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Glycogen synthase kinase 3β (GSK3β) is a well-known marker and potential therapeutic target in non-insulin-dependent diabetes mellitus and Alzheimer’s disease. Our recent demonstration that GSK3β has a previously unrecognized role in colorectal cancer facilitates the development of a nonradioisotopic in vitro kinase assay (NRIKA) for detecting GSK3β activity in gastrointestinal cancer cells. The NRIKA uses a sequential combination of immunoprecipitations to isolate GSK3β in sample cells’ lysates, and an in vitro kinase reaction that uses recombinant β-catenin protein (substrate) and nonradioisotopic ATP, followed by immunoblotting to detect β-catenin phosphorylated in serine 33, 37 and/or threonine 41 residues. The NRIKA detected higher expression of active GSK3β in stomach, colon, pancreas and liver cancer cell lines than in human embryonic kidney cells (HEK293) considered nonneoplastic. Inhibition of cancer cell-derived GSK3β activity by GSK3β inhibitors (SB-216763, AR-A014418) was detected by the NRIKA. GSK3β inhibition attenuated survival and proliferation and induced apoptosis in all types of cancer cells but not in HEK293. These findings supported the idea that the pathologic roles of GSK3β are definite and common in various types of cancer. The NRIKA provides a basis for evolving a high-throughput tool for testing substances for GSK3β inhibition, and for screening and identifying novel GSK3β inhibitors with a view to discovering drugs for treatment of cancer as well as non-insulin-dependent diabetes mellitus and Alzheimer’s disease. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically. [ABSTRACT FROM AUTHOR]

We report a rare case of an epidermoid cyst in an accessory spleen at the pancreatic tail with producing CA19-9. A 55-year-old female was admitted to our hospital, Cancer Research Institute, Kanazawa University, for close examination of a cystic lesion at the pancreatic tail and a high serum CA19-9-value (176 U/mL). There were almost no abdominal symptoms related to the cystic lesion. A cystic tumor approximately 3 cm in diameter and composed of multilocular cysts without a protruding portion of the inner surface was found at the pancreatic tail by ultrasound sonography, computed tomography, and magnetic resonance imaging. Endoscopic retrograde pancreatography revealed that the main pancreatic duct shifted at the pancreatic tail and there was no communication between the main pancreatic duct and cystic lesion. Based on a preoperative diagnosis of mucinous cystic tumor, distal pancreatectomy with splenectomy was performed. Histological findings suggested an epidermoid cyst (3.5 × 3.0 cm) originating from an intrapancreatic accessory spleen. Immunohistochemical analysis of CA19-9 in the epidermoid cyst showed clear staining of the inner epithelium of the cyst and amorphous or hyalinous cystic contents. The serum CA19-9 value was confirmed to decline to normal 2 months after resection. Physicians should not forget this disease during differential diagnosis related to pancreatic cystic lesions with elevated levels of serum tumor markers, such as CA19-9 or carcinoembryonic antigen, although this disease is extremely rare. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Autoimmune pancreatitis (AlP) with a mass formation or swollen pancreas located in one or two segments of the gland (focal type AlP) has been reported. The aims of this study were to elucidate the relationship of the disease entity between this focal variant and so-called tumor-forming pancreatitis (TFP) and to describe the clinical and imaging features discriminating focal AlP from pancreatic carcinoma (Pca). METHODS: The clinical, radiologic, and pathologic profiles of nine patients with focal AlP were reviewed retro spectively and compared with those of 11 patients with alcohol-induced TFP and 80 patients with Pca. RESULTS: The patients with focal AlP were predominantly older (mean age 64.7 ± 13.6 yr, range 28-78 yr), male, and presenting with obstructive jaundice or focal pancreatic enlargement accompanied by mild abdominal symptoms. In comparison, the patients with alcohol-induced TFP who were mostly middle-aged (mean age 50.1 ± 7.95 yr, range 39-62 yr), male, and often had attacks of pancreatitis associated with findings of CT scans showing pseudocysts or peripancreatic effusion. Focal AlP usually demonstrated no abnormalities on pancreatograms downstream from the stricture or obstruction and often presented few contrast- filled side branches in the area of main pancreatic duct (MPD) stenosis. These characteristics were similar to the imaging features of Pca. Significant factors differentiating focal AlP from Pca were lower serum levels of CA19-9, homogeneous delayed enhancement evident in dynamic CT scans, and ERCP findings exhibiting a longer steno sed MPD and a thinner MPD upstream from the stricture. CONCLUSIONS: Focal AlP is associated with clinical and radiologic features that are different from those of alcohol-induced TFP. In TFP there are two causative factors, namely, AlP and alcohol-induced chronic pancreatitis. Differential diagnosis of focal AlP from Pca seems to be possible in many cases by evaluating imaging findings such as dynamic CT and ERCP, although focal AlP sometimes shows clinical and radiologic features similar to those of Pca. [ABSTRACT FROM AUTHOR]

Pancreatitis-associated protein (PAP) is almost absent in normal pancreas, but is strongly induced in acute pancreatitis. PAP mRNA is also expressed in cancer cells, including pancreatic ductal adenocarcinoma. However, the clinicopathological significance of PAP in human pancreatic cancer is not clear. We examined PAP expression in pancreatic tissues from individuals with pancreatic ductal adenocarcinoma using immunohistochemistry. PAP was overexpressed in 79% (30 of 38) of pancreatic ductal adenocarcinoma, 19% (7 of 36) of chronic pancreatitis, and 29% (2 of 7) of mucinous cystadenoma. PAP was found in malignant ductular structures in pancreatic carcinomas as well as in benign proliferating ductules and acinar cells in chronic pancreatitis. It was not expressed in normal pancreas. The incidence of PAP overexpression was significantly higher in pancreatic cancer than in the other pancreatic diseases (P < 0.01). PAP overexpression was significantly correlated with nodal involvement, distant metastasis (P < 0.05), and short survival (P < 0.01) in pancreatic cancer. These results suggest that overexpression of PAP in human pancreatic ductal adenocarcinoma indicates tumor aggressiveness. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the therapeutic effects of the carboxamide derivative IS-741 on spontaneous chronic pancreatitis (CP) in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed with MB-3, and IS-741 (0.012% in MB-3) was orally administered for 12 weeks. Cytokine-induced neutrophil chemoattractant (CINC), interleukin (IL) -6, pancreatitis-associated protein (PAP), and p8 mRNAs in the pancreas were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Histological examination of the pancreas showed that hemorrhage, interstitial edema, and inflammatory cell infiltration were markedly less severe at 12 weeks, while fibrosis and acinar degeneration were also milder at 16 weeks, in the IS-741-treated rats than in untreated rats. The above-mentioned genes were significantly suppressed in IS-741-treated rats at 12 weeks. Our results show that IS-741 exerts a potentially therapeutic effect on experimental CP by suppressing the expressions of the proinflammatory cytokines (IL-6 and CINC) and pancreatic acute phase proteins (PAP and p8). [ABSTRACT FROM AUTHOR]

The p8 gene is barely expressed in the normal pancreas, but is overexpressed in acute pancreatitis. To elucidate the dynamic expression of p8 mRNA and its significance in the course of chronic pancreatitis, we investigated the p8 expression in spontaneous chronic pancreatitis in the WBN/Kob rat as well as in humans and arginine-treated rat pancreatic acinar AR4-2J cells. p8 mRNA was significantly increased at 12 weeks when chronic pancreatitis first appeared in the WBN/Kob rats. p8 was immunolocalized in the acinar cell nuclei. Acinar cell apoptosis was significantly increased at 12 and 20 weeks in the WBN/Kob rats. In AR4-2J cells, p8 mRNA was significantly induced at 4 hr after arginine addition. Apoptosis of AR4-2J cells was not increased during the strong expression of p8 mRNA. These results suggest that p8 is induced in the acinar cells during chronic pancreatitis as the self-defence mechanism against proapoptotic insults. [ABSTRACT FROM AUTHOR]

We report a 76-year-old man with hepatic peribiliarycysts diagnosed by magnetic resonance cholangiopancreatography(MRCP). On his first admission, in 1991,the patient was misidentified as having localized dilatationof the left intrahepatic bile ducts, from the ultrasound(US) and computed tomographic (CT) findings,or primary sclerosing cholangitis from endoscopic retrogradecholangiopancreatography (ERCP). However,US and CT in 1998 suggested worsening of the lesions.MRCP was performed for the first time, revealing hepaticperibiliary cysts in the hepatic hilum and along theleft hepatic ducts. Drip infusion cholangiography(DIC)-CT confirmed the extraluminal compression of the bile ducts, caused by the cysts, without an influx ofcontrast medium into the hepatic peribiliary cysts. Retrospectiveevaluation showed increases in the size andnumber of the cysts in 1998 compared with the findingsin 1996. [ABSTRACT FROM AUTHOR]

The Fas/Fas ligand (FasL) system is suggested to be correlated to the onset of inflammation and apoptosis in various diseases. However, whether Fas and FasL are expressed in chronic pancreatitis is unknown. The aim of this study was to examine the expression of the Fas/FasL system and to analyze its correlation with apoptosis in a spontaneous chronic pancreatitis model (the WBN/Kob rat). Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3). Different groups of rats were killed every four weeks, and pancreata were histopathologically examined. Fas and FasL mRNAs in the pancreas were detected with a reverse transcription-polymerase chain reaction method. The cellular localization of Fas and FasL mRNA and protein was determined with in situ hybridization (ISH) and immunohistochemistry (IHC). Apoptosis was detected with a terminal deoxynucleotidyltransferase-mediated method. Fas and FasL mRNA were expressed when the pancreas was still pathologically normal, and showed a biphasic peak at 12 and 20 weeks. ISH and IHC confirmed that Fas and FasL are expressed in the cytoplasm of acinar cells, ductal cells, and lymphocytes. An apoptotic index in acinar cells correlated to the expression of Fas and FasL mRNAs. These results suggest that the expression of the Fas/FasL system is involved in acinar cell apoptosis and the onset and progression of chronic pancreatitis in the WBN/Kob rat. [ABSTRACT FROM AUTHOR]

Background. In an attempt to obtain evidence of the beneficial effects of TJ-10, we investigated the gene expression of PAP, an acute phase protein specific for pancreatitis in rat spontaneous chronic pancreatitis. Methods. Four-wk-old male WBN/Kob rats were fed with MB-3 pellet diet containing herbal medicine. There were two administration groups for each drug: the prophylactic group administered from 4–12 wk, and the therapeutic group administered from 12–20 wk. Untreated control rats were fed with MB-3 alone. Histopathologic changes and PAP gene expressions were analyzed at 12 and 20 wk. Results. In the prophylactic group, TJ-10-treated WBN/Kob rats showed no evidence of pancreatitis, and there was the amelioration of pancreatitis in the pancreata of the rats treated with other herbal medicines except TJ-24 at 12 wk. PAP mRNA was not expressed in the TJ-10-treated rats, and PAP gene expression was suppressed in rats treated with other drugs except TJ-107. In the therapeutic group, the amelioration of pancreatitis was seen only in TJ-10-treated rats, but PAP gene expression was significantly suppressed in the rats treated with all herbal medicines tested, compared with that in untreated control rats. Conclusion. An herbal medicine Saiko-keishi-to (TJ-10) delayed the onset of chronic pancreatitis in the WBN/Kob rat, and suppressed the pancreatitis-associated protein (PAP) gene expression more significantly than other herbal medicines. [ABSTRACT FROM AUTHOR]

Transforming growth factor-beta1 (TGF-beta1) is suggested to be a mediator of fibrosis in chronic pancreatitis, but the serial change of TGF-beta1 expression in the onset and progression of chronic pancreatitis is still unclear. We investigated the TGF-beta1 expression in the spontaneous chronic pancreatitis model. Four-week-old male WBN/Kob rats were fed with special pellet diet (MB-3) for 20 weeks. TGF-beta1 mRNA in the pancreas was detected by reverse transcription-polymerase chain reaction assay from four weeks, and its expression peaked at 12 weeks when the pancreatic fibrosis first appeared. The localizations of TGF-beta1 mRNA and protein were confirmed in the cytoplasm of pancreatic acinar and ductal cells by in situ hybridization and immunohistochemistry, respectively. Although fibronectin expression peaked at 12 weeks and correlated with that of TGF-beta1, its elevated expression tended to be prolonged. Pancreatic fibrosis peaked at 16 weeks after the peak of TGF-beta1 expression. These results suggest that TGF-beta1 expression may be a trigger of the fibrotic process of chronic pancreatitis in the WBN/Kob rat. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with no approved treatment. Zonarol, an extract from brown algae, has been proven to have anti-inflammatory and antioxidant effects. In this study, we investigated the role of zonarol in the progression of methionine- and choline-deficiency (MCD) diet-induced NAFLD in mice. After oral treatment with zonarol, a lighter body weight was observed in zonarol group (ZG) mice in comparison to control group (CG) mice. The NAFLD scores of ZG mice were lower than those of CG mice. Hepatic and serum lipid levels were also lower in ZG mice with the reduced expression of lipid metabolism-related factors. Furthermore, ZG mice showed less lipid deposition, less inflammatory cell infiltration and lower inflammatory cytokine levels in comparison to CG mice. Moreover, the numbers of 8-hydroxy-20-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic and serum thiobarbituric acid reactive substances (TBARS) were significantly lower in comparison to CG mice. The expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), as well as its upstream and downstream molecules, changed in ZG mice. Zonarol could prevent the progression of NAFLD by decreasing inflammatory responses, oxidative stress and improving lipid metabolism. Meanwhile the Nrf2 pathway may play an important role in these effects. [ABSTRACT FROM AUTHOR]

The serum levels of pancreatitis-associated protein (PAP) were measured in 196 patients with digestive diseases and 15 healthy subjects by an enzyme-linked immunosorbent assay. The serum PAP levels were significantly elevated in the patients with gastric, colorectal, biliary tract, hepatocellular, or pancreatic cancers compared with the healthy subjects. After curative resection of the tumor, serum PAP levels were significantly decreased. The serum PAP levels were not related to clinicopathological factors except for the tumor size of pancreatic cancer. There were some cases of PAP-positive and carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9 -negative gastric and colorectal cancers. The serum PAP levels were also significantly elevated in the patients with acute pancreatitis compared with those in not only the healthy subjects but also the patients with chronic pancreatitis. The peak PAP levels were significantly correlated with the severity of acute pancreatitis and reflected the clinical healing of the disease. The peak of serum PAP was significantly delayed compared with those of other pancreatic enzymes. These results suggest that the increase of serum PAP levels in patients with gastrointestinal cancers reflects an ectopic expression of PAP in cancer cells and that increased serum levels of PAP in acute pancreatitis are correlated with the disease severity and are prolonged than those of other pancreatic markers. [ABSTRACT FROM AUTHOR]

We report a case of mucin-producing biliary papillomatosis in a 78-year-old woman. Abdominal ultrasound (US) and computed tomography (CT) showed wall thickening and dilatation of the intrahepatic bile duct (IHBD), as well as a nodular lesion, 1.2 cm in diameter, in the left branch of the IHBD. Gastric endoscopy revealed excretion of bile-containing mucin on the anterior wall of the body of the stomach. Endoscopic ultrasonography (EUS) showed gastrobiliary fistula and discharge of mucin into the stomach. Needle biopsy of the biliary tumor revealed papillary proliferation, but no malignant cells were recognized histologically. Therefore this patient was diagnosed as having mucin-producing biliary papillomatosis forming gastrobiliary fistula. She did not present with obstructive jaundice, probably because of the fistula. She is alive, without obstructive jaundice, 16 months after the diagnosis without having had surgery. This is, to our knowledge, the first reported case of biliary papillomatosis forming gastrobiliary fistula and with the patient free of obstructive jaundice. [ABSTRACT FROM AUTHOR]

Epithelial cells of several types of hepatic cysts were examined by mucin histochemistry and immunohistochemically. There were some differences in mucus and antigenic expression among the hepatic cysts examined. Epithelial cells of non-parasitic simple cysts and adult-type polycystic liver showed similar mucin-histochemical and immunohistochemical features, and were characterized by little mucin and weak immunoreactivities to several antibodies examined. Epithelial cells of hepatic hilar cysts were characterized by much mucin and moderate immunoreactivities to carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Epithelial cells of ciliated hepatic foregut cysts were characterized by much mucin and immunoreactivities to actin and tubulin which were positive in cilia. Epithelial cells of biliary cystadenoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. Epithelial cells of biliary cystadenocarcinoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. These differences in epithelial mucus and antigenic expression among several types of hepatic cysts may reflect differences in their origin and biological characteristics. These differences may be helpful in the differential diagnosis of hepatic cysts in small biopsy specimens. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to investigate the characteristic features of mutinous gastric carcinoma on endoscopic ultrasonography (EUS) and to demonstrate the usefulness of EUS in the preoperative diagnosis of this disease. Methods: Twelve patients with mucinous gastric carcinoma who underwent EUS examination between April 1984 and April 1995 were enrolled in this study. All patients subsequently underwent surgery. Histopathologically, tumors were classified according to the mucin content (high or moderate) and the glandular formation of the tumor cells (well or poorly differentiated). Finally, the histological and endosonographic features were compared. Results: In all patients, the infiltrated wall appeared echogenic because of diffusely distributed, reticular, highly echoic speckles in the submucosa and muscularis propria. The presence of mucinous lakes surrounded by reactive fibrous tissue correlated well with reticular, highly echoic speckles on EUS. There was an increase in echogenicity and thickness of the muscularis propria, depending on the invasion of the mucin. Although the boundary between submucosa and muscularis propria was distinct and the five-layered gastric wall structure was generally preserved, the mucosal layer was not discriminated in patients with poorly differentiated mutinous carcinoma with high mucin content. Conclusions: As a preoperative diagnostic procedure, EUS may be useful in recognizing the mucinous component of gastric tumors and may facilitate the differentiation of mucinous carcinoma from other gastric epithelial tumors. [ABSTRACT FROM AUTHOR]

Pancreatitis-associated protein (PAP) mRNA is expressed in some cases of gastric and colorectal cancers resulting from an ectopic expression in dedifferentiated cancer cells. The PAP gene is identical to the hepatoma-intestine-pancreas ( HIP) gene, which is expressed in hepatoma. Expression in cancer might be another characteristic of PAP. Fresh surgical specimens of 100 gastrointestinal cancers, 14 benign digestive diseases, and six normal organs were studied with nonisotopic in situ hybridization (ISH) using biotin-labeled cDNA probe. PAP mRNA was detected in 10% (6/60) of gastric cancers, 21.4% (6/28) of colorectal cancers, 20.0% (1/5) of pancreatic cancers and 0% of biliary tract (three), esophageal (one), and hepatocellular cancers (three). Reverse transcription-polymerase chain reaction (RT-PCR) detected PAP mRNA in these ISH-positive cases. PAP mRNA was not detected in noncancerous portions, benign disease tissues, or normal organs except for the small intestine. There was no relationship between PAP mRNA expression and any clinicopathological factors. [ABSTRACT FROM AUTHOR]

Pancreatic undifferentiated (anaplastic) carcinoma contained two components: sarcomatous change of spindle-cell type and a neoplastic cyst. Immunohistochemical analysis suggested that both the sarcomatous and the cystic portions were of epithelial origin. This case showed a “dual” differentiation both into the sarcomatous change and into the cystic lesion. Pancreatic sarcoma or sarcomatous change is very rate. The origin of the sarcomatous change is unknown. On the other hand, pancreatic adenocarcinoma sometimes shows necrosis and forms a cystic lesion during its growth, but a neoplastic cyst formation is very rare except for cystadenomas. We report a case of pancreatic undifferentiated (anaplastic) carcinoma associated with sarcomatous change and neoplastic cyst formation. Clinicopathological and immunohistochemical analyses were performed. A 75-yr-old male was admitted because of low back pain and body weight loss. He died 7 d after admission presenting obstructive jaundice. Autopsy disclosed that the large mass was a poorly differentiated ductal adenocarcinoma, which mostly consisted of sarcomatous components of spindle-cell type. The cystic lesion was a neoplastic cyst with the wall composed of epithelial tumor cells. There was no necrosis or hemorrhage in the cystic cavity. Immunohistochemical analyses suggested that both the tumor and the cystic lesion were of epithelial origin. Sarcomatous changes were recognized also in the metastatic lesions in the liver and lymph nodes. The tumor is considered to be labeled undifferentiated (anaplastic) carcinoma of the pancreas. [ABSTRACT FROM AUTHOR]

Sclerosing pancreatitis might develop repeatedly or might rapidly extend to the whole pancreas with recurrent mass formation. Nothing is known concerning course or development of sclerosing pancreatitis. A 63-yr-old male was followed up for 2.5 yr. The patient was admitted because of a tumor in the body and tail of the pancreas. Serum pancreatic enzymes were transiently elevated, but tumor markers were all negative. Imaging studies showed a tumor 7 cm in size. The main pancreatic duct was normal in the head and obstructed at the body on endoscopic retrograde pancreatography (ERCP). The K- ras oncogene mutation was positive in pure pancreatic juice. Distal pancreatectomy was performed because pancreatic cancer was highly suspected. Pathological findings showed that the tumor was a densely fibrotic mass without malignant cells. Inflammatory cell infiltration was observed in the stroma. One year later, another mass 3 cm in size was noted in the remnant pancreatic head. ERCP revealed diffuse irregular narrowing of the main pancreatic duct, its branches, and the common bile duct. Liver dysfunction improved and an elevation of serum pancreatic enzymes subsided without any specific treatment, and the mass diminished in size. The patterns of various imaging studies on the second tumor were the same as those of the previous resected mass. Corticosteroid was not administered. [ABSTRACT FROM AUTHOR]

A 72-year-old woman was admitted because of jaundice and hepatocellular dysfunction. She was diagnosed with autoimmune hepatitis from laboratory test results showing high titers of antinuclear antibodies and negativity for hepatitis viral markers. Steroid i.v. pulse therapy and oral administration of prednisolone were effective in improving the liver function test results, except for hyperbilirubinemia. Elevated serum bilirubin levels, of approximately 20mg/dl persisted for more than 6 months, despite the administration of ursodeoxycholic acid. Insulin-glucagon therapy was given for normalization of transaminases and then withdrawn 3 weeks after admission, but it was resumed at 3 months, resulting in a dramatic decrease in serum bilirubin levels, which then normalized in 2.5 months. Liver biopsy 6 months after onset showed chronic active hepatitis with bile plugs. Insulin-glucagon therapy, because of its choleretic effect, may be worth continuing even after recovery of acute hepatic failure. [ABSTRACT FROM AUTHOR]

We report a case of Cruveihier-Baumgarten syndrome associated with portal vein thrombosis that developed, slowly during a 2-year period after endoscopic variceal sclerotherapy. The thrombosis led to the disappearance of the venous hum and the dilated abdominal wall veins characteristic of this syndrome. A 73-year-old woman was hospitalized for treatment of esophageal varices in April 1988. Her spleen was markedly enlarged, and the histologic findings of her liver were not consistent with hepatic cirrhosis, but with idiopathic portal hypertension. A venous hum was audible in the upper abdomen. Superior mesenteric angiography revealed a porto-systemic shunt vessel under the abdominal wall, originating from the umbilical vein. She was injected four times with a sclerosant, and this brought about disappearance of the esophageal varices. Two years after the first admission, the venous hum was no longer audible, but there was a recurrence of the esophageal varices. More than 2 years later (4 years after the first admission), ultasonographic study, computed tomography, and angiography showed a large thrombus, which completely obstructed the portal vein at the origin of the umbilical vein, and the development of collateral vessels, seen as a "cavernous transformation." [ABSTRACT FROM AUTHOR]

An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1 and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was developed to determine the concentration of this protein in serum from individuals with various diseases. The serum concentration of PSP/reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system, and was extremely high in all patients tested with chronic renal failure. A significant correlation was apparent between the serum concentration of PSP/reg-protein and elastase-I in 68 patients with chronic pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a normal serum PSP/reg-protein concentration and a significantly increased elastase-I concentration, 15 of these patients showed a significantly increased serum PSP/reg-protein concentration and a normal serum elastase-I concentration. These results indicate that the serum PSP/reg-protein concentration may reflect pancreatic damage, especially in acute pancreatitis, and may be a sensitive a marker for such damage as elastase-1, although false positivity was apparent in renal failure and in some patients with hepatic dysfunction or digestive system malignancies. [ABSTRACT FROM AUTHOR]

The clinical significance of the measurement of c-erbB-2 oncogene product was evaluated. The subjects consisted of 404 patients, including 248 with cancer of the digestive organs and 128 with benign digestive diseases. Serum c-erbB-2 protein levels were measured by sandwich immunoenzyme assay. The positive rates of c-erbB-2 protein, at a cut-off value of 17.0 U/ml, were, for cancers: hepatocellular carcinoma 61.6%, biliary tract cancer 54.8%, pancreatic cancer 25.0%, esophageal cancer 33.3%, gastric cancer 16.9%, and colorectal cancer 5.0%. For benign digestive diseases, the rates were: liver cirrhosis 63.3%, chronic hepatitis 43.2%, acute hepatitis 42.9%, other liver diseases 42.8%, cholelithiasis 30.0%, and chronic pancreatitis 0%. Serum c-erbB-2 protein levels were significantly correlated with the markers of hepatic functional reserve, the indocyanine green retention rate and the hepaplastin test. These findings suggest that serum c-erbB-2 protein levels are greatly influenced by liver dysfunction and that their clinical usefulness as a serum tumor marker is questionable. [ABSTRACT FROM AUTHOR]

ABSTRACT- Expression of epidermal growth factor (EGF) and fibroblast growth factor (FGF) was examined in 56 patients with hepatocellular carcinoma (HCC) using an immunohistochemical method. EGF and FGF were expressed on carcinoma cells in 14 (25%) and 23 cases (41%), respectively. In the 23 FGF-positive cases, 11 cases were positive for both acidic and basic FGF, while 18 were positive for acidic FGF, and 16 were positive for basic FGF. In non-cancerous hepatic tissues, FGF was weakly positive in macrophages, hepatocytes and vascular endothelial cells in some cases, while EGF was totally negative. There were no significant correlations between the expression of EGF or FGF on carcinoma cells and the various clinicopathologic factors examined. These data suggest that EGF and FGF are produced by human HCC cells in vivo. The roles of the expression of these growth factors in the development and progression of HCC remain only speculative. [ABSTRACT FROM AUTHOR]

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration + 2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer. [ABSTRACT FROM AUTHOR]

In order to elucidate the characteristics of reg-protein, which is identical to pancreatic stone protein (PSP/ reg-protein), and the relationship between the generation and evolution of chronic pancreatitis and the expression of PSP/ reg-protein in the pancreas, we investigated the expression of PSP/ reg-protein in normal and diseased human pancreatic tissues by immunohistochemistry. The PSP/ reg-protein was expressed in all cases with normal pancreas or chronic pancreatitis, and in 70.6% of cases with pancreatic cancer. This protein was present in the cytoplasm of acinar cells and, in some cases, in the intraluminal contents of ductules in nonmalignant tissues. From the view of distribution and cellular localization, PSP/ reg-protein was expressed more broadly and densely in chronic pancreatitis with mild to moderate injury than in the normal pancreas. However, the protein was less expressed in severely damaged chronic pancreatitis tissue, such as calcifying pancreatitis, than in the normal pancreas. These findings suggest that mild to moderate injury to pancreatic tissue may stimulate the synthesis of PSP/ reg-protein, whereas more severe injury tends to depress it. [ABSTRACT FROM AUTHOR]