Marked alkaline phosphatase elevation with partial common bile duct obstruction due to calcific pancreatitis.

This study characterizes a syndrome of partial common bile duct obstruction and marked elevation in serum alkaline phosphatase in 6 male alcoholic patients with calcific pancreatitis. In each patient, a marked elevation in serum alkaline phosphatase was associated with minimal, if any, elevation in serum bilirubin. In all cases, the alkaline phosphatase was hepatic in origin, and intravenous or operative cholangiography showed a dilated common bile duct. Liver biopsy showed canalicular bile stasis in 4 patients and bile duct proliferation in 2 patients. This study demonstrates that calcific pancreatitis may cause partial bile duct obstruction which differentially increases serum alkaline phosphatase without altering bilirubin or bromsulphthalein excretion.     

Chronic pancreatitis: a cause of cholestasis.

The bile ducts were visualised using endoscopic retrograde cholangiopancreatography (ERCP), percutaneous or intravenous cholangiography in 38 patients with non-gallstone chronic pancreatitis. Stenosis of the intrapancreatic portion of the distal common bile duct was demonstrated in 11 patients. Ten of the 11 developed transient cholestasis during exacerbations of their chronic pancreatitis. In six cholestasis eventually persisted requiring surgical relief. Secondary biliary cirrhosis was present in one patient. No evidence of pancreatic carcinoma was found in the patients explored surgically. Ten of the patients are alive more than one year after diagnosis.Chronic pancreatitis was of alcoholic aetiology in 10 of the patients with biliary stenosis. Cholestasis and biliary stricture are common but poorly recognised complications of non-gallstone chronic pancreatitis, especially when pancreatitis is severe and due to alcohol.     

Suspected malignant cancer of the pancreas associated with pseudo-invasive duodenal hamartomas in a patient with Peutz-Jeghers syndrome

A 29-year-old man with a previously known Peutz-Jeghers syndrome (PJS) was admitted for epigastric pain, emesis and weight loss due to both intestinal intussusception causing bowel obstruction and obstructive pancreatitis. The patient had cholestasis with an enlarged common bile duct on imaging. Because duodenal and/or pancreatic cancer was suspected due to weight loss, the pancreatic and bile duct obstruction, and the increased risk of small intestine and pancreatic adenocarcinoma in patients with PSJ, a pancreatoduodenectomy was performed. Pathological examination revealed a duodenal polyp with epithelial misplacement invading the ampulla and compressing the main bile duct. Twenty months after surgery, there was no relapse of symptoms or cholestasis. This is the first case showing a direct role of pseudo-invasive duodenal harmatomas in the development of biliary obstruction and chronic obstructive pancreatitis.     

Effect of sensory denervation with capsaicin on liver fibrosis induced by common bile duct ligation in rat

Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by common bile duct obstruction has been studied both in capsaicin- and vehicle-treated rats. Common bile duct-induced liver fibrosis was less marked in capsaicin-treated rats than in vehicle-treated rats. Diffuse alterations of liver parenchyma structure with marked collagen deposition and nodular regeneration occurred 8 weeks after common bile duct ligation in vehicle-treated animals, while none of the capsaicin-treated rats exhibited the formation of complete connective septa altering the parenchyma architecture. Both vehicle- and capsaicin-treated rats showed an increasing number of desmin-positive cells in the perivenular zone, but the density of these cells was lower in treated animals than in untreated rats. The hydroxyproline content of the liver increased after common bile duct ligation in a time-dependent manner. Eight weeks after bile duct obstruction vehicle-treated rats showed a 7-fold increase of liver collagen content in comparison to normal animals. This enhancement was about 3.5-fold in capsaicin-treated rats. These findings raise the possibility that the peripheral release of neuropeptides stored in sensory nerves might participate in the development of liver fibrosis following common bile duct obstruction.     

The variable appearance of distal common bile duct stenosis in chronic pancreatitis

Cholangiograms of 15 patients with stenosis of distal portion of common bile duct due to chronic alcoholic pancreatitis were critically evaluated for stricture shape, length, and maximal diameter of the common bile duct. In these cholangiograms, different shapes of strictured segments were present, including the smooth tapering variety in eight, "funnel shape" in three, and "rat tail," "bent knee," "hourglass," and complete obstruction in one case each. The length of strictured segment ranged from 16 to 57 mm with a mean (+/- S.E.) of 40.7 +/- 4.1 mm. The mean (+/- S.E.) maximal diameter of the dilated portion of common bile duct was 18.9 +/- 1.3 mm with a range of 13-28 mm. There is a wide variety in the shape and length of the stenotic segments of the distal common bile duct in chronic alcoholic pancreatitis. Moreover, a particular radiologic configuration of common bile duct stricture is not helpful in predicting the nature of the underlying process in this group of patients.     

Genistein decreases liver fibrosis and cholestasis induced by prolonged biliary obstruction in the rat

Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment with the aim of modifying the clinical course of this disease is evident. The aim of this work is to determine whether genistein, which has been shown to modulate the physiology and pathophysiology of liver, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of genistein (5 microg rat-1, day-1, p.o.) began four weeks after biliary obstruction and continued for a further four weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel(R) and collagen type I was determined in homogenized liver. Bilirubins and enzyme activities were measured in serum. Genistein was able to improve normal liver histology, ultrastructure, collagen content, and biochemical markers of liver damage. It also increased Matrigel(R) and collagen type I degradation. In summary, the present report shows that genistein inhibits the fibrosis and cholestasis induced by prolonged biliary obstruction in the rat. Genistein has therapeutic potential against liver fibrosis.     

Biliary obstruction

Extrahepatic biliary obstruction resulted from chronic alcoholic pancreatitis in seven patients. All cases had a characteristic smooth symmetrical narrowing of the intrapancreatic portion of the common bile duct on retrograde cholangiography. Both medical and surgical therapy for their disorder is discussed.     

Endoscopic pancreatography in chronic pancreatitis of the tropics

The ERCP findings in 13 patients with chronic pancreatitis of the tropics are reported. 7 of the patients had pancreatic calculi on plain film of abdomen and 6 had no calcification. The changes observed in the pancreatograms were tortuosity, dilatation, stenosis, obstruction, cyst formation and presence of calculi in the main pancreatic ducts and their finer branches. The calcific variety showed a greater degree of ductal derangement compared to the non-calcific variety. The common bile duct was normal in all the patients. The pancreatographic changes observed are similar to those described in the alcoholic and other varieties of chronic pancreatitis.     

Clinical features of patients with chronic pancreatitis complicated by bile duct strictures

BACKGROUND/AIMS: Distal bile duct stenosis is relatively rare in patients with non-alcoholic chronic pancreatitis. METHODOLOGY: The clinical features of eight patients who had chronic pancreatitis complicated by bile duct strictures who underwent surgical treatments were reviewed. RESULTS: Ages ranged from 38 to 80 years, with a mean of 53.4 years. All but one patient were male. Six patients had moderate or slight epigastric pain. Five patients had obstructive jaundice and underwent biliary drainage. All patients had liver dysfunction due to biliary obstruction. Although four of the eight patients were heavy or moderate drinkers, none of the patients had a history of chronic pancreatitis. Stricture shapes of the common bile ducts were smooth and tapering in five patients, funnel-shaped in two, and rat-tail in one. Four patients underwent a pancreatoduodenectomy and one patient underwent a pylorus-preserving pancreatoduodenectomy for clinically suspected pancreatic malignancy that was later proven histopathologically to be chronic pancreatitis. The other three patients underwent a choledochoduodenostomy. There were no postoperative complications or deaths. During the follow-up period, all patients were asymptomatic. CONCLUSIONS: In conclusion, bile duct stricture potentially occurs not only in patients with alcoholic chronic pancreatitis but also in patients with nonalcoholic chronic pancreatitis. Furthermore, in some cases, it is impossible to differentiate chronic pancreatitis from pancreatic or periampullary malignancy.     

Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct]

We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.     

Complications of Chronic Pancreatitis

Summary: Alcohol-induced chronic pancreatitis has many complications. This man, since chronic pancreatitis first became clinically apparent, has developed diabetes mellitus, steatorrhoea, ascites (pancreatic) with a possible pseudocyst and a peripancreatic abscess, gallstones, partial common bile duct obstruction, gastric and duodenal deformities (due to adjacent pancreatitis, or peptic duodenal ulceration) and hepatic portal cirrhosis. Pulmonary tuberculosis was present at the time of onset of his pancreatitis. The course of his disease is followed illustrating the spectrum of complications which may develop during the course of chronic pancreatitis.     

Pressure measurements from biliary and pancreatic segments of sphincter of oddi

Using a minimally compliant infusion system and a triple-lumen pressure recording catheter, we obtained endoscopic manometric measurements from both the common bile duct and pancreatic duct segments of the sphincter of Oddi (SO) in 58 patients. Fifteen patients (ages 27–69) had the diagnosis of functional abdominal pain, 19 patients (ages 30–76) had partial biliary obstruction, and 24 patients (ages 15–80) had idiopathic acute recurrent pancreatitis. Resting ductal pressure was similar in the common bile duct and pancreatic duct in all patient groups. In the group with functional pain, basal SO pressure was similar, whether obtained from the common bile duct or pancreatic duct sphincteric segment. Eight of 19 patients with partial biliary obstruction had elevated basal SO pressure. Five of these eight patients had elevated basal SO pressure confined exclusively to the common bile duct segment of the sphincter, while three patients had elevated basal SO in both segments. Conversely seven of 24 patients with acute recurrent pancreatitis had an elevated basal SO pressure, with five patients having pressure elevation only in the pancreatic duct segment while two patients had abnormal basal SO pressure in both segments. We conclude that selective cannulation of the common bile duct and/or the pancreatic duct during manometric study of the SO is necessary in order to diagnose segmental SO dysfunction responsible for partial biliary obstruction or episodes of acute recurrent pancreatitis.     

Cholestasis in alcoholic chronic pancreatitis. Diagnostic value of the transaminase ratio for differentiation between extra- and intra-hepatic cholestasis

In our long-term study of alcoholic chronic pancreatitis (median follow-up time, 10.4 years) 84 of 173 patients (48.6%) developed transient or persistent cholestasis with or without hyperbilirubinemia. We studied the discriminative value of the ASAT/ALAT ratio to differentiate intrahepatic (IHC) and extrahepatic cholestasis (EHC; due to stenosis of the distal common bile duct) in 75 of these patients. In 45 patients with persistent or recurrent cholestasis (group A) the cause of cholestasis was documented by accurate morphological methods. Thirty of the other 39 patients with transient cholestasis (group B) were classified on the basis of the overall clinical evaluation. Of 37 patients with IHC 36 had an ASAT/ALAT ratio of 1.5 or higher (one patient had normal values for both transaminases). Out of 38 patients classified as EHC 29 had an ASAT/ALAT ratio of 1.4 or lower (9 with normal transaminases being excluded). One patient with cholangitis secondary to EHC had a transient elevation of the ASAT/ALAT ratio to above 2.5. Thus our data suggest that in alcoholic chronic pancreatitis associated with cholestasis an ASAT/ALAT ratio of 1.4 or lower (or normal transaminases) usually indicates EHC. Diagnostic study and surgical decompression is mandatory in these cases if EHC persists.     

Description and rationale of a new operation for chronic pancreatitis

An operation is described that is useful in the management of patients with chronic pancreatitis and its complications. The operation features duodenal-preserving resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy of the body and tail of the pancreas. The operation has application to patients with pain or complications of chronic pancreatitis with dilated ducts in the body and tail of the pancreas who have small strictured ducts and/or small pseudocysts or ducts impacted with calculi in a markedly enlarged fibrotic pancreatic head. It also has application to patients with chronic pancreatitis complicated by common duct obstruction from small pseudocysts, fibrosis, or inflammation in the head of the pancreas. With this procedure, the common duct can often be freed up from the structures compressing it within the substance of the pancreas doing away with the necessity of a separate biliary bypass. The operation also has application to patients with a previous longitudinal pancreaticojejunostomy who have recurrent or persistent pain associated with small strictured ducts in an enlarged fibrotic pancreatic head with or without common bile duct obstruction.     

Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary?

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63‐year‐old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.     

Treatment of benign biliary strictures in chronic pancreatitis by self-expandable metal stents

AIM: To determine the efficacy the value of self-expandable metal stents in patients with benign biliary strictures caused by chronic pancreatitis. METHOD: 61 patients with symptomatic common bile duct strictures caused by alcoholic chronic pancreatitis were treated by interventional endoscopy. RESULTS: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. Of 45 patients who needed definitive therapy after a 12-months interval of interventional endoscopy, 12 patients were treated with repeated plastic stent insertion (19.7%) or by surgery (n = 30; 49.2%). In 3 patients a self-expandable metal stent was inserted into the common bile duct (4.9%). In patients treated with metal stents, no symptoms of biliary obstruction occurred during a mean follow-up period of 37 (range 18-53) months. The long-term success rate of treatment with metal stents was 100%. CONCLUSIONS: Endoscopic drainage of biliary obstruction by self-expandable metal stents provides excellent long-term results. To identify patients who benefit most from self-expandable metal stent insertion, further, prospective randomized studies are necessary.     

The liver in biliary obstruction due to chronic pancreatitis

Biliary obstruction is an important complication of chronic calcifying pancreatitis. In this study, liver biopsies were examined to determine the nature and severity of hepatic complications in 23 such cases. The most striking changes were portal tract expansion due to oedema and fibrosis, with proliferation of bile ducts. Although common, these changes were not severe, and no patient had developed secondary biliary cirrhosis. Other features of note were intrahepatic cholestasis, iron overload (56.5%), copper-associated protein stained with the orcein technique (34.7%) and mild fatty change or perivenular sclerosis in 13%. It is concluded that no serious, irreversible pathological changes occurred in the liver despite clinically marked biliary obstruction.     

High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo

BACKGROUND/AIMS: Models of fatty liver diseases and fibrosis suggest a hepatoprotective effect of adiponectin, an adipocyte-derived hormone with antidiabetic, antiobesity, antiatherogenic and anti-inflammatory effects. METHODS: We studied adiponectin serum levels in 111 chronic liver disease (CLD) patients and 226 healthy controls and the impact of cholestasis on adiponectin by bile duct ligation experiments in mice. RESULTS: Adiponectin was significantly elevated in CLD, and correlated with stage of liver cirrhosis, liver cell injury, e.g. aminotransferase activity, and inflammatory markers, but not with liver synthesis capacity, insulin sensitivity (HOMA index) or clinical complications. As patients with biliary liver diseases and cholestasis exhibited the highest adiponectin levels, we experimentally investigated a potential biliary route of adiponectin excretion. Following bile duct ligation in mice adiponectin levels rapidly increased without affecting hepatic adiponectin gene expression. Also, adiponectin was detectable in human bile. High adiponectin concentrations were associated with severe cholangitis and/or cholestasis on liver histology. CONCLUSIONS: Adiponectin is elevated in chronic liver disease and correlates with inflammation and liver damage. High adiponectin levels after bile duct ligation in mice and in human bile from cholestatic patients suggest that biliary secretion is involved in adiponectin clearance and that adiponectin could serve as a novel marker indicating cholestasis in liver cirrhosis.     

Common bile duct stenosis from chronic pancreatitis: a clinical and pathologic spectrum

The chronic pancreatitis population of Wadsworth VA Hospital over the past five years was screened for two-fold or greater alkaline phosphatase elevation at any time during their course, as a marker for either distal common bile duct stenosis or other hepatobiliary disease. Forty-seven of 207 patients screened met this criterion and are reviewed in detail. Of the 16 patients with persistent alkaline phosphatase elevation (group B), 15 had proven common bile duct stenosis, demonstrating a clear pathophysiologic role of partial bile duct obstruction in their liver disease. Three had developed secondary biliary cirrhosis, marking this entity the commonest cause of secondary biliary cirrhosis at our hospital. Of the remaining 31 patients with transient alkaline phosphatase elevation (group A), only 4 had proven duct abnormalities which may resolve during recovery. Alcoholic liver disease was demonstrated with normal extrahepatic ducts in the remainder in group A adequately studies. Persistent greater than two-fold alkaline phosphatase elevation in pancreatitis thus represents a reliable marker of distal common bile duct stenosis, whose sequelae may include cholangitis and secondary biliary cirrhosis and which requires operative intervention in these cases. When a persistent alkaline phosphatase elevation greater than two-fold is encountered in a chronic pancreatitis patient, adequate cholangiography and liver histology are both necessary to confirm and grade this frequent and treatable complication.     

Percutaneous transhepatic insertion of a permanent endoprosthesis in obstructive lesions of the extrahepatic bile ducts

A Teflon endoprosthesis for permanent bile drainage was inserted in 13 patients following percutaneous transhepatic puncture and catheterization of the bile duct system. Twelve patients had extrahepatic cholestasis because of a malignant tumor, whereas one patient had chronic inflammation involving the hepatoduodenal ligament (secondary to Crohn's disease) with obstruction of the extrahepatic bile ducts. The drainage periods varied from 1 week to 8 months. The endoprosthesis was regarded as partially effective in seven patients whereas in six cases the drainage through the endoprosthesis was insufficient and external bile drainage through a percutaneous transhepatic catheter was necessary. Infection of the bile duct system during the drainage period with a percutaneous transhepatic catheter and/or bile duct endoprosthesis occurred in 10 patients. Spontaneous dislocation of the endoprosthesis occurred in varying degrees in five patients. One patient developed an intrahepatic aneurysm adjacent to the puncture tract and died because of liver insufficiency following therapeutic embolization of the aneurysm and most of the hepatic arteries by injection of gelfoam particles into the common hepatic artery. Patients in whom palliative treatment by insertion of a permanent bile duct endoprosthesis may be suitable were defined.