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.

Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial.

BACKGROUND: International guidelines advise laparoscopic cholecystectomy to treat symptomatic, uncomplicated gallstones. Usual care regarding cholecystectomy is associated with practice variation and persistent post-cholecystectomy pain in 10-41% of patients. We aimed to compare the non-inferiority of a restrictive strategy with stepwise selection with usual care to assess (in)efficient use of cholecystectomy. METHODS: We did a multicentre, randomised, parallel-arm, non-inferiority study in 24 academic and non-academic hospitals in the Netherlands. We enrolled patients aged 18-95 years with abdominal pain and ultrasound-proven gallstones or sludge. Patients were randomly assigned (1:1) to either usual care in which selection for cholecystectomy was left to the discretion of the surgeon, or a restrictive strategy with stepwise selection for cholecystectomy. For the restrictive strategy, cholecystectomy was advised for patients who fulfilled all five pre-specified criteria of the triage instrument: 1) severe pain attacks, 2) pain lasting 15-30 min or longer, 3) pain located in epigastrium or right upper quadrant, 4) pain radiating to the back, and 5) a positive pain response to simple analgesics. Randomisation was done with an online program, implemented into a web-based application using blocks of variable sizes, and stratified for centre (academic versus non-academic and a high vs low number of patients), sex, and body-mass index. Physicians and patients were masked for study-arm allocation until after completion of the triage instrument. The primary, non-inferiority, patient-reported endpoint was the proportion of patients who were pain-free at 12 months' follow-up, analysed by intention to treat and per protocol. A 5% non-inferiority margin was chosen, based on the estimated clinically relevant difference. Safety analyses were also done in the intention-to treat population. This trial is registered at the Netherlands National Trial Register, number NTR4022. FINDINGS: Between Feb 5, 2014, and April 25, 2017, we included 1067 patients for analysis: 537 assigned to usual care and 530 to the restrictive strategy. At 12 months' follow-up 298 patients (56%; 95% CI, 52·0-60·4) were pain-free in the restrictive strategy group, compared with 321 patients (60%, 55·6-63·8) in usual care. Non-inferiority was not shown (difference 3·6%; one-sided 95% lower CI -8·6%; pnon-inferiority=0·316). According to a secondary endpoint analysis, the restrictive strategy resulted in significantly fewer cholecystectomies than usual care (358 [68%] of 529 vs 404 [75%] of 536; p=0·01). There were no between-group differences in trial-related gallstone complications (40 patients [8%] of 529 in usual care vs 38 [7%] of 536 in restrictive strategy; p=0·16) and surgical complications (74 [21%] of 358 vs 88 [22%] of 404, p=0·77), or in non-trial-related serious adverse events (27 [5%] of 529 vs 29 [5%] of 526). INTERPRETATION: Suboptimal pain reduction in patients with gallstones and abdominal pain was noted with both usual care and following a restrictive strategy for selection for cholecystectomy. However, the restrictive strategy was associated with fewer cholecystectomies. The findings should encourage physicians involved in the care of patients with gallstones to rethink cholecystectomy, and to be more careful in advising a surgical approach in patients with gallstones and abdominal symptoms. FUNDING: The Netherlands Organization for Health Research and Development, and CZ healthcare insurance.

Hospital Variation in Cholecystectomies in The Netherlands: A Nationwide Observational Study.

BACKGROUND: Practice variation generally raises concerns about the quality of care. This study determined the longitudinal degree of hospital variation in proportion of patients with gallstone disease undergoing cholecystectomy, while adjusted for case-mix, and the effect on clinical outcomes. METHODS: A nationwide, longitudinal, database study was performed in all hospitals in the Netherlands in 2013-2015. Patients with gallstone disease were collected from the diagnosis-related group database. Hospital variation in case-mix-adjusted cholecystectomy rates was calculated per year. Clinical outcomes after cholecystectomy were compared between hospitals in the lowest/highest 20th percentile of the distribution of adjusted cholecystectomy rates in all 3 subsequent years. RESULTS: In total, 96,673 patients with gallstones were included. The cholecystectomy rate was 73.6%. In 2013-2015, the case-mix-adjusted performance of cholecystectomies was in hospitals with high rates 1.5-1.6 times higher than in hospitals with low rates. Hospitals with a high adjusted cholecystectomy rate had a higher laparoscopy rate, shorter time to surgery, and less emergency department visits after a cholecystectomy compared to hospitals with a low-adjusted cholecystectomy rate. CONCLUSION: Hospital variation in cholecystectomies in the Netherlands is modest, cholecystectomy rates varies by <2-fold, and variation is stable over time. Cholecystectomies in hospitals with high adjusted cholecystectomy rates are associated with improved outcomes.

Overtreatment of Nonneoplastic Gallbladder Polyps due to Inadequate Routine Ultrasound Assessment.

BACKGROUND: The primary aim was to assess the diagnostic accuracy of routine ultrasound assessment for gallbladder polyps. The secondary aim was to identify the characteristics that differentiate neoplastic polyps from nonneoplastic polyps. METHODS: A total of 156 patients with histopathologically proven gallbladder polyps in 4 Dutch hospitals between 2003 and 2013 were included. Sensitivity and specificity of ultrasound for polyp size, number of polyps, and polyp type were assessed using histopathological findings as a reference standard. In addition, diagnostic accuracy of sonographic size ≥1 cm for neoplasia was assessed. Subgroup analysis for patients with polyps as primary indication for cholecystectomy was performed. The sonographic polyp characteristics on preoperative routine ultrasound were described. RESULTS: Fifty-six percent of gallbladder polyps were preoperatively identified on ultrasound, of which 31% were neoplastic. Sensitivity and specificity of ultrasound to estimate polyp size were 93 and 43% (subgroup; 92 and 33%). Sensitivity and specificity of sonographic polyp size ≥1 cm for neoplasia were 86 and 32% (subgroup; 94 and 26%). No specific sonographic characteristics for neoplastic polyps could be established due to lack of reporting. CONCLUSION: Routine ultrasound assessment of polyps is associated with overestimation of polyp size and low specificity of sonographic size ≥1 cm for neoplasia, which contributes to surgical overtreatment of nonneoplastic polyps.

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.

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.

Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones: 5-Year Follow-Up of the SECURE Randomized Clinical Trial.

Importance: The 1-year results of the SECURE trial, a randomized trial comparing a restrictive strategy vs usual care for select patients with symptomatic cholelithiasis for cholecystectomy, resulted in a significantly lower operation rate after restrictive strategy. However, a restrictive strategy did not result in more pain-free patients at 1 year. Objective: To gauge pain level and determine the proportion of pain-free patients, operation rate, and biliary and surgical complications at the 5-year follow-up. Design, Setting, and Participants: This randomized clinical trial was a multicenter, parallel-arm, noninferiority, prospective study. Between February 2014 and April 2017, patients from 24 hospitals with symptomatic, uncomplicated cholelithiasis were included. Uncomplicated cholelithiasis was defined as gallstone disease without signs of complicated cholelithiasis, ie, biliary pancreatitis, cholangitis, common bile duct stones, or cholecystitis. Follow-up data for this analysis were collected by telephone from July 11, 2019, to September 23, 2023. Interventions: Patients were randomized (1:1) to receive usual care or a restrictive strategy with stepwise selection for cholecystectomy. Main Outcomes and Measures: The primary, noninferiority end point was proportion of patients who were pain free as evaluated by Izbicki pain score at the 5-year follow-up. A 5% noninferiority margin was chosen. The secondary end points included cholecystectomy rates, biliary and surgical complications, and patient satisfaction. Results: Among 1067 patients, the median (IQR) age was 49.0 years (38.0-59.0 years); 786 (73.7%) were female, and 281 (26.3%) were male. At the 5-year follow-up, 228 of 363 patients (62.8%) were pain free in the usual care group, compared with 216 of 353 patients (61.2%) in restrictive strategy group (difference, 1.6%; 1-sided 95% lower confidence limit, -7.6%; noninferiority P = .18). After cholecystectomy, 187 of 294 patients (63.6%) in the usual care group and 160 of 254 patients (63.0%) in the restrictive strategy group were pain free, respectively (P = .88). The restrictive care strategy was associated with 387 of 529 cholecystectomies (73.2%) compared with 437 of 536 in the usual care group (81.5%; 8.3% difference; P = .001). No differences between groups were observed in biliary and surgical complications or in patient satisfaction. Conclusions and Relevance: In the long-term, a restrictive strategy results in a significant but small reduction in operation rate compared with usual care and is not associated with increased biliary and surgical complications. However, regardless of the strategy, only two-third of patients were pain free. Further criteria for selecting patients with uncomplicated cholelithiasis for cholecystectomy and rethinking laparoscopic cholecystectomy as treatment is needed to improve patient-reported outcomes. Trial Registration: CCMO Identifier: NTR4022.

Imaging based flowchart for gallbladder polyp evaluation.

BACKGROUND: Preoperative differentiation between neoplastic and nonneoplastic gallbladder polyps, and the subsequent indication for cholecystectomy remains a clinical dilemma. The current 1 cm size threshold for neoplasia is unspecific. The aim of this study was to improve diagnostic work-up for gallbladder polyps using sonographic and MRI characteristics of neoplastic and nonneoplastic polyps. METHODS: A prospective, exploratory study including patients undergoing cholecystectomy for gallbladder polyp(s) was conducted. Patients underwent targeted transabdominal ultrasound (TAUS) and MRI. Outcomes were sensitivity and specificity for polyp diagnosis, and the radiological characteristics of neoplastic and nonneoplastic polyp types. Histopathology after cholecystectomy was used as reference standard. RESULTS: Histopathology demonstrated gallbladder polyps in 20/27 patients (74%): 14 cholesterol polyps, three adenomyomatosis, two adenomas and one gastric heterotopia. Sensitivity of polyp identification were 72% (routine TAUS) and 86% (targeted TAUS and MRI). Both adenomas were identified as neoplastic on targeted TAUS and MRI. Sonographic presentation as multiple, pedunculated polyps, either heterogeneous or with hyperechoic foci, or as single polyps containing cysts were limited to nonneoplastic polyps. On MRI hyperintense polyps on T1-weighted image were cholesterol polyps. An adenoma with high-grade dysplasia showed foci of decreased ADC values. We propose a checklist for polyp evaluation by targeted TAUS and a flowchart for radiological work-up of gallbladder polyps. CONCLUSIONS: The presented checklist and flowchart could aid diagnostic work-up for gallbladder polyps compared to current routine ultrasound, by elimination of nonneoplastic polyps and ultimately improve treatment decision for patients with gallbladder polyps.

Unsuspected choledocholithiasis found by routine intra-operative cholangiography during laparoscopic cholecystectomy.

BACKGROUND: The true incidence of unsuspected choledocholithiasis found during laparoscopic cholecystectomy (LC) is unknown. Untreated 'silent' stones may be associated with significant long-term risks. The aim of this study was to establish the incidence of unsuspected common bile duct stones (CBDS) and to determine the management and associated risk factors for unsuspected CBDS. METHODS: Retrospective review of a large consecutive series of patients from Australia who underwent LC in a tertiary referral setting. Percentages of unsuspected CBDS, management and complications were reported. Pre-operative and intra-operative factors associated with unsuspected CBDS were determined using multivariable logistic regression analysis. RESULTS: From a total of 1998 patients who underwent LC, 747 (37.4%) patients with no pre-operative suspicious factors were the subject of this study. CBDS were detected in 24 (3.2%) patients and all were managed either laparoscopically or endoscopically. Risk factors independently associated with unsuspected CBDS included patients >55 years of age (odds ratio 2.93, P = 0.038) and a large cystic duct size (odds ratio = 3.13, P < 0.001) on multivariable analysis. CONCLUSION: The incidence of patients with unsuspected CBDS on intra-operative cholangiography is low. Complete clearance of these stones can be achieved using a combination of laparoscopic and endoscopic methods.

Predicting operative difficulty of laparoscopic cholecystectomy in patients with acute biliary presentations.

BACKGROUND: Early laparoscopic cholecystectomy (LC) is advocated in patients with an acute biliary presentation but may require some precaution. We aimed to assess the intra-operative difficulty of cholecystectomy in patients who underwent early intervention, and to establish a prediction model for a 'complicated' LC. METHODS: Retrospective analysis of prospectively collected data from patients presenting to the emergency department with acute biliary symptoms, and who subsequently underwent early LC between 2015 and 2018. Operative difficulty was assessed by standardized grading of intra-operative findings (grades 1-4). Pre-operative predictors for a 'complicated' LC (grades 3/4) were assessed using univariable and multivariable logistic regression analysis. A prediction model was created using variable regression coefficients. Cut-off and accuracy of the model were assessed using a receiver operating characteristic curve. RESULTS: A total of 185 patients were included and 59% presented with acute cholecystitis. In this cohort 113 (61%) patients underwent a 'complicated' LC. A prediction model for a 'complicated' LC (0-4.5 points) included: clinical diagnosis of acute cholecystitis (2 points), C-reactive protein >10.5 mg/L (1.5 points) and pericholecystic fluid on pre-operative imaging (1 point). A score ≥2.5 had a sensitivity of 77.7%, specificity of 81.7% and positive and negative predictive values of 87.0% and 69.9%, respectively. CONCLUSION: Early LC may be 'complicated' in up to 60% of cases. The presented prediction model uses readily available information in the emergency department and is a simple but accurate way to predict a likely 'complicated' LC in patients with acute biliary presentations.

Etiologies of Long-Term Postcholecystectomy Symptoms: A Systematic Review.

BACKGROUND: Cholecystectomy does not relieve abdominal symptoms in up to 40% of patients. With 700,000 cholecystectomies performed in the US, annually, about 280,000 patients are left with symptoms, making this a serious problem. We performed a systematic review to determine the different etiologies of long-term postcholecystectomy symptoms with the aim to provide guidance for clinicians treating these patients. METHODS: A systematic search of the literature was performed using MEDLINE, EMBASE, and Web of Science. Articles describing at least one possible etiology of long-term symptoms after a laparoscopic cholecystectomy were included in this review. Long-term symptoms were defined as abdominal symptoms that were present at least four weeks after cholecystectomy, either persistent or incident. The etiologies of persistent and incident symptoms after LC and the mechanism or hypothesis behind the etiologies are provided. If available, the prevalence of the discussed etiology is provided. RESULTS: The search strategy identified 3320 articles of which 130 articles were included. Etiologies for persistent symptoms were residual and newly formed gallstones (41 studies, prevalence ranged from 0.2 to 23%), coexistent diseases (64 studies, prevalence 1-65%), and psychological distress (13 studies, no prevalence provided). Etiologies for incident symptoms were surgical complications (21 studies, prevalence 1-3%) and physiological changes (39 studies, prevalence 16-58%). Sphincter of Oddi dysfunction (SOD) was reported as an etiology for both persistent and incident symptoms (21 studies, prevalence 3-40%). CONCLUSION: Long-term postcholecystectomy symptoms vary amongst patients, arise from different etiologies, and require specific diagnostic and treatment strategies. Most symptoms after cholecystectomy seem to be caused by coexistent diseases and physiological changes due to cholecystectomy. The outcome of this research is summarized in a decision tree to give clinical guidance on the treatment of patients with symptoms after cholecystectomy.

Persistent abdominal pain after laparoscopic cholecystectomy is associated with increased healthcare consumption and sick leave.

BACKGROUND: Although, 33% to 40% of symptomatic gallstone patients reported persistent abdominal pain after laparoscopic cholecystectomy, there is no data on the burden of this pain to the healthcare system and society at large. This study determined healthcare consumption, sick leave, and costs in patients with persistent abdominal pain after laparoscopic cholecystectomy. Secondly, predictive factors for healthcare consumption were assessed. METHODS: This cross-sectional study included all 146 patients with persistent abdominal pain (patient-reported on Gastro-Intestinal Quality of Life Index (score 0-3) 24 weeks after laparoscopic cholecystectomy, derived from a previous prospective cohort. Healthcare consumption was assessed using Medical Consumption Questionnaire and medical records, and sick leave using Productivity Cost Questionnaire. Costs were calculated according "Guideline for performing economic evaluations in healthcare." Predictors of healthcare consumption were assessed using logistic regression analysis. RESULTS: In the study, 124/146 patients (85%) responded after mean follow-up of 31.0 months (standard deviation 6.5); 104 were female, mean age of responders was 52 years. Sixty-nine patients needed additional healthcare; 30.6% primary care; 37.1% secondary care; 16% emergency department admission; 8.9% hospital admission; 33.9% diagnostic procedures; 17.7% medication; 5.6% other interventions. Medical costs were $555 (BCa 95% confidence interval, $329-$852) and costs of sick leave were $361 (Bias-corrected and accelerated (BCa) 95% confidence interval, $189-$566) per year per patient. Younger age (odds ratio 0.95, 95% confidence interval, 0.92-0.98) and higher postoperative pain score (odds ratio 1.02, 95% confidence interval, 1.01-1.04) were associated with increased healthcare consumption. CONCLUSION: Persistent abdominal pain after laparoscopic cholecystectomy is associated with additional healthcare in 56% of patients. Yearly, medical costs and costs of sick leave are 20% of the initial costs of laparoscopic cholecystectomy.

Statistical analysis plan of a randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy (SECURE trial).

BACKGROUND: Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. However, persistent pain after cholecystectomy for symptomatic cholecystolithiasis is reported in up to 40% of patients. The aim of the SECURE trial is to compare the effectiveness of usual care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. The SECURE trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound-proven gallstones or sludge. Randomization was performed to either usual care (standard practice, according to the physician's knowledge and experience, and physician's and patient's preference) or a restrictive standardized strategy: treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy based on fulfilment of pre-specified criteria. This article presents in detail the statistical analysis plan (SAP) of this trial and was submitted before outcomes were available to the investigators. RESULTS: The primary end point of this trial is defined as the proportion of patients being pain-free at 12 months' follow-up. Pain will be assessed with the Izbicki Pain Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, quality of life, the association between the patients' symptoms and treatment, work performance, and cost-effectiveness. DISCUSSION: The data from the SECURE trial will provide evidence whether or not a restrictive strategy in patients with symptomatic cholecystolithiasis is associated with similar patient reported outcomes and a reduction in the number of cholecystectomies compared to usual care. The data from this trial will be analyzed according to this pre-specified SAP. TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 . Registered on 5 June 2013.