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.

Deep learning for surgical phase recognition using endoscopic videos.

BACKGROUND: Operating room planning is a complex task as pre-operative estimations of procedure duration have a limited accuracy. This is due to large variations in the course of procedures. Therefore, information about the progress of procedures is essential to adapt the daily operating room schedule accordingly. This information should ideally be objective, automatically retrievable and in real-time. Recordings made during endoscopic surgeries are a potential source of progress information. A trained observer is able to recognize the ongoing surgical phase from watching these videos. The introduction of deep learning techniques brought up opportunities to automatically retrieve information from surgical videos. The aim of this study was to apply state-of-the art deep learning techniques on a new set of endoscopic videos to automatically recognize the progress of a procedure, and to assess the feasibility of the approach in terms of performance, scalability and practical considerations. METHODS: A dataset of 33 laparoscopic cholecystectomies (LC) and 35 total laparoscopic hysterectomies (TLH) was used. The surgical tools that were used and the ongoing surgical phases were annotated in the recordings. Neural networks were trained on a subset of annotated videos. The automatic recognition of surgical tools and phases was then assessed on another subset. The scalability of the networks was tested and practical considerations were kept up. RESULTS: The performance of the surgical tools and phase recognition reached an average precision and recall between 0.77 and 0.89. The scalability tests showed diverging results. Legal considerations had to be taken into account and a considerable amount of time was needed to annotate the datasets. CONCLUSION: This study shows the potential of deep learning to automatically recognize information contained in surgical videos. This study also provides insights in the applicability of such a technique to support operating room planning.

Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial.

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7-100] vs 71·7% [95% CI 60·1-83·3], hazard ratio 2·79 [95% CI 1·86-4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). INTERPRETATION: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). FUNDING: Netherlands Organisation for Health Research and Development.

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.

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.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037).

BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037.

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial).

BACKGROUND: Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. METHODS: A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included. CONCLUSION: A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach. TRIAL REGISTRATION NUMBER: NCT01111253.

The anal fistula plug versus the mucosal advancement flap for the treatment of anorectal fistula (PLUG trial).

BACKGROUND: Low transsphincteric fistulas less than 1/3 of the sphincter complex are easy to treat by fistulotomy with a high success rate. High transsphincteric fistulas remain a surgical challenge. Various surgical procedures are available, but recurrence rates of these techniques are disappointingly high. The mucosal flap advancement is considered the gold standard for the treatment of high perianal fistula of cryptoglandular origin by most colorectal surgeons. In the literature a recurrence rate between 0 and 63% is reported for the mucosal flap advancement. Recently Armstrong and colleagues reported on a new biologic anal fistula plug, a bioabsorbable xenograft made of lyophilized porcine intestinal submucosa. Their prospective series of 15 patients with high perianal fistula treated with the anal fistula plug showed promising results. The anal fistula plug trial is designed to compare the anal fistula plug with the mucosal flap advancement in the treatment of high perianal fistula in terms of success rate, continence, postoperative pain, and quality of life. METHODS/DESIGN: The PLUG trial is a randomized controlled multicenter trial. Sixty patients with high perianal fistulas of cryptoglandular origin will be randomized to either the fistula plug or the mucosal advancement flap. Study parameters will be anorectal fistula closure-rate, continence, post-operative pain, and quality of life. Patients will be followed-up at two weeks, four weeks, and 16 weeks. At the final follow-up closure rate is determined by clinical examination by a surgeon blinded for the intervention. DISCUSSION: Before broadly implementing the anal fistula plug results of randomized trials using the plug should be awaited. This randomized controlled trial comparing the anal fistula plug and the mucosal advancement flap should provide evidence regarding the effectiveness of the anal fistula plug in the treatment of high perianal fistulas. TRIAL REGISTRATION: ISRCTN: 97376902.