The impact of bariatric surgery on liver enzymes in people with obesity: A 5-year observational study.

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. METHODS: We performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FINDINGS: Bariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. CONCLUSIONS: Bariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.

Systematic review of health-related quality of life (HRQoL) issues associated with gastric cancer: capturing cross-cultural differences.

The treatment landscape for gastric cancer (GC) is constantly evolving with therapies affecting all aspects of health-related quality of life (HRQoL) which need careful monitoring. While there are HRQoL measures designed specifically to capture issues relevant to patients with GC, these might be outdated and only relevant to patients in westernised cultures. This review identifies the patient-reported measures used to assess HRQoL of patients with GC and compares the HRQoL measures used across cultures including East Asia, where GC is more prevalent. We conducted a systematic review of publications between January 2001 and January 2021. A total of 267 papers were identified; the majority (66%) of studies involved patients from East Asian countries. Out of the 24 HRQoL questionnaires captured, the European Organisation for Research and Treatment of Cancer Core Cancer measure (QLQ-C30) was the most widely used (60% of all studies and 62% of those involving patients from East Asian countries), followed by its gastric cancer-specific module (QLQ-STO22, 34% of all studies and 41% from East Asia). Eight questionnaires were developed within East Asian countries and, of the 20 studies including bespoke questions, 16 were from East Asia. There were six qualitative studies. HRQoL issues captured include diarrhoea, constipation, reflux, abdominal pain and abdominal fulness or bloating, difficulty swallowing, restricted eating, and weight loss. Psychosocial issues related to these problems were also assessed. Issues relating to the compatibility of some of the westernised measures within East Asian cultures were highlighted.

Is Re-introducing Major Open and Minimally Invasive Surgery during COVID-19 Safe for Patients and Healthcare Workers? An International, Multi-centre Cohort Study in the Field of Oesophago-gastric Surgery.

INTRODUCTION: The COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery. PATIENTS AND METHODS: This was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group. RESULTS: In total, 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy). Overall, 87 patients (57%) underwent MIS (59 oesophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19. CONCLUSIONS: Precautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.

Weight Loss Following Bariatric Surgery in People with or without Metabolic Syndrome: A 5-Year Observational Comparative Study.

AIM: Whilst bariatric surgery is the most effective treatment for severe obesity, the aim of this study was to evaluate whether postoperative weight loss is similar in patients with or without metabolic syndrome. METHODS: We performed a 5-year observational retrospective comparative cohort analysis of bariatric surgery in 333 patients (72% women) without (Group A, n = 133) or with (Group B, n = 200) metabolic syndrome at baseline. RESULTS: Overall mean (SD) baseline body mass index was 51.7 (7.5) with no significant difference between groups. Overall mean percent total weight loss (%TWL) was 31.9% by 24 months after surgery. Although %TWL was greater in Group A (34.9%) than in Group B (30.2%, p = 0.006) at 24 months, there were no significant differences between groups subsequently up to 60 months of follow-up. Systolic and diastolic blood pressures and lipid profiles improved in both groups. In patients with metabolic syndrome at baseline, mean HbA1c reduced by 36.4% at 12 months and was sustained over the study period. CONCLUSIONS: We report that bariatric surgery results in comparable long-term weight loss in patients with or without metabolic syndrome alongside expected improvements in metabolic comorbidities.

Serious Impacts of Postponing Bariatric Surgery as a Result of the COVID-19 Pandemic: The Patient Perspective.

BACKGROUND: The global COVID-19 pandemic has resulted in the widespread suspension of bariatric surgical programs. Although this rapid adaption was initially necessary, the implications of delaying the most effective treatment for weight loss in a population at risk from this crisis are not well known. Moreover, as the health care trusts plan the reintroduction of elective services, it is vital to also consider the patient's perspectives, to adequately weigh up the benefits and risks of this recommencement in the current climate. OBJECTIVES: We aimed to investigate the impacts that postponing bariatric surgery has had on patients, and their priorities when restarting elective surgery. METHODS: An online survey of patients awaiting surgery was undertaken, examining the physical and psychological impacts of pandemic isolation policies and postponing surgery, and exploring patient preferences regarding surgery during the pandemic. RESULTS: Of 71 patients, 67.6% gained a median of 4 kg (interquartile range: 2.6-6.4), and 74.6% had adverse psychological effects; 93.0% were keen to proceed with surgery. Thematic analysis of qualitative data revealed delays have worsened physical symptoms, increased anxiety, and delayed secondary life-altering treatments. CONCLUSION: From the patient's perspective, postponing surgery has been deleterious and efforts to safely reintroduce bariatric programs should be promoted.

How are trial outcomes prioritised by stakeholders from different regions? Analysis of an international Delphi survey to develop a core outcome set in gastric cancer surgery.

BACKGROUND: International stakeholder participation is important in the development of core outcome sets (COS). Stakeholders from varying regions may value health outcomes differently. Here, we explore how region, health income and participant characteristics influence prioritisation of outcomes during development of a COS for gastric cancer surgery trials (the GASTROS study). METHODS: 952 participants from 55 countries participating in a Delphi survey during COS development were eligible for inclusion. Recruits were grouped according to region (East or West), country income classification (high and low-to-middle income) and other characteristics (e.g. patients; age, sex, time since surgery, mode of treatment, surgical approach and healthcare professionals; clinical experience). Groups were compared with respect to how they categorised 56 outcomes identified as potentially important to include in the final COS ('consensus in', 'consensus out', 'no consensus'). Outcomes categorised as 'consensus in' or 'consensus out' by all 3 stakeholder groups would be automatically included in or excluded from the COS respectively. RESULTS: In total, 13 outcomes were categorised 'consensus in' (disease-free survival, disease-specific survival, surgery-related death, recurrence of cancer, completeness of tumour removal, overall quality of life, nutritional effects, all-cause complications, intraoperative complications, anaesthetic complications, anastomotic complications, multiple organ failure, and bleeding), 13 'consensus out' and 31 'no consensus'. There was little variation in prioritisation of outcomes by stakeholders from Eastern or Western countries and high or low-to-middle income countries. There was little variation in outcome prioritisation within either health professional or patient groups. CONCLUSION: Our study suggests that there is little variation in opinion within stakeholder groups when participant region and other characteristics are considered. This finding may help COS developers when designing their Delphi surveys and recruitment strategies. Further work across other clinical fields is needed before broad recommendations can be made.

Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review.

BACKGROUND: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. METHODS: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. RESULTS: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. CONCLUSION: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.

15 years of litigation following laparoscopic cholecystectomy in England.

OBJECTIVE: We aimed to analyze trends in litigation following laparoscopic cholecystectomy (LC) in England and compare our findings with data from the United States. BACKGROUND: Several studies from the United States have highlighted the medico-legal repercussions of complications following LC. In 2007-2008, litigation claims cost the National Health Service in England over 660 million Great British Pounds (GBP) (1.1 billion USD). Despite this, there has been little examination of litigation following LC in England. METHODS: Data from the National Health Service Litigation Authority on clinical negligence claims between 1995 and 2009 following LC were obtained and analyzed. RESULTS: Four hundred eighteen claims were made of which 303 were settled. One hundred ninety-eight (65%) were found to be in the claimants favor for a total cost of 20.4 million GBP (33.4 million USD). Litigation claims have leveled since 2001. Operator error was the most likely cause to result in a claim and the only cause associated with a successful claim (P = 0.023). A delay in the recognition of complications was the second most common reason for initiation of a claim. Bile duct injury was the most frequent injury resulting in litigation and the most likely injury associated with a successful claim (P < 0.001). The average payout for a successful claim was 102,827 GBP/168,337 USD. Findings from US studies were similar, although the magnitude of payouts was 4 times higher. CONCLUSION: Strategies that minimize bile duct injury and speed up recognition of injuries should be adopted to reduce the litigation burden and improve patient care.

"Vicarious thinking" was a key driver of score change in Delphi surveys for COS development and is facilitated by feedback of results.

OBJECTIVE: The objectives of this nested study were to (1) assess whether changes in scores between rounds altered the final degree of consensus achieved in three Delphi surveys conducted as part of COS development projects (anal, gastric, and prostate cancer), and (2) explore participants' reasons for changing scores between rounds. STUDY DESIGN AND SETTING: All Delphi surveys were conducted online using DelphiManager software and included healthcare professionals and participating patients. Participants were invited to give a free-text reason whenever they changed their score across an important threshold on a 1-9 Likert scale (1-3 not important, 4-5 important, 7-9 critically important). Reasons for score change were coded by four researchers independently using an inductive-iterative approach. RESULTS: In all three Delphi surveys, the number of outcomes reaching criteria for consensus was greater in R2 than R1. Twelve themes and 23 subthemes emerged from 2298 discrete reasons given for score change. The most common reasons for the change were "time to reflect" (482 responses, 23%) and vicarious thinking (424, 21%), with 68% (291) of vicarious thinking attributed to seeing other participant's scores. CONCLUSION: Our findings support conducting a Delphi survey over the use of a single questionnaire where building consensus is the objective. Time to reflect and vicarious thinking, facilitated by seeing other participant's scores, were important drivers of score change. How results are presented to participants between rounds and the duration of and time between rounds in a Delphi survey may, therefore, influence the results and should be clearly reported.

Patient priorities in relation to surgery for gastric cancer: qualitative interviews with gastric cancer surgery patients to inform the development of a core outcome set.

OBJECTIVE: The reporting of outcomes in surgical trials for gastric cancer is inconsistent. The GASTROS study (GAstric Cancer Surgery TRials Reported Outcome Standardisation) aims to address this by developing a core outcome set (COS) for use in all future trials within this field. A COS should reflect the views of all stakeholders, including patients. We undertook a series of interviews to identify outcomes important to patients which would be considered for inclusion in a COS. SETTING: All interviews took place within the UK. Interviews were carried out face-to-face at hospitals and cancer support centres or via the telephone. PARTICIPANTS: Twenty participants at varying stages of recovery following surgery for gastric cancer with curative intent. DESIGN: Qualitative design using semistructured interviews, supported by an interview guide which was iteratively modified; thematic analysis was used to explore patient priorities. RESULTS: Six themes enveloping 38 outcomes were identified; surviving and controlling cancer, technical aspects of surgery, adverse events from surgery, recovering from surgery, long-term problems following surgery and long-term life impact of surgery. The 'most important' patient priority was to be 'cured of cancer'. CONCLUSION: Surgical trials for gastric cancer should consider broader priorities of patients when choosing which outcomes to report. This study highlighted the importance of longer-term outcomes such as cancer survival. Outcomes identified in this study will be used to inform an international Delphi survey to develop a COS in this field.

CPET and cardioesophagectomy: A single centre 10-year experience.

INTRODUCTION: CPET is a routine investigation prior to cardioesophagectomy. Over a 10-year period 200 patients had CPET before elective cardioesophagectomy. We examine the relationship between CPET and outcomes in these patients. MATERIALS AND METHODS: Complication data were prospectively collected using the Clavien-Dindo system. Logistic regression analysis was used to determine whether 90-day mortality and morbidity were significantly different between fitter and less fit patients. RESULTS: 90-day mortality was 5.5%. In univariate analysis the following factors were associated with a significantly increased risk of death at 90 days: anaerobic threshold <11 ml kg-1 min-1 OR (95% CI) = 4.38 (1.23,15.6), p = 0.023; V̇O2 peak <15 ml kg-1 min-1 O2 OR (95% CI) = 5.0 (1.42,15.55), p = 0.012; V̇E/V̇CO2 > 34 OR (95% CI) = 4.07 (1.19,14.0), p = 0.026; diabetes mellitus OR (95% CI) = 5.76 (1.55,21.35) p = 0.009. In multivariate logistic regression analysis both diabetes (OR = 5.76 [1.55,21.4] p = 0.009) and presence of ≥ 1 subthreshold CPET value (OR = 6.72 [1.32,29.8] p = 0.021) were significantly associated with increased risk of death at 90 days. Median (95% CI) survival for patients who had a CPET with 'normal' parameters was 1176 (565, 1787) days, compared with 642 (336, 948) days for patients with ≥ one subthreshold parameter. 15.5% of patients had ECG ischaemia; there were no deaths in this group. CONCLUSION: Presence of at least one sub-threshold CPET value at pre-operative testing is associated with increased risk of 90-day mortality and shorter long term survival. These results allow us to better define risks during shared decision-making with patients.

Prognostic significance of positive circumferential resection margin post neoadjuvant chemotherapy in patients with esophageal or gastro-esophageal junction adenocarcinoma.

BACKGROUND: The aim of the present study was to assess the prognosis of patients with esophageal or gastroesophageal junction (E/GEJ) adenocarcinoma extending beyond the muscularis propria layer (≥ypT3) and positive circumferential resection margin (CRM), post neoadjuvant chemotherapy. METHODS: 177 patients were retrospectively studied. The majority (94.9%) received ECX (epirubicin, cisplatin, capecitabine), and all had clear proximal/distal resection margins. CRM was defined as positive (CRM+) when it was directly infiltrated (infiltrated CRM) or when tumor cells were detected within 1 mm from CRM (close CRM) and as negative (CRM-) when tumor cells were found in a distance > 1 mm from CRM. RESULTS: CRM+ was found in 83 patients (46.9%). Of them, infiltrated CRM was recorded in 36 (20.3%) and close CRM in 47 (26.6%). Adjuvant chemotherapy was administered to 132 patients (74.6%). Lymphovascular invasion and primary site in the lower esophagus were independently associated with higher risk of CRM+. Patients with infiltrated CRM, compared to those with close CRM and those CRM-, had the shortest median time-to-relapse (11.4 vs. 15.6 vs. 22.1 months, respectively, p = 0.005) and overall survival (18.7 vs. 23.1 vs. 38.8 months, respectively, p = 0.001). However, CRM status was not an independent predictor of poor outcome. Symptomatic isolated locoregional recurrences were rare in both CRM+ and CRM-patients (4/56 [7.1%] vs. 5/52 [9.6%], p = 0.736), as well as in infiltrated vs. non-infiltrated CRM (CRM- and close CRM) (0/26 [0%] vs. 9/82 [11.0%], p = 0.110). CONCLUSION: Although CRM status is associated with poor outcome, it does not represent an independent prognostic factor. The status of CRM did not significantly influence the pattern of cancer relapse.

Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer-the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT).

INTRODUCTION: Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life. METHODS AND ANALYSIS: We will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery. ETHICS AND DISSEMINATION: This study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN10386621.

Reporting of outcomes in gastric cancer surgery trials: a systematic review.

BACKGROUND: The development of clinical guidelines for the surgical management of gastric cancer should be based on robust evidence from well-designed trials. Being able to reliably compare and combine the outcomes of these trials is a key factor in this process. OBJECTIVES: To examine variation in outcome reporting by surgical trials for gastric cancer and to identify outcomes for prioritisation in an international consensus study to develop a core outcome set in this field. DATA SOURCES: Systematic literature searches (Evidence Based Medicine, MEDLINE, EMBASE, CINAHL, ClinicalTrials.gov and WHO ICTRP) and a review of study protocols of randomised controlled trials, published between 1996 and 2016. INTERVENTION: Therapeutic surgical interventions for gastric cancer. Outcomes were listed verbatim, categorised into groups (outcome themes) and examined for definitions and measurement instruments. RESULTS: Of 1919 abstracts screened, 32 trials (9073 participants) were identified. A total of 749 outcomes were reported of which 96 (13%) were accompanied by an attempted definition. No single outcome was reported by all trials. 'Adverse events' was the most frequently reported 'outcome theme' in which 240 unique terms were described. 12 trials (38%) classified complications according to severity, with 5 (16%) using a formal classification system (Clavien-Dindo or Accordion scale). Of 27 trials which described 'short-term' mortality, 15 (47%) used one of five different definitions. 6 out of the 32 trials (19%) described 'patient-reported outcomes'. CONCLUSION: Reporting of outcomes in gastric cancer surgery trials is inconsistent. A consensus approach to develop a minimum set of well-defined, standardised outcomes to be used by all future trials examining therapeutic surgical interventions for gastric cancer is needed. This should consider the views of all key stakeholders, including patients.

Standardising the reporting of outcomes in gastric cancer surgery trials: protocol for the development of a core outcome set and accompanying outcome measurement instrument set (the GASTROS study).

BACKGROUND: Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Whilst surgery is the mainstay of curative treatment, it is associated with significant risks. Surgical strategies for treating gastric cancer should be based on evidence from systematic reviews of well-designed randomised controlled trials. However, inconsistencies in the reporting of outcomes from these trials makes evidence synthesis unreliable. We present a protocol for an international consensus study to develop a standardised set of outcomes and measurement tools - a 'core outcome set' (COS) - to be used by all future trials examining therapeutic surgical interventions for gastric cancer. The GASTROS study aims to standardise the reporting of outcomes in gastric cancer surgery trials through an international consensus process of key stakeholders including health care professionals and patients. METHODS: The first of three stages in the study will identify a 'long-list' of potentially important outcomes to be prioritised. These will be extracted from a systematic review of relevant academic literature and patient interviews. Stage 2 will comprise an eDelphi survey which will consider the views of patients, nurse specialists and surgeons to prioritise the most important outcomes. A meeting of stakeholder representatives will ratify the COS. Stage 3 will focus on identifying appropriate instruments to measure the prioritised outcomes by means of quality assessment of available measurement instruments and stakeholder consultation. DISCUSSION: This study aims to standardise the reporting of outcomes in future trials examining therapeutic surgical interventions for gastric cancer. It is anticipated that standardisation of outcome reporting in these surgical effectiveness trials will enhance the evidence base for clinical practice. Highlighting outcomes of greatest importance to patients will ensure that their perspectives are central to research in this field.