Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts.

BACKGROUND: In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. METHODS: Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. RESULTS: Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). CONCLUSION: Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

18F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction: Accuracy and Long-Term Implications.

PURPOSE: The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10-40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. METHODS: Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. RESULTS: Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. CONCLUSION: Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.

Treatment of haemorrhoids: rubber band ligation or sclerotherapy (THROS)? Study protocol for a multicentre, non-inferiority, randomised controlled trial.

INTRODUCTION: Haemorrhoidal disease (HD) is a common condition with significant epidemiologic and economic implications. While it is possible to treat symptomatic grade 1-2 haemorrhoids with rubber band ligation (RBL) or sclerotherapy (SCL), the effectiveness of these treatments compatible with current standards has not yet been investigated with a randomised controlled trial. The hypothesis is that SCL is not inferior to RBL in terms of symptom reduction (patient-related outcome measures (PROMs)), patient experience, complications or recurrence rate. METHODS AND ANALYSIS: This protocol describes the methodology of a non-inferiority, multicentre, randomised controlled trial comparing rubber band ligation and sclerotherapy for symptomatic grade 1-2 haemorrhoids in adults (> 18 years). Patients are preferably randomised between the two treatment arms. However, patients with a strong preference for one of the treatments and refuse randomisation are eligible for the registration arm. Patients either receive 4 cc Aethoxysklerol 3% SCL or 3 × RBL. The primary outcome measures are symptom reduction by means of PROMs, recurrence and complication rates. Secondary outcome measures are patient experience, number of treatments and days of sick leave from work. Data are collected at 4 different time points. DISCUSSION: The THROS trial is the first large multicentre randomised trial to study the difference in effectivity between RBL and SCL for the treatment of grade 1-2 HD. It will provide information as to which treatment method (RBL or SCL) is the most effective, gives fewer complications and is experienced by the patient as the best option. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers, location AMC (nr. 2020_053). The gathered data and results will be submitted for publication in peer-reviewed journals and spread to coloproctological associations and guidelines. TRIAL REGISTRATION: Dutch Trial Register NL8377 . Registered on 12-02-2020.

Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort.

Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings.

Cost-effectiveness of on-demand removal of syndesmotic screws.

PURPOSE: Syndesmotic screw removal following acute syndesmotic injury is a commonly performed procedure. However, recent studies suggest that the removal does not result in improved patient reported outcome, while the procedure has proved not to be without complications. The aim of this study was to present a health-economic evaluation of on-demand removal (ODR) compared to routine removal (RR) of the syndesmotic screw. METHODS: Data were collected from the RODEO trial, a randomized controlled non-inferiority trial comparing functional outcome of ODR with RR. Economic evaluation resulted in total costs, costs (in Euro) per quality adjusted life year (QALY) and costs per point improvement on the Olerud Molander Ankle Score (OMAS). This included both direct and indirect costs. RESULTS: Total costs for ODR were significantly lower with a mean difference of 3160 euro compared to RR (p < 0.001). The difference in QALY was not significant. The difference in OMAS at 12 months was 1.79 with an incremental cost-effectiveness ratio (ICER) of €-1763 (p = 0.512). The ICER was well below the willingness to pay. Although unit costs might vary between hospitals and countries, these results provide relevant data of cost-effectiveness. CONCLUSION: The clinical effectiveness of both ODR and RR can be considered equal. The costs are lower for patients treated with ODR, which leads to the conclusion that ODR is cost-effective.

Value of routine intraoperative frozen sections of proximal bile duct margins in perihilar cholangiocarcinoma, a retrospective multicenter and matched case-control study.

BACKGROUND: Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. MATERIALS AND METHODS: A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved 'additional' R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. RESULTS: Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as "true" R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5-36.5) compared to 30 months (95%CI:24.4-35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7-59.3) after initial R0 (P = 0.348). CONCLUSION: There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.

Cost Analysis of Volar Plate Fixation Versus Plaster Cast Immobilization for Intra-Articular Distal Radial Fractures.

BACKGROUND: The aim of this study was to compare the cost-effectiveness and cost-utility between plaster cast immobilization and volar plate fixation for acceptably reduced intra-articular distal radial fractures. METHODS: A cost-effectiveness analysis was conducted as part of a randomized controlled trial comparing operative (volar plate fixation) with nonoperative (plaster cast immobilization) treatment in patients between 18 and 75 years old with an acceptably reduced intra-articular distal radial fracture. Health-care utilization and use of resources per patient were documented prospectively and included direct medical costs, direct non-medical costs, and indirect costs. All analyses were performed according to the intention-to-treat principle. RESULTS: The mean total cost per patient was $291 (95% bias-corrected and accelerated confidence interval [bcaCI] = -$1,286 to $1,572) higher in the operative group compared with the nonoperative group. The mean total number of quality-adjusted life-years (QALYs) gained at 12 months was significantly higher in the operative group than in the nonoperative group (mean difference = 0.15; 95% bcaCI = 0.056 to 0.243). The difference in the cost per QALY (incremental cost-effectiveness ratio [ICER]) was $2,008 (95% bcaCI = -$9,608 to $18,222) for the operative group compared with the nonoperative group, which means that operative treatment is more effective but also more expensive. Subgroup analysis including only patients with a paid job showed that the ICER was -$3,500 per QALY for the operative group with a paid job compared with the nonoperative group with a paid job, meaning that operative treatment is more effective and less expensive for patients with a paid job. CONCLUSIONS: The difference in QALYs gained for the operatively treated group was equivalent to an additional 55 days of perfect health per year. In adult patients with an acceptably reduced intra-articular distal radial fracture, operative treatment is a cost-effective intervention, especially in patients with paid employment. Operative treatment is slightly more expensive than nonoperative treatment but provides better functional results and a better quality of life. LEVEL OF EVIDENCE: Economic and Decision Analysis Level I. See Instructions for Authors for a complete description of levels of evidence.

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial).

BACKGROUND: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. METHODS: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. RESULTS: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were €25 809 (95 per cent bias-corrected and accelerated (bca) c.i. €22 617 to €29 137) for the iTBCT group and €26 155 (€23 050 to €29 344) for the STWU group, a difference per patient in favour of iTBCT of €346 (€4987 to €4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). CONCLUSION: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury.

Rubber band ligation versus haemorrhoidectomy for the treatment of grade II-III haemorrhoids: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The aim of this study was to review clinical outcome of haemorrhoidectomy and rubber band ligation in grade II-III haemorrhoids. METHODS: A systematic review was conducted. Medline, Embase, Cochrane Library, Clinicaltrials.gov, and the WHO International Trial Registry Platform were searched, from inception until May 2018, to identify randomised clinical trials comparing rubber band ligation with haemorrhoidectomy for grade II-III haemorrhoids. The primary outcome was control of symptoms. Secondary outcomes included postoperative pain, postoperative complications, anal continence, patient satisfaction, quality of life and healthcare costs were assessed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Three hundred and twenty-four studies were identified. Eight trials met the inclusion criteria. All trials were of moderate methodological quality. Outcome measures were diverse and not clearly defined. Control of symptoms was better following haemorrhoidectomy. Patients had less pain after rubber band ligation. There were more complications (bleeding, urinary retention, anal incontinence/stenosis) in the haemorrhoidectomy group. Patient satisfaction was equal in both groups. There were no data on quality of life and healthcare costs except that in one study patients resumed work more early after rubber band ligation. CONCLUSIONS: Haemorrhoidectomy seems to provide better symptom control but at the cost of more pain and complications. However, due to the poor quality of the studies analysed/it is not possible to determine which of the two procedures provides the best treatment for grade II-III haemorrhoids. Further studies focusing on clearly defined outcome measurements taking patients perspective and economic impact into consideration are required.

Predictors for Survival in an International Cohort of Patients Undergoing Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Surgical factors, including resection of Gerota's fascia, R0-resection, and lymph node yield, may be associated with survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC), but evidence from large multicenter studies is lacking. This study aimed to identify predictors for overall survival after DP for PDAC, especially those related to surgical technique. PATIENTS AND METHODS: Data from an international retrospective cohort including patients from 11 European countries and the USA who underwent DP for PDAC (2007-2015) were analyzed. Cox proportional hazard analyses were performed and included Gerota's fascia resection, R0 resection, lymph node ratio, extended resection, and a minimally invasive approach. RESULTS: Overall, 1200 patients from 34 centers with median follow-up of 15 months [interquartile range (IQR) 5-31 months] and median survival period of 30 months [95% confidence interval (CI), 27-33 months] were included. Gerota's fascia resection [hazard ratio (HR) 0.74; p = 0.019], R0 resection (HR 0.70; p = 0.006), and decreased lymph node ratio (HR 0.28; p < 0.001) were associated with improved overall survival, whereas extended resection (HR 1.75; p < 0.001) was associated with worse overall survival. A minimally invasive approach did not improve survival as compared with an open approach (HR 1.14; p = 0.350). Adjuvant chemotherapy (HR 0.67; p = 0.003) was also associated with improved overall survival. CONCLUSIONS: This international cohort identified Gerota's fascia resection, R0 resection, and decreased lymph node ratio as factors associated with improved overall survival during DP for PDAC. Surgeons should strive for R0 resection and adequate lymphadenectomy and could also consider Gerota's fascia resection in their routine surgical approach.

Implementing structured team debriefing using a Black Box in the operating room: surveying team satisfaction.

BACKGROUND: Surgical safety may be improved using a medical data recorder (MDR) for the purpose of postoperative team debriefing. It provides the team in the operating room (OR) with the opportunity to look back upon their joint performance objectively to discuss and learn from suboptimal situations or possible adverse events. The aim of this study was to investigate the satisfaction of the OR team using an MDR, the OR Black Box®, in the OR as a tool providing output for structured team debriefing. METHODS: In this longitudinal survey study, 35 gastro-intestinal laparoscopic operations were recorded using the OR Black Box® and the output was subsequently debriefed with the operating team. Prior to study, a privacy impact assessment was conducted to ensure alignment with applicable legal and regulatory requirements. A structured debrief model and an OR Back Box® performance report was developed. A standardized survey was used to measure participant's satisfaction with the team debriefing, the debrief model used and the performance report. Factor analysis was performed to assess the questionnaire's quality and identified contributing satisfaction factors. Multivariable analysis was performed to identify variables associated with participants' opinions. RESULTS: In total, 81 team members of various disciplines in the OR participated, comprising 35 laparoscopic procedures. Mean satisfaction with the OR Black Box® performance report and team debriefing was high for all 3 identified independent satisfaction factors. Of all participants, 98% recommend using the OR Black Box® and the outcome report in team debriefing. CONCLUSION: The use of an MDR in the OR for the purpose of team debriefing is considered to be both beneficial and important. Team debriefing using the OR Black Box® outcome report is highly recommended by 98% of team members participating.

A nationwide database study on colectomy and colorectal cancer in ulcerative colitis: what is the role of appendectomy?

AIM: Although has been suggested that an appendectomy has a positive effect on the disease course in patients with ulcerative colitis (UC), recent studies indicate a potential increase in risk of colectomy and colorectal cancer (CRC). This study aimed to evaluate the rates of colectomy and CRC after appendectomy in UC patients using a nationwide prospective database [the Initiative on Crohn and Colitis Parelsnoer Institute - Inflammatory Bowel Disease (ICC PSI-IBD) database]. METHOD: All UC patients were retrieved from the ICC PSI-IBD database between January 2007 and May 2018. Primary outcomes were colectomy and CRC. Outcomes were compared in patients with and without appendectomy, with a separate analysis for timing of appendectomy (before or after UC diagnosis). RESULTS: A total of 826 UC patients (54.7% female; median age 46 years, range 18-89 years) were included. Sixty-three (7.6%) patients had previously undergone appendectomy: 24 (38.1%) before and 33 (52.4%) after their diagnosis of UC. In multivariate analysis, appendectomy after UC diagnosis was associated with a significantly lower colectomy rate compared with no appendectomy [hazard ratio (HR) 0.16, 95% C: 0.04-0.66, P = 0.011], and the same nonsignificant trend was seen in patients with an appendectomy before UC diagnosis (HR 0.35, 95% CI 0.08-1.41, P = 0.138). Appendectomy was associated with delayed colectomy, particularly when it was performed after diagnosis of UC (P = 0.009). No significant differences were found in the CRC rate between patients with and without appendectomy (1.6% vs 1.2%; P = 0.555). CONCLUSION: Appendectomy in established UC is associated with an 84% decreased risk of colectomy and a delay in surgery. Since the colon is in situ for longer, the risk of developing CRC remains, which underscores the importance of endoscopic surveillance programmes.

Quantitative fluorescence-guided perfusion assessment of the gastric conduit to predict anastomotic complications after esophagectomy.

BACKGROUND: Fluorescence angiography (FA) assesses anastomotic perfusion during esophagectomy with gastric conduit reconstruction, but its interpretation is subjective. This study evaluated time to fluorescent enhancement in the gastric conduit, with the aim to determine a threshold to predict postoperative anastomotic complications. METHODS: In a prospective cohort study, all consecutive patients undergoing esophagectomy with gastric conduit reconstruction from July 2018 to October 2019 were included. FA was performed before anastomotic reconstruction following injection of indocyanine green (ICG). During FA, the following time points were recorded: ICG injection, first fluorescent enhancement in the lung, at the base of the gastric conduit, at the planned anastomotic site, and at ICG watershed or in the tip of the gastric conduit. Anastomotic complications including anastomotic leakage and clinically relevant strictures were documented. RESULTS: Eighty-four patients were included, the majority (67 out of 84, 80%) of which underwent an Ivor Lewis procedure. After a median follow-up of 297 days, anastomotic leakage was observed in 12 out of 84 (14.3%) and anastomotic stricture in 12 out of 82 (14.6%). Time between ICG injection and enhancement in the tip was predictive for anastomotic leakage (P = 0.174, area under the curve = 0.731), and a cut-off value of 98 seconds was derived (specificity: 98%). All times to enhancement at the planned anastomotic site and ICG watershed were significantly predictive for the occurrence of a stricture, however area under the curves were <0.7. CONCLUSIONS: The identified fluorescent threshold can be used for intraoperative decision making or to identify potentially high-risk patients for anastomotic leakage after esophagectomy with gastric conduit reconstruction.

IMARI: multi-Interventional program for prevention and early Management of Anastomotic leakage after low anterior resection in Rectal cancer patIents: rationale and study protocol.

BACKGROUND: Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program. METHODS: IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power. DISCUSSION: The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL. TRIAL REGISTRATION: Trialregister.nl ( NL8261 ), January 2020.

Optimal timing for surgical reconstruction of bile duct injury: meta-analysis.

BACKGROUND: Major bile duct injury (BDI) after cholecystectomy generally requires surgical reconstruction by means of hepaticojejunostomy. However, there is controversy regarding the optimal timing of surgical reconstruction. METHODS: A systematic review was performed by searching PubMed, Embase and Cochrane databases for studies published between 1990 and 2018 reporting on the timing of hepaticojejunostomy for BDI (PROSPERO registration CRD42018106611). The main outcomes were postoperative morbidity, postoperative mortality and anastomotic stricture. When individual patient data were available, time intervals of these studies were attuned to render these comparable with other studies. Data for comparable time intervals were pooled using a random-effects model. In addition, data for all included studies were pooled using a generalized linear model. RESULTS: Some 21 studies were included, representing 2484 patients. In these studies, 15 different time intervals were used. Eight studies used the time intervals of less than 14 days (early), 14 days to 6 weeks (intermediate) and more than 6 weeks (delayed). Meta-analysis revealed a higher risk of postoperative morbidity in the intermediate interval (early versus intermediate: risk ratio (RR) 0·73, 95 per cent c.i. 0·54 to 0·98; intermediate versus delayed: RR 1·50, 1·16 to 1·93). Stricture rate was lowest in the delayed interval group (intermediate versus delayed: RR 1·53, 1·07 to 2·20). Postoperative mortality did not differ within time intervals. The additional analysis demonstrated increased odds of postoperative morbidity for reconstruction between 2 and 6 weeks, and decreased odds of anastomotic stricture for delayed reconstruction. CONCLUSION: This meta-analysis found that surgical reconstruction of BDI between 2 and 6 weeks should be avoided as this was associated with higher risk of postoperative morbidity and hepaticojejunostomy stricture.

ANTECEDENTES: La lesión mayor de la vía biliar (bile duct injury, BDI) después de la colecistectomía generalmente requiere reconstrucción quirúrgica mediante una hepaticoyeyunostomía. Sin embargo, existe controversia en relación al momento óptimo para la reconstrucción quirúrgica. MÉTODOS: Se realizó una revisión sistemática mediante la búsqueda en las bases de datos de Pubmed, Embase y Cochrane de los estudios que proporcionaban información sobre el momento de la realización de la hepaticoyeyunostomía por la BDI, publicados entre 1990-2018 (registro PROSPERO: CRD42018106611). Los resultados principales fueron la morbilidad postoperatoria, la mortalidad postoperatoria y las estenosis de la anastomosis. Cuando se disponía de datos individuales de los pacientes, los intervalos de tiempo de estos estudios se ajustaron para hacerlos comparables con otros estudios. Los datos de los intervalos de tiempo comparables se agruparon utilizando un modelo de efectos aleatorios. Además, los datos de todos los estudios incluidos se agruparon mediante un modelo lineal generalizado. RESULTADOS: Se incluyeron 21 estudios con un total de 2.229 pacientes. En estos estudios, se utilizaron 15 intervalos de tiempo diferentes. Ocho estudios utilizaron los intervalos de tiempo < 14 días (precoz), 14 días-6 semanas (intermedio) y > 6 semanas (tardío). El metaanálisis reveló un mayor riesgo de morbilidad postoperatoria en el intervalo intermedio (precoz versus intermedio: riesgo relativo, RR 0,73; i.c. del 95%: 0,54-0,98; intermedio versus tardío RR 1,50, 1,16-1,93). La tasa de estenosis fue más baja en el grupo del intervalo tardío (RR intermedio versus tardío, RR 1,50, 1,07-2,20). La mortalidad postoperatoria no difirió entre los distintos intervalos de tiempo. El análisis adicional demostró mayores probabilidades de morbilidad postoperatoria para la reconstrucción entre 2-6 semanas y menores probabilidades de estenosis anastomóticas en el caso de reconstrucción tardía. CONCLUSIÓN: Este metaanálisis muestra que la reconstrucción quirúrgica de la BDI entre 2 y 6 semanas debe evitarse, ya que este intervalo se asoció con un mayor riesgo de morbilidad postoperatoria y estenosis de la hepaticoyeyunostomía.

Correction to: Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

An amendment to this paper has been published and can be accessed via the original article.

Safe, selective histopathological examination of gallbladder specimens: a systematic review.

BACKGROUND: Routine histopathological examination after cholecystectomy is costly, but the prevalence of unsuspected gallbladder cancer (incidental GBC) is low. This study determined whether selective histopathological examination is safe. METHODS: A comprehensive search of PubMed, Embase, Web of Science and the Cochrane Library was performed. Pooled incidences of incidental and truly incidental GBC (GBC detected during histopathological examination without preoperative or intraoperative suspicion) were estimated using a random-effects model. The clinical consequences of truly incidental GBC were assessed. RESULTS: Seventy-three studies (232 155 patients) were included. In low-incidence countries, the pooled incidence was 0·32 (95 per cent c.i. 0·25 to 0·42) per cent for incidental GBC and 0·18 (0·10 to 0·35) per cent for truly incidental GBC. Subgroup analysis of studies in which surgeons systematically examined the gallbladder revealed a pooled incidence of 0·04 (0·01 to 0·14) per cent. In high-incidence countries, corresponding pooled incidences were 0·83 (0·58 to 1·18), 0·44 (0·21 to 0·91) and 0·08 (0·02 to 0·39) per cent respectively. Clinical consequences were reported for 176 (39·3 per cent) of 448 patients with truly incidental GBC. Thirty-three patients (18·8 per cent) underwent secondary surgery. Subgroup analysis showed that at least half of GBC not detected during the surgeon's systematic examination of the gallbladder was early stage (T1a status or below) and of no clinical consequence. CONCLUSION: Selective histopathological examination of the gallbladder after initial macroscopic assessment by the surgeon seems safe and could reduce costs.

ANTECEDENTES: El examen histopatológico rutinario después de la colecistectomía es caro y la prevalencia de cáncer de vesícula biliar (gallbladder cancer, GBC) no sospechado o incidental es baja. Este estudio determinó si el examen histológico selectivo es seguro. MÉTODOS: Se realizó una búsqueda exhaustiva en PubMed, Embase, Web of Science y en la Biblioteca Cochrane. Se estimaron las incidencias agrupadas de GBC incidental y realmente incidental (GBC detectado durante el examen histopatológico sin sospecha previa o intraoperatoria) utilizando un modelo de efectos aleatorios. Además, se evaluaron las consecuencias clínicas del GBC realmente incidental. RESULTADOS: Se incluyeron 73 estudios (n = 232.155). En los países de baja incidencia, la incidencia agrupada fue de 0,32% para el GBC incidental (i.c. del 95% 0,25 a 0,42) y de 0,18% (0,10 a 0,35) para GBC realmente incidental. El análisis de subgrupos que incluye estudios en los que los cirujanos examinaron sistemáticamente la vesícula biliar reveló una incidencia agrupada de 0,04% (0,01 a 0,14). En los países de alta incidencia, las incidencias agrupadas correspondientes fueron 0,83% (0,58 a 1,18), 0,44% (0.2 a 0.91) y 0,08% (0,02 a 0,39), respectivamente. Se describieron consecuencias clínicas en 176 (39,3%) de 448 pacientes con GBC realmente incidental. Treinta y tres pacientes (18,6%) se sometieron a cirugía secundaria. El análisis por subgrupos mostró que al menos la mitad de los GBC no detectados durante el examen sistemático de la vesícula biliar por parte del cirujano eran tumores de estadio precoz (≤ T1a) y sin consecuencias clínicas. CONCLUSIÓN: El examen histológico selectivo de vesículas biliares después de la evaluación macroscópica inicial realizada por el cirujano parece seguro y podría reducir los costes.

Cost-effectiveness of sigmoid resection with primary anastomosis or end colostomy for perforated diverticulitis: an analysis of the randomized Ladies trial.

BACKGROUND: Several studies have been published favouring sigmoidectomy with primary anastomosis over Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis (Hinchey grade III or IV), but cost-related outcomes were rarely reported. The present study aimed to evaluate costs and cost-effectiveness within the DIVA arm of the Ladies trial. METHODS: This was a cost-effectiveness analysis of the DIVA arm of the multicentre randomized Ladies trial, comparing primary anastomosis over Hartmann's procedure for Hinchey grade III or IV diverticulitis. During 12-month follow-up, data on resource use, indirect costs (Short Form Health and Labour Questionnaire) and quality of life (EuroQol Five Dimensions) were collected prospectively, and analysed according to the modified intention-to-treat principle. Main outcomes were incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios, expressed as the ratio of incremental costs and the incremental probability of being stoma-free or incremental quality-adjusted life-years respectively. RESULTS: Overall, 130 patients were included, of whom 64 were allocated to primary anastomosis (46 and 18 with Hinchey III and IV disease respectively) and 66 to Hartmann's procedure (46 and 20 respectively). Overall mean costs per patient were lower for primary anastomosis (€20 544, 95 per cent c.i. 19 569 to 21 519) than Hartmann's procedure (€28 670, 26 636 to 30 704), with a mean difference of €-8126 (-14 660 to -1592). The ICER was €-39 094 (95 per cent bias-corrected and accelerated (BCa) c.i. -1213 to -116), indicating primary anastomosis to be more cost-effective. The ICUR was €-101 435 (BCa c.i. -1 113 264 to 251 840). CONCLUSION: Primary anastomosis is more cost-effective than Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis.

ANTECEDENTES: Se han publicado varios estudios en favor de la sigmoidectomía con anastomosis primaria (primary anastomosis, PA) sobre la intervención de Hartmann (Hartmann's procedure, HP) para la diverticulitis perforada con peritonitis purulenta o fecal (Hinchey grado III ó IV), pero apenas existe información de los resultados relacionados con el coste. Por lo tanto, el presente estudio tuvo como objetivo evaluar los costes y el coste efectividad del brazo DIVA en el ensayo clínico Ladies. MÉTODOS: Se realizó un análisis de coste-efectividad del brazo DIVA del ensayo clínico multicéntrico y aleatorizado Ladies, que comparó PA y HP para la diverticulitis Hinchey de grado III ó IV. Durante un seguimiento de 12 meses, se recogieron datos prospectivamente del uso de recursos, costes indirectos (SF-HLQ) y calidad de vida (EQ-5D), y se analizaron de acuerdo con una modificación del principio por intención de tratar. Los resultados principales fueron la relación coste-efectividad incremental (incremental cost-effectiveness ratio, ICER) y la relación coste-utilidad incremental (incremental cost-utility ratio, ICUR), expresados como la razón del incremento de costes y el incremento en la probabilidad de no requerir estoma o años de vida ajustados por calidad, respectivamente. RESULTADOS: En total, se incluyeron 130 pacientes, 64 de los cuales fueron asignados a PA (Hinchey III/IV: 46/20) y 66 a HP (Hinchey III/IV: 46/18). Los costes medios globales por paciente fueron más bajos para la PA (€20.544 (i.c. del 95%: 19.569 a 21.519)) en comparación con HP (€ 28.670 (i.c. del 95%: 26.636 a 30.704)), con una diferencia media de €−8.126 (i.c. del 95% −14.660 a −1.592)). Además, se observó un ICER de € −39.094 (95% bias-corrected and accelerated boodstrap confidence interval, BCaCI −1.213 a −116), lo que indica que PA es más coste efectiva. El ICUR fue € −101.435 (BCaCI del 95%: −1.113.264 a 251.840). CONCLUSIÓN: La anastomosis primaria es más rentable que el procedimiento de Hartmann para la diverticulitis perforada con peritonitis purulenta o fecal.

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.