Dorian J. Wilson

Locoregional recurrences are frequent after radiofrequency ablation for hepatocellular carcinoma

BACKGROUND Enthusiasm for radiofrequency ablation (RFA) therapy for patients with unresectable hepatocellular carcinoma (HCC) has increased. The data for recurrence after RFA for patients with HCC is not well documented. The purpose of this study was to evaluate tumor recurrence patterns after RFA in patients with unresectable HCC. STUDY DESIGN Over a 3-year period, 50 patients having RFA for unresectable HCC were identified at a single institution. Medical records and radiologic studies were reviewed and outcomes factors analyzed. RESULTS Of the entire cohort, 46 patients underwent RFA by a percutaneous approach under CT guidance. Most patients underwent either one (n = 22) or two ablations (n = 23). At the time of this report, 14 patients (28%) were tumor-free by radiologic and biochemical (alpha-fetoprotein) parameters. Eighteen additional patients had persistence of tumor at the ablation site and 14 patients had recurrence in the liver at sites different from the ablation site. An additional four patients had recurrence in extrahepatic sites. Twelve patients underwent orthotopic liver transplantation after RFA. Of these 12, 5 (42%) demonstrated no viable tumor in the explanted liver. Independent predictors of tumor recurrence included tumor size, serum AFP levels, and the presence of hepatitis. CONCLUSIONS These data suggest that factors such as tumor size should be considered before employing RFA therapy. In addition to treating the primary tumor, other therapies aimed at the livers inflammatory state might also be important in achieving a durable response after RFA.

Ischemic preconditioning in deceased donor liver transplantation: A prospective randomized clinical trial of safety and efficacy

Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1 : 1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 ± .4 vs. 2.0 ± .8; and day 3 INR 1.3 ± .2 vs. 1.4 ± .3; all P > .05. No instances of nonfunction occurred. The 6‐month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed. (Liver Transpl 2005;11:196–206.)

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

While animal studies show that ischemic preconditioning (IPC) is beneficial in liver transplantation (LT), evidence from few smaller clinical trials is conflicting. From October 2003 to July 2006, 101 deceased donors (DD) were randomized to 10 min IPC (n = 50) or No IPC (n = 51). Primary objective was efficacy of IPC to decrease reperfusion (RP) injury. Both groups had similar donor risk index (DRI) (1.54 vs. 1.57). Aminotransferases on days 1 and 2 were significantly greater (p < 0.05) in IPC recipients. In multivariate analyses, IPC had an independent effect only on day 2 aspartate transferase. Prothrombin time, bilirubin and histological injury were similar in both groups. IPC had no significant effect on plasma TNF‐α, IL‐6 and IL‐10 in the donor and TNF‐α and IL‐6 in the recipient. In contrast, IPC recipients had a significant rise in systemic IL‐10 levels after RP (p < 0.05) and had fewer moderate/severe rejections within 30 days (p = 0.09). Hospital stay was similar in both groups. One‐year patient and graft survival in IPC versus No IPC were 88% versus 78% (p = 0.1) and 86 versus 76% (p = 0.25), respectively. IPC increases RP injury after DDLT, an ‘IPC paradox’. Other potential benefits of IPC are limited. IPC may be more effective in combination with other preconditioning regimens.

Donors with cardiac arrest: improved organ recovery but no preconditioning benefit in liver allografts.

Background. Historically, organ recovery rates in donors with cardiac arrest (CA) have been low, presumably from hemodynamic instability. We hypothesized that donor resuscitation has improved hemodynamic stability and organ recovery in CA donors, and that CA triggers ischemic preconditioning (IP) in liver grafts. Methods. A total of 131 donor pairs with and without CA were matched in age, gender, and year of recovery. Hemodynamic stability was determined by vasopressor use. Abdominal and thoracic organs recovered and livers transplanted were compared between the groups. Liver graft function, injury, and IP benefit were examined by comparing liver chemistries after transplantation and postperfusion biopsies between recipients of grafts from both groups (n=40 each). Results. Hemodynamic stability was similar in both groups, but recovery of thoracic organs was significantly lower in CA versus non-CA donors (35 vs. 53%, P <0.01). On the other hand, recovery rates of three or more abdominal organs from CA donors approached those of non-CA donors (77 vs. 87%, not significant). Although significantly fewer livers were transplanted from CA donors (69 vs. 85%, P <0.01), posttransplantation graft function and injury parameters were similar between the two groups, and CA did not appear to trigger IP. Conclusion. Compared with historical data, cardiovascular stability and abdominal organ recovery rates have improved considerably in CA donors. Liver grafts from CA donors function similarly to grafts from non-CA donors with no IP from CA. Our data support the increased use of livers and other organs from donors with CA.

Effect of Sirolimus on Infection Incidence in Liver Transplant Recipients

Sirolimus is a new immunosuppressive agent that lacks the nephrotoxicity and neurotoxicity associated with calcineurin inhibitors. 1–3 The addition of sirolimus to immunosuppressive protocols may thus allow sparing of calcineurin inhibitors and reduction or elimination of associated toxicities. 1 , 6 Between January 2000 and July 2001, sirolimus was administered to 55 of 116 consecutive liver recipients. The remaining 61 patients served as the comparison group in the retrospective analysis. In the sirolimus group, perioperative steroids were reduced, and calcineurin inhibitor initiation was delayed. All infectious episodes that occurred within 60 days of liver transplantation were evaluated but were limited to 1 per patient for statistical analysis of sepsis. Demographic variables were comparable between groups. Patients receiving sirolimus experienced more infection (47.2% vs. 18.03%, P<0.001), and this effect persisted across high and low dosage ranges and sirolimus levels. A trend toward increased length of stay was noted (P=0.07). No difference between groups was found in acute rejection rates (17.5% vs. 22.5%), 1‐year graft (81% vs. 89%), patient survival (86% vs. 89%), or hepatic artery thrombosis. In conclusion, despite reduction of other immunosuppressants, patients receiving even low doses of sirolimus experienced increased sepsis rates. This agent may have greater usefulness for patients with threatened renal function or patients with chronic rejection after wound healing has occurred. (Liver Transpl 2004;10:193–198.)

Primary non-Hodgkin's lymphoma of the bile ducts mimicking cholangiocarcinoma.

BACKGROUND Primary non-Hodgkins lymphoma (NHL) of the liver and bile duct mimicking cholangiocarcinoma is rare. METHODS The clinical and radiologic features and the treatment of 2 patients with primary NHL of the bile ducts are presented and analyzed together with cases collected from a review of the English literature between 1966 and 2003. RESULTS Fifteen patients with primary NHL, including our 2 patients, presented with clinical features mimicking cholangiocarcinoma. All had jaundice; 9 had systemic symptoms; 7 had abdominal pain; and 5 had mass lesions. All had biliary strictures as shown on cholangiography. Two patients were infected with human immunodeficiency virus-1. In only 1 patient was the diagnosis established without surgery. Immunophenotyping in 10 patients showed 9 B-cell tumors and 1 T-cell tumor. Twelve patients underwent resection. Seven received chemotherapy immediately after the diagnosis was made. Only 3 patients have survived more than 3 years, with the longest survival being 68 months. CONCLUSIONS Non-Hodgkins lymphoma of the liver and bile duct must be considered in the differential diagnosis of patients with obstructive jaundice. If the correct diagnosis is made before surgery, current protocols of chemotherapy may be the primary modality of therapy. Surgical resection should be reserved to address complications of biliary obstruction or the failure of chemotherapy to eradicate localized disease.

De Novo Diagnosis of Portopulmonary Hypertension Following Liver Transplantation

Portopulmonary hypertension occurs in 2–8% of liver recipients. However, new onset of pulmonary hypertension following liver transplantation has been reported only once. We report de novo occurrences of portopulmonary hypertension in two liver recipients following successful liver transplantation. Although both patients had recurrent hepatitis C after the transplant, both had excellent clinical graft function. In one patient, upper endoscopy and aortogram showed evidence of persistent venous collaterals in the abdomen. Both patients presented with shortness of breath. Portopulmonary hypertension was diagnosed late, thus contributing directly to their deaths. Autopsy in one patient confirmed the absence of significant liver pathology and failed to demonstrate any source of deep venous thrombosis. This, and our earlier case report, highlights the potential for the occurrence of pulmonary hypertension following liver transplantation. Further studies are needed to determine the scope of the problem and identify patients at risk for this complication.

Hepatitis Status, Child-Pugh Classification, and Serum AFP Levels Predict Survival in Patients Treated With Transarterial Embolization for Unresectable Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents one of the most prevalent cancers worldwide. Most patients are not surgical candidates, and transarterial embolization (TAE) has been used to treat patients with unresectable HCC. The purpose of this study was to identify factors that predict survival in patients treated with TAE at a Western medical center. Review of a prospective database identi.ed 345 patients treated for HCC at University Hospital (Newark, NJ) between July 1998 and July 2004. Of these patients, 109 patients underwent TAE. Eleven of these patients were subsequently treated surgically and excluded from this study. Of the remaining 98 patients, demographic data and laboratory values were analyzed to predict survival by univariate and multivariate analysis. Several factors, including hepatitis status, Child-Pugh classification, serum alpha fetoprotein levels <500 ng/ml, bilirubin <2.0 mg/dl, prothrombin time <16 seconds, platelet count <200 × 10 9/l, albumin >3.5 gm/dl, and multiple treatments, predicted survival by univariate analysis. Serum alpha fetoprotein levels, Child-Pugh classification, and hepatitis status were found by multivariate analysis to independently predict survival. These factors may help to select patients with unresectable HCC who might benefit from TAE.

A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era.

Knowledge of risk factors for posttransplant complications is likely to improve patient outcomes. Few large studies of all early postoperative complications after deceased donor liver transplantation (DDLT) exist. Therefore, we conducted a retrospective, cohort study of 30‐day complications, their risk factors, and the impact on outcomes after DDLT. Three centers contributed data for 450 DDLTs performed from January 2005 through December 2009. Data included donor, recipient, transplant, and outcome variables. All 30‐day postoperative complications were graded by the Clavien‐Dindo system. Complications per patient and severe (≥ grade III) complications were primary outcomes. Death within 30 days, complication occurrence, length of stay (LOS), and graft and patient survival were secondary outcomes. Multivariate associations of risk factors with complications and complications with LOS, graft survival, and patient survival were examined. Mean number of complications/patient was 3.3 ± 3.9. At least 1 complication occurred in 79.3%, and severe complications occurred in 62.8% of recipients. Mean LOS was 16.2 ± 22.9 days. Graft and patient survival rates were 84% and 86%, respectively, at 1 year and 74% and 76%, respectively, at 3 years. Hospitalization, critical care, ventilatory support, and renal replacement therapy before transplant and transfusions during transplant were the significant predictors of complications (not the Model for End‐Stage Liver Disease score). Both number and severity of complications had a significant impact on LOS and graft and patient survival. Structured reporting of risk‐adjusted complications rates after DDLT is likely to improve patient care and transplant center benchmarking. Despite the accomplished reductions in transfusions during DDLT, opportunities exist for further reductions. With increasing transplantation of sicker patients, reduction in complications would require multidisciplinary efforts and institutional commitment. Pretransplant risk characteristics for complications must factor in during payer contracting. Liver Transpl 21:1160‐1168, 2015.

Does liver ischemic preconditioning in brain death donors induce kidney preconditioning? A retrospective analysis.

Background It is unclear whether ischemic preconditioning (IPC) of solid organs induces remote IPC (RIPC) in donors after brain death (DBD). Methods Outcomes in kidney recipients from 163 DBD in two randomized trials of liver IPC (5 min=62 and 10 min=101) were obtained retrospectively from the Scientific Registry of Transplant Recipients. Controls were kidney recipients from donors without IPC. Mean cold ischemia times were less than 20 hr. Primary outcomes were delayed graft function, defined as dialysis during the first posttransplantation week, and death-censored graft survival. Secondary outcomes were duration of initial hospital stay, patient survival, and estimated glomerular filtration rate 6, 12, 36, and 60 months after transplantation. Results After exclusions (40 kidneys not recovered, 21 not transplanted, 8 en bloc, 23 with extrarenal organs, and 6 with missing records), 228 recipients were included. Delayed graft function occurred in 23% of No RIPC and 28% of RIPC kidneys (P=0.54). One- and 3-year graft survival rates were 92% and 90%, respectively, in the No RIPC and 90% and 81%, respectively, in the RIPC group (P=0.12), and mean hospital stay was 9.3±13.9 and 9.7±8.2 days, respectively (P=0.15). There were no significant between group differences in patient survival and estimated glomerular filtration rate at any time point. Conclusions Despite design and power limitations, our results suggest that liver IPC in DBD is of no clinical benefit to kidney recipients. Inconsistent efficacy and impracticality severely limit the usefulness of IPC in DBD. Other modalities of preconditioning should be tested.