Cholangiographic features of biliary strictures after liver transplantation for primary sclerosing cholangitis: evidence of recurrent disease

Cervico-vaginal smears were quite difficult to accept when they were first introduced in France, during the fifties, probably due to a fear that cytology might replace surgical pathology, whereas both methods may develop close together. At last, bridging the gap was accomplished by the pathologists and, nowadays, a number of cytopathologists have been trained and have become quite clever. Obviously, clinicians cannot do without the method described by George N. Papanicolaou (the so-called Pap test). Although cervical carcinoma is the very one cancer that should have been eradicated, as complete recovery is the rule when the diagnosis is made in time, at the preinvasive stage of the tumor, in France it is still responsible for 2000 annual deaths. Systematical target population screening should be organized, as well as in other countries and should become one of the main priorities of health care control.     

Endoscopic management of biliary tract strictures in primary sclerosing cholangitis

BACKGROUND AND STUDY AIMS: In a subgroup of patients, primary sclerosing cholangitis (PSC) is complicated by high-grade focal strictures of the bile ducts, and this can have an unfavorable influence on the natural course of the disease. The aim of this study was to evaluate the efficacy and safety of endoscopic treatment in this selected patient group. PATIENTS AND METHODS: Twelve symptomatic patients with primary sclerosing cholangitis and major ductal strictures were included in a prospective study of endoscopic treatment. All patients were managed by repeated angioplasty-type balloon dilation and nasobiliary catheter perfusion. A minimum of two treatment sessions was used, and therapy was continued until satisfactory reopening of the strictures was obtained. Routine endoscopic follow-up was performed after three, six, 12, 18, and 24 months, and then at yearly intervals. The efficacy of therapy was assessed by evaluating clinical symptoms, laboratory data, and cholangiograms. RESULTS: The long-term follow-up averaged 23 months (range: 12-50 months). Two to nine (mean: three) treatment sessions were required to obtain satisfactory reopening of major biliary strictures. Eight patients showed considerable and sustained improvement. The mean serum bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase, and alanine aminotransferase levels felt significantly by 73% (P = 0.0164), 46% (P = 0.0022), 55% (P = 0.0022), and 58% (P = 0.0022), respectively. The average radiographic stricture score before treatment was 3.2 +/- 0.8 (P = 0.0033). Three patients required liver transplantation seven, 12, and 40 months after the initiation of endoscopic treatment, due to a deterioration in hepatic function or an inability to exclude complex biliary malignancy. No major procedure-related side effects were observed. CONCLUSIONS: Our results suggest that the endoscopic treatment of PSC patients with dominant bile duct strictures is effective, safe, and well-tolerated. However, it is important not to overlook the potential development of cholangiocarcinoma.     

Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis

We measured levels of glucose and glycated hemoglobin in the blood of three of the world's smallest nectarivorous birds, the Anna's (Calypte anna), Costa's (Calypte costae), and ruby-throated hummingbirds (Archilochus colubris). Plasma glucose levels of hummingbirds that were fasted overnight (17 mM) were higher than those in any mammal and are among the highest ever measured in a fasting vertebrate. Glucose levels in hummingbirds just after feeding were extreme, rising as high as 42 mM. The surprisingly high blood glucose concentrations in hummingbirds were accompanied by glycated hemoglobin levels that are the highest ever measured in birds but are lower than those of non-diabetic humans. How hummingbirds tolerate blood glucose levels that cause serious neurological and microvascular pathologies in diabetic humans and animals remains unknown.     

An atypical presentation for primary sclerosing cholangitis

We describe the clinical course of a group of patients with primary sclerosing cholangitis who at presentation were diagnosed to have autoimmune hepatitis. The history of one such patient is described in detail. We also compare this atypical sclerosing cholangitis (group I) to typical sclerosing cholangitis (group II) and to autoimmune hepatitis with (group III) and without (group IV) cholestasis. At presentation, mean AST in groups I and III was similar and significantly higher than in group II (P < 0.05). Mean ALP was higher in sclerosing cholangitis than in autoimmune hepatitis but not significantly so. Triaditis was present in all patients in groups I, III, and IV. Piecemeal necrosis and multilobular collapse/fibrosis were equally frequent in groups I, III, and IV. Only the response to corticosteroids helped differentiate among groups. Groups III and IV responded by normalizing AST. In group I, AST improved, but never became normal. As ALP became disproportionately abnormal (ALP-predominant pattern), cholangiography was performed, and the diagnosis of primary sclerosing cholangitis was made in all group I patients. We recommend that cholangiography be performed early in patients with suspected autoimmune hepatitis who partially respond to corticosteroids and develop an ALP-predominant pattern.     

Overview: biliary reconstruction after liver transplantation

Changes of intracellular calcium homeostasis in epithelial cell damage of renal tubules caused by cadmium and its relationship with the damage were studied in isolated tubular cells of rabbits. Results showed levels of free calcium (Ca++) in tubular cytoplasm increased significantly with the treatment of cadmium, and a series of cellular ultrastructure were damaged. A calcium channel blocker, phenothiazine, showed blocking and protecting effects on it. This suggested calcium overload played a very important role in kidney damage caused by cadmium.     

MR cholangiography in primary sclerosing cholangitis

OBJECTIVE: The purpose of this study was to evaluate the ability of MR cholangiography to reveal the characteristics of biliary abnormalities found in primary sclerosing cholangitis. CONCLUSION: Our results suggest that MR cholangiography could be useful in the diagnosis of primary sclerosing cholangitis. Slightly dilated peripheral bile ducts unconnected to the central ducts in several hepatic segments are a characteristic MR sign of primary sclerosing cholangitis. However, other studies are necessary to establish the usefulness of MR cholangiography in relation to other imaging techniques for evaluating primary sclerosing cholangitis.     

Recurrent primary sclerosing cholangitis after orthotopic liver transplantation: is chronic rejection part of the disease process?

BACKGROUND: The possibility of primary sclerosing cholangitis (PSC) recurrence after liver transplantation has been debated. The aim of this study is to examine whether recurrent PSC and chronic rejection (CR) are different expressions of the same disease process. METHODS: One hundred consecutive patients receiving 118 grafts for the diagnosis of PSC were reviewed and placed into three groups: group A, recurrent disease, as evidenced by cholangiographic and pathologic findings with radiographic arterial flow to the liver (n=18; 15.7%); group B, those who developed CR (n=15; 13.0%); and group C, all others (n=82; 71.3%). Cholangiograms and histopathologic specimens were examined in a blinded fashion. RESULTS: Demographic factors were similar, except for age, with a significantly younger age and more episodes of rejection in groups A and B (P<0.03). Group A had a higher incidence of cytomegalovirus hepatitis (P=0.008). Five-year graft survivals for A, B, and C were 64.6%, 33.3%, and 76.1%, respectively (P=0.0001), 5-year patient survivals were 76.2%, 66.7%, and 89.1%, respectively (P=0.0001), and repeat transplantation rates were 27.8%, 46.7%, and 8.5%, respectively (P=0.005). Radiographically, 90% of cholangiograms in patients with recurrent disease showed at least multiple intrahepatic strictures. Histopathologically, patients with recurrent disease and CR shared many features. CONCLUSIONS: We have described a high incidence of recurrent PSC and CR in patients who received transplants for PSC. Histopathologic analysis suggests that CR and recurrent PSC could represent a spectrum of indistinguishable disease. However, the distinct difference in clinical outcome, as evidenced by an increased repeat transplantation rate and lower graft and patient survival in the CR group, clearly suggests that they are two distinct entities that require very different treatment strategies.     

Biliary tract calculi in primary sclerosing cholangitis

By conventional criteria the diagnosis of primary sclerosing cholangitis (PSC) is excluded if biliary tract calculi are present. OBJECTIVE: To compare patients with sclerosing cholangitis with and without calculi. METHODS: Retrospective review between 8/91 and 9/93 identified 63 patients with sclerosing cholangitis alone (Group A) and 22 patients with sclerosing cholangitis and biliary tract calculi (Group B). The mean follow-up was 13.6 months. Clinical features reviewed were age, sex, associated inflammatory disease (IBD), and clinical presentation. Cholangiographic features compared were site and extent of disease. Endoscopic stone extraction was reviewed for success and complications. RESULTS: Both groups had the following features in common: 1) mean age (45.9 vs 46.3 yr), 2) prevalence of IBD (68.3 vs 72.7%), 3) extent of bile duct strictures (intrahepatic: 28.5% vs 27.2%; extrahepatic: 12.7% vs 13.6%; both: 58.7% vs 54.5%). There were proportionately more women in Group B (45.5% vs 33.3%). Symptomatic presentation (pain, pruritus, jaundice, and cholangitis) was seen more often in Group B: 86.4% compared with Group A: 39.7% (specifically cholangitis was seen in 22.7% vs 4.7%). Among Group B, calculi developed subsequent (mean 40.2 months) after the diagnosis of sclerosing cholangitis in 77.3% of patients. The distribution of calculi was cholelithiasis: 7 (31.8%); choledocholithiasis: 9 (40.9%); and both: 6 (27.2%). Of the patients with choledocholithiasis alone, 78% had undergone previous cholecystectomy. Endoscopic stone extraction was successful in 13 (86.6%) of the patients with choledocholithiasis. Complications included mild pancreatitis in one patient and bleeding from sphincterotomy site in another patient which responded to sclerotherapy. In follow-up, only one patient had recurrent calculi and underwent successful stone extraction. CONCLUSION: We suggest that biliary tract calculi are a part of the spectrum of otherwise typical PSC and therefore their presence should not necessarily exclude the diagnosis.     

Current therapeutic methods in primary sclerosing cholangitis

The authors synthesize the main etiopathogenetic, physiopathologic and clinic findings of CSP and describe the pharmacs employed in the treatment of disease: corticosteroids, cyclosporin, penicillamine, colchicine, tacrolimus, metotrexate, hydrophylic bile salts. They outline the poor or none therapeutic activity of the majority of these and stress the improvement of some clinical parameters after prolonged use of hydrophilic bile salts. However none of the used pharmacs can stop the pathologic course of the disease. At the end authors remember the usefulness of liposoluble vitamins to prevent carential syndromes.     

Liver transplantation in a 29-year-old patient with gallbladder carcinoma complicating primary sclerosing cholangitis

Patients with primary sclerosing cholangitis (PSC) are at increased risk for cholangiocarcinoma. This tumor usually is a fatal complication, median survival after diagnosis is less than six months. In an asymptomatic 29-year-old patient with long-standing PSC and ulcerative colitis, routine abdominal ultrasound demonstrated an irregular mass, 11 x 13 mm, in the gallbladder. Cholecystectomy was performed, and histological examination demonstrated a moderately differentiated adenocarcinoma with infiltration of all layers of the gallbladder and invasion of local lymphatic vessels. Extensive diagnostic work-up failed to consistently demonstrate metastatic disease, and the patient was offered a liver transplantation. 24 months after the operation, the patient feels well and there is no indication of tumor recurrence. In carefully selected patients with gallbladder carcinoma complicating PSC, liver transplantation may be a therapeutic option.     

The radiological management of biliary complications following liver transplantation

PURPOSE: Biliary complications contribute significantly to morbidity and mortality in the liver transplant recipient. Surgery has been the mainstay of therapy, but interventional radiological techniques have made significant progress. METHODS: Diagnostic percutaneous transhepatic cholangiography (PTC) was performed in 12 patients; percutaneous transhepatic drainage (PTD) was performed in 10 patients. Additional interventional procedures included laser lithotripsy, biopsy, dilatation, and stent implantation. RESULTS: In 6 patients PTC revealed anastomotic, and in 6 patients nonanastomotic biliary strictures. Four patients had intrahepatic stones. Biliary strictures were treated by implantation of Palmaz stents in 5 of 6 patients with anastomotic strictures, and in 3 of 6 patients with nonanastomotic strictures. The intrahepatic stones were fragmented with dye laser lithotripsy under cholangioscopic control in 3 of 4 patients. One spontaneous stent migration after 24 months and one stent occlusion were observed; the remaining stents are still patent. Patients with anastomotic strictures had a more favorable outcome: 5 of 6 of these patients are still alive and symptom-free after an average of 27.4 months, but only 3 of 6 patients with nonanastomotic strictures are alive after an average of 9.8 months. CONCLUSION: The different outcomes in patients with anastomotic versus nonanastomotic strictures may be explained by the different causes of these types of stricture.     

Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis

Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well-characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC-E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre- and post-orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non-PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that supports the concept of recurrence of PBC after OLT. The appearance of biliary epithelial abnormalities before the clinical appearance of disease is important not only for liver transplantation but also for understanding the natural history of PBC.     

Diffuse biliary tract involvement mimicking primary sclerosing cholangitis in an experimental model of chronic graft-versus-host disease in mice

In a previous study, protein components purified from latex gloves that elicited allergenic reactions were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and yielded apparent molecular weights of 14, 22, 30, 34, 46, and 58 kD. These allergenic components were isolated for further characterization by capillary zone electrophoresis and N-terminal amino acid sequence analysis. These components all migrated at approximately 25 and 35 min on capillary zone electrophoresis. Diode array spectral analysis detected indistinguishable characteristics between these two protein peaks. In addition, complex formation of these components with patients' immunoglobulin was demonstrated by capillary zone electrophoresis. Analysis of components separated by SDS-PAGE on a polyvinylidene difluoride membrane showed that the first 13 residues were identical to the sequence of hevein. Based on the criteria of charge-to-mass ratio and N-terminal amino acid sequence, our results suggest that these components of latex proteins are similar in the primary structure.     

Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases

OBJECTIVE: We report five cases (four male; median age 20 yr, range 14-38 yr) of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. The patients presented with jaundice, elevated serum aminotransferase and alkaline phosphatase activities, hyperglobulinemia with high immunoglobulin G (IgG) levels, circulating antinuclear and/or smooth muscle autoantibodies (> or = 1:40), and moderate to severe interface hepatitis on liver biopsy (with biliary features in four). METHODS: All five fulfilled criteria for diagnosis of "definite" autoimmune hepatitis and showed marked responses to prednisolone and azathioprine therapy, with relapses occurring during reduction or withdrawal of treatment. Cholangiographic features of primary sclerosing cholangitis were found in three patients at presentation and after intervals of 7 and 14 yr in the other two. Only two had evidence of inflammatory bowel disease. Diagnostic criteria for identifying those patients who may benefit from immunosuppressive therapy were reviewed. RESULTS: Review of the literature revealed only 11 similar cases that were sufficiently well described for comparison. However, in contrast to these and the present cases, preliminary data from other studies have suggested a marked association with ulcerative colitis and a poor response to immunosuppressive therapy. CONCLUSIONS: It is recommended that the possibility of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome responsive to immunosuppressive therapy should be considered in any patient presenting with a hepatitic illness with hyperglobulinemia, antinuclear or smooth muscle autoantibodies, and biliary changes on liver biopsy. Cholangiography should be considered in such patients.