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Despite an aging population and underrepresentation of elderly patients in clinical trials, studies on elderly patients with metastatic pancreatic cancer are scarce. This study investigated the use of chemotherapy and survival in elderly patients with metastatic pancreatic cancer. From the Netherlands Cancer Registry, all 9407 patients diagnosed with primary metastatic pancreatic adenocarcinoma in 2005-2013 were selected to investigate chemotherapy use and overall survival ( OS), using Kaplan-Meier and Cox proportional hazard regression analyses. Over time, chemotherapy use increased in all age groups (<70 years: from 26 to 43%, 70-74 years: 14 to 25%, 75-79 years: 5 to 13%, all P < 0.001, and ≥80 years: 2 to 3% P = 0.56). Median age of 2,180 patients who received chemotherapy was 63 years (range 21-86 years, 1.6% was ≥80 years). In chemotherapy-treated patients, with rising age (<70, 70-74, 75-79, ≥80 years), microscopic tumor verification occurred less frequently (91-88-87-77%, respectively, P = 0.009) and OS diminished (median 25-26-19-16 weeks, P = 0.003). After adjustment for confounding factors, worse survival of treated patients ≥75 years persisted. Despite limited chemotherapy use in elderly age, suggestive of strong selection, elderly patients (≥75 years) who received chemotherapy for metastatic pancreatic cancer exhibited a worse survival compared to younger patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improved over the last two decades. Approximately 15 % of all patients have resectable disease at diagnosis, and of those, only a subgroup has a resectable tumour at surgical exploration. Data from cohort studies have suggested that outcome can be improved by preoperative radiochemotherapy, but data from well-designed randomized studies are lacking. Our PREOPANC phase III trial aims to test the hypothesis that median overall survival of patients with resectable or borderline resectable pancreatic cancer can be improved with preoperative radiochemotherapy.Methods/design: The PREOPANC trial is a randomized, controlled, multicentric superiority trial, initiated by the Dutch Pancreatic Cancer Group. Patients with (borderline) resectable pancreatic cancer are randomized to A: direct explorative laparotomy or B: after negative diagnostic laparoscopy, preoperative radiochemotherapy, followed by explorative laparotomy. A hypofractionated radiation scheme of 15 fractions of 2.4 gray (Gy) is combined with a course of gemcitabine, 1,000 mg/m(2)/dose on days 1, 8 and 15, preceded and followed by a modified course of gemcitabine. The target volumes of radiation are delineated on a 4D CT scan, where at least 95 % of the prescribed dose of 36 Gy in 15 fractions should cover 98 % of the planning target volume. Standard adjuvant chemotherapy is administered in both treatment arms after resection (six cycles in arm A and four in arm B). In total, 244 patients will be randomized in 17 hospitals in the Netherlands. The primary endpoint is overall survival by intention to treat. Secondary endpoints are (R0) resection rate, disease-free survival, time to locoregional recurrence or distant metastases and perioperative complications. Secondary endpoints for the experimental arm are toxicity and radiologic and pathologic response.Discussion: The PREOPANC trial is designed to investigate whether preoperative radiochemotherapy improves overall survival by means of increased (R0) resection rates in patients with resectable or borderline resectable pancreatic cancer.Trial Registration: Trial open for accrual: 3 April 2013 The Netherlands National Trial Register - NTR3709 (8 November 2012) EU Clinical Trials Register - 2012-003181-40 (11 December 2012). [ABSTRACT FROM AUTHOR]

Background Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes. Methods/design The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs. Discussion The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis. [ABSTRACT FROM AUTHOR]

Background: For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%). Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. Methods/design: This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ⩾18 and ⩽80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. Discussion: This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. [ABSTRACT FROM AUTHOR]

Background: The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design: 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion: The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. Methods/design: PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. Conclusion: The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.Methods/design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.Trial Registration: Netherlands Trial Register [ NTR4243 , 11 October 2013]. [ABSTRACT FROM AUTHOR]

Introduction:Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis. Methods:Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls. Results:Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology. Conclusion:Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2. [ABSTRACT FROM AUTHOR]

Background: Benign liver tumours (e.g., hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH), and haemangioma) are occasionally resected for alleged symptoms, although data on long-term outcomes is lacking. The aim of this cross-sectional study was to assess long-term outcomes of surgical intervention. Methods: Forty patients with benign tumours (HCA 20, FNH 12, giant haemangioma 4, cysts 4) were included. Patients filled in Validated McGill Pain Questionnaires, preoperatively and after a median of 54 months after resection. Outcomes were evaluated using paired sample t-test and (M) ANOVA. Results: Relief of symptoms sustained in 30/40 patients, within a follow-up of 54 (24-148) months after resection. VAS scores were reduced from 5.5 preoperatively to 1.6 postoperatively (p < 0.001). Patients with left-sided tumours had higher postoperative Pain Rating Index (PRI), compared to patients with right-sided tumours: 15.3 vs. 5.8 (p = 0.018). If patients could reconsider undergoing surgery, 34/38 would again choose resection. Discomfort at the operative scar was the most common complaint: 8/40 patients, all after open surgery, of whom 3/40 had an incisional hernia. 7/40 patients had a laparoscopic resection. Conclusion: Resection relieved symptoms in 30/40 patients. The operative scar was a frequent source for remaining postoperative complaints, suggesting an advantage for a laparoscopic approach when feasible. [ABSTRACT FROM AUTHOR]

Background: Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will continue the resection while others abort the exploration. Methods: A systematic search was performed in PubMed, EMBASE and Cochrane Library for studies investigating survival in patients with intra-operatively detected hepatic-artery or para-aortic LNM. Survival was stratified for node positive (N1) disease. Results: After screening 3088 studies, 13 studies with 2045 patients undergoing pancreatoduodenectomy were included. No study reported survival data after detection of LNM and aborted surgical exploration. In 110 patients with hepatic-artery LNM, median survival ranged between 7 and 17 months. Estimated pooled mean survival in 84 patients with hepatic-artery LNM was 15 [95%CI 12-18] months (13 months in PDAC), compared to 19 [16-22] months in 270 patients with N1-disease without hepaticartery LNM (p = 0.020). In 192 patients with para-aortic LNM, median survival ranged between 5 and 32 months. Estimated pooled mean survival in 169 patients with para-aortic LNM was 13 [8-17] months (11 months in PDAC), compared to 17 (6-27) months in 506 patients with N1-disease without para-aortic LNM (p < 0.001). Data on the impact of (neo)adjuvant therapy on survival were lacking. Conclusion: Survival after pancreatoduodenectomy in patients with intra-operatively detected hepaticartery and especially para-aortic LNM is inferior to patients undergoing pancreatoduodenectomy with other N1 disease. It remains unclear what the consequence of this should be since data on (neo-) adjuvant therapy and survival after aborted exploration are lacking. [ABSTRACT FROM AUTHOR]