Background: Gastrojejunostomy (GJJ) is the most commonly used palliative treatment modality for malignant gastric outlet obstruction. Recently, stent placement has been introduced as an alternative treatment. We reviewed the available literature on stent placement and GJJ for gastric outlet obstruction, with regard to medical effects and costs. Methods: A systematic review of the literature was performed by searching PubMed for the period January 1996 and January 2006. A total of 44 publications on GJJ and stents was identified and reported results on medical effects and costs were pooled and evaluated. Results from randomized and comparative studies were used for calculating odds ratios (OR) to compare differences between the two treatment modalities. Results: In 2 randomized trials, stent placement was compared with GJJ (with 27 and 18 patients in each trial). In 6 comparative studies, stent placement was compared with GJJ. Thirty-six series evaluated either stent placement or GJJ. A total of 1046 patients received a duodenal stent and 297 patients underwent GJJ. No differences between stent placement and gastrojejunostomy were found in technical success (96% vs. 100%), early and late major complications 7% vs. 6% and 18% vs. 17%, respectively) and persisting symptoms (8% vs. 9%). Initial clinical success was higher after stent placement (89% vs. 72%). Minor complications were less frequently seen after stent placement in the patient series (9% vs. 33%), however the pooled analysis showed no differences (OR: 0.75, p = 0.8). Recurrent obstructive symptoms were more common after stent placement (18% vs. 1%). Hospital stay was prolonged after GJJ compared to stent placement (13 days vs. 7 days). The mean survival was 105 days after stent placement and 164 days after GJJ. Conclusion: These results suggest that stent placement may be associated with more favorable results in patients with a relatively short life expectancy, while GJJ is preferable in patients with a more prolonged prognosis. The paucity of evidence from large randomized trials may however have influenced the results and therefore a trial of sufficient size is needed to determine which palliative treatment modality is optimal in (sub)groups of patients with malignant gastric outlet obstruction.

Background: Increasing evidence suggests that diabetes mellitus (DM) is associated with increased cancer incidence and mortality. Several mechanisms involved in diabetes, such as promotion of cell proliferation and decreased apoptosis, may foster carcinogenesis. This study investigated the association between DM and cancer incidence and cancer-specific mortality in patients with breast and colorectal carcinoma. Methods: A meta-analysis of controlled trials, prospective cohort studies and pooled cohort studies published after 2007 was conducted. Embase, PubMed and the Cochrane Library were searched. Summary hazard ratios (HRs) were calculated using a random-effects model. Sensitivity and subgroup analyses were performed to adjust for confounders, mode of DM assessment and follow-up time. Results: Twenty studies were included to investigate the association between DM and breast and colorectal cancer incidence and cancer-specific mortality. The studies predominantly comprised patients with type II DM. The overall HR for breast cancer incidence was 1·23 (95 per cent confidence interval 1·12 to 1·34) and that for colorectal cancer was 1·26 (1·14 to 1·40) in patients with DM compared with those without diabetes. The overall HR was 1·38 (1·20 to 1·58) for breast cancer- and 1·30 (1·15 to 1·47) for colorectal cancer-specific mortality in patients with DM compared with those without diabetes. Conclusion: This meta-analysis indicated that DM is a risk factor for breast and colorectal cancer, and for cancer-specific mortality.

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.

Objective We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals. Design From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit. Results 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001). Conclusion The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

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. 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/m2/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. 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 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)