Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial.

BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

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).

Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer.

INTRODUCTION: In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. METHODS: A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT's plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed. RESULTS: 53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients' characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%. CONCLUSIONS: For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated. TRIAL REGISTRATION NUMBER: Dutch Trial Registry (NTR3142).

Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram.

BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Hospital of diagnosis and likelihood of surgical treatment for pancreatic cancer.

BACKGROUND: Surgical resection for pancreatic cancer offers the only chance of cure. Assessment of the resectability of a pancreatic tumour is therefore of great importance. The aim of the study was to investigate whether centre of diagnosis influences the likelihood of surgery and whether this affects long-term survival. METHODS: Patients diagnosed with non-metastasized pancreatic cancer (M0) between 2005 and 2013 in the Netherlands were selected from the Netherlands Cancer Registry. Hospitals were classified as a pancreatic centre (at least 20 resections/year) or a non-pancreatic centre (fewer than 20 resections/year). The relationship between centre of diagnosis and likelihood of surgery was analysed by multivariable logistic regression. Influence of centre on overall survival was assessed by means of multivariable Cox regression analysis. RESULTS: Some 8141 patients were diagnosed with non-metastasized pancreatic cancer, of whom 3123 (38·4 per cent) underwent surgery. Of the 2712 patients diagnosed in one of 19 pancreatic centres, 52·4 per cent had exploratory laparotomy compared with 31·4 per cent of 5429 patients diagnosed in one of 74 non-pancreatic centres (P < 0·001). A pancreatectomy was performed in 42·8 and 24·6 per cent of the patients respectively (P < 0·001). Multivariable analysis revealed that patients diagnosed in a pancreatic centre had a higher chance of undergoing surgery (odds ratio 2·21, 95 per cent c.i. 1·98 to 2·47). Centre of diagnosis was not associated with improved long-term survival (hazard ratio 0·95, 95 per cent c.i. 0·91 to 1·00). CONCLUSION: Patients with non-metastasized pancreatic cancer had a greater likelihood of having surgical treatment when the diagnosis was established in a pancreatic centre.

Impact of lymph node ratio on survival in patients with pancreatic and periampullary cancer.

BACKGROUND: According to some studies, the number of lymph nodes with metastases in relation to the total number of removed lymph nodes, the lymph node ratio (LNR), is one of the most powerful predictors of survival after resection in patients with pancreatic cancer. However, contradictory results have been reported, and small sample sizes of the cohorts and different definitions of a microscopic positive resection margin (R1) hamper the interpretation of data. METHODS: The predictive value of LNR for 3-year survival was assessed using a Cox proportional hazards model. From 1992 to 2012, all patients with pancreatic and periampullary cancer operated on with pancreatoduodenectomy were selected from a database. Clinicopathological characteristics were analysed. Microscopic positive resection margin was defined as the microscopic presence of tumour cells within 1 mm of the margins. A nomogram was created. RESULTS: Some 760 patients were included. Predictive factors for death in 350 patients with pancreatic ductal adenocarcinoma included in the nomogram were: R1 resection (hazard ratio (HR) 1·55, 95 per cent c.i. 1·07 to 2·25), poor tumour differentiation (HR 2·78, 1·40 to 5·52), LNR above 0·18 (HR 1·75, 1·13 to 2·70) and no adjuvant therapy (HR 1·54, 1·01 to 2·34). The C statistic was 0·658 (0·632 to 0·698), and calibration was good (Hosmer-Lemeshow χ(2) = 5·67, P =0·773). LNR and poor tumour differentiation (HR 4·51 and 3·30 respectively) were also predictive in patients with distal common bile duct (CBD) cancer. LNR, R1 resection and jaundice were predictors of death in patients with ampullary cancer (HR 7·82, 2·68 and 1·93 respectively). CONCLUSION: LNR is a common predictor of poor survival in pancreatic, distal CBD and ampullary cancer.

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.

Systematic review of five feeding routes after pancreatoduodenectomy.

BACKGROUND: Current European guidelines recommend routine enteral feeding after pancreato-duodenectomy (PD), whereas American guidelines do not. The aim of this study was to determine the optimal feeding route after PD. METHODS: A systematic search was performed in PubMed, Embase and the Cochrane Library. Included were studies on feeding routes after PD that reported length of hospital stay (primary outcome). RESULTS: Of 442 articles screened, 15 studies with 3474 patients were included. Data on five feeding routes were extracted: oral diet (2210 patients), enteral nutrition via either a nasojejunal tube (NJT, 165), gastrojejunostomy tube (GJT, 52) or jejunostomy tube (JT, 623), and total parenteral nutrition (TPN, 424). Mean(s.d.) length of hospital stay was shortest in the oral diet and GJT groups (15(14) and 15(11) days respectively), followed by 19(12) days in the JT, 20(15) days in the TPN and 25(11) days in the NJT group. Normal oral intake was established most quickly in the oral diet group (mean 6(5) days), followed by 8(9) days in the NJT group. The incidence of delayed gastric emptying varied from 6 per cent (3 of 52 patients) in the GJT group to 23.2 per cent (43 of 185) in the JT group, but definitions varied widely. The overall morbidity rate ranged from 43.8 per cent (81 of 185) in the JT group to 75 per cent (24 of 32) in the GJT group. The overall mortality rate ranged from 1.8 per cent (3 of 165) in the NJT group to 5.4 per cent (23 of 424) in the TPN group. CONCLUSION: There is no evidence to support routine enteral or parenteral feeding after PD. An oral diet may be considered as the preferred routine feeding strategy after PD.

Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality.

BACKGROUND: The impact of nationwide centralization of pancreaticoduodenectomy (PD) on mortality is largely unknown. The aim of this study was to analyse changes in hospital volumes and in-hospital mortality after PD in the Netherlands between 2004 and 2009. METHODS: Nationwide data on International Classification of Diseases, ninth revision (ICD-9) code 5-526 (PD, including Whipple), patient age, sex and mortality were retrieved from the independent nationwide KiwaPrismant registry. Based on established cut-off points of annually performed PDs, hospitals were categorized as very low (fewer than 5), low (5-10), medium (11-19) or high (at least 20) volume. A subgroup analysis based on a cut-off age of 70 years was also performed. RESULTS: Some 2155 PDs were included. The number of hospitals performing PD decreased from 48 in 2004 to 30 in 2009 (P = 0·011). In these specific years, the proportion of patients undergoing PD in a medium- or high-volume centre increased from 52·9 to 91·2 per cent (P < 0·001). Nationwide mortality rates after PD decreased from 9·8 to 5·1 per cent (P = 0·044). The mortality rate during the 6-year period was 14·7, 9·8, 6·3 and 3·3 per cent in very low-, low-, medium- and high-volume hospitals respectively (P < 0·001). The difference in mortality between medium- and high-volume centres was statistically significant (P = 0·004). The volume-outcome relationship was not influenced by age (P = 0·467). The mortality rate after PD in patients aged at least 70 years was 10·4 per cent compared with 4·4 per cent in younger patients (P < 0·001). CONCLUSION: With nationwide centralization of PD, the in-hospital mortality rate after this procedure decreased. Further centralization of PD is likely to decrease mortality further, especially in the elderly.

[Obtaining medical ethical approval for a multicentre, randomised study: prospective evaluation of a ponderous process]. / Her verkrijgen van medisch-ethische goedkeuring voor een multicentrische, gerandomiseerde trial: prospectieve evaluatie van een moeizaam proces.

OBJECTIVE: To evaluate the procedure to obtain medical ethical approval for a multicentre study in the Netherlands. DESIGN: Prospective and descriptive. METHOD: The application procedure for medical ethical approval of a nationwide randomised multicentre trial (the 'Pancreatitis: surgical necrosectomy versus step up approach' (PANTER)-trial) from the ethics committees (EC) of 9 Dutch hospitals during 2004-2007, was prospectively evaluated. Several predefined variables regarding the duration of the ethical review process, the time invested and material and the type of queries raised by the ECs in all centres were collected. RESULTS: Primary approval by the central EC of the coordinating hospital was obtained after 192 days. The duration of the review process for each of the 18 local participating centres was 105 days (range: 35-361). The maximum review term of 30 days, as defined in the national guideline, was reached by only one centre. It took two years to obtain approval for all participating centres. A median of 14 different documents (range: 5-23) were submitted to the EC of each participating centre. A total of 8314 A4 size papers (about 42 kg) were sent by post, 172 telephone calls were made and 136 e-mail messages were sent by the research fellow coordinating the application procedure. Of the local ECs in the participating centers, 95% requested additional revision of the patient information sheet and 78% requested changes in the informed consent form. CONCLUSION: Obtaining medical ethical approval for this multicentre trial in the Netherlands was a long and inefficient process, requiring a considerable investment of time and resources. Streamlining the application procedure may lead to a substantial reduction in the current unnecessary delay of starting a multicentre study.

[Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial]. / Probioticaprofylaxe bij voorspeld ernstige acute pancreatitis: een gerandomiseerde, dubbelblinde, placebogecontroleerde trial.

OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949. RESULTS: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004). CONCLUSION: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

[Symptomatic gallstone disease: an indication for surgery]. / Symptomatisch galsteenlijden: een operatie-indicatie.

Three patients, men in the ages of 58, 66 and 56 years, respectively, had experienced 'warning colics' a considerable time before gallstone complications or severe recurrent colic. Ultrasonographically proven gallstones had not led to cholecystectomy. The 58-year-old man died of sepsis due to infected pancreatic necrosis; the other men underwent laparoscopic cholecystectomy, after which they recovered fully. Approximately 10-5% of the adult Dutch population have gallstones, but only 10% will develop symptoms. The annual risk for developing complicated gallstone disease is 1-2% in asymptomatic gallstone carriers. Of patients admitted with complicated gallstone disease, 58% have had prior 'warning colics'. Complicated gallstone disease can be prevented by timely treatment after recognition of warning colics. Cholecystectomy is indicated in patients with intermittent upper-abdominal pain and proven gallstones or sludge.

[A nationwide Dutch study into the optimal treatment of patients with infected necrotising pancreatitis: the PANTER trial]. / Landelijk onderzoek naar optimale behandeling van patiënten met geïnfecteerde necrotiserende pancreatitis: PANTER-trial.

Surgical intervention in infected necrotising pancreatitis generally consists of necrosectomy via laparotomy. The morbidity and mortality after this procedure might be reduced by minimally invasive strategies. The 20 hospitals of the Dutch Acute Pancreatitis Study Group are currently enrolling patients in a randomised trial to compare (a) laparotomy with necrosectomy and continuous postoperative lavage with (b) CT-guided or endoscopic transgastric drainage, if necessary, followed by videoscopic assisted retroperitoneal debridement (VARD): the PANTER trial ('pancreatitis, necrosectomy versus a minimally invasive step-up approach'). The primary endpoint is the proportion of patients suffering from major postoperative morbidity and mortality. Patients with (suspected) infected necrotising pancreatitis can be put forward for participation in the trial in one of the 20 participating centres.

[Potential role for probiotics in the prevention of infectious complications during acute pancreatitis]. / Potentiële rol voor probiotica bij de preventie van infectieuze complicaties tijdens acute pancreatitis.

Acute pancreatitis has a high mortality in case of secondary infection of (peri-)pancreatic necrosis. Bacterial translocation is held responsible for the majority of these infectious complications of severe acute pancreatitis. Prophylactic strategies should therefore be directed at the three most important pathophysiological mechanisms of bacterial translocation: disturbed small-bowel motility and bacterial overgrowth, failure of the mucosal barrier function and a disturbed response of the immune system. In-vitro studies and research in experimental animals have shown that specially selected probiotics exert an effect on these mechanisms and can prevent bacterial translocation. Recently, several randomised, double-blind, placebo-controlled trials evaluating prophylactic treatment with enteral probiotics have shown good results. A Dutch multicentre trial, 'Probiotics in pancreatitis trial' (PROPATRIA), is currently underway.

Volume matters in the systemic treatment of metastatic pancreatic cancer: a population-based study in the Netherlands.

PURPOSE: In pancreatic surgery, a relation between surgical volume and postoperative mortality and overall survival (OS) has been recognized, with high-volume centers reporting significantly better survival rates. We aimed to explore the influence of hospital volume on administration of palliative chemotherapy and OS in the Netherlands. METHODS: Patients diagnosed between 2007 and 2011 with metastatic pancreatic cancer were identified in the Netherlands Cancer Registry. Three types of high-volume centers were defined: high-volume (1) incidence center, based on the number of patients diagnosed with metastatic pancreatic cancer, (2) treatment center based on number of patients with metastatic pancreatic cancer who started treatment with palliative chemotherapy and (3) surgical center based on the number of resections with curative intent for pancreatic cancer. Independent predictors of administration of palliative chemotherapy were evaluated by means of logistic regression analysis. The multivariable Cox proportional hazard model was used to assess the impact of being diagnosed or treated in high-volume centers on survival. RESULTS: A total of 5385 patients presented with metastatic pancreatic cancer of which 24 % received palliative chemotherapy. Being treated with chemotherapy in a high-volume chemotherapy treatment center was associated with improved survival (HR 0.76, 95 % CI 0.67-0.87). Also, in all patients with metastatic pancreatic cancer, being diagnosed in a high-volume surgical center was associated with improved survival (HR 0.74, 95 % CI 0.66-0.83). CONCLUSIONS: Hospital volume of palliative chemotherapy for metastatic pancreatic cancer was associated with improved survival, demonstrating that a volume-outcome relationship, as described for pancreatic surgery, may also exist for pancreatic medical oncology.

Beneficial effects of ERCP and papillotomy in predicted severe biliary pancreatitis.

BACKGROUND/AIMS: Extensive circumstantial evidence indicates that patients with a predicted severe attack of acute biliary pancreatitis (ABP) should undergo an endoscopic retrograde cholangiography with papillotomy (ERC/PT). However, in clinical practice this procedure is not always performed. This study was conducted to compare outcome in patients with and without ERC/PT. METHODOLOGY: Thirty-five of 80 patients admitted with ABP had a predicted severe attack (three or more Ranson criteria). Only in 24 of these 35 patients was an ERC/PT performed. RESULTS: In the ERC/PT group, significantly less pancreatic necrosis (8 vs. 64%, p<0.001) occurred, hospital stay was shorter (median 22 +/- 5 vs. 51 +/- 19 days, P=0.08) and mortality was lower (8 vs. 36%, P=0.01). Twenty-three patients (66%) underwent cholecystectomy after a median period of 10 weeks (range 0-26 weeks) after discharge. During the waiting period, in the ERC/PT group, two patients developed acute cholecystitis whereas recurrent ABP and common bile duct stones occurred in one patient each. CONCLUSIONS: In patients with a predicted severe attack of ABP, performing ERC/PT is associated with less morbidity and lower mortality.

[Timing and choice of intervention in necrotising pancreatitis]. / Timing en keuze van interventie bij necrotiserende pancreatitis.

Three patients, men aged 49, 62 and 33 years, were admitted with acute abdominal symptoms due to necrotising pancreatitis. They underwent multiple interventions during a hospital stay of several months, but ultimately recovered completely. In case of infected (peri-)pancreatic necrosis, intervention is required. Good clinical judgement in the differentiation between the septic inflammatory-response syndrome, sepsis and infected necrosis as the cause of the clinical condition is important. Because of the different intervention strategies, treatment by a team comprising a radiologist, gastroenterologist, intensive care specialist and gastrointestinal surgeon is required. Randomised studies on intervention in infected pancreatic necrosis are lacking. In 2002, to improve the treatment of patients with acute (necrotising) pancreatitis via a combination of research, consultation and centralisation, the Dutch Acute Pancreatitis Study Group was formed.