Showing papers in "British Journal of Surgery in 2019"

Age of patients undergoing surgery

Abstract: Background Advancing age is independently associated with poor postoperative outcomes. The ageing of the general population is a major concern for healthcare providers. Trends in age were studied among patients undergoing surgery in the National Health Service in England. Methods Time trend ecological analysis was undertaken of Hospital Episode Statistics and Office for National Statistics data for England from 1999 to 2015. The proportion of patients undergoing surgery in different age groupings, their pooled mean age, and change in age profile over time were calculated. Growth in the surgical population was estimated, with associated costs, to the year 2030 by use of linear regression modelling. Results Some 68 205 695 surgical patient episodes (31 220 341 men, 45·8 per cent) were identified. The mean duration of hospital stay was 5·3 days. The surgical population was older than the general population of England; this gap increased over time (1999: 47·5 versus 38·3 years; 2015: 54·2 versus 39·7 years). The number of people aged 75 years or more undergoing surgery increased from 544 998 (14·9 per cent of that age group) in 1999 to 1 012 517 (22·9 per cent) in 2015. By 2030, it is estimated that one-fifth of the 75 years and older age category will undergo surgery each year (1·49 (95 per cent c.i. 1·43 to 1·55) million people), at a cost of €3·2 (3·1 to 3·5) billion. Conclusion The population having surgery in England is ageing at a faster rate than the general population. Healthcare policies must adapt to ensure that provision of surgical treatments remains safe and sustainable.

Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

Abstract: BACKGROUND Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

Norwegian moratorium on transanal total mesorectal excision.

Abstract: A national decision

Impact of resection margin status on recurrence and survival in pancreatic cancer surgery.

Abstract: Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor and selection of patients for surgery is challenging. This study examined the impact of a positive resection margin (R1) on locoregional recurrence (LRR) and overall survival (OS); and also aimed to identified tumour characteristics and/or technical factors associated with a positive resection margin in patients with PDAC. Methods: Patients scheduled for pancreatic resection for PDAC between 2006 and 2016 were identified from an institutional database. The effect of resection margin status, patient characteristics and tumour characteristics on LRR, distant metastasis and OS was assessed. Results: A total of 322 patients underwent pancreatectomy for PDAC. A positive resection (R1) margin was found in 129 patients (40·1 per cent); this was associated with decreased OS compared with that in patients with an R0 margin (median 15 (95 per cent c.i. 13 to 17) versus 22 months; P < 0·001). R1 status was associated with reduced time to LRR (median 16 versus 36 (not estimated, n.e.) months; P = 0·002). Disease recurrence patterns were similar in the R1 and R0 groups. Risk factors for early recurrence were tumour stage, positive lymph nodes (N1) and perineural invasion. Among 100 patients with N0 disease, R1 status was associated with shorter OS compared with R0 resection (median 17 (10 to 24) versus 45 (n.e.) months; P = 0·002), whereas R status was not related to OS in 222 patients with N1 disease (median 14 (12 to 16) versus 17 (15 to 19) months after R1 and R0 resection respectively; P = 0·068). Conclusion: Although pancreatic resection with a positive margin was associated with poor survival and early recurrence, particularly in patients with N1 disease, disease recurrence patterns were similar between R1 and R0 groups.

Meta‐analysis of recurrence pattern after resection for pancreatic cancer

Abstract: Background Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors. Methods MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated. Results Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07). Conclusion Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.

Mortality after liver surgery in Germany

Abstract: BACKGROUND Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or outcome quality. METHODS Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis-Related Groups, ICD-10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Lander in Wiesbaden, Germany. RESULTS A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume-outcome relationship for CRLM surgery in very high-volume centres (mean 26-60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high-volume centres compared with 7·5 per cent in very low-volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P < 0·001). CONCLUSION This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.

5G-assisted telementored surgery

Abstract: Safe and effective implementation of remote surgery and telementoring can have significant limitations. Fifth-generation (5G) wireless networks could be useful in overcoming these drawbacks. As a proof of concept, the authors present technical and clinical details of two procedures assisted by telementoring using 5G that were also broadcast live. Secure remote access advice.

Meta-analysis of clinical outcome after treatment for achalasia based on manometric subtypes.

Abstract: Background The introduction of high-resolution manometry and the Chicago classification has made it possible to diagnose achalasia and predict treatment response accurately. The aim of this study was to compare the effect of the different treatments available on symptomatic outcomes across all achalasia subtypes. Methods The study was conducted according to PRISMA and MOOSE guidelines. A literature search of PubMed and MEDLINE databases was undertaken to identify all relevant articles reporting clinical outcomes of patients with achalasia after botulinum toxin injection, pneumatic dilatation, laparoscopic Heller myotomy (LHM) and peroral endoscopic myotomy (POEM) based on manometric subtypes. Patients were grouped according to the Chicago classification and the success rate in treating symptoms was measured as the primary endpoint. Results Twenty studies (1575 patients) were selected, and data on botulinum toxin, pneumatic dilatation, LHM and POEM were extracted. Success rates for LHM in type I, II and III achalasia were 81, 92 and 71 per cent respectively. Those for POEM were 95, 97 and 93 per cent respectively. POEM was more likely to be successful than LHM for both type I (odds ratio (OR) 2·97, 95 per cent c.i. 1·09 to 8·03; P = 0·032) and type III (OR 3·50, 1·39 to 8·77; P = 0·007) achalasia. The likelihood of success of POEM and LHM for type II achalasia was similar. Conclusion Pneumatic dilatation had a lower but still acceptable success rate compared with POEM or LHM in patients with type II achalasia. POEM is an excellent treatment modality for type I and type III achalasia, although it did not show any superiority over LHM for type II achalasia.

Global surgery and the sustainable development goals.

Abstract: Background The field of global surgery has gained significant recent momentum, catalysed by the 2015 publication of the Lancet Commission on Global Surgery, Disease Control Priorities 3 and World Health Assembly resolution 68.15. These reports characterized the global burden of disease amenable to surgical care, called for global investment in surgical systems, and recognized surgery and anaesthesia as essential components of universal health coverage. Methods A strategy proposed to strengthen surgical care is the development of national surgical, obstetric and anaesthesia plans (NSOAPs). This review examined how NSOAPs could contribute to the achievement of sustainable development goals (SDGs) 1, 3, 5, 8, 9, 10, 16 and 17 by 2030, focusing on their potential impact on the healthcare systems in Ethiopia, Tanzania and Zambia. Results Due to the cross-cutting nature of surgery, obstetrics and anaesthesia, investing in these services will escalate progress to achieve gender equality, economic growth and infrastructure development. Universal health coverage will not be achieved without addressing the financial ramifications to the poor of seeking and receiving surgical care. NSOAPs provide a strategic framework and a data collection platform for evidence-based policy-making, accountability and implementation guidance. Conclusion The development and implementation of data-driven NSOAPs should be recognized as a powerful road map to accelerate achievement of the SDGs by 2030.

Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial)

Abstract: Background: Infectious complications and anastomotic leakage affect approximately 30 per cent of patients after colorectal cancer surgery. The aim of this multicentre randomized trial was to investigate whether selective decontamination of the digestive tract (SDD) reduces these complications of elective colorectal cancer surgery. Methods: The effectiveness of SDD was evaluated in a multicentre, open-label RCT in six centres in the Netherlands. Patients with colorectal cancer scheduled for elective curative surgery with a primary anastomosis were eligible. Oral colistin, tobramycin and amphotericin B were administered to patients in the SDD group to decontaminate the digestive tract. Both treatment and control group received intravenous cefazolin and metronidazole for perioperative prophylaxis. Mechanical bowel preparation was given for left-sided colectomies, sigmoid and anterior resections. Anastomotic leakage was the primary outcome; infectious complications and mortality were secondary outcomes. Results: The outcomes for 228 patients randomized to the SDD group and 227 randomized to the control group were analysed. The trial was stopped after interim analysis demonstrated that superiority was no longer attainable. Effective SDD was confirmed by interspace DNA profiling analysis of rectal swabs. Anastomotic leakage was observed in 14 patients (6·1 per cent) in the SDD group and in 22 patients (9·7 per cent) in the control group (odds ratio (OR) 0·61, 95 per cent c.i. 0·30 to 1·22). Fewer patients in the SDD group had one or more infectious complications than patients in the control group (14·9 versus 26·9 per cent respectively; OR 0·48, 0·30 to 0·76). Multivariable analysis indicated that SDD reduced the rate of infectious complications (OR 0·47, 0·29 to 0·76). Conclusion: SDD reduces infectious complications after colorectal cancer resection but did not significantly reduce anastomotic leakage in this trial. Registration number: NCT01740947 (https://www.clinicaltrials.gov).

Evaluating the collection, comparability and findings of six global surgery indicators

Abstract: Background In 2015, six indicators were proposed to evaluate global progress towards access to safe, affordable and timely surgical and anaesthesia care. Although some have been adopted as core global health indicators, none has been evaluated systematically. The aims of this study were to assess the availability, comparability and utility of the indicators, and to present available data and updated estimates. Methods Nationally representative data were compiled for all World Health Organization (WHO) member states from 2010 to 2016 through contacts with official bodies and review of the published and grey literature, and available databases. Availability, comparability and utility were assessed for each indicator: access to timely essential surgery, specialist surgical workforce density, surgical volume, perioperative mortality, and protection against impoverishing and catastrophic expenditure. Where feasible, imputation models were developed to generate global estimates. Results Of all WHO member states, 19 had data on the proportion of the population within 2h of a surgical facility, 154 had data on workforce density, 72 reported number of procedures, and nine had perioperative mortality data, but none could report data on catastrophic or impoverishing expenditure. Comparability and utility were variable, and largely dependent on different definitions used. There were sufficient data to estimate that worldwide, in 2015, there were 2 038 947 (i.q.r. 1 884 916-2 281 776) surgeons, obstetricians and anaesthetists, and 266·1 (95 per cent c.i. 220·1 to 344·4) million operations performed. Conclusion Surgical and anaesthesia indicators are increasingly being adopted by the global health community, but data availability remains low. Comparability and utility for all indicators require further resolution.

Reducing surgical mortality in Scotland by use of the WHO Surgical Safety Checklist

Abstract: Acknowledgements R. Munro and R. Black of NHS National Services Scotland, UK, provided data intelligence. B. Robson helped review this paper; A. Longmate was involved in the preliminary design of this study; J. Ingram, J. Ferbrache and SPSP managers from health boards in Scotland provided some of the information on surgical checklist implementation practices at hospitals across NHS Scotland. Data, analytical methods and study materials used may be made available to other researchers on request. The lead author affirms that the manuscript is an honest, accurate and transparent account of the study being reported. No important aspects of the study have been omitted. Any discrepancies from the study as planned (and, if relevant, registered) have been explained. This study was not funded by any individual or group. The Research Governance Department of the University of Aberdeen sponsored this project and supported the application through ethical review and data management. Disclosure: A.A.G. has received royalties from multiple publishers for writing on improving healthcare, including through use of checklists: Objetiva, Sextante (Brazil); Profile Books Ltd (British Commonwealth); Cheers Publishing Company, Commonwealth Publishing Co (People's Republic of China); Jesenski & Turk, Mizaik Knjiga, Mozaik Knjiga (Croatia); Dokoran (Czech Republic); Lindhart og Rinhoft Forlag (Denmark); Pilgrim Group (Estonia); Editions Moyen‐Courrier, Fayard, Libraire Artheme Fayard, Moyen‐Courrier (France); Radarami (Georgia), S Fischer, Verlagsgruppe Random House (Germany); Crete University Press (Greece); Tericam Kindo (Hungary); Mehta Publishing House, Penguin Random House Books (India); Gramedia Pustaka Utama, Serambi Ilmu Semesta (Indonesia); Arjmand Press (Iran); Am Oved, Modan (Israel); Einaudi Editore (Italy); Misuzu Shobo, Shinyusha Co Ltd (Japan); Janis Roze Publishers (Latvia); Vaga (Lithuania); Mime Forlag (Norway); Magnum, Znak (Poland); Lua de Papel (Portugal); Codecs, Grup Media Litera, Litera, Streamland Ltd (Romania); Slovant Publishers (Slovakia); Mladinska Knjiga (Slovenia); Antoni Bosch Editor, Editorial Empuries, Galaxia Gutenberg (Spain); Asa Editore, Bookie Publishing House, Book21, Sosoh Publishing (South Korea); Volante (Sweden); Alpina, AST (Russia); Matichon, Openworlds (Thailand); Arbeiderspers, Nieuwezijds, Uitgeverij De Arbeiderspers, Uitgeverij Nieuwezijds (the Netherlands); Domingo, Koton Kitap (Turkey); Verlagsgruppe Vivat (Ukraine); CBS Television, Henry Holt, Houghton Mifflin, Harvard Business School Press, McGraw Hill, Pearson Publishing, Public Broadcasting Service, Picador USA (USA), First News‐Tn Viet Publishing Co, Suc Manh Ngoi But Co (Vietnam); and Harper Collins (World). The authors declare no other conflict of interest.

Propensity score-matched analysis of oncological outcome between stent as bridge to surgery and emergency resection in patients with malignant left-sided colonic obstruction.

Abstract: Background: Although self-expandable metal stent (SEMS) placement as bridge to surgery (BTS) in patients with left-sided obstructing colonic cancer has shown promising short-term results, it is used infrequently owing to uncertainty about its oncological safety. This population study compared long-term oncological outcomes between emergency resection and SEMS placement as BTS. Methods: Through a national collaborative research project, long-term outcome data were collected for all patients who underwent resection for left-sided obstructing colonic cancer between 2009 and 2016 in 75 Dutch hospitals. Patients were identified from the Dutch Colorectal Audit database. SEMS as BTS was compared with emergency resection in the curative setting after 1 : 2 propensity score matching. Results: Some 222 patients who had a stent placed were matched to 444 who underwent emergency resection. The overall SEMS-related perforation rate was 7·7 per cent (17 of 222). Three-year locoregional recurrence rates after SEMS insertion and emergency resection were 11·4 and 13·6 per cent (P = 0·457), disease-free survival rates were 58·8 and 52·6 per cent (P = 0·175), and overall survival rates were 74·0 and 68·3 per cent (P = 0·231), respectively. SEMS placement resulted in significantly fewer permanent stomas (23·9 versus 45·3 per cent; P < 0·001), especially in elderly patients (29·0 versus 57·9 per cent; P < 0·001). For patients in the SEMS group with or without perforation, 3-year locoregional recurrence rates were 18 and 11·0 per cent (P = 0·432), disease-free survival rates were 49 and 59·6 per cent (P = 0·717), and overall survival rates 61 and 75·1 per cent (P = 0·529), respectively. Conclusion: Overall, SEMS as BTS seems an oncologically safe alternative to emergency resection with fewer permanent stomas. Nevertheless, the risk of SEMS-related perforation, as well as permanent stoma, might influence shared decision-making for individual patients.

Multicentre propensity score-matched study of laparoscopic versus open repeat liver resection for colorectal liver metastases.

Abstract: Background: Repeat liver resection is often the best treatment option for patients with recurrent colorectal liver metastases (CRLM). Repeat resections can be complex, however, owing to adhesions and altered liver anatomy. It remains uncertain whether the advantages of a laparoscopic approach are upheld in this setting. The aim of this retrospective, propensity score-matched study was to compare the short-term outcome of laparoscopic (LRLR) and open (ORLR) repeat liver resection. Methods: A multicentre retrospective propensity score-matched study was performed including all patients who underwent LRLRs and ORLRs for CRLM performed in nine high-volume centres from seven European countries between 2000 and 2016. Patients were matched based on propensity scores in a 1 : 1 ratio. Propensity scores were calculated based on 12 preoperative variables, including the approach to, and extent of, the previous liver resection. Operative outcomes were compared using paired tests. Results: Overall, 425 repeat liver resections were included. Of 271 LRLRs, 105 were matched with an ORLR. Baseline characteristics were comparable after matching. LRLR was associated with a shorter duration of operation (median 200 (i.q.r. 123–273) versus 256 (199–320) min; P < 0·001), less intraoperative blood loss (200 (50–450) versus 300 (100–600) ml; P = 0·077) and a shorter postoperative hospital stay (5 (3–8) versus 6 (5–8) days; P = 0·028). Postoperative morbidity and mortality rates were similar after LRLR and ORLR. Conclusion: LRLR for CRLM is feasible in selected patients and may offer advantages over an open approach.

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

Abstract: BACKGROUND: Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create a preclinical platform for the development of more effective intraperitoneal chemotherapy strategies. METHODS: Using organoid technology, five tumour cultures were generated from malignant ascites and resected peritoneal metastases. These were used in an in vitro HIPEC model to assess sensitivity to mitomycin C (MMC) and oxaliplatin, the drugs used most commonly in HIPEC. The model was also used to test a rational combination treatment involving MMC and inhibitors of the checkpoint kinase ATR. RESULTS: MMC was more effective in eliminating peritoneal metastasis-derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines for oxaliplatin, indicating a general resistance to monotherapy. ATR inhibition increased the sensitivity of all peritoneal metastasis-derived organoids to MMC, as the IC50 decreased 2·6-12·4-fold to well below concentrations commonly attained in clinical practice. Live-cell imaging and flow cytometric analysis showed that ATR inhibition did not release cells from MMC-induced cell cycle arrest, but caused increased replication stress and accelerated cell death. CONCLUSION: Peritoneal metastasis-derived organoids can be used to evaluate existing HIPEC regimens on an individual-patient level and for development of more effective treatment strategies. Surgical relevance Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has improved prognosis of patients with peritoneal metastases from colorectal cancer, but disease recurrence is common. More effective and personalized HIPEC is urgently needed. Organoid technology is frequently used for drug screens, as patient-derived organoids can accurately predict clinical therapeutic response in vitro. A panel of organoids was established from peritoneal metastases from colorectal cancer and used to develop a model for testing HIPEC regimens in vitro. Patient-derived organoids differed in sensitivity to commonly used chemotherapeutics, in line with variable clinical outcomes following cytoreductive surgery-HIPEC. Combining MMC with an ATR inhibitor improved the efficacy of MMC. Peritoneal metastasis-derived organoids can be used as a platform to test novel (combination) strategies that increase HIPEC efficacy. In the future, organoids could be used to select patent-tailored HIPEC regimens.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

Abstract: BACKGROUND The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

Long-term functional outcomes and quality of life in patients with Hirschsprung's disease

Abstract: Background: It is unclear whether functional outcomes improve or deteriorate with age following surgery for Hirschsprung's disease. The aim of this cross-sectional study was to determine the long-term functional outcomes and quality of life (QoL) in patients with Hirschsprung's disease. Methods: Patients with pathologically proven Hirschsprung's disease older than 7 years were included. Patients with a permanent stoma or intellectual disability were excluded. Functional outcomes were assessed according to the Rome IV criteria using the Defaecation and Faecal Continence questionnaire. QoL was assessed by means of the Child Health Questionnaire Child Form 87 or World Health Organization Quality of Life questionnaire 100. Reference data from healthy controls were available for comparison. Results: Of 619 patients invited, 346 (55·9 per cent) responded, with a median age of 18 (range 8–45) years. The prevalence of constipation was comparable in paediatric and adult patients (both 22·0 per cent), and in patients and controls. Compared with controls, adults with Hirschsprung's disease significantly more often experienced straining (50·3 versus 36·1 per cent; P = 0·011) and incomplete evacuation (47·4 versus 27·2 per cent; P < 0·001). The prevalence of faecal incontinence, most commonly soiling, was lower in adults than children with Hirschsprung's disease (16·8 versus 37·6 per cent; P < 0·001), but remained higher than in controls (16·8 versus 6·1 per cent; P = 0·003). Patients with poor functional outcomes scored significantly lower in several QoL domains. Conclusion: This study has shown that functional outcomes are better in adults than children, but symptoms of constipation and soiling persist in a substantial group of adults with Hirschsprung's disease. The persistence of defaecation problems is an indication that continuous care is necessary in this specific group of patients.

Systematic review of functional outcome and quality of life after total pancreatectomy

Abstract: Background: Surgeons have traditionally been reluctant to perform total pancreatectomy because of concerns for brittle diabetes and poor quality of life (QoL). Several recent studies have suggested that outcomes following total pancreatectomy have improved, but a systematic review is lacking. Methods: A systematic review was undertaken of studies reporting on outcomes after total pancreatectomy for all indications, except chronic pancreatitis. PubMed, EMBASE (Ovid), and Cochrane Library were searched (2005–2018). Endpoints included functional outcome and QoL. Results: A total of 21 studies, including 1536 patients, fulfilled the eligibility criteria. During a median follow-up of 20·8 (range 1·5–96·0) months, 18·6 per cent (45 of 242 patients) were readmitted for endocrine-related morbidity, with associated mortality in 1·6 per cent (6 of 365 patients). No diabetes-related mortality was reported in studies including only patients treated after 2005. Symptoms related to exocrine insufficiency were reported by 43·5 per cent (143 of 329 patients) during a median follow-up of 15·9 (1·5–96·0) months. Overall QoL, reported by 102 patients with a median follow-up of 28·6 (6·0–66·0) months, using the EORTC QLQ-C30 questionnaire, showed a moderately reduced summary score of 76 per cent, compared with a general population score of 86 per cent (P = 0·004). Conclusion: Overall QoL after total pancreatectomy is affected adversely, in particular by the considerable impact of diarrhoea that requires better treatment. There is also room for improvement in the management of diabetes after total pancreatectomy, particularly with regards to prevention of diabetes-related morbidity.

Perioperative outcomes and long-term quality of life after total pancreatectomy

Abstract: BACKGROUND Total pancreatectomy is required to treat diseases involving the entire pancreas, and is characterized by high morbidity rates and impaired long-term quality of life (QoL). To date, risk factors associated with perioperative and long-term outcomes have not been determined fully. METHODS Data from patients undergoing total pancreatectomy between 2000 and 2014 at two high-volume centres were analysed retrospectively to assess risk factors for major surgical complications. Short Form (SF) 36, European Organisation for Research and Treatment of Cancer QLQ-PAN26 and Audit of Diabetes Dependent questionnaires, as well as an original survey were used to investigate factors influencing QoL. RESULTS A total of 329 consecutive patients underwent total pancreatectomy in the two centres. Overall, total pancreatectomy was associated with a morbidity rate of 59·3 per cent and a 30-day mortality rate of 2·1 per cent. Age over 65 years and long duration of surgery (more than 420 min) were independently associated with major complications (at least Clavien-Dindo grade III). QoL analysis was available for 94 patients (28·6 per cent) with a median follow-up of 63 (i.q.r. 20-109) months; the most common indication for total pancreatectomy in these patients was intraductal papillary mucinous neoplasms (46 per cent). Both physical (PCS) and mental (MCS) component summary scores of SF-36® were lower after total pancreatectomy compared with scores for a normative population (P = 0·020 and P < 0·001 respectively). Linear regression analysis showed that young age, abdominal pain and worse perception of body image were negatively associated with the PCS, whereas diabetes, sexual satisfaction and perception of body image affected MCS. CONCLUSION Total pancreatectomy can be performed with acceptable morbidity and mortality rates. Older patients had a higher risk of postoperative complications but reported better QoL than younger patients.

Functional outcomes from a randomized trial of early closure of temporary ileostomy after rectal excision for cancer.

Abstract: Background Low anterior resection syndrome (LARS) has a significant impact on postoperative quality of life. Although early closure of an ileostomy is safe in selected patients, functional outcomes have not been investigated. The aim was to compare bowel function and the prevalence of LARS in patients who underwent early or late closure of an ileostomy after rectal resection for cancer. Methods Early closure (8-13 days) was compared with late closure (after 12 weeks) of the ileostomy following rectal cancer surgery in a multicentre RCT. Exclusion criteria were: signs of anastomotic leakage, diabetes mellitus, steroid treatment and postoperative complications. Bowel function was evaluated using the LARS score and the Memorial Sloan Kettering Cancer Center Bowel Function Instrument (BFI). Results Following index surgery, 112 participants were randomized (55 early closure, 57 late closure). Bowel function was evaluated at a median of 49 months after stoma closure. Eighty-two of 93 eligible participants responded (12 had died and 7 had a permanent stoma). Rates of bowel dysfunction were higher in the late closure group, but this did not reach statistical significance (major LARS in 29 of 40 participants in late group and 25 of 42 in early group, P = 0·250; median BFI score 63 versus 71 respectively, P = 0·207). Participants in the late closure group had worse scores on the urgency/soiling subscale of the BFI (14 versus 17; P = 0·017). One participant in the early group and six in the late group had a permanent stoma (P = 0·054). Conclusion Patients undergoing early stoma closure had fewer problems with soiling and fewer had a permanent stoma, although reduced LARS was not demonstrated in this cohort. Dedicated prospective studies are required to evaluate definitively the association between temporary ileostomy, LARS and timing of closure.

Systematic review of outcomes after total neoadjuvant therapy for locally advanced rectal cancer.

Abstract: Background Advances in surgical technique and the development of combined-modality therapy have led to significantly improved local control in rectal cancer. Distant failure rates however, remain high, ranging between 20 and 30 per cent. Additional systemic chemotherapy in the preoperative period has been proposed as a means of eradicating subclinical micrometastases and improving long-term survival. The purpose of this systematic review was to evaluate the current evidence regarding induction chemotherapy in combination with standard neoadjuvant chemoradiotherapy, in terms of oncological outcomes, in patients with rectal cancer. Methods A systematic review of the literature was performed to evaluate oncological outcomes and survival in patients with rectal cancer who underwent induction chemotherapy and neoadjuvant chemoradiotherapy, followed by surgical resection. Four major databases (PubMed, Embase, Scopus and Cochrane) were searched. The review included all original articles published in English reporting long-term outcomes, specifically survival data, and was limited to prospective studies only. Results A total of 686 studies were identified. After applying inclusion and exclusion criteria, ten studies involving 648 patients were included. Median follow-up was 53·7 (range 26-80) months. Five-year overall and disease-free survival rates were 74·4 and 65·4 per cent respectively. Weighted mean local recurrence and distant failure rates were 3·5 (range 0-7) and 20·6 (range 5-31) per cent respectively. Conclusion Total neoadjuvant therapy should be considered in patients with high-risk locally advanced rectal cancer owing to improved chemotherapy compliance and disease control. Further prospective studies are required to determine whether this approach translates into improved disease-related survival or increases the proportion of patients suitable for non-operative management.

Systematic review of the current status of cadaveric simulation for surgical training.

Abstract: Background: There is growing interest in and provision of cadaveric simulation courses for surgical trainees. This is being driven by the need to modernize and improve the efficiency of surgical training within the current challenging training climate. The objective of this systematic review is to describe and evaluate the evidence for cadaveric simulation in postgraduate surgical training. Methods: A PRISMA‐compliant systematic literature review of studies that prospectively evaluated a cadaveric simulation training intervention for surgical trainees was undertaken. All relevant databases and trial registries were searched to January 2019. Methodological rigour was assessed using the widely validated Medical Education Research Quality Index (MERSQI) tool. Results: A total of 51 studies were included, involving 2002 surgical trainees across 69 cadaveric training interventions. Of these, 22 assessed the impact of the cadaveric training intervention using only subjective measures, five measured impact by change in learner knowledge, and 23 used objective tools to assess change in learner behaviour after training. Only one study assessed patient outcome and demonstrated transfer of skill from the simulated environment to the workplace. Of the included studies, 67 per cent had weak methodology (MERSQI score less than 10·7). Conclusion: There is an abundance of relatively low‐quality evidence showing that cadaveric simulation induces short‐term skill acquisition as measured by objective means. There is currently a lack of evidence of skill retention, and of transfer of skills following training into the live operating theatre.

Diffusion-weighted MRI assessment of the peritoneal cancer index before cytoreductive surgery

Abstract: Background Patients with limited peritoneal metastases from colorectal cancer may be candidates for an aggressive surgical approach including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Selection is based on surgical inspection during laparoscopy or laparotomy. The aim of this study was to investigate whether diffusion-weighted MRI (DW-MRI) can be used to select patients for CRS-HIPEC. Methods This was a prospective study at a tertiary referral centre. Patients with confirmed or suspected colorectal peritoneal metastases scheduled for exploratory laparotomy or laparoscopy were eligible. Two radiologists assessed the peritoneal cancer index (PCI) on CT (CT-PCI) and DW-MRI (MRI-PCI). The reference standard was PCI at surgery. Radiologists were blinded to the surgical PCI and to each other's findings. The main outcome was the accuracy of DW-MRI in predicting whether patients had resectable disease (PCI less than 21) or not. Results Fifty-six patients were included in the study, of whom 49 could be evaluated. The mean(s.d.) PCI at surgery was 11·27(7·53). The mean MRI-PCI was 10·18(7·07) for reader 1 and 8·59(7·08) for reader 2. Readers 1 and 2 correctly staged 47 of 49 and 44 of 49 patients respectively (accuracy 96 and 90 per cent). Both readers detected all patients with resectable disease with a PCI below 21 at surgery (sensitivity 100 per cent). No patient was overstaged. The intraclass correlation (ICC) between readers was excellent (ICC 0·91, 95 per cent c.i. 0·77 to 0·96). MRI-PCI had a stronger correlation with surgical PCI (ICC 0·83-0·88) than did CT-PCI (ICC 0·39-0·44). Conclusion DW-MRI is a promising non-invasive tool to guide treatment selection in patients with peritoneal metastases from colorectal cancer.

Long-term follow-up of the AVOD randomized trial of antibiotic avoidance in uncomplicated diverticulitis.

Abstract: Background The aim of this study was to assess the long-term results in patients with uncomplicated diverticulitis who had participated in the Antibiotics in Acute Uncomplicated Diverticulitis (AVOD) RCT, which randomized patients with CT-verified left-sided acute uncomplicated diverticulitis to management without or with antibiotics. Methods The medical records of patients who had participated in the AVOD trial were reviewed for long-term results such as recurrences, complications and surgery. Quality-of-life questionnaires (EQ-5D™) were sent to patients, who were also contacted by telephone. Descriptive statistics were used for the analysis of clinical outcomes. Results A total of 556 of the 623 patients (89·2 per cent) were followed up for a median of 11 years. There were no differences between the no-antibiotic and antibiotic group in recurrences (both 31·3 per cent; P = 0·986), complications (4·4 versus 5·0 per cent; P = 0·737), surgery for diverticulitis (6·2 versus 7·1 per cent; P = 0·719) or colorectal cancer (0·4 versus 2·1 per cent; P = 0·061). The response rate for the EQ-5D™ was 52·8 versus 45·2 per cent respectively (P = 0·030), and no differences were found between the two groups in any of the measured dimensions. Conclusion Antibiotic avoidance for uncomplicated diverticulitis is safe in the long term.

Meta-analysis of the molecular associations of mucinous colorectal cancer.

Abstract: Background Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer. Methods This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis. Results Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P Conclusion The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

Abstract: Background: Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non-surgical management (antibiotics with or without percutaneous drainage (PCD)). The aim was to assess outcomes of non-surgical treatment and to identify risk factors for adverse outcomes. Methods: Patients with a first episode of CT-diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non-surgically. Baseline characteristics, short-term (within 30 days) and long-term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no-PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery. Results: Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow-up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74⋅3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short-term treatment failure (Hinchey I: 22⋅3 versus 33 per cent, P = 0⋅359; Hinchey II: 25⋅9 versus 36 per cent, P = 0⋅149) or emergency surgery (Hinchey I: 5⋅1 versus 6 per cent, P = 0⋅693; Hinchey II: 10⋅4 versus 15 per cent, P = 0⋅117), but significantly more complications were found in patients with Hinchey II disease undergoing PCD (12 versus 3⋅7 per cent; P = 0⋅032). Multivariable analyses showed that treatment strategy (PCD versus no PCD) was not independently associated with short-term treatment failure (odds ratio (OR) 1⋅47, 95 per cent c.i. 0⋅81 to 2⋅68), emergency surgery (OR 1⋅29, 0⋅56 to 2⋅99) or long-term surgery (hazard ratio 1⋅08, 95 per cent c.i. 0⋅69 to 1⋅69). Abscesses of at least 3 cm in diameter were associated with short-term treatment failure (OR 2⋅05, 1⋅09 to 3⋅86), and abscesses of 5 cm or larger with the need for surgery during short-term follow-up (OR 2⋅96, 1⋅03 to 8⋅13). Conclusion: The choice between PCD with antibiotics or antibiotics alone as initial non-surgical treatment of Hinchey Ib and II diverticulitis does not seem to influence outcomes.

Observational study of the medical management of patients with peripheral artery disease

Abstract: Background: Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target-based risk factor modification. Methods: The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal-directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART-REACH model, a validated cardiovascular prediction tool for patients with PAD. Results: Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL-cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high-dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44–62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL-cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10-year cardiovascular risk by 29 (20–38) per cent with 6·3 (4·0–9·3) cardiovascular disease-free years gained. Conclusion: The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline-based targets would confer significant patient benefit.

Significance of the surgical hepatic resection margin in patients with a single hepatocellular carcinoma.

Abstract: Background The impact of a wide surgical margin on the outcome of patients with hepatocellular carcinoma (HCC) has not been evaluated in relation to the type of liver resection performed, anatomical or non-anatomical. The aim of this study was to evaluate the impact of surgical margin status on outcomes in patients undergoing anatomical or non-anatomical resection for solitary HCC. Methods Data from patients with solitary HCC who had undergone non-anatomical partial resection (Hr0 group) or anatomical resection of one Couinaud segment (HrS group) between 2000 and 2007 were extracted from a nationwide survey database in Japan. Overall and recurrence-free survival associated with the surgical margin status and width were evaluated in the two groups. Results A total of 4457 patients were included in the Hr0 group and 3507 in the HrS group. A microscopically positive surgical margin was associated with poor overall survival in both groups. A negative but 0-mm surgical margin was associated with poorer overall and recurrence-free survival than a wider margin only in the Hr0 group. In the HrS group, the width of the surgical margin was not associated with patient outcome. Conclusion Anatomical resection with a negative 0-mm surgical margin may be acceptable. Non-anatomical resection with a negative 0-mm margin was associated with a less favourable survival outcome.

Radiomics approach to distinguish between well differentiated liposarcomas and lipomas on MRI

Abstract: Background: Well differentiated liposarcoma (WDLPS) can be difficult to distinguish from lipoma. Currently, this distinction is made by testing for MDM2 amplification, which requires a biopsy. The aim of this study was to develop a noninvasive method to predict MDM2 amplification status using radiomics features derived from MRI. Methods: Patients with an MDM2-negative lipoma or MDM2-positive WDLPS and a pretreatment T1-weighted MRI scan who were referred to Erasmus MC between 2009 and 2018 were included. When available, other MRI sequences were included in the radiomics analysis. Features describing intensity, shape and texture were extracted from the tumour region. Classification was performed using various machine learning approaches. Evaluation was performed through a 100 times random-split cross-validation. The performance of the models was compared with the performance of three expert radiologists. Results: The data set included 116 tumours (58 patients with lipoma, 58 with WDLPS) and originated from 41 different MRI scanners, resulting in wide heterogeneity in imaging hardware and acquisition protocols. The radiomics model based on T1 imaging features alone resulted in a mean area under the curve (AUC) of 0·83, sensitivity of 0·68 and specificity of 0·84. Adding the T2-weighted imaging features in an explorative analysis improved the model to a mean AUC of 0·89, sensitivity of 0·74 and specificity of 0·88. The three radiologists scored an AUC of 0·74 and 0·72 and 0·61 respectively; a sensitivity of 0·74, 0·91 and 0·64; and a specificity of 0·55, 0·36 and 0·59. Conclusion: Radiomics is a promising, non-invasive method for differentiating between WDLPS and lipoma, outperforming the scores of the radiologists. Further optimization and validation is needed before introduction into clinical practice.

Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation

Abstract: Background Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. Methods Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. Results A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. Conclusion Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.