Poorer survival in patients whose explanted hepatocellular carcinoma (HCC) exceeds Milan or UCSF Criteria. An analysis of liver transplantation in HCC in Australia and New Zealand.

BACKGROUND: Milan and University of California San Francisco (UCSF) Criteria have been used for selection of patients with hepatocellular carcinoma (HCC) for liver transplantation (LTx). The aims of this study were to analyse the results of LTx for HCC in Australia and New Zealand with emphasis on the effects of discordance between pre-LTx radiological and post-LTx pathological staging. METHODS: A total of 186 LTx for HCC carried out between July 1985 and August 2003 were included. Patients were categorized according to the Milan and UCSF Criteria. RESULTS: The median follow-up was 6.55 years (range 2.96-20.93 years). Pre-LTx factors associated with better survival include tumour size < or = 5 cm, number of tumours < or = 3, staging within Milan and UCSF Criteria and more recent transplantation (1996-2003). In all, 14 patients had a pre-LTx stage outside the Milan but within the UCSF Criteria. One- and 5-year patient survival rates were, respectively, 88% and 74% within the Milan Criteria, and 87% and 73% within the UCSF Criteria. Vascular invasion, capsular invasion, lymph node invasion and pathological stage outside UCSF Criteria were associated with poor outcome. Of patients within the Milan and UCSF Criteria pre-LTx, 24% and 18%, respectively, were outside the same criteria post-LTx. These patients had poorer survival rates. CONCLUSIONS: The use of the UCSF Criteria in this cohort increased the number of patients eligible for LTx without compromising 5-year survival rates. Patients whose explant tumours were outside the Milan or UCSF Criteria had poorer outcomes compared with those whose explants remained within these criteria.

Liver transplantation in Jehovah's Witness patients in Australasia.

Until recently, liver transplantation was contraindicated in Jehovah's Witness patients because of recipient-imposed restrictions on use of blood products. However, recent improvements in surgical and anaesthetic techniques and new procoagulant agents challenge this practice. We describe two Jehovah's Witness patients who had successful liver transplantation without blood transfusion. To our knowledge, these are the first such cases in Australasia. The techniques used to minimise blood loss and transfusion requirements could potentially benefit all patients undergoing major surgery.

Analysis of the outcomes of a visiting surgical service to small rural communities.

BACKGROUND: A team of visiting surgeons has provided regular clinics and day surgery to rural locations in country towns away from resident surgical centres. This format has provided continuity of care for 7 years despite a constantly changing medical workforce. The aim of the present study was to review the results of the group and to compare them against national standards and to provide a model for future outreach programmes. METHODS: All patient diagnoses, procedures and clinical outcomes were recorded prospectively. This record of activity was then collated. District hospital records and clinical notes have been rechecked for complications over a discrete 4 year period. RESULTS: There have been 7419 items of service provided, including 2676 procedures. The diagnostic grouping and subsequent day-surgery activity are consistent with the top 30 surgical separations from all Australian hospitals. These patients have been found suitable to remain in their own home environment for treatment. CONCLUSION: Experienced surgeons operating on selected patients with careful nursing care, in small country hospitals have outcomes similar to urban hospitals.

A short course of mycophenolate immunosuppression inhibits rejection, but not tolerance, of rat liver allografts in association with inhibition of interleukin-4 and alloantibody responses.

BACKGROUND: Some immunosuppressive drug therapies inhibit transplant tolerance in animal models, and we have shown that treatment of recipients with methylprednisolone, but not cyclosporine, inhibits spontaneous acceptance of liver transplants. This study investigates the effects of mycophenolate mofetil (MMF) on liver acceptance and rejection. METHODS: Piebald Virol Glaxo rat livers were transplanted into Dark Agouti recipients, which spontaneously tolerate (TOL) the liver, or into Lewis recipients, which reject (REJ) the liver. MMF (40 mg/kg/day subcutaneously) was given for 5 days from days 0 to 4 (early) or from days 3 to 7 (late). In separate experiments, liver grafts were collected for assessment of infiltrate and of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma mRNA expression. RESULTS: TOL liver transplants had a median survival time (MST) of more than 100 days (n=6), and neither early nor late MMF treatment of TOL transplants reduced survival (MST 85 days, P=0.19 and 78 days, P=0.08, respectively). Liver failure in most of these animals was the result of biliary problems, not rejection. There were few consistent differences between treated and untreated TOL animals in infiltrate or liver cytokine expression, although there was a moderate reduction in T-cell infiltrate in MMF-treated TOL animals (P=0.003 on day 5 TOL). In contrast, REJ transplants had an MST of 13 days (n=10), and early MMF treatment led to five of six animals surviving more than 100 days (P=0.0002), whereas late treatment was much less effective, with one of six animals surviving more than 100 days. REJ livers had significantly more IL-4 mRNA expression and immunoglobulin G1 deposition in the graft than TOL livers, and this was inhibited by early, but not late, MMF treatment. CONCLUSIONS: MMF treatment inhibited rejection but not acceptance of liver allografts. Early administration was more effective in preventing rejection and demonstrated a more marked effect on IL-4 expression and alloantibody deposition than on graft T-cell infiltrate and expression of other cytokines.

Chylous ascites caused by portal vein thrombosis treated with octreotide.

Chylous ascites is an uncommon entity with variable causes and rarely arises from portal vein thrombosis. This is a case report of chylous ascites caused by idiopathic portal vein thrombosis that was refractory to medical therapy and shunt surgery, which showed an impressive response to treatment with subcutaneous octreotide. We review the literature on chylous ascites with particular reference to the role of somatostatin analogs in the management of this rare condition.

A short course of cyclosporine immunosuppression inhibits rejection but not tolerance of rat liver allografts.

BACKGROUND: Orthotopic liver transplants in many animal models are spontaneously accepted without requiring immunosuppression. Liver transplant acceptance is associated with early immune activation, and immunosuppressive drugs such as methylprednisolone inhibit acceptance. We investigated whether cyclosporine (CsA) inhibits rat liver transplant acceptance. We also examined the effects of CsA on infiltration and cytokine gene expression. METHODS: Orthotopic liver transplantation was performed in the PVG donor to Dark Agouti recipient rat strain combination, which accepts the graft (tolerance; TOL), and in the PVG-to-Lewis combination, which rejects the graft in 9 to 16 days (rejection; REJ). CsA (1.5 mg/kg per day subcutaneously) was given to recipients for 5 days, starting from the day of transplantation to day 4 or from day 3 to day 7. In a separate experiment, transplanted livers were collected at days 1, 3, 5, and 7 after transplantation and examined for infiltration by immunohistochemistry and for expression of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma mRNA by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Both early and delayed treatment with CsA significantly increased survival in the REJ strain combination, with a median survival time of 81 days and more than 100 days, respectively, compared with 13 days in the untreated group. Neither treatment affected survival of TOL animals, and all TOL groups had a median survival time of more than 100 days. Delayed treatment did not reduce survival; more animals survived for greater than 100 days after delayed treatment, although this did not reach significance ( P=0.08). T-cell infiltrate was inhibited in CsA-treated TOL animals compared with untreated animals at all times after treatment, whereas CD25 cells were only inhibited on day 3. CsA treatment of TOL grafts markedly reduced expression of IL-2, IL-4, and interferon-gamma compared with untreated recipients. CONCLUSIONS: CsA did not significantly inhibit liver transplant acceptance and allowed some activation of T cells and CD25 expression but almost completely inhibited IL-2 and IL-4, which are required for survival of activated T cells.

Disease recurrence after liver transplantation in Western Australia.

BACKGROUND AND AIM: Orthotopic liver transplantation (OLT) is now the accepted therapy for end-stage chronic liver disease. Long-term survival is now expected in the majority of patients and, consequently, disease recurrence has emerged as a major concern. Our aim was to document the rate of disease recurrence after liver transplantation for conditions other than hepatitis C, in patients followed up by the Western Australian Liver Transplant Service (WALTS). METHODS: The case notes of all post-OLT patients followed up by WALTS were reviewed. Patients were excluded if survival was less than 3 months post-OLT; OLT was performed for hepatitis C alone or follow up was unavailable. Detection and definition of disease recurrence depended on pretransplant diagnosis, and were based on patient interview, biochemical, immunological and serological tests. Radiological and histological confirmation were obtained where clinically indicated. RESULTS: Eighty-seven patients were identified (89 OLTs performed). The overall rate of recurrence was 10%. Recurrence rates by disease were: primary sclerosing cholangitis (17%), primary biliary cirrhosis (12%), autoimmune hepatitis (17%), hepatitis B (40%) and alcoholic liver disease (4%). Alcohol use relapse after transplantation occurred in 25%. The overall survival post-OLT was 87%, with a mean follow up of 53 months. Survival in patients with recurrent disease was 89%. CONCLUSIONS: Disease recurrence after OLT does occur, but overall, it is relatively uncommon. Recurrence rates vary significantly and depend, in part, on indication for OLT. With medium-term follow up, recurrent disease does not have an effect on mortality.

Open access endoscopy in rural and remote Western Australia: does it work?

BACKGROUND: Access to diagnostic endoscopy is limited in rural and remote Western Australia. Published reports suggest open access referrals may result in over-servicing, this is reduced by adherence to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines. The aim was to assess whether an outreach surgical service offering open access endoscopy to rural areas was being over utilized. METHODS: Prospective data collection from all patients undergoing upper and lower endoscopy procedures between January 1996 and June 2000 were included in the present study. Indications for referral between the general practitioners and the visiting surgeons were reviewed in patient records and assessed for compliance with the ASGE guidelines. The groups were analysed for appropriateness of referrals and frequency of positive pathology investigations. Records for all patients undergoing colonoscopy were reviewed to determine the reason and number of cancelled procedures. RESULTS: A total of 772 endoscopies were performed and 75% were booked as open access services. The referral rate for procedures was greater for general practitioners (583) compared to the visiting surgeons (189), the overall compliance rate for approved indications using the ASGE guidelines for both groups was 92%. There was no significant difference in pathology found between groups. CONCLUSION: The present study shows that an outreach rural surgical service programme in Western Australia offering open access endoscopy conforms to international guidelines and does not induce unnecessary procedures. Rural patients benefit from a personal cost savings and convenience. There is an associated reduction in government-assisted travel costs to larger centres as well as decreased waiting lists.