Hoonbae Jeon

Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers.

BACKGROUND & AIMS Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. METHODS We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site. RESULTS The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy. CONCLUSIONS Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.

Long-term outcome of controlled, non-heart-beating donor liver transplantation.

Background. Previous reports have established the feasibility of using livers from controlled, non–heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. Methods. Retrospective database review for the last 7 years (1995–2002), encompassing 19 patients receiving CNHBD, with follow-up period of 1,000±694 days, median 762 days. Detailed review of recipient characteristics, operative and clinical course, immunosuppression, complications, survival rates, and comparison with the results obtained in patients receiving transplants of allografts procured in standard fashion, from heart-beating donors Results. Kaplan-Meier patient survival rates were 100%, 89.5%, and 83.5% at 30 days, 1, and 2 years, respectively, which is not different from recipients of livers procured from heart-beating cadaveric donors (P=0.74, log-rank test). Five patients died at a mean follow-up time of 492 (range 46–1,103) days. The causes of death were related to secondary sclerosing cholangitis (n=1), cardiac failure (n=1), and sepsis (n=3). Two (10.5%) recipients underwent retransplantation, one for primary graft nonfunction and one because of biliary cast syndrome with cholangitis. Significant preservation damage (ALT>2,000) developed in five patients, but this did not affect survival. The incidence of vascular (15.6% vs. 9.6%, P=0.34) and biliary complications (10.55 vs. 13.8%, P=0.68) was no different than for those recipients receiving standard cadaveric donors. Conclusions. CNHBD safely expands the donor pool with similar long-term results as those obtained in patients receiving organs from brain-dead donors under standard procurement techniques.

An in vitro study of liposomal curcumin: Stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells

Curcumin is a multi-functional and pharmacologically safe natural agent. Used as a food additive for centuries, it also has anti-inflammatory, anti-virus and anti-tumor properties. We previously found that it is a potent inhibitor of cyclosporin A (CsA)-resistant T-cell co-stimulation pathway. It inhibits mitogen-stimulated lymphocyte proliferation, NFkappaB activation and IL-2 signaling. In spite of its safety and efficacy, the in vivo bioavailability of curcumin is poor, and this may be a major obstacle to its utility as a therapeutic agent. Liposomes are known to be excellent carriers for drug delivery. In this in vitro study, we report the effects of different liposome formulations on curcumin stability in phosphate buffered saline (PBS), human blood, plasma and culture medium RPMI-1640+10% FBS (pH 7.4, 37 degrees C). Liposomal curcumin had higher stability than free curcumin in PBS. Liposomal and free curcumin had similar stability in human blood, plasma and RPMI-1640+10% FBS. We looked at the toxicity of non-drug-containing liposomes on (3)H-thymidine incorporation by concanavalin A (Con A)-stimulated human lymphocytes, splenocytes and Epstein-Barr virus (EBV)-transformed human B-cell lymphoblastoid cell line (LCL). We found that dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) were toxic to the tested cells. However, addition of cholesterol to the lipids at DMPC:DMPG:cholesterol=7:1:8 (molar ratio) almost completely eliminated the lipid toxicity to these cells. Liposomal curcumin had similar or even stronger inhibitory effects on Con A-stimulated human lymphocyte, splenocyte and LCL proliferation. We conclude that liposomal curcumin may be useful for intravenous administration to improve the bioavailability and efficacy, facilitating in vivo studies that could ultimately lead to clinical application of curcumin.

Minimally Invasive Robotic Kidney Transplantation for Obese Patients Previously Denied Access to Transplantation

Epidemiological data indicate that 20-50% of patients on dialysis for end-stage renal disease (ESRD) are obese (body mass index [BMI] ≥30 kg/m2) (1). Obese patients with chronic renal failure have longer wait times until kidney transplantation (2) and inferior patient outcomes (3-7). In the US, for example, patients with a BMI 40 kg/m2 (2). Higher BMIs in kidney transplant recipients are associated with excess risk of surgical site infections (SSIs), which negatively impact graft survival (8). Obesity is also associated with comorbidities such as diabetes, although data on whether obesity increases mortality in kidney transplanted patients remains unclear (8,9). Provider perceptions of these risks accompanied by the expectation of some centers to give obese patients time to lose weight are the main reasons why a number of transplant centers are reluctant to list obese patients for transplantation (2,10). Unfortunately, many of these obese patients have diabetes and hypertension likely secondary to their obesity (11) and such patients who remain on dialysis have a very high mortality rate. The 5-year mortality rate for diabetic and hypertensive dialysis patients is 75 and 70%, respectively (1). A recent study demonstrated that obese patients who did not present with any SSIs had the same kidney transplant success rate as patients with a normal BMI (8). If surgical procedures could be developed that prevent SSIs and demonstrate successful outcomes, transplant centers may become less reluctant to list obese patients for kidney transplantation. Although any benefit would still have to be weighed against potential increased risks from obesity-related comorbidities. The prevalence of obesity and ESRD is higher among racial and ethnic minority populations, including African-Americans and Hispanics, compared to Non-Hispanic whites (12-15). These observations suggest developing kidney transplantation options for obese patients with ESRD may also help to reduce health disparities in racial and ethnic minorities. We therefore developed a new, minimally invasive, robotic-assisted kidney transplantation method using a short epigastric incision. This method avoids any incision in the infection prone lower quadrants of the abdomen. We hypothesized a priori that the robotic approach would reduce SSIs and improve outcomes in obese kidney transplant patients. Herein, we present our experience and outcomes of the patients undergoing minimal invasive, robotic kidney transplantation at a single institution compared to patients who underwent the conventional open procedure.

Robotic transabdominal kidney transplantation in a morbidly obese patient.

Kidney transplantation in morbidly obese patients can be technically demanding. Furthermore, morbidly obese patients experience a high rate of wound infections and related complications, which mostly result from the longer length and extent of the incision. These complications can be avoided through minimally invasive surgery; however, conventional laparoscopic instruments are unsuitable for the safe performance of a kidney transplant in morbidly obese patients. Herein, we report the first minimally invasive, total robotic kidney transplant in a morbidly obese patient. A left, deceased donor kidney was transplanted into a 29‐year‐old woman with a body mass index (BMI) of 41 kg/m2 who had been on hemodialysis for 5 years. The operation was performed intraabdominally using the DaVinci Robotic Surgical System with 4 trocars and a 7 cm midline incision. The operative time was 223 min, and the blood loss was less than 50 cc. The kidney had immediate graft function. No perioperative complications were observed, and the patient was discharged on postoperative day 5 with normal kidney function. Minimally invasive access and robotic technology facilitated the safe performance of a successful kidney transplant in a morbidly obese patient.

A simple new formula to assess liver weight

INTRODUCTION In cadaveric or segmental liver transplantation, accurate assessment of graft volume is desirable but not always easy to achieve based on donor morphometric data. We sought to establish a simple, reliable formula for accurate prediction of liver volume. METHODS Data from 1,413 cadaveric adult and pediatric liver donors were analyzed using simple and multiple regression analysis. Liver weight (LW) was plotted against age, height, body weight (BW), body surface area (BSA) or body mass index (BMI); a formula was developed using simple regression: LW (g) = 772 (g/m(2)) x BSA, r = 0.73, P <.01. For donors with BSA </=1.0, a pediatric factor (PF) of 1.0 was included, resulting in the formula: LW (g) = 772 (g/m(2)) x BSA - 38PF, r = 0.73, P <.01. We then applied our formula on 5 published formulae to estimate LW of our donors. RESULTS Among donors with BSA >1.0, there was no significant difference between the actual and the estimated mean LW as calculated by the new formula. For pediatric donors, there was no significant difference between estimated and actual mean liver weight with any formula. When the new formula was applied, the difference between the actual and the estimated liver weight was acceptable (<20%) in 1040 (73.6%) cases. In all races, there was no significant difference between actual and estimated mean liver weight as calculated by this formula. CONCLUSIONS A simple formula to calculate liver weight in donors with BSA >1.0 is: LW = 772 x BSA, and for donors with BSA </=1.0: Liver Weight = 772 x BSA - 38.

Robot‐assisted right lobe donor hepatectomy

Recent advances in robotic surgical technology have enabled application to complex surgical procedures. Following extensive institutional experience with major robotic liver resections, we determined that it was safe to apply this technology to right lobe donor hepatectomy (RLDH). The procedure was performed using the Da Vinci Robotic Surgical System, in an entirely minimally invasive fashion, during which the liver graft was safely extracted through a limited lower abdominal incision. Both donor and recipient recovered well, without acute complications. To our knowledge, this is the first case reported in the literature. The technical feasibility of this minimally invasive approach is demonstrated, exemplifying the novel exciting opportunities offered by robotic technology.

Predictors of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease.

Background. Alcoholic liver disease (ALD) is a common indication for transplantation worldwide. This study identifies factors predicting posttransplant recidivism. Methods. Clinical and laboratory data were reviewed. Uni- and multivariate analyses for survival and relapse to alcohol and illicit drugs were performed. Result. Between July 1995 and November 2007, 387 patients underwent liver transplantation at our institution. Of these, 147 patients (38%) were found to have ALD. Five patients (3.4%) were excluded because of perioperative mortality. Overall survival was 96.2%, 89.6%, and 84.4% at 1, 3, and 5 years, respectively, with a median follow-up of 41.2 months. Twenty-seven patients (19%) returned to alcohol after transplantation. By univariate analysis, depression was the only significant factor affecting survival (P=0.01), whereas posttransplant relapse to alcohol trended toward significance (P=0.059). Multivariate analysis showed both factors to be independently associated with poor survival (P=0.008 and 0.017, respectively). Factors associated with relapse included less than 12 months of abstinence before transplant (P=0.019) and participation in rehabilitation (P=0.026). Multivariate analysis showed pretransplant abstinence less than 12 months as the only independent factor (P=0.037) associated with alcohol relapse after transplantation. Twenty-five patients (17.2%) had documented drug use after transplantation. Drug abuse before transplantation was the only independent predictor of drug abuse after transplantation (P=0.017). Conclusions. Excellent results can be obtained in patients undergoing liver transplantation for ALD, though depression and recidivism adversely impact survival. In our series, abstinence less than 12 months was associated with relapse to alcohol. Similarly, those with prior drug abuse are more likely to continue drug use after transplantation.

Obesity, diabetes, and smoking are important determinants of resource utilization in liver resection: a multicenter analysis of 1029 patients.

Objective:To investigate independent contributions of obesity, diabetes, and smoking to resource utilization in patients following liver resection. Summary Background Data:Despite being highly resource-intensive, liver resections are performed with increasing frequency. This study evaluates how potentially modifiable factors affect measures of resource utilization after hepatectomy. Methods:The American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) public-use database was queried for patients undergoing liver resection. Resource variables were operative time (OT), intraoperative transfusion, length of stay (LOS), ventilator support at 48 hours, and reoperation. Bivariable and multivariable linear and logistic regressions were performed. Results:There were 1029 patients identified. Most resections involved less than a hemiliver (599 patients, 58.2%). Mean BMI was 28.0 ± 6.0. Mean OT was 253 ± 122 minutes (range, 27 to 794) but varied by procedure (P < 0.001). Mean LOS was 8.7 ± 10.7 days (range, 0 to 202). Morbid obesity added 48 minutes to OT (P = 0.018), 1.1 units to transfusions (P = 0.049), 2.2 days to LOS (P < 0.001), and accounted for delayed ventilator weaning (odds ratio, 4.5; P = 0.022). Underweight patients had shorter OT, but stayed 3.3 days longer than normal weight patients (P < 0.001). Insulin-treated patients with diabetes had longer OT (P < 0.001), increased transfusions (P < 0.001), and delayed ventilator weaning (odds ratio, 6.7; P < 0.001), while orally-treated patients with diabetes showed opposite trends. Smokers stayed 1.9 days longer (P < 0.001), with increased risk of prolonged ventilation (odds ratio, 3.3; P = 0.002) and reoperation (odds ratio, 2.3; P = 0.015). Conclusion:Obesity, diabetes, and smoking are each associated with important components of healthcare expenditure. Education and prevention programs are needed to limit their impact on overall resource utilization.

Sensitivity of expanded‐criteria donor kidneys to cold ischaemia time

Abstract:  The United Network for Organ Sharing (UNOS), working in conjunction with organ procurement organizations and transplant programmes, has recently defined a class of cadaver kidney grafts for special allocation procedures to enhance utilization of those organs. The criteria defining these expanded‐criteria donor (ECD) kidneys are donor age ≥ 60 yr or donor age between 50 and 59 yr plus two of the following characteristics: donor history of cerebrovascular accident (CVA), donor history of hypertension (htn), and elevated creatinine (>1.5) at any time during donor management. Kidney grafts from ECD donors carry an increased relative risk of non‐function compared to other cadaver kidney grafts. The goal of the special allocation procedure is to reduce the time associated with placement by matching ECD grafts with patients previously designated as being willing to accept them. In assessing the potential impact of these allocation procedures, the sensitivity of ECD grafts to cold ischaemia time (CIT) became of great significance. Specifically, we questioned whether minimization of CIT might reduce the relative risk of poor graft function, justifying reduction of the geographical range of placement and thereby reducing the time the grafts would spend in‐transit.