Between January 1982 and April 1989, 134 patients with a suspected liver neoplasm were referred to the liver unit, Queen Elizabeth Hospital, Birmingham. In 105 (78 per cent), a primary hepatic neoplasm was histologically confirmed, and 47 patients (45 per cent) proved to have primary hepatocellular carcinoma. Twenty-nine orthotopic liver transplants were performed in 28 of these patients (27 per cent). Twenty patients (71 per cent) survived 30 days or longer (median 11.5 months; range 2-87 months), of whom nine are currently alive. We retrospectively analysed our data to determine the influence of preoperative evaluation, histological type and staging on outcome. Computed tomography proved to be superior to intraoperative assessment (86 versus 58 per cent) in diagnosing tumour positive nodes. Patients with tumour negative lymphadenopathy had a better prognosis. Postoperative stage I/II had a median survival of 16 months (range 3-87 months) compared with 7.5 months (range 2-20 months) for stage III. Non-cirrhotic patients with hepatocellular carcinoma had the best prognosis; cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year. Because of the advanced stage of disease at the time of presentation, the value of liver transplantation in primary liver cancer is limited. For those presenting with advanced disease confined to the liver (stage I/II) in whom conventional hepatic resection is not possible, significant benefit can be achieved in selected cases.

Adenoma, Bile Duct↗

PubMed1990

Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning.

Biliary tract obstruction or anastomotic leakage are common problems following liver transplantation. In a sequential study, 31 patients with a liver transplant were investigated by 99mTc-IODIDA (IODIDA) scanning and T tube cholangiography (TTC) and the results were compared with clinical outcome. Seven patients had an extrahepatic biliary obstruction and one patient had a biliary leak. In the detection of biliary complications TTC and IODIDA scanning were similar in terms of sensitivity (63 per cent for both) but TTC had a better specificity (79 per cent versus 60 per cent) and accuracy (74 per cent versus 60 per cent) than IODIDA scanning. When liver function was taken into account, the diagnostic efficacy of both tests in patients with bilirubin levels of less than 200 mumol/l was similar. With levels greater than 200 mumol/l there was a greater number of false positive results with IODIDA scanning (12 per cent versus 54 per cent). The only significant biliary leak was clearly detected by TTC but not IODIDA scanning. TTC remains the more effective way of evaluating the biliary tract after transplantation. IODIDA scanning has limited value when bilirubin levels are elevated, but may provide additional information about blood supply, hepatocyte function and intrahepatic cholestasis.

Adolescent↗

PubMed1990

Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection.

The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post-transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0-3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post-transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.

Antibodies, Monoclonal↗

PubMed1990

Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with ciclosporin.

Circulating osteocalcin, a non-collagen bone protein is considered a useful indirect index of turnover. Osteocalcin levels were measured by radioimmunoassay in 57 female patients with primary biliary cirrhosis (PBC) from two centres, 52 normal female controls, 11 female patients following liver transplantation for PBC and seven female patients with PBC treated with Ciclosporin. Serum levels were significantly less in the PBC group (median 10 ng/ml) compared to normals (median 15 ng/ml: p less than 0.001). Patients with PBC treated with Ciclosporin had significantly higher levels than untreated patients (median 23 ng/ml: p less than 0.001). Levels also increased significantly following transplantation when all patients were receiving Ciclosporin (median 40 ng/ml: p less than 0.001). The results suggest that the abnormal bone metabolism of PBC is significantly altered by Ciclosporin and liver transplantation.

Adrenal Cortex Hormones↗

PubMed1990

Drug metabolism in end-stage liver disease. In vitro activities of some phase I and phase II enzymes.

The activities of a number of drug metabolising enzymes were measured in liver samples obtained from three groups of subjects: normal donors, patients with primary biliary cirrhosis (PBC), and patients with other types of liver disease. In the latter group, all the enzyme activities determined were impaired relative to the normal group. In the PBC group, however, enzyme activities were altered more selectively. (a) Activities of the methyl cholanthrene-inducible forms of cytochrome P-450 were decreased compared to normal controls, whereas the activities of the phenobarbitone-inducible isozymes were relatively unaffected. (b) Sulfotransferase activities were decreased significantly compared to the normal group, whereas sulfatase activities remained unaltered.

Adolescent↗

PubMed1990

Portal hypertension secondary to sigmoid colon arteriovenous malformation.

A case of portal hypertension secondary to an arteriovenous malformation of the sigmoid colon is presented. The importance of mesenteric angiography in the diagnosis of this condition is discussed. The dramatic clinical improvement in this case following surgery emphasizes that arteriovenous malformations of the gastrointestinal tract represent a potentially curable cause of portal hypertension.

Adult↗

PubMed1990

Hypocalcaemia and serum levels of inorganic phosphorus, magnesium parathyroid and calcitonin hormones in the last month of pregnancy in Awassi fat-tail ewes.

Serum levels of calcium (Ca), inorganic phosphorus (P), magnesium (Mg), parathyroid (PTH) and calcitonin (CT) hormones of fat-tail Awassi ewes were determined during the last month of pregnancy. The incidence of hypocalcaemia (HCE) was 13.4% of the obstetrical cases examined. Twenty-six (81.3%) of 32 ewes with HCE were 4 yr of age or older. Significant decreases (p less than 0.01) in serum Ca levels from normal values or controls (n = 6; 10.04 +/- 0.22% (w/w)) to pathological values (4.30 +/- 0.35% (w/w)) caused severe clinical manifestations in 75% of affected ewes. This HCE was accompanied by a significant increase in the PTH level (142.6 +/- 9.1 pmol/l in comparison to 99.7 +/- 9.3 pmol/l in controls, p less than 0.05) and significant decrease in serum CT level (98.2 +/- 7.6 pg/ml in comparison to 144.6 +/- 25.7 pg/ml in controls; p less than 0.05). Intravenous administration of Ca borogluconate yielded normal Ca levels which were accompanied by a decrease in serum PTH levels and an increase in CT levels to normal values.

Animals↗

PubMed1990

Inhibition of leukocyte chemotaxis by immunosuppressive agents. Specific inhibition of lymphocyte chemotaxis by cyclosporine.

Since chemotaxis is an important mechanism by which leukocytes are recruited to allografts during rejection, the effect of immunosuppressant agents on in vitro chemotactic responses of neutrophils, monocytes, and lymphocytes was studied. Cyclosporine caused profound inhibition of lymphocyte chemotaxis to three different chemotactic factors at pharmacologic levels but had no effect on neutrophil or monocyte chemotaxis. Methylprednisolone and azathioprine both inhibited chemotactic responses of neutrophils and monocytes as well as lymphocytes. These data suggest that immunosuppressant agents are potent inhibitors of leukocyte chemotaxis and that drugs differ as to which leukocyte cell type they inhibit. The selective action of cyclosporine might explain why this drug is ineffective in reversing established rejection episodes in which monocytes and neutrophils are also involved. Inhibition of leukocyte chemotaxis may be an important mode of action of immunosuppressant drugs, and drug regimes might be adjusted to cause selective inhibition of particular cell types.

Azathioprine↗

PubMed1990

Referral of patients with primary biliary cirrhosis for liver transplantation.

All patients with primary biliary cirrhosis referred to this unit for consideration for transplantation between April 1981 and January 1989 were analysed retrospectively to assess whether disease stage at referral affects the outcome after grafting and whether greater awareness of the benefits of the procedure means that patients are now being referred at an earlier stage. Seventy of the 107 patients have been grafted, with an overall one year actuarial survival of 62%. A better prognosis at the time of referral, as assessed by both serum bilirubin concentration and a mathematically derived prognostic index, was associated with a greater probability of survival after grafting. Patients in the tertile with the best prognosis (median serum bilirubin concentration at referral 84 mumol/l and estimated survival in the absence of transplantation of more than nine months) had a 78% one year actuarial survival after transplantation, whereas those in the tertile with the worst prognosis (median serum bilirubin concentration 467 mumol/l and estimated survival of less than four months) had a one year actuarial survival of only 50%. No trend towards earlier referral of patients, however, was shown using either of these two markers. This retrospective analysis suggests that many patients are being referred too late for an optimal outcome. We recommend that patients with primary biliary cirrhosis who are potential candidates for liver grafting should be referred to a transplant centre before the serum bilirubin concentration approaches 150 mumol/l.

Adult↗

PubMed1990