Routine contrast-enhanced CT is insufficient for TNM-staging of duodenal adenocarcinoma.

PURPOSE: Adequate TNM-staging is important to determine prognosis and treatment planning of duodenal adenocarcinoma. Although current guidelines advise contrast-enhanced CT (CECT) for staging of duodenal adenocarcinoma, literature about diagnostic tests is sparse. METHODS: In this retrospective single-center cohort study, we analyzed the real life performance of routine CECT for TNM-staging and the assessment of resectability of duodenal adenocarcinoma. Intraoperative findings and pathological staging served as reference standard for resectability, T-, and N-staging. Biopsies, 18FDG-PET-CT, and follow-up were used as the reference standard for M-staging. RESULTS: Fifty-two consecutive patients with duodenal adenocarcinoma were included, 26 patients underwent resection. Half of the tumors were isodense to normal duodenum on CECT. The tumor was initially missed in 7/52 patients (13%) on CECT. The correct T-stage was assigned with CECT in 14/26 patients (54%), N-stage in 11/26 (42%), and the M-stage in 42/52 (81%). T-stage was underestimated in (27%). The sensitivity for detecting lymph node metastases was only 24%, specificity was 78%. Seventeen percent of patients had indeterminate liver or lung lesions on CECT. Surgery with curative intent was started in 32 patients, but six patients (19%) could not be resected due to unexpected local invasion or metastases. CONCLUSION: Radiologists and clinicians have to be aware that routine CECT is insufficient for staging and determining resectability in patients with duodenal adenocarcinoma. CECT underestimates T-stage and N-stage, and M-stage is often unclear, resulting in futile surgery in 19% of patients. Alternative strategies are required to improve staging of duodenal adenocarcinoma. We propose to combine multiphase hypotonic duodenography CT with MRI.

Continuity of care experienced by patients in a multi-institutional pancreatic care network: a pilot study.

BACKGROUND: Over the past decades, health care services for pancreatic surgery were reorganized. Volume norms were applied with the result that only a limited number of expert centers perform pancreatic surgery. As a result of this centralization of pancreatic surgery, the patient journey of patients with pancreatic tumors has become multi-institutional. To illustrate, patients are referred to a center of expertise for pancreatic surgery whereas other parts of pancreatic care, such as chemotherapy, take place in local hospitals. This fragmentation of health care services could affect continuity of care (COC). The aim of this study was to assess COC perceived by patients in a pancreatic care network and investigate correlations with patient-and care-related characteristics. METHODS: This is a pilot study in which patients with (pre) malignant pancreatic tumors discussed in a multidisciplinary tumor board in a Dutch tertiary hospital were asked to participate. Patients were asked to fill out the Nijmegen Continuity of Care-questionnaire (NCQ) (5-point Likert scale). Additionally, their patient-and care-related data were retrieved from medical records. Correlations of NCQ score and patient-and care-related characteristics were calculated with Spearman's correlation coefficient. RESULTS: In total, 44 patients were included (92% response rate). Pancreatic cancer was the predominant diagnosis (32%). Forty percent received a repetition of diagnostic investigations in the tertiary hospital. Mean scores for personal continuity were 3.55 ± 0.74 for GP, 3.29 ± 0.91 for the specialist and 3.43 ± 0.65 for collaboration between GPs and specialists. Overall COC was scored with a mean 3.38 ± 0.72. No significant correlations were observed between NCQ score and certain patient-or care-related characteristics. CONCLUSION: Continuity of care perceived by patients with pancreatic tumors was scored as moderate. This outcome supports the need to improve continuity of care within multi-institutional pancreatic care networks.

Diagnostic accuracy of contrast-enhanced diffusion-weighted MRI for liver metastases of pancreatic cancer: towards adequate staging and follow-up of pancreatic cancer - DIA-PANC study: study protocol for an international, multicenter, diagnostic trial.

BACKGROUND: At the time of surgery, approximately 10-20% of the patients with pancreatic cancer are considered unresectable because of unexpected liver metastasis, peritoneal carcinomatosis or locally advanced disease. This leads to futile surgical treatment with all the associated morbidity, mortality and costs. More than 50% of all liver metastases develop in the first six months postoperatively. These (subcentimeter) liver metastases are most likely already present at the time of diagnosis and have not been identified pre-operatively, due to the poor sensitivity of routine preoperative contrast-enhanced CT (CECT). METHODS: The DIA-PANC study is a prospective, international, multicenter, diagnostic cohort study investigating diffusion-weighted, contrast-enhanced MRI for the detection of liver metastases in patients with all stages of pancreatic cancer. Indeterminate or malignant liver lesions on MRI will be further investigated histopathologically. For patients with suspected liver lesions without histopathological proof, follow up imaging with paired CT and MRI at 3-, 6- and 12-months will serve as an alternative reference standard. DISCUSSION: The DIA-PANC trial is expected to report high-level evidence of the diagnostic accuracy of MRI for the detection of liver metastases, resulting in significant value for clinical decision making, guideline development and improved stratification for treatment strategies and future trials. Furthermore, DIA-PANC will contribute to our knowledge of liver metastases regarding incidence, imaging characteristics, their number and extent, and their change in time with or without treatment. It will enhance the worldwide implementation of MRI and consequently improve personalized treatment of patients with suspected pancreatic ductal adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03469726 . Registered on March 19th 2018 - Retrospectively registered.

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

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

A Risk Assessment of Factors for the Presence of Angiodysplasias During Endoscopy and Factors Contributing to Symptomatic Bleeding and Rebleeds.

BACKGROUND: Few studies have assessed factors associated with angiodysplasias during endoscopy or factors associated with symptomatic disease. AIMS: To evaluate risk factors for the presence of and contribution to symptomatic disease in patients with angiodysplasias. METHODS: We performed a systematic MEDLINE, EMBASE and Cochrane Library search according to the PRISMA guidelines for studies assessing risk factors involved in angiodysplasias detected during endoscopy and factors that lead to anemia or overt bleeding. Study quality was assessed with the Newcastle-Ottawa scale. A risk assessment was performed by selecting risk factors identified by two independent studies and/or by a large effect size. RESULTS: Twenty-three studies involving 92,634 participants were included. The overall quality of the evidence was moderate. Risk factors for the diagnosis of angiodysplasias during endoscopy confirmed by at least two studies were increasing age (OR 1.09 per year, 95% CI 1.04-1.1), chronic kidney disease (OR 4.5, 95% CI 1.9-10.5) and cardiovascular disease (2.9, 95% CI 1.4-6.2). The risk of rebleeds was higher in the presence of multiple lesions (OR 4.2, 95% CI 1.1-16.2 and 3.8, 95% CI 1.3-11.3 and 8.6, 95% CI 1.4-52.6), liver cirrhosis (OR 4.0, 95% 1.1-15.0) and prothrombin time < 30% (OR 4.2, 95% 1.1-15.4) with a moderate effect size. Multiple comorbidities were associated with an increased in-hospital mortality (OR 2.29, 95% CI 1.2-4.3). CONCLUSIONS: This systematic review identified age, chronic kidney disease and cardiovascular disease as the most important risk factors for the diagnosis of angiodysplasias during endoscopy. Multiple lesions increase the risk of recurrent bleeding.

Clips for managing perforation and bleeding after colorectal endoscopic mucosal resection.

INTRODUCTION: The most commonly used treatment for advanced colorectal adenomas is endoscopic mucosal resection (EMR). The increased number of EMRs since the introduction of the screening program for colorectal cancer has resulted in an increase in EMR-related complications. This review summarizes the current knowledge for the use of clips for the treatment and prevention of complications after EMR. AREAS COVERED: The historical development of clips is summarized and their properties are evaluated. An overview is presented of the evidence for therapeutic and prophylactic clipping for bleeding or perforation after EMR in the colon. Several clipping techniques are discussed in relation to the efficacy of wound closure. Furthermore, new techniques that will likely influence the use of clips in the future endoscopic practice, such as endoscopic full-thickness resection (eFTR) are also highlighted. EXPERT COMMENTARY: Most research focuses on prophylactic clipping for delayed bleeding after EMR of large adenomas. We advocate a distance of 0.5-1.0 cm between aligning clips. This focus may likely shift from bleeding to perforation. Here, endoscopic treatment with through-the-scope clips and large-diameter clips may well replace surgery. The future role of clips will also depend on the further development of new endoscopic technologies, such as eFTR.

Improving preoperative detection of synchronous liver metastases in pancreatic cancer with combined contrast-enhanced and diffusion-weighted MRI.

PURPOSE: To explore the value of gadolinium-enhanced MRI combined with diffusion-weighted MRI (Gd-enhanced MRI with DWI) in addition to contrast-enhanced CT (CECT) for detection of synchronous liver metastases for potentially resectable pancreatic cancer. METHODS: By means of a retrospective cohort study we included patients with potentially resectable pancreatic cancer on CECT, who underwent Gd-enhanced MRI with DWI between January 2012 and December 2016. A single observer evaluated MRI and CT and was blinded to imaging, pathology, and surgery reports. Liver lesions were scored in both modalities, using a 3-point scale: 1-benign, 2-indeterminate, 3- malignant (i.e., metastasis). The primary outcome parameters were the presence of liver metastases on Gd-enhanced MRI with DWI and the sensitivity of Gd-enhanced MRI with DWI for synchronous liver metastases. RESULTS: We included 66 patients (42 men, 24 women; median age 65 years, range 36-82 years). In 19 patients, liver metastases were present, which were confirmed by histopathology (n = 12), 18FDG-PET (n = 6), or surgical inspection (n = 1). Gd-enhanced MRI with DWI showed metastases in 16/19 patients (24%), which resulted in a sensitivity of 84% (95% CI 60-97%). Contrast-enhanced MRI showed 156 and DWI 397 metastases (p = 0.051), and 339 were particularly small (< 5 mm). CONCLUSIONS: In this study, Gd-enhanced MRI with DWI detected synchronous liver metastases in 24% of patients with potentially resectable pancreatic cancer on CECT with a sensitivity of 84%. Diffusion-weighted MRI showed a greater number of metastases than any other sequence, particularly small metastases (< 5 mm).

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.

Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40†mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial.

INTRODUCTION: Gastrointestinal angiodysplasias are an important cause of difficult-to-manage bleeding, especially in older patients. Endoscopic coagulation of angiodysplasias is the mainstay of treatment, but may be difficult for small bowel angiodysplasias because of the inability to reach them for endoscopic intervention. Some patients are red blood cell (RBC) transfusion dependent due to frequent rebleeding despite endoscopic treatment. In small cohort studies, octreotide appears to decrease the number of bleeding episodes in patients with RBC transfusion dependency due to gastrointestinal angiodysplasias. This trial will assess the efficacy of octreotide in decreasing the need for RBC transfusions and parenteral iron in patients with anaemia due to gastrointestinal bleeding of small bowel angiodysplasias despite endoscopic intervention. STUDY DESIGN: Randomised controlled, superiority, open-label multicentre trial. PARTICIPANTS: 62 patients will be included with refractory anaemia due to small bowel angiodysplasias, who are RBC transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation. INTERVENTION: Patients will be randomly assigned (1:1) to standard care or 40 mg long-acting octreotide once every 4 weeks for 52 weeks, in addition to standard care. The follow-up period is 8 weeks. MAIN OUTCOME MEASURES: The primary outcome is the difference in the number of blood and iron infusions between the year prior to inclusion and the treatment period of 1 year. Important secondary outcomes are the per cent change in the number of rebleeds from baseline to end point, adverse events and quality of life. ETHICS AND DISSEMINATION: The trial received ethical approval from the Central Committee on Research Involving Human Subjects and from the local accredited Medical Research Ethics Committee of the region Arnhem-Nijmegen, the Netherlands (reference number: 2014-1433). Results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02384122; Pre-results.

Systematic review: periprocedural hydration in the prevention of post-ERCP pancreatitis.

BACKGROUND: With an overall incidence of 3.5%, pancreatitis is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP). Periprocedural hydration may prevent post-ERCP pancreatitis by maintaining pancreatic microperfusion, thereby inhibiting the pancreatic inflammatory response. However, the evidence for periprocedural hydration as a preventive measure is unclear. AIM: To conduct a systematic review to assess the evidence regarding periprocedural hydration as a preventive measure for post-ERCP pancreatitis. METHODS: We searched PubMed and EMBASE databases and adhered to the PRISMA guidelines. We included studies addressing periprocedural hydration as a preventive measure to reduce frequency and severity of post-ERCP pancreatitis. Study quality was assessed by using the MINORS and Cochrane Collaboration's tool. RESULTS: Six studies with a total of 1102 patients were included. Two randomised controlled trials reported a decreased incidence of post-ERCP pancreatitis after hydration: 0% vs. 17% (P = 0.016) and 5.3% vs. 22.7% (P = 0.002). A third trial and two case-controls studies did not report significant differences. Two retrospective studies found that patients with mild post-ERCP pancreatitis had received significantly more fluids during (mean 940 mL vs. 810 mL; P = 0.031) or after ERCP (median 2834 mL vs. 2044 mL; P < 0.02) compared to patients with moderate/severe disease. Adverse events of periprocedural hydration were not reported in any of the included studies. The different methodologies of the included studies precluded a formal data synthesis. CONCLUSIONS: There is some evidence to suggest that hydration affords protection against post-ERCP pancreatitis, but study heterogeneity precludes firm conclusions. Adequately powered randomised trials are needed to evaluate the preventive effect of periprocedural hydration.

Azathioprine or mercaptopurine-induced acute pancreatitis is not a disease-specific phenomenon.

BACKGROUND: Several reports suggest an increased rate of adverse reactions to azathioprine in patients with Crohn's disease. AIM: To compare the incidence of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease (IBD) with that in patients with vasculitis. METHODS: This retrospective analysis was performed using data collected in three databases by two university hospitals (241 patients with IBD and 108 patients with vasculitis) and one general district hospital (72 patients with IBD). RESULTS: The cumulative incidence of thiopurine-induced acute pancreatitis in Crohn's disease equalled that of ulcerative colitis (UC) (2.6% vs. 3.7%) and this did not differ from vasculitis patients (2.6% vs.1.9%). In addition, the cumulative incidence of thiopurine-induced acute pancreatitis in UC patients was not different from that in vasculitis patients. In the IBD group, 100% of thiopurine-induced acute pancreatitis patients were women, whereas in the vasculitis group the two observed thiopurine-induced acute pancreatitis cases (n = 2 of 2) concerned were men (P = 0.012). CONCLUSIONS: In this study, the alleged higher cumulative incidence of thiopurine-induced acute pancreatitis in Crohn's disease compared with vasculitis or UC patients was not confirmed. Female gender appears to be a risk factor for developing thiopurine-induced acute pancreatitis in IBD patients.

Recurrent acute biliary pancreatitis: the protective role of cholecystectomy and endoscopic sphincterotomy.

BACKGROUND: Recurrent attacks of acute biliary pancreatitis (RABP) are prevented by (laparoscopic) cholecystectomy. Since the introduction of endoscopic retrograde cholangiopancreaticography (ERCP), several series have described a similar reduction of RABP after endoscopic sphincterotomy (ES). This report discusses the different treatment options for preventing RABP including conservative treatment, cholecystectomy, ES, and combinations of these options as well as their respective timing. METHODS: A search in PubMed for observational studies and clinical (comparative) trials published in the English language was performed on the subject of recurrent acute biliary pancreatitis and other gallstone complications after an initial attack of acute pancreatitis. RESULT: Cholecystectomy and ES both are superior to conservative treatment in reducing the incidence of RABP. Cholecystectomy provides additional protection for gallstone-related complications and mortality. Observational studies indicate that cholecystectomy combined with ES is the most effective treatment for reducing the incidence of RABP attacks. CONCLUSION: From the literature data it can be concluded that ES is as effective in reducing RABP as cholecystectomy but inferior in reducing mortality and overall morbidity. The combination of ES and cholecystectomy seems superior to either of the treatment methods alone. A prospective randomized clinical trial comparing ES plus cholecystectomy with cholecystectomy alone is needed.