BACKGROUND:Various strategies have been explored to reduce perineal wound-related morbidity after abdominoperineal resection for rectal cancer. The two BIOPEX trials evaluated the role of biological mesh closure and gluteal turnover flap, but both were negative at their primary endpoint (30-day wound healing). However, several secondary endpoints at different time points might be of clinical relevance. MATERIALS AND METHODS:This was a post-hoc analysis of the BIOPEX and BIOPEX-2 trials. A composite endpoint was defined based on Southampton wound score 2-3 or 4-5 at five different time points during the 12-month postoperative period, presacral abscess, perineal-wound related radiological or surgical reintervention, and readmission. Win-ratio analysis was used, which prioritizes outcomes based on their importance. Sensitivity analyses were conducted and additionally a points-based scoring system was applied to evaluate the degree of wound healing complications. RESULTS:A total of 269 patients were included. The win-ratio analysis revealed a net benefit for biological mesh closure in the BIOPEX study (15.4%, 95%CI -5.4%-36.7%), and for gluteal turnover flap in the BIOPEX-2 study (16.9%, 95%CI 0.1%-33.2%) compared to primary perineal closure, but only the latter reached statistical significance. Various sensitivity analyses showed robustness of the win-ratio results with comparable estimates. Points-based regression analysis did not reveal significant differences: IRR 0.76 (95%CI 0.38-1.52, p = 0.441) and IRR 0.67 (95%CI 0.40-1.14, p = 0.139), respectively. CONCLUSION:This post-hoc analysis sheds new light on perineal wound healing in randomized studies by integrating various outcome measures. Although a similar numerical advantage of the intervention was shown in both BIOPEX trials using win-ratio analysis, it only reached statistical significance for the gluteal turnover flap.

Abstract Background Potentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking. Methods OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA < 4) and have resectable (≦ cT4aN3bM0) primary gastric cancer. Patients will be 1:1 randomized between (sub)total gastrectomy with omentum preservation distal of the gastroepiploic vessels versus complete omentectomy. For a power of 80%, the target sample size is 654 patients. The primary objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of 3-year overall survival. Secondary endpoints include intra- and postoperative outcomes, such as blood loss, operative time, hospital stay, readmission rate, quality of life, disease-free survival, and cost-effectiveness. Discussion The OMEGA trial investigates if omentum preservation during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of 3-year overall survival, with non-inferiority being determined based on results from both the intention-to-treat and the per-protocol analyses. The OMEGA trial will elucidate whether routine complete omentectomy could be omitted, potentially reducing overtreatment. Trial registration ClinicalTrials.gov NCT05180864. Registered on 6th January 2022.

Background and AimMore insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling.MethodsA long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed.ResultsOverall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP.ConclusionDisease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

3517 Background: Primary tumor resection (PTR) in patients with synchronous metastatic colorectal cancer (CRC) has been associated with a survival benefit in comparative cohort studies. In the CAIRO4 phase III randomized trial, the potential benefit of upfront PTR followed by systemic therapy versus systemic therapy alone was investigated. Methods: Main eligibility criteria included histologically confirmed CRC, unresectable metastases, resectable primary tumor in situ without related severe symptoms, and WHO performance status (PS) 0-2. Eligible patients were randomized to first-line fluoropyrimidine-based chemotherapy plus bevacizumab with or without upfront PTR strategy. Randomization was stratified for number of metastatic sites (1 versus more), institution, WHO PS (0-1 versus 2), serum LDH (normal versus > ULN), and location of the primary tumor (left versus right-sided). The primary endpoint was overall survival (OS), which was analyzed by intention-to-treat (ITT) using the MaxCombo test. The original sample size of 306 patients was amended to 206 participants due to slow accrual. With final primary analysis based on 181 events, the study had 71% power to detect the OS difference of 19 versus 13 months deemed clinically relevant in the original sample size calculation. The trial is registered as NCT01606098. Results: Between August 2012 and February 2021, 206 patients were randomized: 103 patients to each arm. Two patients in the upfront PTR arm were excluded due to ineligibility. A total of 204 patients (57% male, median age 65 [IQR 59 -71] years, 50% right-sided CRC and 98% WHO PS 0-1) were included with a median follow-up of 63.6 months. In the upfront PTR arm 5% of patients did not undergo PTR and 13% did not receive subsequent systemic therapy. In the arm without upfront PTR, 1% of patients did not receive systemic therapy. The median number of cycles was 9 [IQR 4-15] in the upfront PTR arm versus 11 [6-16] in the arm without upfront PTR. Median OS was 20.5 (95% CI 17.0 – 25.1) months in the upfront PTR arm and 18.3 (95% CI 16.0 – 22.2) months in the arm without upfront PTR (p = 0.345). Median PFS was 10.1 (95% CI 8.7-11.7) months in the upfront PTR arm and 10.1 (95% CI 8.6-11.8) months in the arm without upfront PTR (p = 0.805). At a later point in their disease course, 1.9% of patients in the arm without upfront PTR underwent a colostomy and 16.5% required PTR for symptom palliation. Conclusions: In patients with synchronous metastatic CRC amenable to palliative systemic therapy without severe symptoms related to the primary tumor, upfront PTR did not result in a significant median OS difference compared to immediate start with systemic treatment. Funding: This work was funded by the Dutch Cancer Society (grant KUN 2012-5697) and Hoffmann-La Roche Ltd. Clinical trial information: NCT01606098 .

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients >= 70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54e0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

In patients with colorectal cancer (CRC), surgical resection is the mainstay of treatment. Older patients are at an increased risk for postoperative complications due to a higher prevalence of frailty, which can be defined as the aging-associated decline in functioning across organ systems that leads to a higher vulnerability towards stressors (such as surgery) [1]. Measuring frailty next to standard risk screening may aid in risk prediction and guide the implementation of preoperative interventions such as prehabilitation (preoperative physical optimization).

BACKGROUND:Abdominal cancer surgery is associated with considerable morbidity in older patients. Assessment of preoperative physical status is therefore essential. The aim of this review was to describe and compare the objective physical tests that are currently used in abdominal cancer surgery in the older patient population with regard to postoperative outcomes.METHODS:Medline, Embase, CINAHL and Web of Science were searched until 31 December 2020. Non-interventional cohort studies were eligible if they included patients ≥65 years undergoing abdominal cancer surgery, reported results on objective preoperative physical assessment such as Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle strength, and on postoperative outcomes.RESULTS:23 publications were included (10 CPET, 13 non-CPET including Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental shuttle walk test (ISWT)). Meta-analysis was precluded due to heterogeneity between study cohorts, different cut-off points, and inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic threshold and minute ventilation/carbon dioxide production gradient were associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two studies. Tests addressing muscle strength and function were of limited value. No study compared different physical tests.DISCUSSION:CPET has the ability to predict adverse postoperative outcomes, but it is time-consuming and requires expert assessment. ISWT or 6MWT might be a feasible alternative to estimate aerobic capacity. Muscle strength and function tests currently have limited value in risk prediction. Future research should compare the predictive value of different physical instruments with regard to postoperative outcomes in older surgical patients.

Introduction: Older patients have a higher risk for complications after rectal cancer surgery. Although screening for geriatric impairments may improve risk prediction in this group, it has not been studied previously. Methods: We retrospectively investigated patients >= 70 years with elective surgery for non-metastatic rectal cancer between 2014 and 2018 in nine Dutch hospitals. The predictive value of six geriatric parameters in combination with standard preoperative predictors was studied for postoperative complications, delirium, and length of stay (LOS) using logistic regression analyses. The geriatric parameters included the four VMS -questionnaire items pertaining to functional impairment, fall risk, delirium risk, and malnutrition, as well as mobility problems and polypharmacy. Standard predictors included age, sex, body mass index, American Society of Anesthesiologists (ASA)-classification, comorbidities, tumor stage, and neoadjuvant therapy. Changes in model performance were evaluated by comparing Area Under the Curve (AUC) of the regression models with and without geriatric parameters. Results: We included 575 patients (median age 75 years; 32% female). None of the geriatric parameters improved risk prediction for complications or LOS. The addition of delirium risk to the standard preoperative prediction model improved model performance for predicting postoperative delirium (AUC 0.75 vs 0.65, p = 0.03). Conclusions: Geriatric parameters did not improve risk prediction for postoperative complications or LOS in older patients with rectal cancer. Delirium risk screening using the VMS-questionnaire improved risk prediction for delirium. Older patients undergoing rectal cancer surgery are a pre-selected group with few impairments. Geriatric screening may have additional value earlier in the care pathway before treatment decisions are made.

Background Among esophagogastric cancer patients, the probability of having undergone treatment with curative intent has been shown to vary, depending on the hospital of diagnosis. However, little is known about the factors that contribute to this variation. In this study, we sought to understand the organization of clinical pathways and their association with variation in practice. Methods A mixed-method study using quantitative and qualitative data was conducted. Quantitative data were obtained from the Netherlands Cancer Registry (e.g., outpatient clinic consultations and diagnostic procedures). For qualitative data, thematic content analysis was performed using semi-structured interviews (n = 30), observations of outpatient clinic consultations (n = 26), and multidisciplinary team meetings (MDTM, n = 16) in eight hospitals, to assess clinicians' perspectives regarding the clinical pathways. Results Quantitative analyses showed that patients more often underwent surgical consultation prior to the MDTM in hospitals associated with a high probability of receiving treatment with curative intent, but more often consulted with a geriatrician in hospitals associated with a low probability of such treatment. The organization of clinical pathways was analyzed quantitatively at three levels: regional, local, and patient levels. At a regional level, hospitals differed in terms of the number of patients discussed during the MDTM. At the local level, the revision of radiological images and restaging after neoadjuvant treatment varied. At the patient level, some hospitals routinely conduct fitness tests, whereas others estimated the patient's physical fitness during an outpatient clinic consultation. Few clinicians performed a standard geriatric consultation in older patients to assess their mental fitness and frailty. Conclusion Surgical consultation prior to MDTM was more often conducted in hospitals associated with a high probability of receiving treatment with curative intent, whereas a geriatrician was consulted more often in hospitals associated with a low probability of receiving such treatment.

Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. Background: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. Methods: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. Results: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6–4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4–23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65–0.84). Conclusions: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

Introduction: Perforation and fistula of the gastrointestinal (GI)-tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes and treatment are lacking. Methods: We performed a post-hoc analysis of 896 patients with necrotizing pancreatitis, prospectively included in 23 Dutch hospitals (2005-2015). Multivariable logistic regression was used to explore risk factors and to adjust for confounders in comparing clinical outcomes of patients with or without perforation and fistula of the GI-tract. Results: GI-tract perforations and fistulas were identified in 139 (16%) patients, mostly in the duodenum (40%) and colon (64%). Independent risk factors were highest C-reactive protein within 48-hours after admission (OR 1.20 [95%-CI 1.02–1.41]), organ-failure in the first week (OR 2.81 [95%-CI 1.80–4.39]) and infected necrosis before diagnosis (OR 1.81 [95%-CI 1.11–2.97]). GI-tract perforation and fistula were associated with poor clinical outcomes, especially when the colon was affected. This is exemplified by an increase in prolonged ICU-stays (OR 6.64 [95%-CI 13.02–15.18]) and more invasive interventions (OR 4.54 [95%-CI 1.82-13.19]). Perforations and fistulas of the stomach and duodenum were treated conservatively in 66% and surgically in 8%. Colon perforations and fistulas were treated conservatively in 27% and surgically in 57%. Conclusions: Perforations and fistulas of the GI-tract occur in one in six patients with necrotizing pancreatitis and poorly affects clinical outcomes, especially colon perforations and fistulas. Risk factors are C-reactive protein within 48 hours, early organ-failure and infected necrosis. Overall, more than half of the patients are treated conservatively.

Background: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase. Materials and methods: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance. Results: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged <= 70 years. Conclusion: With nationwide centralization, travel distance increased for patients undergoing oesophageal, gastric, and pancreatic cancer surgery. Younger patients travelled longer distances and experienced a lower travel burden, as compared to elderly patients. Nevertheless, on a global scale, travel distances in the Netherlands remain limited. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Neuromuscular blocking agents are used in the ICU for various reasons, such as during status asthmaticus and patient-ventilator dyssynchrony. We report a 76-year-old man with adenocarcinoma of the oesophagus treated with laparoscopic transthoracic oesophagectomy, which was complicated by a fistula between the gastric reconstruction and the right main bronchus. He developed extensive ICU-acquired weakness and was treated with differential lung ventilation followed by continuous rocuronium infusion. Evaluation of neuromuscular blockade by train-of-four (TOF) stimulation showed a discrepancy in facial and ulnar TOF monitoring. The different number of neuromuscular junctions at each muscle group could be an explanation for this. Therefore, it is suggested to use facial TOF monitoring in ICU patients instead of ulnar TOF monitoring to differentiate between an intoxication of neuromuscular blockade and ICU-acquired weakness.

BACKGROUND Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).

Purpose The aim of this research was to study the effectiveness on return to work (RTW) of an early tailored work-related support intervention in patients diagnosed with curative gastrointestinal cancer. Methods A multicenter randomized controlled trial was undertaken, in which patients were assigned randomly to the intervention or the control group (usual care). The intervention encompassed three psychosocial work-related support meetings, starting before treatment. Five self-reported questionnaires were sent over twelve months of follow-up. Primary outcome was days until RTW (fulltime or partial) and secondary outcomes included work status, quality of life, work ability, and work limitations. Descriptive analysis, Kaplan–Meier analysis, relative risk ratio and linear mixed models were applied. Results Participants (N = 88) had a mean age of 55 years; 67% were male and the most common cancer type was colon cancer (66%). Of the participants, 42 were randomized to the intervention group. The median time from sick leave until RTW was 233 days (range 187–279 days) for the control group, versus 190 days (range 139–240 days) for the intervention group (log-rank p = 0.37). The RTW rate at twelve months after baseline was 83.3% for the intervention group and 73.5% for the control group. Work limitations did statistically differ between the groups over time (p = 0.01), but quality of life and work ability did not. Conclusion Patients in the intervention group seem to take fewer days to RTW, albeit not to a statistically significant extent. Trial registration Trial NL4920 (NTR5022) (Dutch Trial Register https://www.trialregister.nl )

Purpose: Frailty screening in the emergency department may identify frail patients at risk for adverse outcomes. This study investigated if the Dutch Safety Management Program (VMS) screener predicts outcomes in older patients in the emergency department. Methods: In this prospective cohort study, patients aged 70 years or older presenting to the emergency department were recruited on workdays between 10:00 AM and 7:00 PM from May 2017 until August 2017. Patients were screened in four domains: activities of daily living, malnutrition, risk of delirium, and risk of falling. After 90 days of follow up, mortality, functional decline, living situation, falls, readmission to the emergency department, and readmission to the hospital were recorded. VMS was studied using the total VMS score as a predictor with ROC curve analysis, and using a cut-off point to divide patients into frail and non-frail groups to calculate positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 249 patients were included. Higher VMS score was associated with 90-day mortality (AUC 0.65, 95% CI 0.54-0.76) and falling (AUC 0.67, 95% CI 0.56-0.78). VMS frailty predicted mortality (PPV 0.15, NPV 0.94, p = 0.05) and falling (PPV 0.22, NPV 0.92, p = 0.02), but none of the other outcomes. Conclusion: In this selected group of patients, higher VMS score was associated with 90-day mortality and falls. The low positive predictive value shows that the VMS screener is unsuitable for identifying high-risk patients in the ED. The high negative predictive value indicates that the screener can identify patients not at risk for adverse medical outcomes. This could be useful to determine which patients should undergo additional screening.

Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit.