Biomedical subjects
R W Strong
Publications and source records attributed to R W Strong.
Acute liver failure in children: A regional experience.
OBJECTIVE: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia. METHODOLOGY: A retrospective review was conducted of all paediatric patients referred with acute liver failure between 1985 and 2000 to the Queensland Liver Transplant Service, a paediatric liver transplant centre based at the Royal Children's Hospital, Brisbane, that is one of three paediatric transplant centres in Australia. RESULTS: Twenty-six patients were referred with ALF. Four patients did not require transplantation and recovered with medical therapy while two were excluded because of irreversible neurological changes and died. Of the 20 patients considered for transplant, three refused for social and/or religious reasons, with 17 patients listed for transplantation. One patient recovered spontaneously and one died before receiving a transplant. There were 15 transplants of which 40% (6/15) were < 2 years old. Sixty-seven per cent (10/15) survived > 1 month after transplantation. Forty per cent (6/15) survived more than 6 months after transplant. There were only four long-term survivors after transplant for ALF (27%). Overall, 27% (6/22) of patients referred with ALF survived. Of the 16 patients that died, 44% (7/16) were from neurological causes. Most of these were from cerebral oedema but two patients transplanted for valproate hepatotoxicity died from neurological disease despite good graft function. CONCLUSIONS: Irreversible neurological disease remains a major cause of death in children with ALF. We recommend better patient selection and early referral and transfer to a transplant centre before onset of irreversible neurological disease to optimize outcome of children transplanted for ALF.
Overseas liver transplantation for hepatitis C in Japanese patients: a comparison with patients from Australia/New Zealand.
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Iatrogenic bile duct injury: the scourge of laparoscopic cholecystectomy.
BACKGROUND: Laparoscopic cholecystectomy (LC) has become the first-line surgical treatment of calculous gall-bladder disease and the benefits over open cholecystectomy are well known. In the early years of LC, the higher rate of bile duct injuries compared with open cholecystectomy was believed to be due to the 'learning curve' and would dissipate with increased experience. The purpose of the present paper was to review a tertiary referral unit's experience of bile duct injuries induced by LC. METHODS: A retrospective analysis was performed on all patients referred for management of an iatrogenic bile duct injury from 1981 to 2000. For injuries sustained at LC, details of time between LC and recognition of the injury, time from injury to definitive repair, type of injury, use of intraoperative cholangiography (IOC), definitive repair and postoperative outcome were recorded. The type of injury sustained at open cholecystectomy was similarly classified to allow the severity of injury to be compared. RESULTS: There were 131 patients referred for management of an iatrogenic bile duct injury that occurred at open cholecystectomy (n = 62), liver resection (n = 5) and at LC (n = 64). Only 39% of bile duct injuries were recognized at the time of LC. Following conversion to open operation, half the subsequent procedures were considered inappropriate. When the injury was not recognized during LC, 70% of patients developed bile leak/peritonitis, almost half of whom were referred, whereas the rest underwent a variety of operative procedures by the referring surgeon. The remainder developed jaundice or abnormal liver function tests and cholangitis. An IOC was performed in 43% of cases, but failed to identify an injury in two-thirds of patients. The bile duct injuries that occurred at LC were of greater severity than with open cholecystectomy. Following definitive repair, there was one death (1.6%). Ninety-two per cent of patients had an uncomplicated recovery and there was one late stricture requiring surgical revision. CONCLUSIONS: The early prediction that the rate of injury during LC would decline substantially with increased experience has not been fulfilled. Bile duct injury that occurs at LC is of greater severity than with open cholecystectomy. Bile duct injury is recognized during LC in less than half the cases. Evidence is accruing that the use of cholangiography reduces the risk and severity of injury and, when correctly interpreted, increases the chance of recognition of bile duct injury during the procedure. Prevention is the key but, should an injury occur, referral to a specialist in biliary reconstructive surgery is indicated.
Liver transplantation: current status and future prospects.
The enormous progress that has been made in liver transplantation over the past two decades has culminated in survival approaching 90% at 12 months. The success of the procedure combined with the widening spectrum of disease processes deemed amenable to liver transplantation has meant that there are too few donors for those awaiting transplantation. This has extrapolated to many patients having such advanced disease by the time a suitable donor liver is available, that they are almost non-transplantable. The immediate options facing the transplant community are to decrease the number of patients listed or to increase the number of living donor transplants. Alternatives to liver transplantation such as hepatocyte transplantation, gene therapy, xenotransplantation and the bioartificial liver are being sought but, at best, are some way from clinical application. It is anticipated that a number of liver diseases that are indications for liver transplantation at this time will have progression arrested or will be cured by medical therapy in the future.
J.H. Louw Memorial Lecture. Liver surgery: 'traveller, there is no path, a path is made by walking'.
Liver resection today is a product of rapid development over the past two decades. The description of the functional anatomy of the liver was the foundation of modern liver surgery. However, it has been the technological advances in radiology that have had the biggest impact in the management of hepatobiliary disease. Major hepatectomies dominated the earlier experience of modern liver surgery, but segment-orientated resections now play a more prominent role. Resections may be performed for both malignant and benign lesions or as an emergency procedure for trauma or other catastrophic event. At Princess Alexandra Hospital, Brisbane, 1,108 liver resections have been undertaken. Of the elective resections, 45% were for metastases, 29% for primary malignancy and 26% for benign disease. Two-thirds of the 102 emergency hepatectomies were for severe liver trauma. The 30-day mortality was 3.2% for the total series, 2.6% for the elective cases and 1.5% for the elective, non-jaundiced patients. Innovative graft reduction techniques have become a major component in liver transplantation. The successful transplantation of a reduced-size segmental graft from an adult donor liver to an infant paved the way for other procedures such as split-liver, auxiliary partial orthotopic and living-donor transplantation.
Clinicopathological analysis of liver allograft biopsies with late centrilobular necrosis: a comparative study in 54 patients.
BACKGROUND: Centrilobular necrosis (CLN) in liver allografts can be a difficult lesion to interpret histologically. Although long recognized in association with developing chronic rejection, recent studies have described the lesion in association with a number of other disease processes. To clarify the histologic features that could allow a specific diagnosis to be made and to determine the outcome in different diagnostic groups, we assessed biopsies from 54 patients with CLN. METHODS: Biopsies were classified as CLN with acute cellular rejection (ACR), CLN with hepatitis, CLN with developing chronic rejection (CR), and CLN of other etiology. Histologic features were assessed and then compared between groups, and clinical outcomes were noted. RESULTS: Discriminating features for the different groups were as follows: CLN and ACR showed bile duct injury, endothelialitis, and acinar congestion. CLN and CR showed severe bile duct injury, bile duct loss, or centrilobular swelling. CLN and hepatitis was often a diagnosis of exclusion, although interface hepatitis was more common in this group. Cases of autoimmune hepatitis usually demonstrated plasma cell predominance in the portal and acinar inflammatory infiltrate. Significantly, there was considerable overlap in the histologic features between the groups, accounting for the diagnostic difficulty. Patients in whom the CLN was associated with CR or vascular complications generally required retransplantation or died, but in the groups with ACR and hepatitis, the outcome was more favorable. CONCLUSIONS: With regard to most liver allograft biopsies showing late CLN, it is possible to make a specific diagnosis despite overlapping histologic features; this allows specific therapy to be instituted. Ultimately this is likely to contribute to improved graft survival.
Liver transplantation for familial amyloidotic polyneuropathy in Australia.
Familial amyloidotic polyneuropathy type 1 (FAP-1) is a type of systemic amyloidosis caused by mutant transthyretin (mTTR) that is mainly produced in the liver. Most patients have progressive peripheral and autonomic neuropathy. Ten patients with FAP underwent orthotopic liver transplantation (OLT) at the Queensland Liver Transplant Service (Princess Alexandra Hospital, Brisbane, Australia). Nine patients are still alive, and one patient died of cardiac failure 10 days after OLT. Some symptoms of FAP were alleviated in some of the patients. OLT seems to be a worthwhile treatment for FAP, because it halts the progression of symptoms and achieves improvement in some patients.
Successful conversion from cyclosporine to tacrolimus for immunosuppression.
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Expression of cytokines and factors modulating apoptosis by human sinusoidal leucocytes.
BACKGROUND/AIMS: Liver sinusoids contain a large population of spontaneously cytotoxic cells (NK cells), CD8+ T cells and macrophages. The physiological role of these leucocytes remains unclear. They may participate in immune surveillance and peripheral tolerance by deleting tumour cells, virus-infected cells and activated T cells as they traffic through the liver. In order to gain further information about the function of these leucocytes within the hepatic sinusoids, we examined their production of immunomodulatory cytokines and apoptosis-related molecules. METHODS: Semi-quantitative polymerase chain reaction and immunohistochemistry were used to determine the spontaneous production of cytokines and apoptosis-related molecules by sinusoidal leucocytes isolated from donor liver preservation solution. RESULTS: In comparison with matched peripheral blood mononuclear cells, sinusoidal leucocytes produced more mRNA for IL-10, IL-15, TNF-alpha, IL-18, IFN-gamma, FasL, perforin and granzyme. IL-4 and IL-12 were not detected and IL-2 was only faintly detected in the liver-derived CD4+ population. Less bcl-2 was expressed in liver-derived CD4+ and CD8+ cells in comparison with matched peripheral blood cell populations. CONCLUSIONS: The cytokines produced spontaneously by sinusoidal leucocytes are consistent with their high level of activation and spontaneous cytotoxicity. Their strong expression of apoptosis-mediating molecules (FasL, perforin, granzyme and TNF-alpha) support a role for these cells in immune surveillance and peripheral tolerance induction.
Fibrous obliterative lesions of veins contribute to progressive fibrosis in chronic liver allograft rejection.
Fibrosis in liver allografts undergoing chronic rejection (CR) is variable and poorly understood. The temporal and spatial relationships of venous, arterial, and biliary lesions were studied to clarify their potential contributions to graft fibrosis. The severity, prevalence, and morphology of intimal lesions of vessels were analyzed and compared with the fibrosis stage. Three groups were found; group 1 (n = 5) with no hepatic vein (HV) lesions, group 2 (n = 5) with HV lesions only, and group 3 with lesions of both HV and portal veins (PV). The earliest lesion to develop, in 71% of grafts, was concentric intimal thickening of small HV. This was significantly more severe and frequent in grafts from group 3. With increasing frequency and severity of small HV sclerosis, fibrosis developed in medium/large veins. The morphology of larger vessel lesions suggested organized thrombus. Centrilobular fibrosis was significantly more severe in group 3 and developed unpredictably and sometimes rapidly. Conversely, portal fibrosis scores were significantly higher in grafts with ductular proliferation and did not correlate with venous lesions. This suggests that in CR, veno-occlusive-like lesions develop commonly in terminal hepatic venules, probably caused by immune-mediated damage. In only a proportion, with increased frequency and severity of the lesions, stasis and thrombosis in portal and larger veins occur and could result in loss of hepatic and portal venous outflow, which leads to ischemia and fibrosis. The stage of fibrosis did not correlate with foam-cell arteriopathy. A second pathway of portal fibrosis occurs in patients with longstanding biliary proliferation.
Confirmation of the role of the Mayo Risk Score as a predictor of resource utilization after orthotopic liver transplantation for primary biliary cirrhosis.
Resource utilization is an important consideration when patients are selected for orthotopic liver transplantation (OLT). The Mayo Risk Score has been proposed to help predict optimum time for OLT. We assessed the relation between Mayo risk score, Child-Pugh score, and resource utilization and outcome after OLT for primary biliary cirrhosis. The mean Mayo risk score was greater in patients who died than in the survivors (8.6 +/- 1.4 v 7.1 +/- 1.8; P <.05). There was a positive correlation between Mayo risk score and the 4 resource variables studied (intraoperative blood requirements, time ventilated, and duration of intensive care unit and hospital stays). Patients with a Mayo risk score greater than 7.8 used almost twice the resources of patients with a risk score less than 7.8. A positive correlation also existed between Child-Pugh score and duration of hospital stay. The mean Child-Pugh score in patients who died was greater than that in survivors (10.7 +/- 2.0 v 8.5 +/- 2.8, P =.03). This study confirms that Mayo Risk score is an important predictor of resource utilization and outcome after OLT.
Role of donor leukocyte chimerism in establishing the etiology of neutropenia after liver transplantation.
BACKGROUND: The quantitation of donor leukocyte chimerism may aid in establishing the etiology of neutropenia after liver transplantation. METHODS: The incidence and clinical and laboratory characteristics of severe neutropenia were studied in adults who have undergone liver transplantation at our institution over the last 4 years. RESULTS: Severe neutropenia developed in 5 of 156 patients (3%). The clinical and pathological features were nonspecific. In two patients with a delayed diagnosis of graft-versus-host disease (GVHD), donor leukocytes comprised > or = 50% of the circulating peripheral blood mononuclear cells. In a third patient, an earlier diagnosis of GVHD was suspected on the basis of a donor leukocyte count of 3-10% in the peripheral blood. In contrast, donor leukocyte chimerism was < or = 0.01% in two patients with probable drug-induced neutropenia CONCLUSIONS: The determination of donor leukocyte chimerism has an important role in the investigation of neutropenia after liver transplantation, allowing early diagnosis and treatment of GVHD.
Whither living donor liver transplantation?
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Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation.
Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft.
The effects of circulating interleukin-8 and adhesion molecules on pulmonary dysfunction in pediatric orthotopic liver transplantation.
We investigated the effects of circulating inflammatory cytokines and adhesion molecules induced by ortho-topic liver transplantation (OLT) on pulmonary function. Although the plasma interleukin-8 (IL-8) levels increased gradually, peaking at the end of the operation, these increases were considered minimal. The baseline endothelial adhesion molecule (E-selectin) level was several times higher than the normal value, but after reperfusion of the new transplanted liver, the plasma E-selectin concentrations decreased to within the normal range and remained almost normal during the postoperative period. Similar changes were observed in the plasma levels of other types of adhesion molecules. Although PaO(2)/FIO(2) showed a significant inversed correlation with the peak IL-8 concentration, after the exclusion of two patients, one of whom died and one of whom rejected the transplanted liver, no correlation was able to be found between the PaO(2)/FIO(2) ratio and the maximum IL-8 concentration. Furthermore, there was no correlation between the adhesion moleclues and PaO(2)/FIO(2). These results suggest that IL-8 exerts only a slight effect on respiratory function following successful pediatric liver transplantation, and that circulating adhesion molecules do not affect perioperative lung function.
Late bile duct cancer complicating biliary-enteric anastomosis for benign disease.
BACKGROUND: Anastomosis between the biliary tree and the intestinal tract has been, and is, a relatively common procedure. Aside from cholangitis secondary to anastomotic stricture, it is generally regarded as innocuous. METHODS: The recent experience with 3 patients who developed bile duct cancer many years after biliary-enteric anastomosis for benign disease prompted a review of whether the procedure was potentially carcinogenic. RESULTS: There have been very few reports of late cholangiocarcinoma complicating this surgery for benign disease. However, there is some experimental evidence to support the hypothesis, and the time interval between surgery and the development of malignancy may be important. CONCLUSIONS: Reflux of duodenal or small intestinal contents into the biliary tree causes changes in the biliary epithelium that may be adaptive to the new environment but also have the potential to progress to malignant transformation.
The management of blunt liver injuries.
Although the general surgeon who takes emergency call may be confronted with a patient who has sustained a blunt liver injury, the decrease in road trauma and work-place accidents has meant that this will be an infrequent occurrence. Minimal exposure will, of necessity, extrapolate to difficulty in coping with a catastrophic event which comes unheralded, at an inconvenient time and usually when there is less than ideal support. During the past 15 years, there has been an evolution in the treatment of liver injuries which is exemplified by a non-operative approach in selected patients and more conservative procedures in those who require operative intervention. At present, 'damage control' is in vogue; do the least possible to control life-threatening injuries and come back another day. This is a cogent and admirable philosophy, provided that the pendulum does not swing too far and that a planned course of action is in place. This paper reviews the present status of managing blunt liver injuries, with an emphasis on the general surgeon who has little cause to be involved with surgery of the liver.