Pathogenesis of duct hyperplasia in the pancreas

Causative factors in duct hyperplasia were histologically examined by using 1,388 autopsied pancreases. Duct hyperplasia was frequent in pancreases having primary carcinoma and in those having necrotizing pancreatitis, but it was not frequent in those with interstitial pancreatitis, ductal pancreatitis, and other disorders. Duct hyperplasia was almost always found in ducts which connected with small ducts having a feature of adenomatous hyperplasia or ductular aggregation in foci of intralobular fibrosis. A histologic examination revealed that these fibrous foci are likely the vestiges of fat necrosis, mostly of a subclinical one.     

Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas

Growth hormone (GH) secretion declines during normal aging along with reproductive activity in mammalian species. Various behavioral changes also occur in aged animals. In these experiments we have studied the effects of GH administration on behavioral and endocrine alterations exhibited by aged (18 months old) female rats of the Sprague-Dawley strain. Animals were selected showing at least 2 weeks of cornified vaginal smears (constant estrous) and treated with GH (0.1 mg/kg SC) daily for 8 weeks. Vaginal smears performed during the drug treatment revealed a recovery of estrous cycle in 60% of animals. GH treatment was also followed by an increased acquisition of shuttle-box active avoidance behavior and a facilitated retention of passive avoidance response. Compared to saline-injected controls, female rats treated with GH also exhibited a decrease of novelty-induced excessive grooming. The endocrine pattern of GH-treated aged female rats revealed a decrease in plasma prolactin levels and an increase in luteinizing hormone and 17 beta-estradiol levels as compared to those of control animals. These results support the concept that behavioral and endocrine alterations occurring in aging are not irreversible and that GH may interfere with these changes probably by means of its trophic action on different target organs.     

Ventral duct pancreaticolithiasis in pancreas divisum

Pancreas divisum, partial or nonfusion of the dorsal and ventral pancreatic ductal systems, affects up to 10 per cent of the population. Approximately 25 per cent of patients with pancreas divisum will develop complications such as recurrent pancreatitis as a consequence of stenosis of the minor papilla with altered dorsal duct drainage. Surgical and endoscopic therapy usually include minor papilla sphincterotomy or sphincteroplasty to facilitate drainage of the dorsal ductal system. The following case represents an unusual complication of pancreas divisum with primarily ventral duct disease and pancreaticolithiasis.     

Influence of corticotropin-releasing factor on pancreatic and islet blood flow in different regions of the rat pancreas

Corticotropin-releasing factor (CRF) has previously been shown to selectively dilate the mesenteric vascular bed, without affecting other vascular beds. Pancreatic blood flow and islet blood flow were therefore measured separately with a microsphere technique in the two regions of the rat pancreas perfused by the superior mesenteric artery (SMA) or celiac artery (CA) respectively. Intravenous infusion of CRF (0.25 microgram/kg b.w./min) caused an increase in both whole pancreatic blood flow and islet blood flow in the region of the pancreas perfused by the SMA. The fraction of whole pancreatic blood flow diverted through the islets in this part of the pancreas was, however, unaffected by CRF infusion (approximately 10%). CRF did not change either pancreatic or islet blood flow in the CA-perfused part of the pancreas, and did not affect the release of insulin.     

Intraluminal brachytherapy in the treatment of pancreas and bile duct carcinoma

PURPOSE: A new method of palliation of malignant obstructive jaundice is presented. METHODS AND MATERIALS: Twelve patients with carcinoma of the extrahepatic bile ducts (EHBD-five patients) or pancreatic head (PH-seven patients) received radiation therapy between 1988 and 1991. Percutaneous transhepatic biliary drainage was performed in four EHBD patients and an endoprosthesis was placed during endoscopic retrograde cholangiopancreatography (ERCP) in the other eight patients. All 12 received intraluminal brachytherapy (ILBT): 20-50 Gy calculated at 1 cm from the Iridium-192 (192Ir) wire. In four PH patients the source was placed in the duct of Wirsung; in the other eight patients ILBT was performed via the common bile duct. Five of the seven PH patients and one of the five EHBD patients received External Beam Radiation Therapy (EBRT): 26-50 Gy, alone or with concomitant 5-Fluorouracil (5-FU). RESULTS: Cholangitis occurred in six patients. Three PH patients treated with EBRT+ILBT developed gastrointestinal toxicities. With a minimum follow-up of 18 months, median survival times were 14 months (EHBD) and 11.5 months (PH); one of the seven PH patients is alive (29 months) and two of the EHBD patients are alive (18 and 43 months). All patients had satisfactory control of jaundice. CONCLUSIONS: The results in the EHBD patients suggest that the addition of ILBT after biliary drainage prolongs survival. Further experience is necessary to determine whether ILBT in the common bile duct and/or in the duct of Wirsung may be, in PH patients, an alternative boost technique to Interstitial Brachy-therapy (IBT) or Intraoperative Electron Beam Radiation Therapy (IOEBRT).     

Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bile duct epithelium, rather than through hepatocytes. Measurements of cAMP, cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide directly activates Na+-K+-2Cl- cotransport, rather than other transporters or conventional second-messenger systems that link to secretory pathways in these cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions. These findings suggest that bile duct epithelia may represent an important new therapeutic target for treatment of cholestatic disorders.     

Wirsung's duct and chronic pancreatitis. Changes in the morphology of the pancreatic ducts after pancreatic duct shunts. 23 cases followed-up

The authors study in chronic pancreatitis the morphology of Wirsung's duct in 31 patients who had undergone repeated operations, 23 of them were submitted in a first stage to an anastomosis between the pancreatic duct and the digestive tract. The main causes of failure were obstructions of the anastomosis, biliary complications and continuation of the pancreatic disease. The difference in prognosis between pancreatitis with a dilated pancreatic duct, and those with a filiform duct, is perhaps due to lesions of different histological appearance and course. The best results were obtained in patients able to give up alcohol and in whom it was possible to carry out a broader anastomosis on a dilated and unobstructed pancreatic duct.     

Hemangioendothelioma of the pancreas obstructing the common bile duct and duodenum

A 6-mo-old male with a hemangioendothelioma of the pancreas obstructing the common bile duct and duodenum required temporary bypass of these structures while awaiting involution of the tumor treated primarily by corticosteroids and radiation therapy.     

Definitive surgery for duct cell carcinomas of the pancreas

BACKGROUND AND DESIGN: As changes in the health care system aim to reduce the cost of medical care, physicians need to understand and be able to justify their reasons for referring patients. To learn the basis for making referrals, we asked 116 referring physicians why they made referrals to one university-based physician. We also assessed the referring physicians' satisfaction. RESULTS: A total of 112 of the 116 physicians responded in reference to 114 patients. The responses fit into five categories. Fifty of 114 patient were referred for therapy; 16 patients, for a diagnosis; and 16, for a combination of diagnosis and therapy. Other reasons in descending order of frequency were (1) a nondermatologist referring the patient to a dermatologist, (2) self-referral, ie, the patient was not referred by the physician, and (3) the patient's personality was difficult. The referring physicians were satisfied in 94 instances. CONCLUSIONS: The most frequent reason for referral was for therapy. This observation may be generally true for many physicians, since it is consistent with results of two other studies, in different fields, that we were able to find. Eighty-two percent of referrals were satisfactory to the referring physicians. Most of the physicians who were unsatisfied with the referral process stated they had not received a follow-up letter from the consulted physician.     

Pyloric gland adenoma of the main pancreatic duct

A case of a pyloric gland type adenoma of the main pancreatic duct in a 69-year-old woman is reported. The tumor led to occlusion and cystic dilatation of the main duct in the pancreatic tail. The surgical resection specimen disclosed a polypoid, bilobed mass attached to the wall of the main pancreatic duct by a thin fibrous stalk. Light-microscopic examination revealed a well-demarcated nodule composed of closely packed tubular glands lined by columnar, mucin-secreting cells with abundant clear cytoplasm and basally oriented nuclei. Focal, mild cytologic atypia was seen. Pyloric metaplasia and focal papillary hyperplasia was present in the adjacent ductal epithelium. Periodic acid-Schiff reactions, with and without diastase predigestion, showed reactivity in the tubular glands, whereas alcian blue (pH 2.5) was negative. Immunohistochemical stains for chromogranin, serotonin, somatostatin, and gastrin failed to detect the respective antigens. Genetic analysis using polymerase chain reaction with mutant enrichment and allele specific oligonucleotide hybridization detected a single mutation at codon 12 of K-ras, which changed the wild-type glycine to arginine. This mutation is commonly found in invasive pancreatic ductal carcinomas. Although tumors with microscopic and immunohistochemical features consistent with pyloric gland adenoma have been described in the gallbladder, to our knowledge, this is the first reported case within the pancreatic ductal system. The finding of a K-ras, codon 12 mutation and the presence of focal dysplasia may denote neoplastic potential in association with this lesion.     

Volume-activated chloride currents in pancreatic duct cells

OBJECTIVE: To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue. METHODS: Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads. RESULTS: Treatment with SLN resulted in a time- and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN: Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with high-frequency streaming potential measurements. CONCLUSION: Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.     

Gray-scale ultrasonic properties of the normal and inflamed pancreas

Eighty-seven examinations of the pancreas in 52 patients with acute or chronic pancreatitis and 31 examinations in 31 normal subjects were reviewed. Demonstration of the portal and splenic veins served as a guidepost to the pancreas. The normal pancreas was indistinguishable from the surrounding tissues in a substantial minority of examinations, and the ultrasonic characteristics of the normal pancreas were quite variable. Acute pancreatitis was found to be characterized by swelling, loss of internal echoes, and loss of distinction between the pancreas and splenic vein. In 50% of patients with chronic inactive pancreatitis, the pancreas could not be identified. Ultrasound should precede endoscopic retrograde cholangiopancreatography whenever a pseudocyst might be present.     

Flow parameters of the normal arterial duct in the fetus

The increasing interest in arterial duct flow patterns in the fetus warrants the establishment of an accurate range of normal flow parameters throughout gestation. We therefore undertook a prospective echocardiographic study of 181 normal fetuses from the 16th to the 40th week of gestation. Adequate Doppler interrogation of the duct was obtained in 71% of the fetuses examined. Peak gradient, mean gradient and flow velocity integral in systole and diastole were digitized. The peak systolic gradient throughout pregnancy measured 2.7 +/- 1.4 mmHg with a slight tendency to increase with gestational age (r = 0.58). The peak ratio, defined as peak systolic gradient divided by peak diastolic gradient (28.1 +/- 14.9), did not vary significantly with gestational age. This time-independent index complements peak systolic flow in the assessment of normal and abnormal ductal flow. The definition of the normal range for ductal flow parameters, based on this relatively large fetal population, should facilitate the accurate diagnosis of fetal duct constriction.     

Three-dimensional structure of the yeast ribosome

The 80S ribosome from Saccharomyces cerevisiae has been reconstructed from cryo electron micrographs to a resolution of 35 A. It is strikingly similar to the 70S ribosome from Escherichia coli, while displaying the characteristic eukaryotic features familiar from reconstructions of ribosomes from higher eukaryotes. Aside from the elaboration of a number of peripherally located features on the two subunits and greater overall size, the largest difference between the yeast and E.coli ribosomes is in a mass increase on one side of the large (60S) subunit. It thus appears more elliptical than the characteristically globular 50S subunit from E.coli. The interior of the 60S subunit reveals a variable diameter tunnel spanning the subunit between the interface canyon and a site on the lower back of the subunit, presumably the exit site through which the nascent polypeptide chain emerges from the ribosome.     

Combined resection of the pancreas and portal vein for pancreatic cancer

Between March 1976 and December 1992, 137 (57 per cent) of 239 patients with pancreatic duct cell cancer underwent resection; 79 (58 per cent) of the 137 had combined resection of the pancreas and portal vein. Sixty-three of the 79 patients underwent resection of the portal vein alone; six died (mortality rate 10 per cent). The mortality rate was the same as that in 58 patients with no resection of the portal vein. In the remaining 16 patients adjacent arteries were also resected, with seven deaths. Of patients with resection of the portal vein alone who underwent curative resection, four survived more than 5 years, accounting for nearly half of the nine 5-year survivors. Combined resection of the pancreas and portal vein is associated with both an increased resectability rate and improved long-term survival.