Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article

Extensive cytogenetic heterogeneity in a benign retroperitoneal schwannoma

A benign retroperitoneal schwannoma from a patient without prior exposure to radiotherapy or chemotherapy was analyzed by chromosome banding after short-term culture. An extensive intratumor heterogeneity in the form of 29 karyotypically related as well as unrelated clones was found. The aberrant clones were diploid or near-diploid and displayed both numerical and structural changes. All chromosomes, except 11, 16, and 20, were affected. Numerical changes included trisomies X, 7, 9, 17, and 18, and monosomies 13 and 18. No clonal loss of chromosome 22, the most characteristic abnormality in schwannomas of other locations, was, however, detected. The structural aberrations resulted in a total of 58 chromosomal breakpoints, with chromosomes 18, 1, and 15 participating in rearrangements most frequently, followed by chromosomes 14, 2, and 22. A striking finding was the clonal involvement of 18p11 in eight rearrangements affecting different chromosomes, suggesting alteration of telomeric function. The molecular mechanisms underlying the observed massive polyclonality in the schwannoma, particularly the presence of cytogenetically unrelated clones, are unknown and probably heterogeneous

Potentially fatal bleeding in acute pancreatitis: Pathophysiology, prevention, and treatment

INTRODUCTION: Massive bleeding may complicate the course of either acute or chronic pancreatitis. Although the latter is more frequently involved when bleeding occurs in the acute form, a poorer prognosis is to be expected. Abscess, severe inflammation, regional necrosis, and pseudocysts may cause major vessel erosion, with or without pseudoaneurysm formation, whose eventual rupture may result in massive bleeding into the gastrointestinal tract, retroperitoneum, and peritoneal cavity. AIMS: To define the most important pathophysiologic mechanisms and factors that might contribute to a better understanding, better prevention, and more efficient treatment of severe hemorrhage complicating acute necrotizing pancreatitis. Awareness of high-risk conditions occurring during the natural evolution of the disease (from extensive local severe enzymatic damage to late septic sequelae), avoidance of a too early and too aggressive approach to sterile pancreatic necrosis, and providing prompt and effective treatment of local septic complications, when they occur, are crucial steps for bleeding prevention. METHODOLOGY: Forty-four cases of severe bleeding following acute pancreatitis that were reported during the last decade since 1992 (including the six cases reported here) are reviewed, analyzed, and summarized. RESULTS: The overall mortality rate was 34.1%. Splenic artery, portal vein, spleen, and unspecified peripancreatic vessels were the most commonly involved sources of bleeding, with associated mortality rates of 33.3%, 50.0%, 30%, and 28.5%, respectively. Massive hemorrhage was more frequently associated with severe necrosis, with a mortality rate of 37.9%. CONCLUSION: The increased use of diagnostic and interventional radiology, in association with prompt surgical treatment, appears to be the way to improve survival rates in cases of arterial bleeding. Venous bleeding due to lesion of major peripancreatic veins or diffuse bleeding represents a therapeutic challenge, and treatment of these conditions should be tailored to the individual case, as no general rule can be suggested. In extreme cases, open packing or salvage emergency pancreatectomy may represent the only chances for survival

Rectal carcinoma: double-contrast MR imaging for preoperative staging

PURPOSE: To evaluate and compare the imaging findings and staging of rectal carcinoma by using conventional magnetic resonance (MR) imaging, MR imaging with an enema of superparamagnetic ferristene-based contrast material, and MR imaging with an enema of ferristene solution plus intravenous injection of gadodiamide. MATERIALS AND METHODS: Twenty-nine patients (17 women, 12 men; age range, 39-91 years) referred with a diagnosis of rectal carcinoma were examined. Analysis of the rectal wall and staging of the tumor were performed. In all patients, the MR imaging findings were correlated with the histopathologic findings. RESULTS: The contrast material enema caused distention of the rectum and an intraluminal signal void, whereas the gadodiamide injection caused enhancement of the mucosa on T1-weighted images. This enhancement enabled evaluation of the normal rectal wall and differentiation of the mucosa, tunica muscularis, and perirectal space, which was not possible on the nonenhanced images. Double-contrast (ferristene solution plus gadodiamide) MR imaging was superior to imaging with only ferristene-based contrast material and had a sensitivity of 100%, specificity of 70%, and accuracy of 90% in distinguishing tumor stages worse than Dukes A. CONCLUSION: Double contrast material-enhanced MR imaging enables accurate rectal carcinoma staging, which is not possible at nonenhanced imaging

Total parenteral nutrition influences both endocrine and exocrine function of rat pancreas

The aim of this study was to examine the effect of total parenteral nutrition (TPN) on the endocrine and exocine function of the pancreas. Endocrine function was investigated using an intravenous glucose tolerance test (IGTT) in rats with TPN for 7 or 14 days. Exocrine function was evaluated by measuring amylase secretion from isolated acini as well as pancreatic weight, water content, protein, and enzymes after 7 days of TPN. When the TPN rats were compared with the controls, the glucose tolerance curve after an IGTT was unchanged, the basal plasma insulin levels were slightly lower and the insulin secretory response to intravenous glucose was markedly impaired. No differences could be seen between the insulin response after 7 days and that after 14 days of TPN. The weight of pancreas, the total content and concentration of pancreatic protein, and the total amylase content of the pancreas were lower, whereas the total content of both chymotrypsin and trypsin was higher. The concentration of DNA remained intact, whereas the total DNA content decreased. The levels of lipolytic enzymes, except for carboxylesterlipase, were unaffected. After TPN treatment, the insulin secretory response to glucose is impaired, the exocrine pancreas is hypoplastic and the storage pattern of pancreatic exocrine enzymes is altered