A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction: A hint for early diagnosis of gallbladder carcinoma.

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19,900 IU/L and that of the gallbladder was 127,000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.

Amylase level in extrahepatic bile duct in adult patients with choledochal cyst plus anomalous pancreatico-biliary ductal union.

AIM: To investigate the relationship between pancreatic amylase in bile duct and the clinico-pathological features in adult patients with choledochal cyst and anomalous pancreatico-biliary ductal union (APBDU). METHODS: From 39 patients who underwent surgery for choledochal cyst between March 1995 and March 2003, we selected 15 adult patients who had some symptoms and were radiologically diagnosed as APBDU, and their clinico-pathological features were subsequently evaluated retrospectively. However, we could not obtain biliary amylase in all the patients because of the surgeon's slip. Therefore, we measured the amylase level in gall bladder of 10 patients and in common bile duct of 11 patients. RESULTS: Levels of amylase in common bile duct and gall bladder ranged from 11,500 to 212,000 IU/L, and the younger the patients, the higher the biliary amylase level (r = -0.982, P<0.01). Pathologically, significant correlation was found between the size of choledochal cyst and the grade of inflammation (r = 0.798, P<0.01). And, significant correlation was found between the level of amylase in gall bladder and the grade of hyperplasia. On the other hand, there was no correlation to the age of symptomatic onset or inflammatory grade (r = 0.743, P<0.05). Level of lipase was elevated from 6,000 to 159,000 IU/L in bile duct and from 14,400 to 117,000 IU/L in the gall bladder; however, there was no significant correlation with age or clinico-pathological features. CONCLUSION: The results support the notion that amylase has a particular role in the onset of symptoms, and suggest that a large amount of biliary amylase induces early onset of symptom, thereby making early diagnosis possible.

Assessment of occult pancreatobiliary reflux in patients with pancreaticobiliary disease by ERCP.

BACKGROUND: The aim of this study was to evaluate the degree of occult pancreatobiliary reflux by measuring the biliary amylase levels in the common bile duct (CBDA) and gallbladder (GBA) at endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with pancreatobiliary maljunction (PBM) were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in 8 cases. RESULTS: Twenty-two cases (26%) revealed a CBDA level higher than serum amylase (high bile amylase level, HBA group) and 64 cases exhibited a CBDA level lower than serum (LBA group). The mean values of CBDA in the HBA and LBA groups were 5502 IU/l and 29 IU/l, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and those with choledocholithiasis (P <0.05). Three cases (16%) showed a CBDA greater than twice the GBA. Eleven cases (58%) exhibited a GBA higher than the CBDA. The values of GBA obtained during ERCP and cholecystectomy were consistent. CONCLUSIONS: These findings suggest that even non-PBM cases can exhibit occult pancreatobiliary reflux, which can thereby cause biliary disease.

Gastropathy and defense mechanisms in common bile duct ligated portal hypertensive rats.

Portal hypertensive gastropathy is associated with a broad spectrum of gastric mucosal damage inspite of decreased gastric acid secretion, suggestive of compromised endogenous protective mechanisms. To determine the mechanisms of damage in portal hypertensive gastropathy we measured lipid peroxidation, glutathione, antioxidant and lysosomal enzymes in gastric mucosal homogenates from male Wistar rats with elevated intrasplenic pulp pressure, eighteen days after common bile duct ligation. Thiobarbituric acid-reactive substances and lysosomal enzymes (beta-glucuronidase and acid phosphatase) were increased in the common bile duct ligated group as compared to the sham-operated group. The levels of antioxidant defense enzymes, superoxide dismutase, glutathione peroxidase, catalase and glutathione were decreased as compared to the sham-operated controls. Pre-operative vitamin E administration decreased mucosal lipid peroxidation increased the levels of antioxidant defense enzymes and lowered the lysosomal enzymes. The plasma vitamin E levels in this group were lower when compared to animals receiving it post-operatively. In conclusion, free radical and lysosomal enzyme mediated damage may play a role in portal hypertensive gastropathy.

beta-Glucuronidase in common duct bile, methodological aspects, variation of pH optima and relation to gallstones.

beta-Glucuronidase of human or bacterial origin may deconjugate bilirubin diglucuronide, causing pigment gallstones. Intrinsic interference by biliary compounds must be minimized for accurate assay of beta-glucuronidase. We report a modified ion-pair extraction of interfering substances by tetrahexylammonium chloride (THAC) in ethyl acetate in the presence of albumin, and a microtitre plate assay for biliary beta-glucuronidase activity in bile with the substrate p-nitrophenol-glucuronide. Adding albumin improved the recovery of beta-glucuronidase activity to 99.8% (CV 1.9%), and 92.2% of the bilirubin in bile samples was extracted in one step. Competitive inhibition was overcome by increasing the substrate concentration. In endoscopically obtained common duct bile from 44 patients, five different beta-glucuronidase activity peaks were identified, at pH 3.9, 4.8, 5.3, 5.8 and 7.2. The pH profiles were classified into one bacterial pattern and five patterns for presumed human beta-glucuronidase. Of the latter patterns, four displayed dual activity peaks. In a second sample, obtained at follow up in four patients, their original pH profile was maintained. In conclusion, using the modified purification and assay system, we found functionally diverse subcategories of human beta-glucuronidase with respect to activity at variable pH. Our results indicate that several pH optima have to be taken into consideration in order to clarify the role of human biliary beta-glucuronidase in the pathogenesis of pigment gallstones. Bacterial beta-glucuronidase activity was associated with duodenal diverticula (p < 0.05) and common duct stones (p < 0.05).

Ultrastructural neurohistochemical evidence for a neuro-endocrine link in the regulation of the extra-hepatic biliary dynamics.

Electron microscopical neurohistochemical studies of the choledocho-duodenal junction of the cat revealed acetylcholinesterase-positve nerve terminals closely abutting on ("ectopic"), mono-amine(s)-containing alpha-cells (of the islets of Langerhans) scattered in small clusters between bundles of the sphincteric smooth muscle (of Oddi). The cell membrane of the alpha-cells at and near the site of the neuro-effector contacts was reactive, too. This finding may be considered as some evidence for cholinergic innervation of cholinoceptive neuro-endocrine cells, and obviously represents one of the neuro-endocrine links involved in the regulation of the extra-hepatic biliary dynamics, demonstrated earlier in physiological and pharmacological studies.

Enzyme histochemical studies of rabbit bile ducts with and without bile flow.

The histochemical enzyme pattern in normal, extra-hepatic bile ducts from rabbits was studied. A difference between the duct epithelium and the crypt epithelium was noted mainly in the activity of gamma-glutamyl-transpeptidase and alkaline phosphatase which only stained positively in the crypts. No difference from the normal enzyme pattern was noted after diversion of the bile flow for up to 30 days.

Enzyme histochemistry studies of transverse and longitudinal incisions in the common bile duct in rabbits.

The healing process of longitudinal and transverse incisions of the common bile duct in rabbits was studied by identification of 10 different enzymes in the duct wall at various times after the operation. Bile was deviated during the healing. An almost complete disappearance of the subepithelial alkaline phosphatase activity was noted early after longitudinal incisions in contrast to unchanged alkaline phosphatase activity after transverse incisions. Transversely incised ducts almost uniformly developed stricutre formation. The size of the lumen after longitudinal incisions was generally normal. The difference in enzyme pattern following the two types of lesion might reflect a different response of the tissues to the two different types of trauma.