Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study.

BACKGROUND: Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. PATIENTS AND METHODS: An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. RESULTS: Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort.

BACKGROUND AND AIM: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design.

BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Pancreatic exocrine insufficiency following pancreatoduodenectomy: A prospective bi-center study.

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication following pancreatoduodenectomy (PD) leading to malnutrition. The course of PEI and related symptoms and vitamin deficiencies is unknown. This study aimed to assess the (long-term) incidence of PEI and vitamin deficiencies after PD. METHODS: A bi-centre prospective observational cohort study was performed, including patients who underwent PD for mainly pancreatic and periampullary (pre)malignancies (2014-2018). Two cohorts were formed to evaluate short and long-term results. Patients were followed for 18 months and clinical symptoms were evaluated by questionnaire. PEI was based on faecal elastase-1 (FE-1) levels and/or clinical symptoms. RESULTS: In total, 95 patients were included. After three months, all but three patients had developed PEI and 27/29 (93%) patients of whom stool samples were available showed abnormal FE-1 levels, which did not improve during follow-up. After six months, all patients had developed PEI. During follow-up, symptoms resolved in 35%-70% of patients. Vitamin D and K deficiencies were observed in 48%-79% of patients, depending on the moment of follow-up; 0%-50% of the patients with deficiencies received vitamin supplementation. DISCUSSION: This prospective study found a high incidence of PEI after PD with persisting symptoms in one-to two thirds of all patients. Limited attention was paid to vitamin deficiencies. Improved screening and treatment strategies for PEI and vitamins need to be designed.

Completion pancreatectomy or a pancreas-preserving procedure during relaparotomy for pancreatic fistula after pancreatoduodenectomy: a multicentre cohort study and meta-analysis.

BACKGROUND: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. METHODS: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). CONCLUSION: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.

Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial.

BACKGROUND: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. METHODS: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. DISCUSSION: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. TRIAL REGISTRATION: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004.

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry.

BACKGROUND: The treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC. METHODS: Post-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015-December 2017). Patients were divided in three groups according to age (<65, 65-74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders. RESULTS: Overall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65-74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival. CONCLUSION: Elderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.

Recurrence of idiopathic acute pancreatitis after cholecystectomy: systematic review and meta-analysis.

BACKGROUND: Occult biliary disease has been suggested as a frequent underlying cause of idiopathic acute pancreatitis (IAP). Cholecystectomy has been proposed as a strategy to prevent recurrent IAP. The aim of this systematic review was to determine the efficacy of cholecystectomy in reducing the risk of recurrent IAP. METHODS: PubMed, Embase and Cochrane Library databases were searched systematically for studies including patients with IAP treated by cholecystectomy, with data on recurrence of pancreatitis. Studies published before 1980 or including chronic pancreatitis and case reports were excluded. The primary outcome was recurrence rate. Quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses were undertaken to calculate risk ratios using a random-effects model with the inverse-variance method. RESULTS: Overall, ten studies were included, of which nine were used in pooled analyses. The study population consisted of 524 patients with 126 cholecystectomies. Of these 524 patients, 154 (29·4 (95 per cent c.i. 25·5 to 33·3) per cent) had recurrent disease. The recurrence rate was significantly lower after cholecystectomy than after conservative management (14 of 126 (11·1 per cent) versus 140 of 398 (35·2 per cent); risk ratio 0·44, 95 per cent c.i. 0·27 to 0·71). Even in patients in whom IAP was diagnosed after more extensive diagnostic testing, including endoscopic ultrasonography or magnetic resonance cholangiopancreatography, the recurrence rate appeared to be lower after cholecystectomy (4 of 36 (11 per cent) versus 42 of 108 (38·9 per cent); risk ratio 0·41, 0·16 to 1·07). CONCLUSION: Cholecystectomy after an episode of IAP reduces the risk of recurrent pancreatitis. This implies that current diagnostics are insufficient to exclude a biliary cause.

ANTECEDENTES: Se ha sugerido que la enfermedad biliar oculta es una causa subyacente frecuente de pancreatitis aguda idiopática (idiopathic acute pancreatitis, IAP). La colecistectomía se ha propuesto como una estrategia para prevenir la IAP recidivante. El objetivo de esta revisión sistemática era determinar la eficacia de la colecistectomía para reducir el riesgo de la IAP recidivante. MÉTODOS: Se realizó una búsqueda sistemática en PubMed, Embase y Cochrane de estudios que incluían pacientes con IAP tratados con colecistectomía, y con datos sobre la recidiva de la pancreatitis. Se excluyeron los estudios anteriores a 1980, los que incluían pancreatitis crónica y los casos clínicos. El resultado principal fue la tasa de recidiva. La calidad se evaluó utilizando la escala de Newcastle-Ottawa. Se realizaron metaanálisis para calcular la tasa de riesgo utilizando un modelo de efectos aleatorios con el método de varianza inversa. RESULTADOS: En total, se incluyeron 10 estudios, de los cuales 9 se utilizaron para realizar análisis agrupados. La población de estudio incluyó 524 pacientes en los que se habían efectuado 126 colecistectomías. De estos 524 pacientes, 154 (29% (i.c. del 95% 25,5-33,3)) presentaron recidiva de la enfermedad. La tasa de recidiva fue significativamente menor después de la colecistectomía que después del tratamiento conservador (14/126 (11%) versus 140/398 (35)); tasa de riesgo 0,44 (i.c. del 95% 0,27-0,71)). Incluso en pacientes en los que se diagnosticó IAP tras haber efectuado pruebas diagnósticas más extensas, incluyendo ultrasonografía endoscópica o colangiopancreatografía por resonancia magnética, la tasa de recidiva después de la colecistectomía era menor (4/36 (11%) versus 42/108 (39%); tasa de riesgo 0,41 (i.c. del 95% 0,16-1,07)). CONCLUSIÓN: La práctica de una colecistectomía después de un episodio de IAP disminuye el riesgo de pancreatitis recidivante. Esto implica que los diagnósticos actuales son insuficientes para excluir una causa biliar (PROSPERO CRD42017055275).

The association between portal system vein diameters and outcomes in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) progresses to necrotizing pancreatitis in 15% of cases. An important pathophysiological mechanism in AP is third spacing of fluids, which leads to intravascular volume depletion. This results in a reduced splanchnic circulation and reduced venous return. Non-visualisation of the portal and splenic vein on early computed tomography (CT) scan, which might be the result of smaller vein diameter due to decreased venous flow, is associated with infected necrosis and mortality in AP. This observation led us to hypothesize that smaller diameters of portal system veins (portal, splenic and superior mesenteric) are associated with increased severity of AP. METHODS: We conducted a post-hoc analysis of data from two randomized controlled trials that included patients with predicted severe and mild AP. The primary endpoint was AP-related mortality. The secondary endpoints were (infected) necrotizing pancreatitis and (persistent) organ failure. We performed additional CT measurements of portal system vein diameters and calculated their prognostic value through univariate and multivariate Poisson regression. RESULTS: Multivariate regression showed a significant inverse association between splenic vein diameter and mortality (RR 0.75 (0.59-0.97)). Furthermore, there was a significant inverse association between splenic and superior mesenteric vein diameter and (infected) necrosis. Diameters of all veins were inversely associated with organ failure and persistent organ failure. CONCLUSIONS: We observed an inverse relationship between portal system vein diameter and morbidity and an inverse relationship between splenic vein diameter and mortality in AP. Further research is needed to test whether these results can be implemented in predictive scoring systems.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis.

BACKGROUND: Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. METHODS: For this randomized controlled non-inferiority trial, adult patients with mild acute calculous cholecystitis undergoing cholecystectomy at six major teaching hospitals in the Netherlands, between April 2012 and September 2014, were assessed for eligibility. Patients were randomized to either a single preoperative dose of cefazolin (2000 mg), or antibiotic prophylaxis for 3 days after surgery (intravenous cefuroxime 750 mg plus metronidazole 500 mg, three times daily), in addition to the single dose. The primary endpoint was rate of infectious complications within 30 days after operation. RESULTS: In the intention-to-treat analysis, three of 77 patients (4 per cent) in the extended antibiotic group and three of 73 (4 per cent) in the standard prophylaxis group developed postoperative infectious complications (absolute difference 0·2 (95 per cent c.i. -8·2 to 8·9) per cent). Based on a margin of 5 per cent, non-inferiority of standard prophylaxis compared with extended prophylaxis was not proven. Median length of hospital stay was 3 days in the extended antibiotic group and 1 day in the standard prophylaxis group. CONCLUSION: Standard single-dose antibiotic prophylaxis did not lead to an increase in postoperative infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. Registration number: NTR3089 (www.trialregister.nl).

Diagnostic performance of imaging modalities in chronic pancreatitis: a systematic review and meta-analysis.

OBJECTIVES: Obtain summary estimates of sensitivity and specificity for imaging modalities for chronic pancreatitis (CP) assessment. METHODS: A systematic search was performed in Cochrane Library, MEDLINE, Embase and CINAHL databases for studies evaluating imaging modalities for the diagnosis of CP up to September 2016. A bivariate random-effects modeling was used to obtain summary estimates of sensitivity and specificity. RESULTS: We included 43 studies evaluating 3460 patients. Sensitivity of endoscopic retrograde cholangiopancreatography (ERCP) (82%; 95%CI: 76%-87%) was significant higher than that of abdominal ultrasonography (US) (67%; 95%CI: 53%-78%; P=0.018). The sensitivity estimates of endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and computed tomography (CT) were 81% (95%CI: 70%-89%), 78% (95%CI: 69%-85%), and 75% (95%CI: 66%-83%), respectively, and did not differ significantly from each other. Estimates of specificity were comparable for EUS (90%; 95%CI: 82%-95%), ERCP (94%; 95%CI: 87%-98%), CT (91%; 95% CI: 81%-96%), MRI (96%; 95%CI: 90%-98%), and US (98%; 95%CI: 89%-100%). CONCLUSIONS: EUS, ERCP, MRI and CT all have comparable high diagnostic accuracy in the initial diagnosis of CP. EUS and ERCP are outperformers and US has the lowest accuracy. The choice of imaging modality can therefore be made based on invasiveness, local availability, experience and costs. KEY POINTS: • EUS, ERCP, MRI and CT have high diagnostic sensitivity for chronic pancreatitis • Diagnostic specificity is comparable for all imaging modalities • EUS and ERCP are outperformers and US has the lowest accuracy • The choice of imaging can be made based on clinical considerations.

Cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis in the PONCHO trial.

BACKGROUND: Same-admission cholecystectomy is indicated after gallstone pancreatitis to reduce the risk of recurrent disease or other gallstone-related complications, but its impact on overall costs is unclear. This study analysed the cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis. METHODS: In a multicentre RCT (Pancreatitis of biliary Origin: optimal timiNg of CHOlecystectomy; PONCHO) patients with mild gallstone pancreatitis were randomized before discharge to either cholecystectomy within 72 h (same-admission cholecystectomy) or cholecystectomy after 25-30 days (interval cholecystectomy). Healthcare use of all patients was recorded prospectively using clinical report forms. Unit costs of resources used were determined, and patients completed multiple Health and Labour Questionnaires to record pancreatitis-related absence from work. Cost-effectiveness analyses were performed from societal and healthcare perspectives, with the costs per readmission prevented as primary outcome with a time horizon of 6 months. RESULTS: All 264 trial participants were included in the present analysis, 128 randomized to same-admission cholecystectomy and 136 to interval cholecystectomy. Same-admission cholecystectomy reduced the risk of acute readmission for recurrent gallstone-related complications from 16·9 to 4·7 per cent (P = 0·002). Mean total costs from a societal perspective were €234 (95 per cent c.i. -1249 to 738) less per patient in the same-admission cholecystectomy group. Same-admission cholecystectomy was superior to interval cholecystectomy, with a societal incremental cost-effectiveness ratio of -€1918 to prevent one readmission for gallstone-related complications. CONCLUSION: In mild biliary pancreatitis, same-admission cholecystectomy was more effective and less costly than interval cholecystectomy.

Health-related quality of life after pancreatic resection for malignancy.

BACKGROUND: Health-related quality of life (QoL) is of major importance in pancreatic cancer, owing to the limited life expectation. The aim of this prospective longitudinal study was to describe QoL in patients undergoing resection for pancreatic or periampullary malignancy. METHODS: QoL was measured on a scale of 0-100 in patients who underwent pancreatic resection for malignancy or premalignancy at the University Medical Centre Utrecht before resection, and 1, 3, 6 and 12 months after surgery. Measures consisted of the RAND-36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the EORTC pancreatic cancer-specific module (QLQ-PAN26). RESULTS: Between March 2012 and November 2013, 68 consecutive patients with a malignancy (59 patients) or premalignancy (9) were included. Physical role restriction, social and emotional domains showed a significant and clinically relevant deterioration directly after operation in 53 per cent (RAND-36, P < 0.001), 63 and 78 per cent (QLQ-C30 and RAND-36 respectively, P < 0.001) and 37 per cent (RAND-36, P < 0.001) of patients respectively. Most domains demonstrated recovery to preoperative values or better at 3 months, except for physical functioning. Emotional functioning at 3, 6 and 12 months was better than at baseline (P < 0.001). Symptom scores revealed a deterioration in vitality, pain (P = 0.002), fatigue (P < 0.001), appetite loss (P < 0.001), altered bowel habit (P = 0.001) and side-effects (P < 0.001) after 1 month. After 3 months, only side-effects were worse than preoperative values (P < 0.001). CONCLUSION: QoL after pancreatic resection for malignant and premalignant tumours decreased considerably in the early postoperative phase. Full recovery of QoL took up to 6 months after the operation.

Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. METHODS: A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. RESULTS: After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. CONCLUSION: Ablative therapies in patients with LAPC appear to be feasible and safe.

Dutch Chronic Pancreatitis Registry (CARE): design and rationale of a nationwide prospective evaluation and follow-up.

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.

Peritoneal carcinomatosis in t4 colorectal cancer: occurrence and risk factors.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy improves outcome of patients with peritoneal carcinomatosis (PC) of colorectal carcinoma. Data on the occurrence of PC in T4 colorectal carcinoma are scarce. We investigated the occurrence and risk factors for PC in these patients. METHODS: This was a retrospective cohort study of patients undergoing a first resection of a T4 colorectal carcinoma in a tertiary hospital between January 2000 and December 2007. Primary outcome was the occurrence of synchronous or metachronous PC. The association with PC and several patient and tumor characteristics was evaluated using logistic regression. RESULTS: A total of 200 patients underwent resection of a T4 colorectal carcinoma. Median follow-up censored for death was 66 months (18-89 months). Synchronous PC was found in 46 of 200 patients (23 %) and metachronous PC in 33 of 154 patients (21 %). In univariable analysis, factors associated with PC were: age (OR 0.97; 95 % CI 0.94-0.99; P = 0.03), radical resection (OR 0.32; 95 % CI 0.11-0.91; P = 0.03), and N stage (OR 1.63; 95 % CI 1.36-2.34; P = 0.008). In multivariable analysis, only N stage was associated with PC (OR 1.62; 95 % CI 1.12-2.34; P = 0.01). This association was not significant for the 154 patients at risk for metachronous PC. CONCLUSIONS: Around 1 in 5 patients undergoing resection of a T4 colorectal carcinoma either have PC during primary resection or develop PC during follow-up. N stage was associated with PC in the entire study population. However, none of the clinical or pathological variables were associated with the risk of metachronous PC and therefore cannot be used to develop targeted surveillance strategies.