Routine MRI With DWI Sequences to Detect Liver Metastases in Patients With Potentially Resectable Pancreatic Ductal Carcinoma and Normal Liver CT: A Prospective Multicenter Study.

OBJECTIVE: The purpose of this study was to evaluate the performance of systematic MRI with DWI for the detection of liver metastases (LM) in patients with potentially resectable pancreatic ductal carcinoma and normal liver findings at CT. SUBJECTS AND METHODS: Patients with potentially resectable pancreatic ductal carcinoma and a normal liver at CT were enrolled in a prospective multicenter study between March 2011 and July 2013 and underwent preoperative MRI. The reference standard was pathologic analysis of detected hepatic lesions. RESULTS: A total of 118 patients were enrolled. MRI depicted liver lesions that were not visible at CT in 16 patients. All lesions were visualized both with and without DWI. Lesions were LM in 12 (10.2%) patients and were confirmed in seven patients by preoperative biopsy, four by intraoperative frozen section, and one at 6-month follow-up evaluation after pancreatic resection. All but one liver metastatic lesion diagnosed with MRI were smaller than 10 mm. Four of 118 (3.4%) patients had a false-positive diagnosis of LM at MRI and remained LM free after a follow-up period of 24 months or longer. Three of 102 (2.9%) patients with normal MRI findings had subcapsular LM that were diagnosed intraoperatively. At follow-up, 99 of 118 (83.9%) patients were LM free after a mean of 24 months. The patient-based sensitivity of MRI for the detection of LM was 80.0% (95% CI, 51.9-95.7%); specificity, 96.1% (95% CI, 90.4-98.9%); positive predictive value, 75.0% (95% CI, 47.6-92.7%); and negative predictive value, 97.1% (95% CI, 91.6-99.4%). CONCLUSION: Compared with CT, preoperative MRI improves the detection of LM in patients with potentially resectable pancreatic ductal carcinoma and may change management and the rate of unnecessary laparotomy and pancreatectomy for 10% of patients.

Structural and Socio-Spatial Determinants Influencing Care and Survival of Patients with a Pancreatic Adenocarcinoma: Results of the PANDAURA Cohort.

Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients' diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers' expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR<5 surgeries/year = 2.236 and HR5-20 surgeries/year = 1.215 versus centers with > 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients' care and outcomes. However, delays of care did not impact patient survival.

Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database.

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient's outcome.

[Maintenance therapy for chronic hepatitis C]. / Traitement d'entretien.

Therapy of chronic hepatitis C presently achieves 60% of sustained virological response, with clear on improvement of liver histology. Failure to eradicate HCV infection does not mean that the patient is non-responsive to therapy and indeed most patients improve biochemically and histologically. The objective of maintenance therapy is therefore to reduce fibrosis progression and its complications. Meta-analysis of 4 registration pivotal trials revealed that 40% of patients who failed to clear HCV at the end of therapy, improved histologically. 3 large long term prospective studies in mostly advanced patients have also addressed the issue of maintenance therapy: HALT-C, COPILOT, EPIC 3. Interim analysis at 2 years of the COPILOT study in particular reveals that only 20% patients receiving low dose peg-interferon versus 39% in the placebo colchicine group reached complication end points. Prospective and retrospective studies, controlled or not, do also indicate a significant trend towards reduced incidence of HCC in patients receiving long term interferon therapy. Potent new anti-HCV small molecules will soon become available and will undoubtedly increase dramatically the cure rate. It is critical therefore for the moment to protect as many patients as possible from irreversible deterioration.

[Ano-rectal symptoms, related to Epstein-Barr Virus-Associated Burkitt's lymphoma in an immunocompetent patient]. / Manifestations anorectales, en rapport avec un lymphome de Burkitt associé au virus Epstein Barr, chez une malade immunocompétente.

We report the case of an immunocompetent 23-year-old Caucasian woman, with symptoms including rectal bleeding, tenesmus and epreint, 6 months after an anal sexual trauma. The rectal examination showed a hardened, inflammatory and painful anal margin, associated with stenosis of the anal canal, suggesting abscess. The neurological examination showed numbing of the chin. Pelvic MRI and CT scan confirmed a bulky posterior tissular pelvic mass more than 7 cm in diameter, infiltrating the rectum and the anal canal. Final diagnosis confirmed by biopsy performed during rectosigmoidoscopy was an Epstein-Barr Virus-Associated Burkitt's lymphoma. Chemotherapy resulted in rapid regression of the tumoral mass.

Estimation of the prevalence and incidence of chronic pancreatitis and its complications.

UNLABELLED: Incidence and prevalence of chronic pancreatitis (CP) are poorly known and prospective nationwide epidemiologic estimation has never been performed. AIMS: To estimate prospectively national incidence and prevalence of patients attending gastroenterologists for CP in France. PATIENTS AND METHODS: Study was proposed to all of the French gastroenterologists (N=3215) of whom 753 accepted to participate (24% private, 40% hospital and 36% both). Were included all patients suffering from proved or suspected CP, from 04-2003 to 07-2003. Certain diagnostic criteria were pancreatic calcifications, ductal or histological abnormalities. For all of non-responder gastroenterologists, a tracking system was used (mail or by phone). RESULTS: A total of 456 gastroenterologists returned at least 1 case on 1748 patients. Median patient age was 51 years; sex-ratio was 5.07. Median duration between the first CP sign and the inclusion was 41 months. CP cause was alcoholism (84%), hereditary (1%), cystic fibrosis (1%), idiopathic (9%), other (6%). CP diagnosis was certain in 77%: calcifications (85%), ductal abnormalities (57%), and histology (8%). CP symptoms were: chronic abdominal pain (53%), acute pancreatitis episodes (67%), pseudocysts (40%), bi-liary tract compression (21%), diabetes mellitus (32%), pancreatic exocrine insufficiency (36%). Maximal annual incidence was 4,646 (crude annual incidence: 7.7 per 100,000; 12.9 in male; 2.6 in female) and prevalence was 15,832 cases (crude prevalence: 26.4 per 100,000; 43.8 in male; 9.0 in female). CONCLUSION: New CP patients attending gastroenterologists are about 5,000 a year. CP prevalence is about 16,000 patients (in France: 60,400,000 inhabitants). Frequency of main complications is close to hospital series, confirming that results issued from these centers are not or a few biased.

Serotonin secretion by human carcinoid BON cells.

BON cells are human carcinoid cells that secrete serotonin (5-HT) and various peptides. Secretion of [(3)H]5-HT by cell cultures was investigated. Acetylcholine (Ach) stimulated secretion through a somatostatin-sensitive muscarinic pathway, whereas isoproterenol was inefficient. [(3)H]5-HT secretion also was induced by Ca(2+) in the presence of the ionophore A-23187 or after digitonin permeabilization. These two processes were insensitive to stomatostatin. Ba(2+) induced an efficient somatostatin-sensitive [(3)H]5-HT secretory response. Secretion also was analyzed at the single-cell level, using carbon fiber amperometry and evanescent-field fluorescence microscopy, after labeling the secretory vesicles by transfection of the cells with a NPY-GFP construct. Both techniques revealed slow kinetics of secretory responses, suggesting that ready-to-fuse vesicles do not accumulate in these cells. Single secretory vesicles were imaged either in resting conditions or after addition of Ca(2+) ions to digitonin-permeabilized cells. The three-dimensional movements of the vesicles before exocytosis were analyzed. The mean velocity of vesicles that released their content was lower than that of silent ones. Even in the case of mobile vesicles, exocytosis often was preceded by a period of arrest lasting at least 15 seconds, consistent with a docking/priming step.

Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors.

BACKGROUND AND AIMS: In many malignant tumors, intratumoral microvascular density (MVD) has been suggested to be a prognostic parameter. We aimed to provide a quantitative evaluation of intratumoral microvascular density in a large series of resected endocrine tumors of the pancreas and to evaluate the potential prognostic significance of this parameter. METHODS: Eighty-two tumors from 77 patients have been studied. MVD was evaluated by 2 observers after CD34 immunostaining and correlated with the following parameters: WHO classification, hormonal profile, tumor size, vascular endothelial growth factor expression, occurrence of metastasis, duration of survival. RESULTS: MVD ranged from 5 to 92 vessels/field. MVD was significantly higher in well-differentiated benign endocrine tumors than in tumors of uncertain behavior and in carcinomas. No close correlation was found between MVD and the hormonal profile. MVD was significantly higher in tumors characterized by the following histoprognostic parameters: size <2 cm, proliferation index <2%, no evidence of metastasis. No close correlation was observed between MVD and VEGF expression. Finally, a MVD <30 vessels/field was associated with the occurrence of metastasis in tumors <2 cm and/or with a proliferation index <2% and with a significantly shorter survival after surgery. CONCLUSIONS: The quantitative analysis of microvessel density in pancreatic endocrine tumors may identify patients who, despite favorable conventional histoprognostic factors, are at risk of unfavorable evolution.