM: A tension-free well vascularized colorectal or coloanal anastomosis is not always possible following rectal or sigmoid resection. The study reports on the short-term and long-term outcome of a modified right colon inversion technique as a means of facilitating a low colorectal or coloanal anastomosis. METHOD: All patients who underwent right colonic inversion, a modified Deloyers' procedure, were identified retrospectively from the prospective database of the Colorectal Department of the Royal Marsden Hospital from October 2008 to December 2013. RESULTS: There were 14 (nine male) patients of median age 58.7 (45-75) years. The main indication was extensive diverticular disease (50%) and previous colonic surgery (21.4%). A defunctioning stoma was performed in 64.3% which was reversed in all within 3-6 months. Three (21.4%) patients developed postoperative complications (Clavien-Dindo 1-2) and none required reoperation. The median duration of follow-up was 11 months. One (7.2%) patient had one bowel movement per day, 10 (71.4%) patients had two bowel movements per day and three (21.4%) patients had three per day. CONCLUSION: The modified right colonic inversion technique is safe and achieves intestinal continuity with a tension-free well vascularized anastomosis. Good function and low morbidity show that the procedure is a credible alternative to ileorectal or ileoanal anastomosis.

Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass spectrometry (MALDI-MSI) reveals novel cancer-associated field effects.

Matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-MSI) is a rapidly advancing technique for intact tissue analysis that allows simultaneous localisation and quantification of biomolecules in different histological regions of interest. This approach can potentially offer novel insights into tumour microenvironmental (TME) biochemistry. In this study we employed MALDI-MSI to evaluate fresh frozen sections of colorectal cancer (CRC) tissue and adjacent healthy mucosa obtained from 12 consenting patients undergoing surgery for confirmed CRC. Specifically, we sought to address three objectives: (1) To identify biochemical differences between different morphological regions within the CRC TME; (2) To characterise the biochemical differences between cancerous and healthy colorectal tissue using MALDI-MSI; (3) To determine whether MALDI-MSI profiling of tumour-adjacent tissue can identify novel metabolic 'field effects' associated with cancer. Our results demonstrate that CRC tissue harbours characteristic phospholipid signatures compared with healthy tissue and additionally, different tissue regions within the CRC TME reveal distinct biochemical profiles. Furthermore we observed biochemical differences between tumour-adjacent and tumour-remote healthy mucosa. We have referred to this 'field effect', exhibited by the tumour locale, as cancer-adjacent metaboplasia (CAM) and this finding builds on the established concept of field cancerisation.

Single-incision laparoscopic surgery (SILS) vs. conventional multiport cholecystectomy: systematic review and meta-analysis.

BACKGROUND: Single-incision laparoscopic surgery (SILS) has gained increasing attention due to the potential to maximize the benefits of laparoscopic surgery. The aim of this systematic review and pooled analysis was to compare clinical outcome following SILS and standard multiport laparoscopic cholecystectomy for the treatment of gallstone-related disease. METHODS: An electronic search of Embase and Medline databases for articles from 1966 to 2011 was performed. Publications were included if they were randomised controlled studies in which patients underwent either single-incision or multiport cholecystectomy. The primary outcome measures for the meta-analysis were postoperative complications and postoperative pain score [visual analogue scale (VAS) on the day of surgery]. Secondary outcome measures were operating time and length of hospital stay. Weighted mean difference was calculated for the effect size of SILS on continuous variables, and pooled odds ratios were calculated for discrete variables. RESULTS: In total, 375 cholecystectomy operations from 7 randomised controlled trials were included, 195 by single-incision (SILS) and 180 by conventional multiport. Operating time was significantly longer in the SILS group compared to the standard multiport laparoscopic cholecystectomy group (weighted mean difference = 2.13; P = 0.0001). There was no significant difference in the incidence of postoperative complications, postoperative pain score (VAS), or the length of hospital stay between the two groups. CONCLUSION: The results of this meta-analysis demonstrate that single-incision laparoscopic cholecystectomy is a safe procedure for the treatment of uncomplicated gallstone disease, with postoperative outcome similar to that of standard multiport laparoscopic cholecystectomy. Future high-powered randomized studies should be focused on elucidating subtle differences in postoperative complications, reported postoperative pain, and cosmesis following SILS cholecystectomy in more severe biliary disease.

Robotic vs. laparoscopic Roux-en-Y gastric bypass in morbidly obese patients: systematic review and pooled analysis.

BACKGROUND: The aim of this study was to provide pooled analysis of individually small trials comparing robotic Roux-en-Y gastric bypass (RRYGB) with standard laparoscopic RYGB (LRYGB). METHODS: A systematic literature search of Medline, Embase and Cochrane Library databases was performed. Primary outcome measures were the incidence of anastomotic leak and stricture. Secondary outcome measures were post-operative complications, operative time and length of hospital stay. RESULTS: Seven relevant studies of 1686 patients were included in this analysis. There was a significantly reduced incidence of anastomotic stricture in the robotic group (POR = 0.43; 95% CI = 0.19 to 0.98; p = 0.04). There was no significant difference between robotic and laparoscopic groups for anastomotic leak, post-operative complications, operative time and length of hospital stay. CONCLUSION: The incidence of anastomotic stricture was reduced with RRYGB compared with LRYGB over a minimum follow-up period of 6 months, thus demonstrating the potential benefit of RRYGB.

Intraperitoneal chemotherapy as first-line treatment in the management of epithelial ovarian cancer.

Recent evidence has suggested improved outcomes following incorporation of intraperitoneal chemotherapy administration with intravenous systemic chemotherapy as first-line treatment of small volume residual epithelial ovarian cancer. This review focuses on the mechanism of actions of the chemotherapeutic drugs and reviews the possible reasons for the superior outcomes of intraperitoneal chemotherapy.

The detection of DNA tumour virus-specific RNA sequences in abnormal human cervical biopsies by in situ hybridization.

We have used the technique of in situ nucleic acid hybridization and autoradiography of thin frozen sections of human tissue to search for virus RNA sequences in human cervical tumours. Of cervical biopsies with abnormal cytology, 67% bound herpes simplex virus type 2 (HSV2) 3H-labelled DNA probes and 39% bound adenovirus type 2 (Ad2) 3H-labelled DNA probes, whereas control experiments with phage lambda 3H-labelled DNA probes, under the same conditions, bound to only 7% of cases. In contrast, normal cervical biopsies bound the three probes in only 23%, 17% and 8% of cases respectively.

Normal human tissues contain RNA and antigens related to infectious adenovirus type 2.

Normal human tissues have been found to contain RNA which hybridises with four regions of the adenovirus type 2 genome, including one which contains the transforming gene(s) of this virus. The RNAs have also been extracted from gorilla organs, but not from those of chickens, suggesting that they are a feature of all normal higher primate tissues. Serological test suggest that these homologous RNAs are translated into proteins connected with essentially normal and virus-infected cell functions.

BSu restriction of DNA from cases exhibiting sex-chromosome abnormalities.

The restriction endonuclease BSu, an isoschizomer of the enzyme HaeIII, cleaves human DNA to yield classes of fragments that are characteristic of the DNA of individuals having a Y chromosome. The fragments concerned are therefore diagnostic of the presence of Y-chromosome DNA and have been studied here with the intention of confirming the origin of various translocations thought, on other grounds, to involve the Y. The absence of the fragments from DNA of a case exhibiting absence of the fluorecent region of Yq suggests that the DNA concerned maps predominantly to Yq. Normal gender in the absence of the BSu fragments indicates that they do not function in sex determination.

The kinetics of derepression of prophage lambda following ultraviolet irradiation of lysogenic cells.

Double lysogens for prophages lambda cI+ and lambda cI ind-ts-857 are induced only by the combined effects of ultraviolet (UV) irradiation and high temperature, not by either treatment alone (Sussman and Jacob, 1962). We have followed the kinetics of inactivation of the cI+ repressor brought about by irradiation in asynchronously and synchronously growing cultures of B/r (lambda cI ind- ts-857). Assays of the yield of phage released as a result of temporary thermal inactivation of the UV-resistant ind- ts-857 repressor at intervals after the irradiation accurately reflect the time course of UV-induced inactivation of the cI+ repressor. The results show that UV-induced derepression takes place in all cells of the population approximately 20 min after the irradiation whether the cells were growing asynchronously or synchronously. Hence UV induction of prophage lambda is not triggered at a particular stage in the cell cycle.