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Biomedical subjects

R W Strong

Publications and source records attributed to R W Strong.

At least 37 records · Page 2Linked to original sources

Liver transplantation in Japanese and Australian/New Zealand children with biliary atresia: a 10-year comparative study.

OBJECTIVE: To compare Japanese with Australian/New Zealand (ANZ) children with biliary atresia who were treated by liver transplantation, and evaluate the indications for and timing of transplantation. DESIGN: Retrospective study. SETTING: Queensland Liver Transplant Service (QLTS), Australia. SUBJECTS: 43 Japanese and 30 ANZ children with biliary atresia who required transplantation between 1985 and 1992. INTERVENTIONS: The 43 Japanese children had 52 transplants, and the 30 ANZ children had 33. MAIN OUTCOME MEASURES: Morbidity, mortality, and long term survival. RESULTS: The Japanese children had significantly lower serum albumin concentrations than the ANZ children preoperatively (mean (SD) 32 (7) g/L compared with 37 (5), p<0.05). The actuarial survival at 7 years of the ANZ children was significantly higher than that of the Japanese children (79% compared with 49%, p<0.05). There were 24 deaths (17 Japanese, 40%, and 7 ANZ, 23%); 2 of the ANZ and 7 of the Japanese children died more than a year after transplantation. All 26 children who were well-nourished at the time of transplantation defined as a Z-score (weight or height minus mean weight or height for age, sex, and race, divided by the SD) of -1 or more were alive at 1 month compared with 11 of the 47 poorly-nourished children (Z-score <-1). Survival among the Japanese declined after 1 year, and there was no association with Z-scores. Overall, Z-scores for weight improved significantly after transplantation, whereas those for height improved a little, but not significantly so. Japanese children were significantly shorter than ANZ children, and their Z-scores for height did not improve after transplantation. CONCLUSION: liver transplantation should be done as soon as possible for children with biliary atresia to maximise survival and growth.

Adolescent↗

1998 Distinguished Academician Lecture: hepatic resection--a Western perspective.

During the past two decades, resection of the liver has progressed from a rarely to a commonly performed operation with a low morbidity and mortality. The description of the functional anatomy of the liver was instrumental in the change from non-anatomic to anatomic resections. Major hepatectomies dominated the early experience but segment orientated resections now play a more prominent role. Resections may be performed for a variety of malignant or benign lesions or as an emergency for trauma or other catastrophic event. In the author's institution, 923 liver resections have been performed. The indications for the 825 elective resections were: metastases (46%), primary malignancy (30%) and non-malignant disease (24%). Two-thirds of the 98 emergency hepatectomies were for severe liver trauma. The 30-day mortality was 3.6% for the total series; 2.9% for elective resection, 1.6% for the non-jaundiced patients. In the last 300 elective resections, there has been one postoperative death and the median blood transfusion was zero. The development of innovative graft reduction techniques has made a major contribution to liver transplantation. The lack of suitable whole liver grafts for paediatric recipients was addressed by volume of reduction of adult donor livers so that the left lateral segment could be implanted safely in an infant's abdomen. This technique was the forerunner of split-liver transplantation, auxiliary partial orthotopic transplantation and living-related liver transplantation.

Adult↗

Additional techniques adopted for major vascular anastomoses during orthotopic liver transplantation.

Of 372 patients who underwent liver transplants between January 1985 and March 1995, 7 required variations in vascular anastomoses due to discrepancies in the size-match of the donor and recipient vessels, the presence of a thrombosed hepatic artery or portal vein, or complete absence of the portal vein. The techniques described herein enabled us to perform successful transplantation in all patients. Although rethrombosis of the portal vein developed in one patient after a third transplant, this patient remains clinically well. The use of an operating microscope and the harvesting of an extended length of donor superior mesenteric vein or vascular grafts of the donor iliac or saphenous vessels, for potentially difficult transplants, are invaluable techniques.

Adult↗

Anatomic resection for severe liver trauma.

BACKGROUND: Most publications during the past decade have condemned the use of anatomic resection for liver trauma and advocated a conservative surgical approach when operative intervention was required. This policy has been supported by the high mortality rate reported by most authorities. The purpose of this study was to assess the results of anatomic hepatic resection for liver trauma in an institution in which the hepatobiliary surgeons are responsible for the management of severe liver injuries. METHODS: During the period 1983 to 1996, 287 patients with liver injuries were admitted to the hospital and 37 patients with severe liver trauma underwent anatomic resection. Demographic, clinical, operative, and postoperative data were collected and analyzed. The resections performed included right hemihepatectomy (n = 27), left hemihepatectomy (n = 1), left lateral segment resection (n = 5), and segmental resection (n = 4). RESULTS: There were three postoperative deaths after right hemihepatectomy (11.1%) and an overall mortality rate of 8.1%. There were no intraoperative deaths. Postoperative complications occurred in 22 patients (60%) and were most frequent in patients with concomitant injuries to other systems. Liver-related morbidity occurred in seven patients (19%). The median postoperative stay was 20 days. CONCLUSIONS: Anatomic hepatic resection for trauma is associated with low mortality and liver-related morbidity rates when performed by experienced hepatobiliary surgeons, and its role in the management of severe hepatic trauma should be reevaluated.

Female↗

Peripheral blood chimerism following human liver transplantation.

The aim of this study was to prospectively investigate the peak levels and kinetics of donor leucocyte chimerism in human recipients following liver transplantation. The peak levels of chimerism were observed within the first 48 hours following transplantation and ranged from 0.15% to 20% of total peripheral blood mononuclear cells. In all but one patient, who developed graft versus host disease, there was an early peak level of chimerism that declined over time such that donor leukocytes were only intermittently detectable after 3 to 4 weeks. In 8 patients who had no episodes of graft rejection, the peak level of donor leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3 patients who were treated for episodes of acute graft rejection during the first four postoperative weeks, the peak level of donor leukocyte chimerism ranged from 0.15% to 0.2% (0.18 +/- 0.02, P = .012). The results demonstrate a marked variation in the total number of donor leukocytes detectable in the peripheral blood early after liver transplantation and also, that lower levels of chimerism may be associated with lower rates of initial graft acceptance and a higher incidence of acute rejection.

Adult↗

Human liver transplant perfusate: an abundant source of donor liver-associated leukocytes.

In vitro studies designed to examine the mechanisms of immune tolerance after liver transplantation in humans have been hampered by the difficulty in obtaining sufficient numbers of donor liver-associated leukocytes (LALs). We have investigated whether the ex vivo perfusion of donor livers releases a population of LALs that can be readily retrieved from the waste fluid. The mean number of cells recovered after Ficoll-Hypaque density-gradient separation was 2.6 +/- 0.5 x 10(8) cells, with a viability of 94% +/- 2%. The perfusate lymphocytes comprised mainly T cells (39% +/- 2%) with a very low CD4/CD8 ratio and natural killer (NK) cells (56% +/- 6%) with an increase in the proportion of the CD3-CD56+CD16- subset. The activation marker CD69 was present on the majority of the perfusate lymphocytes. These are the phenotypic characteristics that have been previously reported for lymphocytes isolated from hepatic sinusoids. In mixed lymphocyte reactions, the perfusate cells showed a marked increase in the ability to stimulate allogeneic responder cells, resulting in 353% +/- 78% (P = .003) greater incorporation of [3H]thymidine in responder cells when compared with stimulation by donor peripheral blood mononuclear cells. The results show that large numbers of viable donor lymphocytes can be readily isolated from the liver perfusate solution. These cells have the characteristics of liver-associated lymphocytes with a predominance of activated NK and CD8+ T cells. This population can now be used in in vitro assays to elucidate the influence of donor leukocytes on the development of graft acceptance.

Humans↗

Evidence that "myofibroblast-like" cells are the cellular source of capsular collagen in hepatocellular carcinoma.

BACKGROUND/AIMS: The prognosis for patients with hepatocellular carcinoma is poor although tumour encapsulation has been associated with improved survival and disease-free rates. While the source of the tumour capsule is unclear, the major role that activated hepatic stellate cells play in the deposition of liver matrix in normal and diseased states suggests the possible involvement of these cells in tumour encapsulation. METHODS: Twenty-four liver tumours (seven encapsulated HCC, seven non-encapsulated HCC, 10 colorectal metastases) were studied. Activated hepatic stellate cells were identified by immunohistochemistry for alpha-smooth muscle actin (alpha-SMA) and in situ hybridization for pro-collagen alpha1 (I) mRNA. Collagen deposition was localized using Masson's trichrome stain. RESULTS: Pro-collagen alpha1 (I) mRNA co-localized to alpha-SMA positive hepatic stellate cells within the region of increased collagen deposition in (i) the tumour capsule of encapsulated HCC, and (ii) the tumour junction of non-encapsulated HCC and colorectal metastasis. In addition, there was marked peritumour expression of alpha-SMA and procollagen alpha1 (I) mRNA, which diminished with distance away from the tumour in all tumour groups. The degree of expression was greatest with encapsulated HCC, less with non-encapsulated HCC and least with colorectal metastasis. This contrasted with the absence of alpha-SMA expression in normal liver from the same patients. Within the tumours, colorectal metastases differed from HCC by demonstrating marked alpha-SMA expression and collagen deposition in the septa. CONCLUSIONS: Our findings demonstrate that activated hepatic stellate cells (i) are responsible for increased peritumour collagen production in non-encapsulated HCC and colorectal metastasis, and (ii) may be implicated in tumour capsule formation in HCC and metastasis stroma development. Thus, stellate cells may influence the local hepatic invasion by these tumours.

Adult↗

Potential for bilateral nephrectomy to reduce oxalate release after combined liver and kidney transplantation for primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH-1) is frequently associated with end stage renal failure due to urinary calculi, obstructive uropathy and interstitial deposits of calcium oxalate. The currently accepted treatment for PH-1 is liver transplantation to replace the deficient enzyme peroxisomal alanine glycoxylate aminotransferase (AGT) and a simultaneous renal transplant to restore renal function. The transplanted kidney may become significantly impaired or fail when systemic calcium oxalate is eliminated by renal excretion. The native kidneys are a major source of this oxalate. This study was undertaken to determine whether there is a difference in oxalate clearance following combined liver-kidney transplant in patients with PH-1 by comparing the effect of native kidney nephrectomy at the time of transplantation against leaving the native kidneys in situ. Regression analysis was used to compare daily urinary oxalate excretion corrected for body surface area. There was a significant reduction in urinary oxalate excretion (P < 0.05) in the patient who had undergone bilateral nephrectomy compared to the patient whose native kidneys remained in situ for the first 100 d following combined liver and kidney transplantation. No difference was observed in the serum oxalate levels between patients over the same period or in the renal function assessed by creatinine clearance corrected for body surface area. Total body oxalate load was not determined in this study. A larger study should be undertaken to examine the benefits of nephrectomy in reducing oxalate deposition in recently inserted allografts for patients with PH-1.

Adult↗

Orthotopic liver transplantation for adult-onset type II citrullinaemia.

Citrullinaemia is a rare autosomal recessive disorder due to a deficiency of argininosuccinate synthetase (ASS). While the clinical course of the adult onset form (Type II) is unpredictable, many patients undergo sudden deterioration with progressive cerebral oedema. Two patients with Type II citrullinaemia were referred for liver transplantation. One patient was successfully transplanted, and his plasma citrulline level decreased from 300 to 69 mumol/l (normal range 20-60 mumol/l); Fisher's ratio increased to a normal range within 24 h of transplantation. The other patient died from cerebral oedema, despite Optimal pharmacological measures, while awaiting a suitable donor organ. Dietary and pharmacological treatment is vital before liver transplantation. The level of serum arginine requires regulation, as it can rise secondary to citrullinaemia in Type II disease. An immunocytochemical study of the liver in both patients showed a clustered distribution of ASS which is associated with a dismal prognosis compared with patients who have a homogenous distribution. Distribution of ASS was normal in the transplanted liver. Liver transplantation is effective therapy for adult-onset Type II citrullinaemia. A clustered pattern of ASS distribution in a liver biopsy is a significant feature to activate early referral for liver transplantation.

Adult↗

Resolution of cirrhosis-related pulmonary shunting in two children with a transplanted liver.

We treated two children with hypoxemia caused by intrapulmonary shunting associated with cirrhosis secondary to extrahepatic biliary atresia. Following orthotopic liver transplantation, digital clubbing and intrapulmonary shunting were resolved, as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction, and perfusion lung scanning with 99mTc-labeled macroaggregates of albumin. We recommend that early liver transplantation be considered for young subjects with a severe hepatopulmonary syndrome.

Biliary Atresia↗

The use of the lidocaine-monoethylglycinexylidide test in the liver transplant recipient.

The lidocaine-monoethylglycinexylidide (MEGX) test is used to monitor liver function in liver transplant recipients. Serial studies have been undertaken after 155 allografts. The initial MEGX concentration is significantly correlated with the donor MEGX concentration. It is also influenced by the recipient's pretransplant bilirubin concentration, being lowest among patients with very high bilirubin levels. Use of segmental grafts is also accompanied by low MEGX concentrations. The flow-dependent clearance of lidocaine makes it a sensitive indicator of disturbed liver blood flow, with decreased MEGX concentrations occurring in hepatic artery thrombosis and rejection and as a result of cardiac failure and pulmonary effusions. Significant hepatic ischemia resulting in delayed initial function or cholestasis also is associated with low MEGX concentrations. The initial median MEGX concentrations were lowest among patients who required retransplantation or who died within 2 months of allografting.

Adolescent↗

Disposition of epirubicin after intraarterial administration in Lipiodol to patients with hepatocellular carcinoma.

Delivering emulsions of anthracycline drugs in Lipiodol, an iodinated poppy-seed oil, via the hepatic artery for the treatment of hepatocellular carcinoma (HCC) has become increasingly popular. However, investigations to determine the extent to which the Lipiodol sequesters the anthracycline in the liver have been limited. Concern has been expressed that such emulsions are not stable and that the anthracycline is, therefore, released rapidly into the circulation. We studied the pharmacokinetics of epirubicin (50 mg m-2) in five patients with nonresectable primary hepatocellular carcinoma after infusion of an epirubicin/Lipiodol emulsion via the hepatic artery. We used a reliable and specific high-performance liquid chromatography assay that allows quantitation of plasma concentrations of epirubicin, epirubicinol, epirubicin glucuronide, and epirubicin aglycone. Although a large interpatient variability in pharmacokinetics was observed, our results were similar to historical data after epirubicin intravenous therapy. Only the results from one patient provided evidence of significant retention of the drug in the liver. It would appear that more stable formulations of epirubicin/Lipiodol are required to increase the efficacy of this form of treatment. We suggest that pharmacokinetic studies should accompany clinical evaluation of emulsions of epirubicin/Lipiodol for the treatment of HCC.

Aged↗

Liver transplantation in the presence of situs inversus totalis: application of reduced-size graft.

Because of the anatomical features associated with situs inversus, technical difficulties will be encountered during orthotopic liver transplantation. This report describes the case of a patient with situs inversus totalis and end-stage liver disease from biliary atresia who was treated by segmental orthotopic liver transplantation. The segmental graft was safely placed in the left subphrenic space, and a suitable orientation was obtained for anastomoses of the hilar vessels. Chronic rejection necessitated retransplantation, by the same method, 19 months later. This technique has potential advantages in coping with anatomical obstacles encountered in patients with situs inversus.

Biliary Atresia↗