Antibiotic prophylaxis for acute cholecystectomy: PEANUTS II multicentre randomized non-inferiority clinical trial.

BACKGROUND: Guidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was to demonstrate that omitting antibiotics is not inferior to their prophylactic use. METHODS: This multicentre, randomized, open-label, non-inferiority clinical trial randomly assigned adults with mild-to-moderate acute calculous cholecystitis (immediate cholecystectomy indicated) to 2 g cefazolin administered before incision or no antibiotic prophylaxis. The primary endpoint was a composite of all postoperative infectious complications in the first 30 days after surgery. Secondary endpoints included all individual components of the primary endpoint, other morbidity, and duration of hospital stay. RESULTS: Sixteen of 226 patients (7.1 per cent) in the single-dose prophylaxis group and 29 of 231 (12.6 per cent) in the no-prophylaxis group developed postoperative infectious complications (absolute difference 5.5 (95 per cent c.i. -0.4 to 11.3) per cent). With a non-inferiority margin of 10 per cent, non-inferiority of no prophylaxis was not proven. The number of surgical-site infections was significantly higher in the no-prophylaxis group (5.3 versus 12.1 per cent; P = 0.010). No differences were observed in the number of other complications, or duration of hospital stay. CONCLUSION: Omitting antibiotic prophylaxis is not recommended.

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.

Contrast medium at the site of the anastomosis is crucial in detecting anastomotic leakage with CT imaging after colorectal surgery.

PURPOSE: The use of computed tomography (CT) to detect anastomotic leakage (AL) is becoming the standard of care. Accurate detection of AL is crucial. The aim of this study was to define CT criteria that are most predictive for AL. METHODS: From January 2006 to December 2012, all consecutive patients who had undergone CT imaging because of clinical suspicion of anastomotic leakage after colorectal surgery were analysed. All CT scans were re-evaluated by two independent abdominal radiologists blinded for clinical outcome. The images were scored with a set of criteria and a conclusion whether or not AL was present was drawn. Each separate criterion was analysed for its value in predicting AL by uni- and multivariable logistic regression RESULTS: Of 668 patients with colorectal surgery, 108 had undergone CT imaging within 16 days postoperatively. According to our standard of reference, 34 (31%) of the patients had AL. Univariable analysis showed that "fluid near anastomosis" (radiologist 1 (rad 1), p < 0.001; radiologist 2 (rad 2), p < 0.001) and "air near anastomosis" (rad 1, p < 0.001; rad 2, p < 0.001), "air intra-abdominally" (rad 1, p = 0.019; rad 2, p = 0.004) and "contrast leakage" (rad 1, p < 0.001; rad 2, p < 0.001) were associated with AL. Contrast leakage was the only independent predictor for AL in multivariable analysis for both radiologists (rad 1, OR 5.43 (95% CI 1.18-25.02); rad 2, OR 8.51 (95% CI 2.21-32.83)). CONCLUSION: The only independent variable predicting AL is leakage of contrast medium. To improve the accuracy of CT imaging, optimal contrast administration near the anastomosis appears to be crucial.

Surgeon's volume is not associated with complication outcome after laparoscopic cholecystectomy.

AIM: Complication rates after laparoscopic cholecystectomy vary but are still reported to be up to 17 %. Identifying risk factors for an adverse complication outcome could help to reduce morbidity after laparoscopic cholecystectomy. Our aim was to analyze whether surgeon volume is a vital issue for complication outcome. METHODS: All complications-minor, major, local and general-were reviewed in a single institution between January 2004 and December 2008 and recorded in a database. Patient's variables, disease related variables and surgeon's variables were noted. The role of surgeon's individual volume per year was analyzed. A stepwise logistic regression model was used. RESULTS: A total of 942 patients were analyzed, among which 70 (7 %) patients with acute cholecystitis and 52 (6 %) patients with delayed surgery for acute cholecystitis. Preoperative endoscopic retrograde cholangiography (ERC) had been performed in 142 (15 %) patients. Complication rates did not differ significantly for surgeon's individual volume (≤10 vs. >10 LC/year, 5.2 vs. 8.2 %, p = 0.203) nor for specialization (laparoscopic vs. non-laparoscopic; 9.2 vs. 6.4 %, p = 0.085) and experience (specialty registration ≤5 vs. >5 years; 5.1 vs. 8.7 %, p = 0.069). The only significant predictors for complications were acute surgery (OR 3.9, 95 % CI 1.8-8.7, p = 0.001) and a history preceding laparoscopic cholecystectomy (LC) (ERC and delayed surgery for cholecystitis) (OR 8.1, 95 % CI 4.5-14.6: p <0.001). CONCLUSION: Complications after LC were not significantly associated with a surgeon's individual volume, but most prominently determined by the type of biliary disease.

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.

Detection of colon cancer recurrences during follow-up care by general practitioners vs surgeons.

BACKGROUND: In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP. METHODS: Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated. RESULTS: Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46). CONCLUSION: Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found.

Cost-effectiveness of general practitioner- versus surgeon-led colon cancer survivorship care: an economic evaluation alongside a randomised controlled trial.

PURPOSE: The aim of this study is to assess cost-effectiveness of general practitioner (GP) versus surgeon-led colon cancer survivorship care from a societal perspective. METHODS: We performed an economic evaluation alongside the I CARE study, which included 303 cancer patients (stages I-III) who were randomised to survivorship care by a GP or surgeon. Questionnaires were administered at baseline, 3-, 6-, 12-, 24- and 36-months. Costs included healthcare costs (measured by iMTA MCQ) and lost productivity costs (SF-HLQ). Disease-specific quality of life (QoL) was measured using EORTC QLQ-C30 summary score and general QoL using EQ-5D-3L quality-adjusted life years (QALYs). Missing data were imputed. Incremental cost-effectiveness ratios (ICERs) were calculated to relate costs to effects on QoL. Statistical uncertainty was estimated using bootstrapping. RESULTS: Total societal costs of GP-led care were significantly lower compared to surgeon-led care (mean difference of - €3895; 95% CI - €6113; - €1712). Lost productivity was the main contributor to the difference in societal costs (- €3305; 95% CI - €5028; - €1739). The difference in QLQ-C30 summary score over time between groups was 1.33 (95% CI - 0.049; 3.15). The ICER for QLQ-C30 was - 2073, indicating that GP-led care is dominant over surgeon-led care. The difference in QALYs was - 0.021 (95% CI - 0.083; 0.040) resulting in an ICER of 129,164. CONCLUSIONS: GP-led care is likely to be cost-effective for disease-specific QoL, but not for general QoL. IMPLICATIONS FOR CANCER SURVIVORS: With a growing number of cancer survivors, GP-led survivorship care could help to alleviate some of the burden on more expensive secondary healthcare services.

Outcome of laparoscopic cholecystectomy conversion: is the surgeon's selection needed?

BACKGROUND: Risk factors for conversion in cholecystectomy may be of clinical value. This study aimed to investigate whether a set of risk factors, including the surgeon's specialization, can be used for the development of a preoperative strategy to optimize conversion outcome. METHODS: The data for all patients who underwent laparoscopic cholecystectomy at a single institution between January 2004 and December 2008 were retrospectively reviewed. Factors predictive for conversion were identified, and a preoperative strategy model was deduced. RESULTS: Of the 1,126 patients analyzed, 106 (9%) underwent laparoscopic cholecystectomy in an emergency setting. Delayed surgery was performed for 63 (46%) of 138 patients (12%) with acute cholecystitis. Preoperative endoscopic retrograde cholangiography was achieved for 161 of the patients (14%). Risk factors predictive of conversion (for 65 patients) were male gender [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.3-3.9; p = 0.004], age older than 65 years (OR, 2.6; 95% CI, 1.4-4.8; p = 0.002), body mass index (BMI) exceeding 25 kg/m(2) (OR, 3.4; 95% CI, 1.7-7.1; p < 0.001), history of complicated biliary disease (HCBD) (OR, 5.6; 95% CI, 3.2-9.8; p = < 0.001), and surgery by a non-gastrointestinal (non-GI) surgeon (OR, 4.9; 95% CI, 2.2-10.6; p < 0.001). The conversion rate for patients with a history of no complications who had two or more risk factors (gender, age, BMI > 25) and for patients with a HCBD who had one or more risk factors was significantly higher if the surgery was performed by non-GI rather than GI surgeons. CONCLUSION: Male gender, age older than 65 years, BMI exceeding 25 kg/m(2), HCBD, and surgery by a non-GI surgeon are predictive for conversion. A preoperative triage for surgeon selection based on risk factors and a HCBD is proposed to optimize conversion outcome.

Early laparoscopic cholecystectomy improves outcomes after endoscopic sphincterotomy for choledochocystolithiasis.

BACKGROUND & AIMS: Patients with choledochocystolithiasis generally undergo endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (LC). However, many patients receive this surgery 6-8 weeks after ES. There is a high conversion rate of elective LC after ES, and patients can develop recurrent biliary events during the waiting period. We investigated whether the timing of surgery influences outcome. METHODS: We performed a randomized trial of patients with choledochocystolithiasis who underwent successful ES. Patients were randomly assigned to groups that received early LC (within 72 hours after ES, n = 49) or delayed LC (after 6-8 weeks, n = 47), based on an expected difference in conversion rate of 25% vs 5%, respectively. Conversion rate, biliary events during follow-up, duration and difficulty of surgeries, postoperative morbidity, and hospital stay were scored. Intention-to-treat analyses were performed. RESULTS: Groups were comparable in age, sex, and comorbidity. There was no difference between groups in conversion rate (4.3% in early vs 8.7% in delayed group) nor were there differences in operating times and/or difficulties or hospital stays. During the waiting period for LC, 17 patients in the delayed group (36.2%) developed recurrent biliary events compared with 1 patient in the early group (P < .001). CONCLUSIONS: In a randomized trial to evaluate timing of LC after ES, recurrent biliary events occurred in 36.2% of patients whose LC was delayed for 6-8 weeks. Early LC (within 72 hours) appears to be safe and might prevent the majority of biliary events in this period following sphincterotomy.

Recruitment challenges to the I CARE study: a randomised trial on general practitioner-led colon cancer survivorship care.

OBJECTIVES: The I CARE study (Improving Care After colon canceR treatment in the Netherlands) aims to compare surgeon-led to general practitioner (GP)-led colon cancer survivorship care. Recruitment to the trial took longer than expected. In this descriptive study, recruitment is critically reviewed. SETTING: Patients were recruited from eight Dutch medical centres. PARTICIPANTS: Patients treated with curative intent for stages I-III colon cancer. Target patient sample size was calculated at 300. INTERVENTIONS: Patients were randomised to surgeon-led (usual) versus GP-led care, with or without access to an eHealth application (Oncokompas). OUTCOME MEASURES: Baseline characteristics of (non-)participants, reasons for non-participation and strategies to improve recruitment were reviewed. RESULTS: Out of 1238 eligible patients, 353 patients were included. Of these, 50 patients dropped out shortly after randomisation and before start of the intervention, resulting in a participation rate of 25%. Participants were on average slightly younger (68.1 years vs 69.3 years) and more often male (67% vs 50%) in comparison to non-participants. A total of 806 patients declined participation for reasons most often relating to research (57%), including the wish to remain in specialist care (31%) and too much effort to participate (12%). Some patients mentioned health (9%) and confrontation with the disease (5%) as a reason. In 43 cases, GPs declined participation, often related to the study objective, need for financial compensation and time restraints. The generally low participation rate led to concerns about reaching the target sample size. Methods to overcome recruitment challenges included changes to the original recruitment procedure and the addition of new study centres. CONCLUSIONS: Challenges were faced in the recruitment to a randomised trial on GP-led colon cancer survivorship care. Research on the transition of care requires sufficient time, funding and support base among patients and healthcare professionals. These findings will help inform researchers and policy-makers on the development of future practices. TRIAL REGISTRATION NUMBER: NTR4860.

A Clinical Decision Tool for Selection of Patients With Symptomatic Cholelithiasis for Cholecystectomy Based on Reduction of Pain and a Pain-Free State Following Surgery.

Importance: There is currently no consensus on the indication for cholecystectomy in patients with uncomplicated gallstone disease. Objective: To report on the development and validation of a multivariable prediction model to better select patients for surgery. Design, Setting, and Participants: This study evaluates data from 2 multicenter prospective trials (the previously published Scrutinizing (In)efficient Use of Cholecystectomy: A Randomized Trial Concerning Variation in Practice [SECURE] and the Standardized Work-up for Symptomatic Cholecystolithiasis [Success] trial) collected from the outpatient clinics of 25 Dutch hospitals between April 2014 and June 2019 and including 1561 patients with symptomatic uncomplicated cholelithiasis, defined as gallstone disease without signs of complicated cholelithiasis (ie, biliary pancreatitis, cholangitis, common bile duct stones or cholecystitis). Data were analyzed from January 2020 to June 2020. Exposures: Patient characteristics, comorbidity, surgical outcomes, pain, and symptoms measured at baseline and at 6 months' follow-up. Main Outcomes and Measures: A multivariable regression model to predict a pain-free state or a clinically relevant reduction in pain after surgery. Model performance was evaluated using calibration and discrimination. Results: A total of 1561 patients were included (494 patients in 7 hospitals in the development cohort and 1067 patients in 24 hospitals in the validation cohort; 6 hospitals included patients in both cohorts). In the development cohort, 395 patients (80.0%) underwent cholecystectomy. After surgery, 225 patients (57.0%) reported that they were pain free and 295 (74.7%) reported a clinically relevant reduction in pain. A multivariable prediction model showed that increased age, no history of abdominal surgery, increased visual analog scale pain score at baseline, pain radiation to the back, pain reduction with simple analgesics, nausea, and no heartburn were independent predictors of clinically relevant pain reduction after cholecystectomy. After internal validation, good discrimination was found (C statistic, 0.80; 95% CI, 0.74-0.84) between patients with and without clinically relevant pain reduction. The model had very good overall calibration and minimal underestimation of the probability. External validation indicated a good discrimination between patients with and without clinically relevant pain reduction (C statistic, 0.74; 95% CI, 0.70-0.78) and fair calibration with some overestimation of probability by the model. Conclusions and Relevance: The model validated in this study may help predict the probability of pain reduction after cholecystectomy and thus aid surgeons in deciding whether patients with uncomplicated cholelithiasis will benefit from cholecystectomy.

Bile leakage after loop closure vs clip closure of the cystic duct during laparoscopic cholecystectomy: A retrospective analysis of a prospective cohort.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most frequently performed surgical procedures. Cystic stump leakage is an underestimated, potentially life threatening complication that occurs in 1%-6% of the patients. With a secure cystic duct occlusion technique during LC, bile leakage becomes a preventable complication. AIM: To investigate the effect of polydioxanone (PDS) loop closure of the cystic duct on bile leakage rate in LC patients. METHODS: In this retrospective analysis of a prospective cohort, the effect of PDS loop closure of the cystic duct on bile leakage complication was compared to patients with conventional clip closure. Logistic regression analysis was used to develop a risk score to identify bile leakage risk. Leakage rate was assessed for categories of patients with increasing levels of bile leakage risk. RESULTS: Of the 4359 patients who underwent LC, 136 (3%) underwent cystic duct closure by a PDS loop. Preoperatively, loop closure patients had significantly more complicated biliary disease compared to the clipped closure patients. In the loop closure cohort, zero (0%) bile leakage occurred compared to 59 of 4223 (1.4%) clip closure patients. For patients at increased bile leakage risk (risk score ≥ 1) rates were 1.6% and up to 13% (4/30) for clip closure patients with a risk score ≥ 4. This risk increase paralleled a stepwise increase of actual bile leakage complication for clip closure patients, which was not observed for loop closure patients. CONCLUSION: Cystic duct closure with a PDS loop during LC may reduce bile leakage in patients at increased risk for bile leakage.

Efficacy of Antibiotic Agents after Spill of Bile and Gallstones during Laparoscopic Cholecystectomy.

Background: Perforation of the gallbladder during laparoscopic cholecystectomy (LC) results in spill of bile or gallstones in the abdominal cavity. The aim of this study was to assess whether antibiotic agents after spill have an effect on post-operative and infectious complications. Patients and Methods: Operative reports and clinical data of patients undergoing LC between 2012 and 2016 in three hospitals were screened retrospectively for spill of bile and spill of gallstones. Included patients were divided into two groups: Patients who were treated with antibiotic agents (either prophylactic or a single administration during or directly post-operatively because of spill) and patients who did not receive any antibiotic agents. Patients were also categorized as to uncomplicated or complicated gallstone disease. Multi-variable logistic regression was used to assess risk factors for overall and infectious complications after spill. Results: Spill was reported in 14.7% (481 of 3,262). The infectious complication rate was 8.7% (42/481). Of 481 patients, 295 (61.3%) had uncomplicated gallstone disease and 239 (49.7%) received antibiotic treatment. Rates of infectious complications were comparable among patients receiving antibiotic agents or no antibiotic agents (8% vs. 9%, respectively; p = 0.779); also when analysis only included patients with complicated gallstone disease (11% vs. 10% respectively, p = 0.861). Spill of stones was the only independent risk factor associated with post-operative complications (odds ratio 2.55, 95% confidence interval 1.23-5.29, p = 0.012). Conclusion: Antibiotic agents (prophylaxis or intra-operative) after spill of bile and spill of gallstones do not reduce the risk of overall and infectious complications. Spill of stones is associated independently with post-operative complications. The present study sample may leave small differences in complication rates undetected.

Systematic review of cystic duct closure techniques in relation to prevention of bile duct leakage after laparoscopic cholecystectomy.

AIM: To study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy (LC) for biliary disease. METHODS: A systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic duct leakage (CDL) was the primary outcome. Risk of bias was evaluated. Odds ratios were analyzed for comparison of techniques and pooled event rates for non-comparative analyses. Pooled event rates were compared for each of included techniques. RESULTS: Out of 1491 articles, 38 studies were included. A total of 47491 patients were included, of which 38683 (81.5%) underwent cystic duct closure with non-locking (metal) clips. All studies were of low-moderate methodological quality. Only two studies reported separate data on uncomplicated and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4 (95%CI: 0.06-2.48) was found for harmonic energy vs clip closure and an odds ratio of 0.17 (95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL rate was around 1% for harmonic energy and metal clips, and 0% for locking clips and ligatures. CONCLUSION: Based on available evidence it is not possible to either recommend or discourage any of the techniques for cystic duct closure during LC with respects to CDL, although data point out a slight preference for locking clips and ligatures vs other techniques. No separate recommendation can be made for complicated gallbladder disease.

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.

Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial.

OBJECTIVE: To assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis. DESIGN: Multicentre, randomised controlled, superiority trial. SETTING: 11 hospitals in the Netherlands, February 2011 to January 2016. PARTICIPANTS: 142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more. MAIN OUTCOME MEASURES: The primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year. RESULTS: The trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001). CONCLUSION: Laparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis. TRIAL REGISTRATION: Dutch Trial Register NTR2666.

Short- and Long-Term Outcomes after a Reconstituting and Fenestrating Subtotal Cholecystectomy.

BACKGROUND: Multiple surgical techniques are recommended to perform cholecystectomy safely in difficult cases, such as conversion to open operation or subtotal cholecystectomy (STC). Reconstituting and fenestrating STC are 2 techniques for STC. The aim of this study was to investigate the short and long-term morbidity and quality of life associated with STC and to compare the outcomes after reconstituting and fenestrating STC. STUDY DESIGN: Patients who underwent STC were identified. Short-term morbidity assessed included bile leakage, bile duct injury, intra-abdominal infection, reinterventions, and readmittance. Long-term morbidity included bile duct stenosis and recurrent biliary events. Differences in the outcomes of fenestrating and reconstituting STC were assessed. Quality of life was assessed by EuroQol 5 Dimensions, Short-Form 36 Questionnaire, and Gastrointestinal Quality of Life Index questionnaires. RESULTS: Subtotal cholecystectomy was performed in 191 patients, of which 102 (53%) underwent fenestrating STC and 73 (38%) underwent reconstituting STC. Bile leakage was significantly more common after fenestrating STC (18% vs 7%, respectively; p < 0.022). After a median of 6 years follow-up (interquartile range 5 to 10 years), recurrence rate of biliary events was lower after fenestrating than reconstituting STC (9% vs 18%, respectively; p < 0.022). Overall reintervention rate did not differ between the 2 groups: 32% in the fenestrating STC group and 26% in the reconstituting STC group (p = 0.211). Completion cholecystectomy was performed significantly more in patients after fenestrating STC (9% vs 4%; p < 0.022). CONCLUSIONS: Subtotal cholecystectomy is a safe and feasible technique for difficult cases for which conversion only will not solve the difficulty of an inflamed hepatocystic triangle. The choice for reconstituting or fenestrating STC depends on intraoperative conditions and both techniques are associated with specific complications.

A case of chylous fistula after axillary dissection in breast-conserving treatment for breast cancer.

Chyle fistula is not a well-known complication of axillary dissection in patients with breast cancer. Although rare, this complication can occur as a result of anatomic variation of the thoracic duct and its venous anastomosis. Injury to the lateral terminating branches or lymphatic trunk, leading to retrograde chyle flow, is more likely than direct injury to the duct. We report a case of chylous fistula after axillary dissection in a patient with breast cancer, review the literature, and discuss the management of this rare complication.