Giant hepatocellular adenoma in a previously obese thirteen-year-old boy.

Hepatocellular adenoma is an uncommon neoplasm, especially in the childhood age group. We describe a previously obese 13-year-old male with a giant hepatocellular adenoma requiring an extensive hepatic resection. The related pediatric tumor literature, diagnosis and clinical management is discussed.

The relationship between adenosine triphosphate within CD4(+) T lymphocytes and acute rejection after liver transplantation.

BACKGROUND: There have been increasing interests in the relationship between CD4(+) T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4(+) T lymphocytes after liver transplantation. METHODS: From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non-acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions. RESULTS: After transplantation, the ATP levels within CD4(+) T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 µg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01). CONCLUSIONS: During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4(+) T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti-rejection treatment.

A reduced segment II/III graft for neonatal liver failure with absence of detectable hepatocytes. A case report and literature review.

When hepatic failure occurs in newborns, most cases are because of viral hepatitis, metabolic diseases, and neonatal hemochromatosis. It is rare to have liver failure presenting in the first day after birth. We report a unique case of a newborn baby with liver failure in the first day of life who received a reduced segment II and III graft when she was 19 days old and became the youngest survivor of LDLT. Common and rare causes of liver failure in this age group were excluded by appropriate testing. She underwent a liver biopsy that showed a liver devoid of hepatocytes. Similar pathological findings were found in the explanted liver. She was discharged from the hospital with normal graft function three months after the transplant.

Immune cell functional assay in monitoring of adult liver transplantation recipients with infection.

PURPOSE: To identify the levels of functional immunity measured by the ImmuKnow assay in Chinese liver transplantation recipients and its application in monitoring the risk of posttransplant infection. METHODS: Forty-five apparent healthy Chinese and 106 adult liver transplant (LT) recipients were under investigation. LTs were grouped in stable status or infection according to their clinical diagnosis. Whole blood samples were collected freshly and cultured within 6 hr, the CD4(+) T cells were selected, and their adenosine triphosphate (ATP) value was assayed the next day. Before stimulation, we also examined the percentage of T-helper (Th; CD3(+) CD4(+)) and T-suppress (Ts; CD3(+) CD8(+)) lymphocyte subpopulations and the ratio of Th/Ts. RESULTS: The average ImmuKnow assay in infectious LT recipients was 128 + or - 84 ng/mL, significantly lower (P<0.05) than that in stable LTs (305 + or - 149 ng/mL) or in normal adults (301+ or - 101 ng/mL). The ImmuKnow values in LTs had a good negative correlation to infection clinically (r = -0.6217, P<0.001). Infectious risk was high when the ImmuKnow value was less than 130 ng/mL (odds ratio=13, 95% confidence interval 6.0-29.4, P<0.01). The sensitivity of low ImmuKnow values in posttransplant infection was 85.2%, significantly higher than those of Th/Ts ratio and immunosuppressant trough levels (P<0.01); specificity was 76.3%, comparable with that of Th/Ts ratio (75.5%), but greatly higher than immunosuppressant trough levels (P<0.01). ImmuKnow ATP values had no correlation with Th/Ts ratio or immunosuppressant trough levels. CONCLUSION: ImmuKnow ATP levels are lower in LT recipients with infection, which provides a new tool in monitoring posttransplant infection, and an index of tailoring immunosuppression clinically.

A single-center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. METHODS: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. RESULTS: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor-node-metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre-operative alpha-fetoprotein (AFP) level were independent risk factors affecting the overall survival and post-operative recurrence-free survival rates of patients with HCC. Pathological staging and pre-operative local treatment of HCC had no obvious correlation with the post-operative recurrence-free survival rate. CONCLUSION: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre-operative AFP level are closely related to the recurrence of HCC following LT.

[Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma].

OBJECTIVE: To report the experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). METHODS: Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. RESULTS: Between January 1988 and February 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 were well without recurrence at 79, 82, 108, 128, 129 and 145 months. CONCLUSIONS: For patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma.

This retrospective study reviews our experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between 1988 and 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 are well without recurrence at 5.7, 7.0, 8.7, 8.8, and 10.1 years. In conclusion, for patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

A multicenter, prospective study of C2-monitored cyclosporine microemulsion in a U.S. population of de novo renal transplant recipients.

BACKGROUND: Monitoring cyclosporine microemulsion (CsA-ME; Neoral) exposure 2 hours postdose (C2) has been reported to optimize the efficacy and safety of CsA-ME therapy. The addition of induction therapy to a maintenance regimen including CsA-ME C2 monitoring has not been evaluated. METHODS: In all, 123 adult renal transplant recipients were recruited at 14 U.S. centers for this 6-month study. CsA-ME dose was to be titrated to attain C2 targets of 1700 and 1500 ng/ml during posttransplant months 1 and 2, respectively. After 2 months, patients were randomized to one of two groups with different, decreasing C2 targets. Basiliximab, mycophenolate mofetil, and corticosteroids completed the study immunosuppression. RESULTS: Of the 119 evaluable patients, 76% were male, 22% African American, and 66% deceased donor recipients. Biopsy-proven acute rejection occurred in 10 patients (9.3%); there were two failed grafts and one death. Serum creatinine and calculated GFR values suggest good renal function, with month 6 medians of 1.5 ng/ml and 67 ml/min/1.73 m. Safety and tolerability assessments revealed no unexpected outcomes. Observed C2 levels were generally lower than protocol targets, particularly in the first weeks posttransplantation. CONCLUSIONS: The striking efficacy and outcomes may have been achieved in this study with lower C2 levels of CsA-ME because of the addition of basiliximab induction.

Vasopressor agents without volume expansion as a safe alternative to venovenous bypass during cavaplasty liver transplantation.

BACKGROUND: Cavaplasty orthotopic liver transplantation (OLT) offers advantages for hepatectomy and implantation and eliminates the risk of outflow obstruction. However, it does require clamping of the cava. This study describes the use of a vasopressor without fluid expansion or venovenous bypass (VB) for hemodynamic control during the anhepatic phase. METHODS: The cavaplasty OLT technique was used routinely. A vasopressor was administered if the mean arterial blood pressure (MAP) was less than 60 mm Hg after clamping of the cava. If the MAP did not reach 60 mm Hg after adjusting the dosage of the vasopressor, femoro-axillary VB would be used. VB was also indicated for preexisting cardiac disease or for massive hemorrhage from severe portal hypertension and extensive adhesions. RESULTS: Among all the 121 adult cavaplasty OLTs, 33 were supported with VB and 50 received a vasopressor. The remaining 38 were excluded. However, baseline variables were well matched, except that preexisting cardiac disease was more frequent in the VB group. The median dosage of epinephrine was 0.07 microg/kg/min (range 0.01-0.6). The VB and vasopressor groups were similar in the reduction in mean MAP and the accumulation in arterial lactate upon clamping as well as in the central venous pressure upon unclamping. Postreperfusion hypotension was more frequent in the VB than in the vasopressor group (27.3% vs. 4.0%, P=0.006). There was no primary graft nonfunction or intraoperative right heart failure. One patient in the vasopressor group required postoperative temporary dialysis. Ninety-day patient and graft survival for the VB and vasopressor groups were 97.0% vs. 98.0% and 97.0% vs. 94.0%, respectively. CONCLUSION: Modest doses of vasopressor without volume expansion or VB can maintain hemodynamic stability during the anhepatic phase of cavaplasty OLT.

Dose-adjusted cyclosporine c2 in a patient with jejunoileal bypass as compared to seven other liver transplant recipients.

Jejunoileal bypass (JIB) is a weight loss procedure in which malabsorption is produced by connecting a short length of proximal jejunum to the distal ileum. Because 90% of the small intestine is bypassed, it may have impact on the dose-concentration response of oral cyclosporine (CsA). The authors characterized the dose-adjusted blood concentrations of CsA obtained 2 hours (C2) after oral microemulsion CsA (ME-CsA) in a liver transplant (LTx) subject with an intact JIB, as compared with those from seven LTx controls without JIB. The biliary reconstruction involved choledochocholedochostomy without external drainage in all patients. ME-CsA was administered via a nasogastric tube within 24 hours after graft reperfusion. Oral fluconazole was given prophylactically to the study subject only for 6 days after LTx. During the first week after LTx, the dose-adjusted C2 (mean +/- SD) for the study subject and for controls was 53 +/- 10 and 106 +/- 47 ng/mL, respectively (P < 0.001). The corresponding value during the period from day 7 to day 107 was 105 +/- 40 and 257 +/- 86 ng/mL, respectively (P < 0.001). Multiple linear regression revealed that dosage, days after LTx, and the presence of a JIB were all independent predictors of C2 (R2 = 0.798, P = 0.037). Lack of bile resulting in malabsorption of ME-CsA was not thought to be significant contributor to her low dose-adjusted C2 because there was no external bile drainage and a portion of terminal ileum, where most bile acid reabsorption occurred, was still available after JIB. The fact that fluconazole failed to increase the dose-adjusted C2 in the study subject supports that enteric clearance of CsA may become clinically unimportant after JIB. Therefore, the low dose-adjusted C2 is most likely explained by the reduced bowel length and associated absorptive surface area after JIB. In conclusion, patients with JIB may require higher doses of ME-CsA.