Deep neuromuscular blockade in adults undergoing an abdominal laparoscopic procedure.

BACKGROUND: Laparoscopic surgery is the preferred option for many procedures. To properly perform laparoscopic surgery, it is essential that sudden movements and abdominal contractions in patients are prevented, as it limits the surgeon's view. There has been a growing interest in the potential beneficial effect of deep neuromuscular blockade (NMB) in laparoscopic surgery. Deep NMB improves the surgical field by preventing abdominal contractions, and it is thought to decrease postoperative pain. However, it is uncertain if deep NMB improves intraoperative safety and thereby improves clinical outcomes. OBJECTIVES: To evaluate the benefits and harms of deep neuromuscular blockade versus no, shallow, or moderate neuromuscular blockade during laparoscopic intra- or transperitoneal procedures in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 July 2023. SELECTION CRITERIA: We included randomised clinical trials (irrespective of language, blinding, or publication status) in adults undergoing laparoscopic intra- or transperitoneal procedures comparing deep NMB to moderate, shallow, or no NMB. We excluded trials that did not report any of the primary or secondary outcomes of our review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. health-related quality of life, and 3. proportion of participants with serious adverse events. Our secondary outcomes were 4. proportion of participants with non-serious adverse events, 5. readmissions within three months, 6. short-term pain scores, 7. measurements of postoperative recovery, and 8. operating time. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 42 randomised clinical trials with 3898 participants. Most trials included participants undergoing intraperitoneal oncological resection surgery. We present the Peto fixed-effect model for most dichotomous outcomes as only sparse events were reported. Comparison 1: deep versus moderate NMB Thirty-eight trials compared deep versus moderate NMB. Deep NMB may have no effect on mortality, but the evidence is very uncertain (Peto odds ratio (OR) 7.22, 95% confidence interval (CI) 0.45 to 115.43; 12 trials, 1390 participants; very low-certainty evidence). Deep NMB likely results in little to no difference in health-related quality of life up to four days postoperative (mean difference (MD) 4.53 favouring deep NMB on the Quality of Recovery-40 score, 95% CI 0.96 to 8.09; 5 trials, 440 participants; moderate-certainty evidence; mean difference lower than the mean clinically important difference of 10 points). The evidence is very uncertain about the effect of deep NMB on intraoperatively serious adverse events (deep NMB 38/1150 versus moderate NMB 38/1076; Peto OR 0.95, 95% CI 0.59 to 1.52; 21 trials, 2231 participants; very low-certainty evidence), short-term serious adverse events (up to 60 days) (deep NMB 37/912 versus moderate NMB 42/852; Peto OR 0.90, 95% CI 0.56 to 1.42; 16 trials, 1764 participants; very low-certainty evidence), and short-term non-serious adverse events (Peto OR 0.94, 95% CI 0.65 to 1.35; 11 trials, 1232 participants; very low-certainty evidence). Deep NMB likely does not alter the duration of surgery (MD -0.51 minutes, 95% CI -3.35 to 2.32; 34 trials, 3143 participants; moderate-certainty evidence). The evidence is uncertain if deep NMB alters the length of hospital stay (MD -0.22 days, 95% CI -0.49 to 0.06; 19 trials, 2084 participants; low-certainty evidence) or pain scores one hour after surgery (MD -0.31 points on the numeric rating scale, 95% CI -0.59 to -0.03; 22 trials, 1823 participants; very low-certainty evidence; mean clinically important difference 1 point) and 24 hours after surgery (MD -0.60 points on the numeric rating scale, 95% CI -1.05 to -0.15; 16 trials, 1404 participants; very low-certainty evidence; mean clinically important difference 1 point). Comparison 2: deep versus shallow NMB Three trials compared deep versus shallow NMB. The trials did not report on mortality and health-related quality of life. The evidence is very uncertain about the effect of deep NMB compared to shallow NMB on the proportion of serious adverse events (RR 1.66, 95% CI 0.50 to 5.57; 2 trials, 158 participants; very low-certainty evidence). Comparison 3: deep versus no NMB One trial compared deep versus no NMB. There was no mortality in this trial, and health-related quality of life was not reported. The proportion of serious adverse events was 0/25 in the deep NMB group and 1/25 in the no NMB group. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw conclusions about the effects of deep NMB compared to moderate NMB on all-cause mortality and serious adverse events. Deep NMB likely results in little to no difference in health-related quality of life and duration of surgery compared to moderate NMB, and it may have no effect on the length of hospital stay. Due to the very low-certainty evidence, we do not know what the effect is of deep NMB on non-serious adverse events, pain scores, or readmission rates. Randomised clinical trials with adequate reporting of all adverse events would reduce the current uncertainties. Due to the low number of identified trials and the very low certainty of evidence, we do not know what the effect of deep NMB on serious adverse events is compared to shallow NMB and no NMB. We found no trials evaluating mortality and health-related quality of life.

Minimally invasive versus open pancreatoduodenectomy in benign, premalignant, and malignant disease.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease.

A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data.

BACKGROUND: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. METHODS: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. RESULTS: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). CONCLUSION: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease.

Functional Dyspepsia and Irritable Bowel Syndrome are Highly Prevalent in Patients With Gallstones and Are Negatively Associated With Outcomes After Cholecystectomy: A Prospective, Multicenter, Observational Study (PERFECT - Trial).

OBJECTIVE: To determine the prevalence of FD and IBS in patients eligible for cholecystectomy and to investigate the association between presence of FD/ IBS and resolution of biliary colic and a pain-free state. SUMMARY BACKGROUND DATA: More than 30% of patients with symptomatic cholecystolithiasis reports persisting pain postcholecystectomy. Coexistence of FD/IBS may contribute to this unsatisfactory outcome. METHODS: We conducted a multicenter, prospective, observational study (PERFECT-trial). Patients ≥18 years with abdominal pain and gallstones were included at 5 surgical outpatient clinics between 01/2018 and 04/2019. Follow-up was 6 months. Primary outcomes were prevalence of FD/IBS, and the difference between resolution of biliary colic and pain-free state in patients with and without FD/IBS. FD/IBS was defined by the Rome IV criteria, biliary colic by the Rome III criteria, and pain-free by an Izbicki Pain Score ≤10 and visual analogue scale ≤4. RESULTS: We included 401 patients with abdominal pain and gallstones (assumed eligible for cholecystectomy), mean age 52 years, 76% females. Of these, 34.9% fulfilled criteria for FD/IBS. 64.1% fulfilled criteria for biliary colic and 74.9% underwent cholecystectomy, with similar operation rates in patients with and without FD/IBS. Postcholecystectomy, 6.1% of patients fulfilled criteria for biliary colic, with no significant difference between those with and without FD/IBS at baseline (4.9% vs 8.6%, P = 0.22). Of all patients, 56.8% was pain-free after cholecystectomy, 40.7% of FD/IBS-group vs 64.4% of no FD/IBS-group, P < 0.001. CONCLUSIONS: One third of patients eligible for cholecystectomy fulfil criteria for FD/IBS. Biliary colic is reported by only a few patients postcholecys-tectomy, whereas nonbiliary abdominal pain persists in >40%, particularly in those with FD/IBS precholecystectomy. Clinicians should take these symptom-dependent outcomes into account in their shared decision-making process. TRIAL REGISTRATION: The Netherlands Trial Register NTR-7307. Registered on 18 June 2018.

Cost-effectiveness of Restrictive Strategy Versus Usual Care for Cholecystectomy in Patients With Gallstones and Abdominal Pain (SECURE-trial).

OBJECTIVE: To perform a cost-effectiveness analysis of restrictive strategy versus usual care in patients with gallstones and abdominal pain. SUMMARY OF BACKGROUND DATA: A restrictive selection strategy for surgery in patients with gallstones reduces cholecystectomies, but the impact on overall costs and cost-effectiveness is unknown. METHODS: Data of a multicentre, randomized-controlled trial (SECURE-trial) were used. Adult patients with gallstones and abdominal pain were included. Restrictive strategy was economically evaluated against usual care from a societal perspective. Hospital-use of resources was gathered with case-report forms and out-of-hospital consultations, out-of-pocket expenses, and productivity loss were collected with questionnaires. National unit costing was applied. The primary outcome was the cost per pain-free patient after 12 months. RESULTS: All 1067 randomized patients (49.0 years, 73.7% females) were included. After 12 months, 56.2% of patients were pain-free in restrictive strategy versus 59.8% after usual care. The restrictive strategy significantly reduced the cholecystectomy rate with 7.7% and reduced surgical costs with €160 per patient, €162 was saved from a societal perspective. The cost-effectiveness plane showed that restrictive strategy was cost saving in 89.1%, but resulted in less pain-free patients in 88.5%. Overall, the restrictive strategy saved €4563 from a societal perspective per pain-free patient lost. CONCLUSIONS: A restrictive selection strategy for cholecystectomy saves €162 compared to usual care, but results in fewer pain-free patients. The incremental cost per pain-free patient are savings of €4563 per pain-free patient lost. The higher societal willingness to pay for 1 extra pain-free patient, the lower the probability that the restrictive strategy will be cost-effective. TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022. Registered on 5 June 2013.

Budget Impact of Restrictive Strategy Versus Usual Care for Cholecystectomy (SECURE-Trial).

OBJECTIVES: A cost-effectiveness analysis of a multicenter randomized-controlled trial comparing restrictive strategy versus usual care in patients with gallstones showed that savings by restrictive strategy could not compensate for the lower proportion of pain-free patients. However, four subgroups based on combined stratification factors resulted in less cholecystectomies and more pain-free patients in restrictive strategy (female-low volume-BMI > 30, female-low volume-BMI25-30, female-high volume-BMI25-30, and male-low volume-BMI < 25). The aim of this study was to explore the budget impact from a hospital healthcare perspective of implementation of restrictive strategy in these subgroups. METHODS: Data of the SECURE-trial were used to calculate the hospital budget impact with a time horizon of four years. Based on a study into practice variation, about 19% of hospitals treat patients according restrictive strategy. This represents the proportion of patients treated according restrictive strategy at the start of budget period. Three subanalyses were performed: a scenario analysis in which 30% of patients fall under a restrictive strategy in clinical practice, a sensitivity analysis in which we calculated the budget impact with the low and high 95% confidence limits of the expected future number of patients, a subgroup analysis in which restrictive strategy was also implemented in two additional subgroups (male-high volume-BMI < 25 and female-high volume-BMI >30). RESULTS: Budget impact analysis showed savings of €6.7-€15.6 million (2.2%-5.6%) for the period 2021-2024/2025 by implementing the restrictive strategy in the four subgroups and provision of usual care in other patients. Sensitivity analysis with 30% of patients already in the restrictive strategy at the start of the budget period, resulted in savings between €5.4 million and €14.0 million (1.7%-5.0%). CONCLUSION: Performing a restrictive strategy for selection of cholecystectomy in subgroups of patients and provision of usual care in other patients will result in a lower overall hospital budget needed to treat patients with abdominal pain and gallstones. TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022. Registered on June 5, 2013.

Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease.

BACKGROUND: Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival after re-resection, RD, and prognostic factors are analyzed. METHODS: Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of re-resected patients were reviewed. Survival and prognostic factors were analyzed. RESULTS: Overall, 463 patients were included; 24% (n = 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval [CI] 11.6-15.6), compared with 52.6 months (95% CI 36.3-68.8) in re-resected patients (p < 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months; p < 0.001). In patients who underwent re-resection, RD in the liver (hazard ratio [HR] 5.54; p < 0.001) and lymph nodes (HR 2.35; p = 0.005) were the only significant prognostic factors in multivariable analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3; p = 0.003) and pN1 stage (HR 23.0; p = 0.022). CONCLUSION: Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages.

Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD): A Multicenter Patient-blinded Randomized Controlled Trial.

OBJECTIVE: This trial followed a structured nationwide training program in minimally invasive distal pancreatectomy (MIDP), according to the IDEAL framework for surgical innovation, and aimed to compare time to functional recovery after minimally invasive and open distal pancreatectomy (ODP). BACKGROUND: MIDP is increasingly used and may enhance postoperative recovery as compared with ODP, but randomized studies are lacking. METHODS: A multicenter patient-blinded randomized controlled superiority trial was performed in 14 centers between April 2015 and March 2017. Adult patients with left-sided pancreatic tumors confined to the pancreas without vascular involvement were randomly assigned (1:1) to undergo MIDP or ODP. Patients were blinded for type of surgery using a large abdominal dressing. The primary endpoint was time to functional recovery. Analysis was by intention to treat. This trial was registered with the Netherlands Trial Register (NTR5689). RESULTS: Time to functional recovery was 4 days [interquartile range (IQR) 3-6) in 51 patients after MIDP versus 6 days (IQR 5-8) in 57 patients after ODP (P < 0.001). The conversion rate of MIDP was 8%. Operative blood loss was less after MIDP (150 vs 400 mL; P < 0.001), whereas operative time was longer (217 vs 179 minutes; P = 0.005). The Clavien-Dindo grade ≥III complication rate was 25% versus 38% (P = 0.21). Delayed gastric emptying grade B/C was seen less often after MIDP (6% vs 20%; P = 0.04). Postoperative pancreatic fistulas grade B/C were seen in 39% after MIDP versus 23% after ODP (P = 0.07), without difference in percutaneous catheter drainage (22% vs 20%; P = 0.77). Quality of life (day 3-30) was better after MIDP as compared with ODP, and overall costs were non-significantly less after MIDP. No 90-day mortality was seen after MIDP versus 2% (n = 1) after ODP. CONCLUSIONS: In patients with left-sided pancreatic tumors confined to the pancreas, MIDP reduces time to functional recovery compared with ODP. Although the overall rate of complications was not reduced, MIDP was associated with less delayed gastric emptying and better quality of life without increasing costs.

Polyp size of 1 cm is insufficient to discriminate neoplastic and non-neoplastic gallbladder polyps.

BACKGROUND: A significant proportion of gallbladder polyps are non-neoplastic, for which resection is not necessary. However, international guidelines advocate cholecystectomy for all polyps ≥ 1 cm. This study assessed a national cohort of histopathologically proven gallbladder polyps to distinguish neoplastic from non-neoplastic polyps. METHODS: PALGA, the nationwide network and registry of histo- and cytopathology, was searched to identify all histopathologically proven gallbladder polyps between 2003 and 2013. All polyps and (focal) wall thickenings > 5 mm were included, and classified as neoplastic or non-neoplastic. Polyp subtype, size, distribution, presentation as wall thickening or protruding polyp, and presence of gallstones were assessed for neoplastic and non-neoplastic polyps. A decision tree to distinguish neoplastic and non-neoplastic polyps was made and diagnostic accuracy of 1 cm surgical threshold was calculated. RESULTS: A total of 2085 out of 220,612 cholecystectomies contained a polyp (0.9%). Of these polyps, 56.4% were neoplastic (40.1% premalignant, 59.9% malignant) and 43.6% non-neoplastic (41.5% cholesterol polyp, 37.0% adenomyomatosis, 21.5% other). Polyp size, distribution, and presence of gallstones were reported in 1059, 1739 and 1143 pathology reports, respectively. Neoplastic polyps differed from non-neoplastic polyps in size (18.1 mm vs 7.5 mm, p < 0.001), singularity (88.2% vs 68.2%, p < 0.001), wall thickening (29.1% vs 15.6%, p < 0.001), and presence of gallstones (50.1% vs 40.4%, p = 0.001). However, adenomyomatosis presented with similar characteristics as neoplastic polyps. Fifty percent of polyps were ≥ 1 cm surgical threshold (optimal surgical threshold based on ROC-curve); sensitivity for indicating neoplastic polyps was 68.1%, specificity was 70.2%, and positive and negative predictive values were 72.9% and 65.1%. CONCLUSIONS: The prevalence of gallbladder polyps on cholecystectomy is low and many of the polyps are non-neoplastic. Clinicopathological characteristics differ between neoplastic and non-neoplastic polyps in general, but these cannot properly indicate neoplasia. The 1 cm surgical threshold has moderate diagnostic accuracy and is insufficient to indicate surgery for neoplastic gallbladder polyps.

Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial.

BACKGROUND: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery. OBJECTIVES: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery. DESIGN: A phase IV, double-blinded, randomised controlled trial. SETTING: Multicentre trial, from November 2016 to December 2017. PATIENTS: A total of 101 living kidney donors scheduled for LDN were enrolled, and 96 patients were included in the analyses. INTERVENTIONS: Patients were randomised to receive profound (posttetanic count 1 to 3) or moderate (train-of-four count 1 to 3) neuromuscular block. MAIN OUTCOME MEASURES: The primary outcome was the early quality of recovery at postoperative day 1, measured by the Quality of Recovery-40 Questionnaire. Secondary outcomes were adverse events, postoperative pain, analgesic consumption and length-of-stay. RESULTS: The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. Less intra-operative adverse events occurred in patients allocated to profound NMB (1/48 versus 6/48). Five patients allocated to a profound NMB received a moderate block and in two patients neuromuscular monitoring failed. The as-treated analysis revealed that pain scores were significantly lower at 6, 24 and 48 h after surgery. Moreover, the quality of recovery was significantly better at postoperative day 2 in patients receiving a profound versus moderate block (179.5 ±â€Š13.6 versus 172.3 ±â€Š19.2). CONCLUSION: Secondary analysis indicates that an adequately maintained profound neuromuscular block improves postoperative pain scores and quality of recovery. As the intention-to-treat analysis did not reveal a difference regarding the primary endpoint, future studies should pursue whether a thoroughly maintained profound NMB during laparoscopy improves relevant patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838134.

Transabdominal ultrasound and endoscopic ultrasound for diagnosis of gallbladder polyps.

BACKGROUND: Approximately 0.6% to 4% of cholecystectomies are performed because of gallbladder polyps. The decision to perform cholecystectomy is based on presence of gallbladder polyp(s) on transabdominal ultrasound (TAUS) or endoscopic ultrasound (EUS), or both. These polyps are currently considered for surgery if they grow more than 1 cm. However, non-neoplastic polyps (pseudo polyps) do not need surgery, even when they are larger than 1 cm. True polyps are neoplastic, either benign (adenomas) or (pre)malignant (dysplastic polyps/carcinomas). True polyps need surgery, especially if they are premalignant or malignant. There has been no systematic review and meta-analysis on the accuracy of TAUS and EUS in the diagnosis of gallbladder polyps, true gallbladder polyps, and (pre)malignant polyps. OBJECTIVES: To summarise and compare the accuracy of transabdominal ultrasound (TAUS) and endoscopic ultrasound (EUS) for the detection of gallbladder polyps, for differentiating between true and pseudo gallbladder polyps, and for differentiating between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder in adults. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, and trial registrations (last date of search 09 July 2018). We had no restrictions regarding language, publication status, or prospective or retrospective nature of the studies. SELECTION CRITERIA: Studies reporting on the diagnostic accuracy data (true positive, false positive, false negative and true negative) of the index test (TAUS or EUS or both) for detection of gallbladder polyps, differentiation between true and pseudo polyps, or differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps. We only accepted histopathology after cholecystectomy as the reference standard, except for studies on diagnosis of gallbladder polyp. For the latter studies, we also accepted repeated imaging up to six months by TAUS or EUS as the reference standard. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts, selected studies for inclusion, and collected data from each study. The quality of the studies was evaluated using the QUADAS-2 tool. The bivariate random-effects model was used to obtain summary estimates of sensitivity and specificity, to compare diagnostic performance of the index tests, and to assess heterogeneity. MAIN RESULTS: A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and not as a combination of tests. All studies were at high or unclear risk of bias, ten studies had high applicability concerns in participant selection (because of inappropriate participant exclusions) or reference standards (because of lack of follow-up for non-operated polyps), and three studies had unclear applicability concerns in participant selection (because of high prevalence of gallbladder polyps) or index tests (because of lack of details on ultrasound equipment and performance). A meta-analysis directly comparing results of TAUS and EUS in the same population could not be performed because only limited studies executed both tests in the same participants. Therefore, the results below were obtained only from indirect test comparisons. There was significant heterogeneity amongst all comparisons (target conditions) on TAUS and amongst studies on EUS for differentiating true and pseudo polyps.Detection of gallbladder polyps: Six studies (16,260 participants) used TAUS. We found no studies on EUS. The summary sensitivity and specificity of TAUS for the detection of gallbladder polyps was 0.84 (95% CI 0.59 to 0.95) and 0.96 (95% CI 0.92 to 0.98), respectively. In a cohort of 1000 people, with a 6.4% prevalence of gallbladder polyps, this would result in 37 overdiagnosed and seven missed gallbladder polyps.Differentiation between true polyp and pseudo gallbladder polyp: Six studies (1078 participants) used TAUS; the summary sensitivity was 0.68 (95% CI 0.44 to 0.85) and the summary specificity was 0.79 (95% CI 0.57 to 0.91). Three studies (209 participants) used EUS; the summary sensitivity was 0.85 (95% CI 0.46 to 0.97) and the summary specificity was 0.90 (95% CI 0.78 to 0.96). In a cohort of 1000 participants with gallbladder polyps, with 10% having true polyps, this would result in 189 overdiagnosed and 32 missed true polyps by TAUS, and 90 overdiagnosed and 15 missed true polyps by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (relative sensitivity 1.06, P = 0.70, relative specificity 1.15, P = 0.12).Differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder: Four studies (1,009 participants) used TAUS; the summary sensitivity was 0.79 (95% CI 0.62 to 0.90) and the summary specificity was 0.89 (95% CI 0.68 to 0.97). Three studies (351 participants) used EUS; the summary sensitivity was 0.86 (95% CI 0.76 to 0.92) and the summary specificity was 0.92 (95% CI 0.85 to 0.95). In a cohort of 1000 participants with gallbladder polyps, with 5% having a dysplastic polyp/carcinoma, this would result in 105 overdiagnosed and 11 missed dysplastic polyps/carcinomas by TAUS and 76 overdiagnosed and seven missed dysplastic polyps/carcinomas by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (log likelihood test P = 0.74). AUTHORS' CONCLUSIONS: Although TAUS seems quite good at discriminating between gallbladder polyps and no polyps, it is less accurate in detecting whether the polyp is a true or pseudo polyp and dysplastic polyp/carcinoma or adenoma/pseudo polyp. In practice, this would lead to both unnecessary surgeries for pseudo polyps and missed cases of true polyps, dysplastic polyps, and carcinomas. There was insufficient evidence that EUS is better compared to TAUS in differentiating between true and pseudo polyps and between dysplastic polyps/carcinomas and adenomas/pseudo polyps. The conclusions are based on heterogeneous studies with unclear criteria for diagnosis of the target conditions and studies at high or unclear risk of bias. Therefore, results should be interpreted with caution. Further studies of high methodological quality, with clearly stated criteria for diagnosis of gallbladder polyps, true polyps, and dysplastic polyps/carcinomas are needed to accurately determine diagnostic accuracy of EUS and TAUS.

Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit.

BACKGROUND: In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated. METHODS: Patients undergoing pancreatoduodenectomy in 2014 and 2015 in The Netherlands were included. Hospitals were divided into quartiles based on mortality rates. The rate of major complications (Clavien-Dindo ≥3) and death after a major complication (FTR) were compared between these quartiles. Independent predictors for FTR were identified by multivariable logistic regression analysis. RESULTS: Out of 1.342 patients, 391 (29%) developed a major complication and in-hospital mortality was 4.2%. FTR occurred in 56 (14.3%) patients. Mortality was 0.9% in the first hospital quartile (4 hospitals, 327 patients) and 8.1% in the fourth quartile (5 hospitals, 310 patients). The rate of major complications increased by 40% (25.7% vs 35.2%) between the first and fourth hospital quartile, whereas the FTR rate increased by 560% (3.6% vs 22.9%). Independent predictors of FTR were male sex (OR = 2.1, 95%CI 1.2-3.9), age >75 years (OR = 4.3, 1.8-10.2), BMI ≥30 (OR = 2.9, 1.3-6.6), histopathological diagnosis of periampullary cancer (OR = 2.0, 1.1-3.7), and hospital volume <30 (OR = 3.9, 1.6-9.6). CONCLUSIONS: Variations in mortality between hospitals after pancreatoduodenectomy were explained mainly by differences in FTR, rather than the incidence of major complications.

Consistency of patient-reported outcomes after cholecystectomy and their implications on current surgical practice: a prospective multicenter cohort study.

BACKGROUND: Persistent postoperative pain (up to 41 %) and significant practice variation necessitate better patient selection for cholecystectomy. Patient-reported outcome measures (PROMs) are nowadays known to serve as a tool for better patient selection, although variability within these subjective outcomes may be a point for debate. This study determines associations of both the preoperative pain and patient characteristics with PROMs at 24 weeks after cholecystectomy. In order to evaluate variability of PROMs, we also determined consistency of these outcomes in time. METHODS: This prospective multicenter cohort study included adult patients diagnosed with uncomplicated symptomatic cholecystolithiasis. Twenty-four weeks after surgery, a questionnaire study was carried out, containing Gastrointestinal Quality of Life Index (GIQLI) and Patients' Experience of Surgery Questionnaire. Results were compared to preoperative data and results 12 weeks post-cholecystectomy. Logistic regression analyses were performed to determine associations. Additional post hoc analysis on associations between preoperative selection criteria and PROMs was done. RESULTS: A total of 360 patients (85 %) responded. Postoperative absence of pain was reported by 59.2 %. Associated characteristics were symptoms ≤1 year prior to surgery [OR 1.85 (95 % CI 1.11-3.09)] and high baseline GIQLI score [OR 1.04 (95 % CI 1.02-1.05)]. General improvement in abdominal symptoms and positive result of surgery were found in 90 %; no preoperative variables were significantly associated. PROMs showed consistency at 12 and 24 weeks postoperatively. Post hoc analysis showed no significant associations. CONCLUSION: PROM-based preoperative selection criteria need to be considered to select those patients who achieve freedom of pain after surgical treatment of uncomplicated symptomatic cholecystolithiasis. Other patients might consider cholecystectomy as successful, but are less likely to be free of pain. Usefulness of PROMs is underscored as they proved to be consistent in time in evaluating surgical outcome.

Cost-effectiveness of a new strategy to identify uncomplicated gallstone disease patients that will benefit from a cholecystectomy.

BACKGROUND: The aim of this study was to determine the cost-effectiveness of a new strategy for the preoperative detection of patients that will likely benefit from a cholecystectomy, using simple criteria that can be applied by surgeons. Criteria for a cholecystectomy indication are: (1) having episodic pain; (2) onset of pain 1 year or less before the outpatient clinic visit. METHODS: The cost-effectiveness of the new strategy was evaluated against current practice using a decision analytic model. The incremental cost-effectiveness of applying criteria for a cholecystectomy for a patient with abdominal pain and gallstones was compared to applying no criteria. The incremental cost-effectiveness ratio (ICER) was expressed as extra costs to be invested to gain one more patient with absence of pain. Scenarios were analyzed to assess the influence of applying different criteria. RESULTS: The new strategy of applying one out of two criteria resulted in a 4 % higher mean proportion of patients with absence of pain compared to current practice with similar costs. The 95 % upper limit of the ICER was €4114 ($4633) per extra patient with relief of upper abdominal pain. Application of two out of two criteria resulted in a 3 % lower mean proportion of patients with absence of pain with lower costs. CONCLUSION: The new strategy of using one out of two strict selection criteria may be an effective but also a cost-effective method to reduce the proportion of patients with pain after cholecystectomy.

Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

BACKGROUND: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. METHODS: Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. RESULTS: Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. CONCLUSIONS: The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level.

Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS).

OBJECTIVE: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). SUMMARY OF BACKGROUND DATA: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. METHODS: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015). RESULTS: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). CONCLUSION: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.

Laparoscopic versus open distal pancreatectomy for pancreatic cancer.

BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance. OBJECTIVES: To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both. SEARCH METHODS: We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non-randomised studies. We also searched the reference lists of included trials to identify additional studies. SELECTION CRITERIA: We considered for inclusion in the review RCTs and non-randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status.. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed-effect and random-effects models with RevMan 5 on the basis of intention-to-treat analysis when possible. MAIN RESULTS: We found no RCTs on this topic. We included in this review 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182 underwent open distal pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided information for one or more outcomes. All of these studies were retrospective cohort-like studies or case-control studies. Most were at unclear or high risk of bias, and the overall quality of evidence was very low for all reported outcomes.Differences in short-term mortality (laparoscopic group: 1/329 (adjusted proportion based on meta-analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR 0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I(2) = 0%), long-term mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I(2) = 0%), proportion of people with serious adverse events (laparoscopic group: 7/89 (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to 6.06; 206 participants; three studies; I(2) = 0%), proportion of people with a clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246 participants; four studies; I(2) = 61%) were imprecise. Differences in recurrence at maximal follow-up (laparoscopic group: 37/81 (adjusted proportion based on meta-analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI 0.32 to 1.05; 184 participants; two studies; I(2) = 13%), adverse events of any severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group: 45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies; I(2) = 18%) and proportion of participants with positive resection margins (laparoscopic group: 49/333 (adjusted proportion based on meta-analysis estimate: 14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466 participants; 10 studies; I(2) = 6%) were also imprecise. Mean length of hospital stay was shorter by 2.43 days in the laparoscopic group than in the open group (MD -2.43 days, 95% CI -3.13 to -1.73; 1068 participants; five studies; I(2) = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements. AUTHORS' CONCLUSIONS: Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow-up. Such studies should include patient-oriented outcomes such as short-term mortality and long-term mortality (at least two to three years); health-related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.

Benefits and harms of adhesion barriers for abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Formation of adhesions after peritoneal surgery results in high morbidity. Barriers to prevent adhesion are seldom applied, despite their ability to reduce the severity of adhesion formation. We evaluated the benefits and harms of four adhesion barriers that have been approved for clinical use. METHODS: In this systematic review and meta-analysis, we searched PubMed, CENTRAL, and Embase for randomised clinical trials assessing use of oxidised regenerated cellulose, hyaluronate carboxymethylcellulose, icodextrin, or polyethylene glycol in abdominal surgery. Two researchers independently identified reports and extracted data. We compared use of a barrier with no barrier for nine predefined outcomes, graded for clinical relevance. The primary outcome was reoperation for adhesive small bowel obstruction. We assessed systematic error, random error, and design error with the error matrix approach. This study is registered with PROSPERO, number CRD42012003321. FINDINGS: Our search returned 1840 results, from which 28 trials (5191 patients) were included in our meta-analysis. The risks of systematic and random errors were low. No trials reported data for the effect of oxidised regenerated cellulose or polyethylene glycol on reoperations for adhesive small bowel obstruction. Oxidised regenerated cellulose reduced the incidence of adhesions (relative risk [RR] 0·51, 95% CI 0·31-0·86). Some evidence suggests that hyaluronate carboxymethylcellulose reduces the incidence of reoperations for adhesive small bowel obstruction (RR 0·49, 95% CI 0·28-0·88). For icodextrin, reoperation for adhesive small bowel obstruction did not differ significantly between groups (RR 0·33, 95% CI 0·03-3·11). No barriers were associated with an increase in serious adverse events. INTERPRETATION: Oxidised regenerated cellulose and hyaluronate carboxymethylcellulose can safely reduce clinically relevant consequences of adhesions. FUNDING: None.