Current status of 21 patients who have survived more than 20 years since undergoing surgery for biliary atresia

Between 1952 and 1993, 289 patients with biliary atresia underwent surgery at the authors' institution. Twenty-two of them survived more than 20 years; one has since died of hepatic failure (at age 28 years). Of the 21 current survivors (age range, 20 to 39 years), 13 underwent hepatic portoenterostomy; the others had hepaticoenterostomy. None of these patients has undergone liver transplantation. Sixteen patients have led near-normal lives. This includes three married women, one of whom has given birth to a healthy baby boy. Of the six patients who had portal hypertension, three underwent both splenectomy and proximal splenorenal shunting in or before 1985. None of these patients has required additional treatment for portal hypertension. The quality of life of one patient has been severely affected by an unrelated condition (Turner's syndrome). A 22-year-old man was diagnosed as having intrahepatic stones 3 years ago. In another 22-year-old man, hepatic dysfunction developed after frequent episodes of cholangitis. He is now being considered for liver transplantation. The majority of the long-term survivors have good quality of life. However, a few continue to suffer from complications including recurrent cholangitis. Close long-term postoperative follow-up is required for patients with biliary atresia.     

Effects of cyclosporin A on various indices of cholestasis in kidney transplant recipients

A cholestatic syndrome has been reported as one of the main side effects of CyA therapy. The aim of the present study was to evaluate frequency and degree of severity of the cholestatic syndrome in a group of patients with renal transplant treated with CyA. In 55 patients we evaluated both clinical: jaundice, pruritus, presence of biliary lithiasis and biochemical parameters: total serum biliary salts (TBS), total bilirubin (TB), alkaline phosphatase (AP), gammaglutamyl transpeptidase (GGT), transaminase (AST, ALT), cholesterol (CT), triglycerides (TG), HDL-cholesterol (HDL-C) and compared them with a control group matched for sex and age. In the transplant patients significantly higher values of TBS, TB, AP (p < 0.05) were found; 55% of the patients had above mean values of at least one of the classical parameters of liver function and an higher frequency of biliary lithiasis was also found, in the absence of the classical risk factors. However, none of the patients presented severe signs of hepatic disease and to date it has never been necessary to stop treatment. In conclusion, our study shows that the dosage of CyA used at present is quite safe; however, it is necessary to monitor in these patients some parameters of liver function to prevent the minor side effects we observed from progressing into more serious damage.     

Reducing the addictiveness of cigarettes. Council on Scientific Affairs, American Medical Association

Biliary atresia is a disorder of infants in which there is obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction of bile flow. Untreated, the resulting cholestasis leads to progressive conjugated hyperbilirubinemia, cirrhosis, and hepatic failure. Biliary atresia has an incidence of approximately one in 10,000 live births worldwide. Evidence to date supports a number of pathogenic mechanisms for the development of biliary atresia. An infectious cause, such as by a virus, would seem most pausible in many cases. The clinical observation that biliary atresia is rarely encountered in premature infants would support an agent acting late in gestation. However, no infectious or toxic agent has been conclusively implicated in biliary atresia. Genetic mechanisms likely play important roles, even regarding susceptibility to other specific causes, but no gene whose altered function would result in obstruction or atresia of the biliary tree has been identified. The variety of clinical presentations support the notion that the proposed mechanisms are not mutually exclusive but may play roles individually or in combination in certain patients. Biliary atresia, when untreated, is fatal within 2 years, with a median survival of 8 months. The natural history of biliary atresia has been favorably altered by the Kasai portoenterostomy. Approximately 25 to 35% of patients who undergo a Kasai portoenterostomy will survive more than 10 years without liver transplantation. One third of the patients drain bile but develop complications of cirrhosis and require liver transplantation before age 10. For the remaining one third of patients, bile flow is inadequate following portoenterostomy and the children develop progressive fibrosis and cirrhosis. The portoenterostomy should be done before there is irreversible sclerosis of the intrahepatic bile ducts. Consequently, a prompt evaluation is indicated for any infant older than 14 days with jaundice to determine if conjugated hyperbilirubinemia is present. If infectious, metabolic, endocrine disorders are unlikely and if the child has findings consistent with biliary atresia, then exploratory laparotomy and intraoperative cholangiogram should be done expeditiously by a surgeon who has experience doing the Kasai portoenteostomy. Biliary atresia represents the most common indication for pediatric liver transplantation, representing more than 50% of cases in most series. Transplantation is indicated when symptoms of end stage liver disease occur, including recurrent cholangitis, progressive jaundice, portal hypertension complications, ascites, decreased synthetic function, and growth/nutritional failure.     

When your patient doesn''t want to leave

This is case report concerning secondary caustic sclerosing cholangitis following scolecide with concentrated sodium chloride solution (30%) during operation on a liver echinococcus cyst with involvement of the extrahepatic biliary apparatus only. Hepatojejunostomy is performed. Histological study of the liver demonstrates evidence of severe cholangitis, purulent cholangiolitis and suspected secondary biliary cirrhosis. In conclusion, it is stressed that dynamic postoperative follow-up of patients is mandatory to make early diagnosis of the complication and undertake operative treatment anticipating the development of a cirrhotic process. The search for new, effective scolicides, not damaging the biliary apparatus and hepatic parenchyma, is strongly recommended.     

A quasi-experimental study on the effect of upper gastrointestinal surgery on liver function tests

BACKGROUND/AIMS: To determine the effect of upper gastrointestinal (UGI) surgery on liver function tests, a study was performed at Loghman Hakim Hospital, Tehran, Iran. METHODOLOGY: In this quasi-experimental study, 60 patients undergoing UGI operations were compared to 20 patients with extra-abdominal surgery. In each case, after obtaining a thorough past medical history and physical exam, 5 ml of fasting venous blood was drawn pre-operatively on the morning of the operation, and liver function tests (LFTs), namely serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH), were measured. The three tests were repeated on the morning of days 2 and 4, post-operatively. Other intra- and post-operative parameters were also recorded. Finally, the results were analyzed in all 80 cases using the Student's t-test, Yate's corrected chi-square and Pearson's coefficient of correlation. RESULTS: The operations performed in the case group were biliary tract operations (75%), surgery on the esophagus and stomach (18.3%) and liver and pancreas operations (6.7%). The control operations consisted of head and neck surgery (45%), breast and thorax operations (35%) and prostate and testes surgery (20%). The mean duration of general anesthesia in the cases and controls was 3.62 and 3.58 hours, respectively, with no statistically significant difference. The SGOT level increased 54% in the study cases on day 2, which significantly differed with the 9% increase in the controls (p<0.05). In the cases studied, SGPT increased 65% on day 2 and 50% on day 4, with a significant difference compared to the 2% decrease and 2% increase on days 2 and 4 in the controls (p<0.005 and p<0.02, respectively). LDH levels also increased 17% on day 2 in the case group with a significant difference compared to the 8% increase in controls (p<0.05). CONCLUSIONS: An increase in the levels of SGOT, SGPT and LDH in the first 4 days following UGI surgery is a common problem which seems to be due to local trauma to the liver rather than the effect of other factors such as anesthetic drugs, the duration of surgery, blood transfusions, hypotension and other underlying conditions.     

Primary biliary stones: diagnosis and management

To review the results of treatment of primary biliary stones, 96 consecutive patients managed from 1991 to 1996 were studied retrospectively. Acute cholangitis and abdominal pain were the presenting symptoms in 57 patients (59%) and 29 patients (30%), respectively. Fifty-four patients (56%) had a history of biliary surgery. Endoscopic retrograde cholangiopancreatography, ultrasonography, and computed tomography were frequently employed for diagnosis of primary biliary stones and were performed on 84 patients (88%), 90 patients (94%), and 89 patients (93%), respectively. Intrahepatic stones were identified in 91 patients (95%) and biliary strictures in 34 patients (35%). Concomitant cholangiocarcinoma occurred in 15 patients (16%). Hepatic resection was required in 55 patients (57%) for removal of an atrophic liver lobe or a segment related to repeated infection, biliary strictures, liver abscesses, or cholangiocarcinoma. Intraoperative choledochoscopy was routinely performed in all patients to detect, remove, or confirm clearance of biliary stones. A hepaticocutaneous jejunostomy (HCJ) was constructed in 70 patients (73%) to facilitate postoperative choledochoscopic examination or biliary stone extraction. Twenty-two patients (23%) had residual stones and required postoperative choledochoscopic extraction. Complete eradication of residual stones was achieved in all patients. Postoperative morbidity occurred in 28 patients (29%), and there was one hospital death (a patient with cholangiocarcinoma). With a median follow-up of 26 months (range 2-62 months), stones recurred in three patients. In conclusion, the early results of treatment of primary biliary stones were satisfactory owing to a systematic, aggressive approach that consisted of hepatic resection, frequent construction of an HCJ, and postoperative choledochoscopy.     

Endoscopic retrograde cholangiopancreatography in the orthotopic liver transplant patient

BACKGROUND AND STUDY AIMS: Diagnostic imaging of the biliary tract is often required in liver transplant recipients, preoperatively to assess extent of biliary tract disease and postoperatively in patients with a suspected biliary complication due to an abnormal postoperative course. PATIENTS AND METHODS: Over a six-year period, 115 patients received 127 liver transplantations at our institution. Twenty-three preoperative ERCPs were performed in 17 patients, while 25 ERCPs were performed on 15 patients after liver transplantation. RESULTS: Preoperative ERCP in seven of 17 patients revealed a dominant biliary stricture as a result of primary sclerosing cholangitis (PSC); five of these patients were managed successfully with the placement of biliary endoprosthesis. An additional nine patients with PSC underwent brush cytology of the extrahepatic bile ducts to rule out coexisting cholangiocarcinoma; there were no positive results, although three were found to have coexisting cholangiocarcinoma after examination of the explanted liver. Postoperatively, nine of 15 patients were found to have biliary tract disease. These included five biliary strictures (three treated successfully by endoscopic dilation and stent therapy), two biliary leaks (treated by biliary endoprosthesis), one biloma (treated by percutaneous drainage) and one intraductal stone (treated successfully by sphincterotomy and stone extraction). The remaining six patients showed no abnormality at ERCP, and were subsequently diagnosed with allograft rejection. CONCLUSIONS: Diagnosis of biliary complications after hepatic transplantation is often problematic. Definitive characterization frequently requires cholangiography. Interventional biliary procedures, both endoscopic and percutaneous, can be used successfully to treat these complications; however, surgical revision and retransplantation are sometimes required.     

Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders

BACKGROUND: Retroviruses have been implicated in the aetiology of various autoimmune diseases. We used immunoblots as a surrogate test to find out whether retroviruses play a part in the development of primary biliary cirrhosis. METHODS: We did western blot tests for HIV-1 and the human intracisternal A-type particle (HIAP), on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers. FINDINGS: HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0.003). Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in four (17%) of those with other biliary diseases. None of the 23 patients with either alcohol-related liver disease or alpha1-antitrypsin deficiency, and only one of the healthy controls showed the same reactivity to HIAP proteins (p<0.0001). Our results showed a strong association between HIAP seroreactivity and the detection of autoantibodies to double-stranded DNA. HIAP seroreactivity was also strongly associated with the detection of mitochondrial, nuclear, and extractable nuclear antigens. INTERPRETATION: The HIV-1 and HIAP antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses.     

Magnetic resonance cholangiography for evaluation of cholestatic jaundice in neonates and infants

Distinguishing extrahepatic biliary atresia from other causes of cholestasis in neonates and infants is important because surgical intervention before 2 months of age allows for long-term survival. The purpose of this prospective study was to evaluate the usefulness of magnetic resonance (MR) cholangiography in differentiating biliary atresia from other causes of cholestatic jaundice in neonates and infants. Nine anicteric infants (control group) aged 10 to 224 days (mean +/- SD, 8 +/- 65 days) and 15 neonates and infants with cholestatic jaundice, aged 22 to 142 days (mean +/- SD, 71 +/- 37) underwent MR cholangiography. The final diagnosis of extrabiliary atresia (6 patients) was based on laparotomy findings (4 patients) or autopsy (2 patients), while neonatal hepatitis (9 patients) was diagnosed according to the liver biopsy findings and clinical recovery during follow-up. Percutaneous liver biopsies were performed in all 15 patients. Results showed that the gall bladder and common bile duct (CBD) could be visualized using MR cholangiography in all patients in the control group. Nonvisualization of the CBD (6/6 patients) and demonstration of a small gall bladder (6/6 patients) characterized MR cholangiography findings in patients with biliary atresia. MR cholangiography failed to depict the CBD in one infant with hepatitis. We conclude that demonstration of the CBD by MR cholangiography in neonates and infants with cholestasis can be used to exclude the diagnosis of biliary atresia. In patients with cholestatic jaundice considered for exploratory laparotomy, preoperative MR cholangiography is recommended to avoid unnecessary surgery.     

Total anomalous pulmonary venous return complicating portoenterostomy for biliary atresia

Cardiovascular anomalies such as absent inferior vena cava and preduodenal portal vein are reported in cases of biliary atresia and make hepatic portoenterostomy a technical challenge. The authors present the case of a severe cardiac anomaly that significantly altered the functional outcome of a Kasai procedure. Baby M., an 8-week-old boy born with total anomalous pulmonary venous return (TAPVR), underwent hepatic portoenterostomy for biliary atresia. Over the next 3 months he remained icteric and febrile, and failed to gain weight. After multiple antibiotic treatments for suspected cholangitis, he underwent reexploration of the portoenterostomy, with no improvement in his overall condition. His prognosis was considered dismal because correction of the cardiac anomaly is associated with a high mortality rate (> 90%). The cardiac surgeon agreed to attempt a cure of the TAPVR, provided liver transplantation is contemplated if the patient survived. Within 48 hours postoperatively, his hepatic function had improved drastically. He became afebrile, had an improved appetite and weight gain, and was finally discharged 203 days after admission. One year later, he is thriving and remains anicteric. The exact reason for this drastic improvement is not well understood, but the right-sided cardiac failure caused by the TAPVR had a significant effect on the functional outcome of the portoenterostomy.     

Preferential V beta3 usage by hepatic T lymphocytes in patients with primary sclerosing cholangitis

BACKGROUND/AIMS: Primary sclerosing cholangitis and primary biliary cirrhosis are two biliary destructive disorders characterized by prominent T lymphocyte infiltrates in areas of portal destruction. The specificity of the T cell is determined by the T cell receptor for antigens. The aim of this study was to investigate the preference by which certain V alpha and V beta gene segments are expressed by peripheral and hepatic T cells in primary sclerosing cholangitis and primary biliary cirrhosis. METHODS: The usage of the alpha/beta T cell receptor (TcR) V gene of liver infiltrating lymphocytes and peripheral blood lymphocytes from 12 primary sclerosing cholangitis patients, 10 primary biliary cirrhosis patients and healthy controls was investigated, using alpha/beta TcR V gene product-specific monoclonal antibodies. HLA class II antigen typing with genomic typing technique was done in 11/12 primary sclerosing cholangitis patients. RESULTS: A significant difference between the studied groups of patients was an increase in the expression of V beta3+ T cells in liver tissue from patients with primary sclerosing cholangitis compared to patients with primary biliary cirrhosis and healthy controls (p<0.01). No significant differences were found in the peripheral blood between the three groups. Furthermore, no relation between the different TcR V alpha/beta cells and histological staging and class II antigen association was observed. CONCLUSIONS: Predominant TcR V beta3 gene usage in liver tissue in primary sclerosing cholangitis may indicate the presence of a specific antigen in this tissue with the capacity of selectively driving T cells, utilizing the V beta3 gene segment product, in primary sclerosing cholangitis patients.     

Altered hepatic hemodynamics and improved liver function following intrahepatic vascular infusion of prostaglandin E1

Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1 influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we carried out an experimental and a clinical study. PGE1 was continuously administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of 0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in eight patients PGE1 was administered through the hepatic artery at a rate of 0.01 micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic hemodynamics and oxygen metabolism did not change during the administration of PGE1 into the portal vein. During administration of PGE1 into the hepatic artery, hepatic arterial flow increased 1.5-fold after administration compared to the rate before administration (P < 0.01). Hepatic arterial pressure, hepatic arterial resistance, and post-sinusoidal resistance significantly decreased after administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen supply increased significantly (P < 0.01). In the patients, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels remained low after surgery, and the recovery of protein synthesis was improved compared with that in eight hepatectomized patients without PGE1 administration (controls). The intrahepatic arterial infusion of PGE1 was considered useful for the recovery of liver function.     

Early stopping of a clinical trial when there is evidence of no treatment benefit: protocol B-14 of the National Surgical Adjuvant Breast and Bowel Project

In patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), risk score models that reflect disease severity have been developed and can serve as an objective measurement to assess and evaluate the effect of the severity of liver disease on the outcome of liver transplantation. Thus, using the established Mayo risk scores for PBC and PSC, one not only can estimate survival for the individual patient but can measure disease activity as well. Indeed, several studies have suggested that the optimal timing of liver transplantation with use of the Mayo PBC model may be an important tool to improve survival, decrease morbidity, and decrease overall related costs. Likewise, studies in patients with PSC have yielded similar results. This review explores how prognostic mathematical survival models for PBC and PSC might be applied to individual patients in need of liver transplantation. The following question is addressed: How can the timing of liver transplantation be optimized to increase survival, decrease postoperative morbidity, and ultimately, decrease the overall resource utilization involved in this procedure?     

A comparison of parameters used to assess liver damage in sheep treated with carbon tetrachloride

Changes in serum enzyme levels, liver histology and liver function tests have been correlated to determine the usefulness of these tests in assessing liver status. The effects of carbon tetrachloride administration on these parameters has been determined in a group of 20 sheep. Normal levels, elevated levels after injury and the effect of elapsed time after injury are reported for serum glutamic dehydrogenase, sorbitol dehydrogenase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, fructose-1-phosphate adlolase, alkaline phosphatase, cholesterol and proteins. Variation in the time of elevation of enzyme activities may be useful in determining the elapsed time between acute injury and serum sampling. In comparison to sheep fed an adequate diet, a diet with a restricted protein intake was associated with increased severity of histological lesions and decreased liver function.     

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.     

Long-term survivors in biliary atresia--findings for a 20-year survival group

Recently, there has been remarkable increase in the survival rate in cases of biliary atresia (BA). However, long-term survivors are as yet a small population. Of the total of 152 patients undergoing surgery for BA during the period from 1969 to 1995 in our institution, 39 of them were operated on more than 20 years ago with follow up for all but one of these, who can no longer be accounted for. Six are still alive, 1 male, and 5 females, two cases being of type I BA, and the other 4 of type III and 1 is unaccounted for. The prognosis of these individuals was clinically evaluated. At the present time, none of them is receiving hospital care, but 3 have experienced sequelae. Two patients required partial splenic embolization (PSE), endoscopic infusion sclerotherapy (EIS), and/or gastroesophageal decongestion and splenectomy (Hassab's operation) (Hassab 1967) for hypersplenism and/or portal hypertension. The other has needed hospital care for recurrent cholangitis. Laboratory investigations revealed a serum total bilirubin (TB) of less than 1.0 mg/100 ml in 3 of the 5 patients for which samples could be obtained, between 1.0 and 2.0 mg/100 ml in 1, and in excess of this in the remaining case. The 1-alanine 2 oxoglutarate aminotransferase (ALT) level was within the normal range in only 1, and was mildly to moderately elevated in 4. The white blood cell count (WBC) was less than 3,000/microliter and the platelet count was less than 10 x 10(4)/microliter in 1, and within the normal ranges in the other 4 patients. The results thus indicate that occult and progressive liver damage may occur in long-term survivors of BA.     

Anatomic anomalies in neonatal cholestatic jaundice

Disorders of the biliary tree are an important cause of cholestatic jaundice in infancy. For the most frequent diseases in this group, biliary atresia and choledochal cyst, prognosis is strongly dependent on timely diagnosis and treatment. In biliary atresia the bile flow is obstructed due to obliteration of the extrahepatic bile ducts. Construction of an hepatic portoenterostomy before 60 days of age will result in restoration of bile flow in the vast majority of patients. When failed, the disease is progressive and ultimately fatal, unless a liver transplantation is performed. For those patients in which restoration of the bile flow succeeds, the subsequent course is strongly dependent on the occurrence of cholangitis. For all patients fat-soluble vitamins should be supplemented and caloric intake should be carefully monitored. Presentation of a choledochal cyst can be either before or after the first year of life. It is mostly characterized by jaundice, with or without abdominal pain. Therapy consists of resection of the cyst, followed by a hepatico-jejunostomy. Paucity of bile ducts is an intrahepatic disorder, in which--almost--no bile ducts can be found in the portal tracts. This anomaly is frequently found in combination with a typical facies, a pulmonary stenosis and vertebral anomalies, a combination which is called Alagille syndrome. Prognosis is generally good.     

Psychiatric disorder and metabolic control among youths with IDDM. A longitudinal study

PURPOSE: To analyze the influence of liver dysfunction and parenchymal pathology on the accumulation of superparamagnetic iron oxide (SPIO). METHODS: We evaluated MR images of 13 patients having small hepatic neoplasms before and after administration of SPIO (10 micronol/kg). Biopsy and laboratory data confirmed the presence of severe cirrhosis in two patients, mild cirrhosis in four, chronic hepatitis in five, and normal livers in two. Degrees of liver dysfunction or liver parenchymal pathology were correlated with reductions in signal intensity of the liver and spleen after administration of SPIO. Signal intensity reduction was evaluated using a 1.5 Tesla MR unit. RESULTS: Response to SPIO of the liver and spleen did not correlate with liver parenchymal pathology, although reductions in signal intensity of the liver were somewhat small in severely cirrhotic livers. There were slight correlations between signal intensity alterations of the liver and laboratory data such as the indocyanine green retention rate (correlation coefficient 0. 47), albumin (0.36), total bilirubin (0.36), and serum glutamic oxaloacetic transaminase (GOT) (0.46). Signal intensity reduction of spleen did not correlate with liver function tests except for serum GOT. In patients with cirrhosis, heterogeneous structures were detected in the nontumorous portions of the liver. However, these did not prevent the diagnosis of small hepatomas. CONCLUSION: The uptake of SPIO showed some correlation with liver function but not with chronic liver parenchymal pathology. SPIO provided sufficient contrast between tumor and surrounding liver parenchyma among patients with chronic liver disease.     

Molecular mechanisms of development of multiple endocrine neoplasia 2 by RET mutations

Although ischemic cholangitis is an important cause of early cholestatic graft failure in hepatic allografts, it rarely leads to biliary tract abnormalities in the late postoperative period. We describe a 54-year-old woman who underwent orthotopic liver transplantation for alcoholic liver cirrhosis in 1988 and presented in April of 1995 with malaise, jaundice, dark urine, clay-colored stools and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated a rapid progressive sclerosing cholangitis. Liver biopsy findings showed mild portal hepatitis, specimens were non-diagnostic with regard to cholangitis, and no infection was found. Duplex ultrasonography suggested obstruction of hepatic artery blood flow and celiac arteriogram confirmed complete hepatic arterial occlusion. Progressive destruction and irregular stricturing and dilatation of the intra- and extrahepatic biliary tree, complicating ascending infectious cholangitis, progressive cholestatic jaundice and insufficient endoscopic biliary drainage made a hepatic retransplantation in 1995 mandatory. Ischemic cholangitis is an important cause of cholestatic graft failure, but this type of cholangitis is difficult to diagnose because of its misleading biopsy manifestations. We conclude that liver transplant recipients who exhibit nonanastomotic strictures on cholangiography should be evaluated for occlusion of the hepatic artery as a possible cause.     

The new age of liver transplantation

The advent of cyclosporin A for immunosuppression (IS) in liver transplantation (LTx) in the early 1980s heralded a new age for LTx, resulting in widespread application, rapidly expanding indications, relaxation of restrictions in donor selection and advances in the preservation of liver grafts and management of LTx operations. Liver transplantation, together with the transplantation of other organs (kidney, pancreas, heart, heart-lung, intestine), became possible. In Australia, around 125 LTx (22% in children) are performed each year. Indications are: primary sclerosing cholangitis; primary biliary cirrhosis; auto-immune hepatitis; chronic viral hepatitis; biliary atresia; metabolic disorders; fulminant hepatic failure (FHF); alcoholic cirrhosis; and malignancy (cancer, CA). Since 1965, 810 patients underwent LTx and 70 (9%) re-Tx. Patient survivals at 1, 5 and 9 years post-Tx are 80, 74 and 66%, respectively. Patients with primary diseases that recur in the LTx (hepatitis B and CA) do less well following LTx, with 5-year survival rates of 55 and 40%, respectively). Recent developments include: increasing the availability of donor organs by the use of living donors, 'split' cadaveric donor (CD) grafts, 'marginal' and non-heart-beating CD grafts and xenografts; expanding the indications for LTx; development of effective liver support systems for patients with FHF; the treatment of diabetics with liver failure with islet Tx (at the time of LTx); more effective immunosuppression; and methods to diminish recurrent disease in LTx. Some understanding of the unique 'tolerogenic' capabilities of the liver has come with the recognition of 'two-way microchimerism'. The satisfactory 5-9 year outcomes for patients underline the cost-effectiveness of LTx.