S. V. Lynch

Living donor liver transplantation—Adult donor outcomes: A systematic review

The objective of this study was to evaluate the safety and efficacy of adult‐to‐adult living donor liver transplantation, specifically donor outcomes. A systematic review, with searches of the literature up to January 2004, was undertaken. Two hundred and fourteen studies provided information on donor outcomes. The majority of these were case series studies, although there were also studies comparing living donor liver transplantation with deceased donor liver transplantation. Both underreporting and duplicate reporting is likely to have occurred, and so caution is required in interpretation of these results. Overall reported donor mortality was 12 to 13 in about 6,000 procedures (0.2%) (117 studies). Mortality for right lobe donors to adult recipients is estimated to be 2 to 8 out of 3,800 (0.23 to 0.5%). The donor morbidity rate ranged from 0% to 100% with a median of 16% (131 studies). Biliary complications and infections were the most commonly reported donor morbidities. Nearly all donors had returned to normal function by 3 to 6 months (18 studies). In conclusion, there are small, but real, risks for living liver donors. Due to the short history of adult‐to‐adult living donor liver transplantation, the long‐term risks for donors are unknown. Liver Transpl 12:24–30, 2006.

Predicting Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis Before Transplantation

Patients with primary sclerosing cholangitis are at an increased risk of developing cholangiocarcinoma, which is difficult to diagnose because the biliary tree is already distorted. Eleven patients with primary sclerosing cholangitis who underwent orthotopic liver transplantation at this hospital were evaluated. Four patients had coincidental histologically proved cholangiocarcinoma. Patients with cholangiocarcinoma in contrast to patients without tumour presented with rapid onset of persistent jaundice, pruritus, and weight loss associated with an appreciable rise in bilirubin (8x v 2x) and alkaline phosphatase (3.5x v 1.2x) over one year. Cholangiography and computed tomography showed appreciably dilated intrahepatic bile ducts (3/4 v 0/7). The diagnosis of cholangiocarcinoma could only be established before operation in one patient by fine needle aspiration cytology. Tumour was recognised at operation in one other. Histological examination of hepatectomy specimens showed that patients with cholangiocarcinoma had less advanced histological features of primary sclerosing cholangitis. Multiple areas of carcinoembryonic antigen positive epithelial atypia and carcinoma in situ were found in all patients with cholangiocarcinoma. Cholangiocarcinoma recurred in two patients at 14 and 39 months after transplantation. Superimposed cholangiocarcinoma can be predicted in most patients with cholangitis before transplantation, although a definitive diagnosis is difficult to make. Their prognosis after successful transplantation is guarded.

Survival, growth and quality of life in children after orthotopic liver transplantation : a 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58‐14.2 years) undergoing OLT for endstage liver disease. Follow‐up studies of growth and quality of life were undertaken in those with a minimum follow‐up period of 12 months (n= 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1,1‐5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <−1 was 57%, >−1 was 95%; P=0.004). Significant catch‐up weight gain was observed by 18 months post‐transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91±19). All school‐aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post‐operative intracerebral complications. Satisfactory long‐term survival can be achieved after OLT in children regardless of age but the importance of pre‐operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch‐up weight gain and growth.

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.

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.

Improvement in chronic hepatocerebral degeneration following liver transplantation

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation.

Malnutrition in children with chronic liver disease accepted for liver transplantation: Clinical profile and effect on outcome

Abstract  The nutritional profiles of 37 children (aged 0.5–14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = 1.4±0.2) and stunted (mean s.d. height = ‐ 2.2±0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium ‐ mean % expected for age = 58±5%, n= 15). Mean ad libitum nutrient intake was 63±5% of recommended daily intake (RDI). Those who died while waiting (n= 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight > ‐ 1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight > ‐ 1.0) was 38% (P<0.003). Declining nutritional status during the waiting period also adversely affected outcome. We conclude that malnutrition and/or declining nutritional status is a major factor adversely affecting survival in children awaiting OLTP. In transplant units where waiting time is greater than 40 days, earlier referral, prioritization of cases and the use of adult donor livers may reduce this risk and efforts to maintain or improve nutritional status deserve further study.

Undifferentiated (embryonal) sarcoma of the liver: Pathologic findings and long-term survival after complete surgical resection

Undifferentiated (embryonal) sarcoma of liver is a rare tumor with a reputed poor prognosis. Four patients with this tumor are reported, of whom three were alive without recurrence 1.5, 2.5, and 12 years after initial complete surgical resection, and two of whom received no adjuvant therapy. The fourth patient, in whom complete surgical resection of tumor was not achieved, died with recurrent tumor at 13 months. The latter tumor differed histologically and consisted mainly of closely packed smaller undifferentiated cells with a higher mitotic and apoptotic rate. Eosinophilic globules, characteristic of embryonal sarcoma, were found in some cases to contain condensed nuclear chromatin, evidence of origin from tumor cells dying by apoptosis. One tumor mainly contained large cysts lined by biliary‐type epithelium; this suggested an origin from a multipotent precursor cell able to differentiate along both stromal and epithelial lines.

Universal occurrence of glomerular abnormalities in patients receiving liver transplants

We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.

Simultaneous Quantification of Tacrolimus and Sirolimus, in Human Blood, by High-Performance Liquid Chromatography-Tandem Mass Spectrometry

In this paper the authors present a validated method for the simultaneous analysis of tacrolimus and sirolimus in human blood by high-performance liquid chromatography–electrospray tandem mass spectrometry. Blood samples (500 &mgr;L) were prepared by C18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring. The assay was linear for both compounds over the range 0.25–100 &mgr;g/L (r2 > 0.996, n = 7). At the limit of quantification (0.25 &mgr;g/L), for both sirolimus and tacrolimus, the interday imprecision was <3% and the analytical recovery was between 97.0% and 102%, respectively. The interbatch and intrabatch coefficients of variation of the method for both analytes, at the three quality control concentrations (0.5, 20, and 80 &mgr;g/L), were <16% and <10%, respectively. The analytical recovery, at the three control concentrations, ranged from 99.2% to 104% of the nominal concentration. The mean absolute recovery (±standard deviation) of tacrolimus, sirolimus, and internal standard was 82 ± 7%, 89 ± 12%, and 77 ± 8%, respectively (n = 12). In conclusion, the method presented can be used for simultaneous determination of tacrolimus and sirolimus and will aid in pharmacokinetic studies and therapeutic drug monitoring of these drugs. Furthermore, this method has economic benefits in the clinical setting where these drugs are coadministered.