Khalid Khwaja

The Medical Evaluation of Living Kidney Donors: A Survey of US Transplant Centers

The use of living donors for kidney transplantation in the United States is common, and long‐term studies have demonstrated the safety of donation by young, healthy individuals. However, transplant programs have little data to guide them in deciding which donors are unacceptable, and which characteristics are associated with kidney disease or poor psychosocial outcomes after donation. To document current practices in evaluating potential donors, we surveyed all US kidney transplant programs. Compared to a survey 12 years ago, medical criteria for donation are more inclusive in several areas. All responding programs now accept living unrelated donors. Most programs no longer have an upper age limit to be eligible. Programs are now more likely to accept donors with treated hypertension, or a history of kidney stones, provided that certain additional criteria are met. In contrast, medical criteria for donation are more restrictive in other areas, such as younger donor age and low creatinine clearance. Overall, significant variability remains among transplant programs in the criteria used to evaluate donors. These findings highlight the need for more data on long‐term outcomes in various types of donors with potential morbidities related to donation.

Evaluating living kidney donors: relationship types, psychosocial criteria, and consent processes at US transplant programs.

We conducted a survey of 132 US kidney transplant programs to examine how they evaluate and select potential living kidney donors, focusing on donor‐recipient relationships, psychosocial criteria, and consent processes. There is heterogeneity in donor‐recipient relationships that are considered acceptable, although most programs (70%) will not consider publicly solicited donors. Most programs (75%) require a psychosocial evaluation for all potential living donors. Most programs agree that knowledge of financial reward (90%), active substance abuse (86%), and active mental health problems (76%) are absolute contraindications to donation. However, there is greater variability in how other psychosocial issues are considered in the selection process. Consent processes are highly variable across programs: donor and recipient consent for the donor evaluation is presumed in 57% and 76% of programs, respectively. The use of 13 different informed consent elements varied from 65% (alternative donation procedures) to 86% (description of evaluation, surgery and recuperative period) of programs. Forty‐three percent use a ‘cooling off’ period. Findings demonstrate high variability in current practice regarding acceptable donor‐recipient relationships, psychosocial criteria, and consent processes. Whether greater consensus should be reached on these donor evaluation practices, especially in the context of more expansive use of living donor kidney transplantation, is discussed.

Outcome at 3 Years with a Prednisone-Free Maintenance Regimen: A Single-Center Experience with 349 Kidney Transplant Recipients

Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow‐up has been short. We herein report on 3‐year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid‐free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone.

Living donor liver transplantation for hepatocellular carcinoma: Increased recurrence but improved survival.

In regions with a limited deceased donor pool, living donor adult liver transplantation (LDALT) has become an important treatment modality for patients with hepatocellular carcinoma (HCC) and cirrhosis. Studies have shown higher recurrence rates of HCC after LDALT in comparison with deceased donor liver transplantation (DDLT). The aim of our study was to examine the outcome results and recurrence rates for patients with HCC who underwent LDALT at our center. During an 8‐year period, 139 patients underwent LDALT, of whom 28 (20.1%) had HCC in their explanted livers. The median follow‐up was 40.8 months. The mean explant tumor size was 3.3 ± 1.2, and the mean number of tumors was 1.5 ± 0.8. Twenty‐one patients (75%) had tumors within the Milan criteria, 5 patients had tumors outside the Milan criteria but within the University of California San Francisco (UCSF) criteria, and 2 patients were beyond the UCSF criteria. The overall 1‐ and 5‐year patient and graft survival rates were 96% and 81%, respectively. Survival following LDALT was significantly better than survival following DDLT for HCC during the same time period (P = 0.02). Eight patients (28.6%) developed tumor recurrence. Poor differentiation of tumor cells was the most significant determinant of recurrence. Despite high recurrence rates of HCC following LDALT, overall 5‐year survival appears to be excellent. Liver Transpl 15:1861–1866, 2009.

Chronic rejection: the next major challenge for pancreas transplant recipients.

Objective. With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. Methods. We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. Results. A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P =0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P <0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P =0.002), cytomegalovirus infection posttransplant (RR=2.41, P =0.001), a retransplant (versus primary transplant) (RR=2.27, P =0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P =0.04). Conclusions. As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.

Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation.

Background. Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. Methods. We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. Results. Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. Conclusions. Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.

Rapid Discontinuation of Prednisone in Higher-risk Kidney Transplant Recipients

Prednisone-minimization protocols have been successful in low-risk recipients. We report on the use of a protocol incorporating rapid discontinuation of prednisone in a cohort of kidney transplant recipients (n = 79) at increased immunologic risk. Our data suggests that such recipients should not be excluded from prednisone-minimization protocols.

Clinical characteristics, treatment, and outcome of pancreatic schwannomas

This article involves the study of a patient with a rare benign schwannoma in the body of the pancreas. After reviewing 39 patient cases previously reported in the literature, a discussion of the schwannoma with regard to clinical presentation, diagnosis, and treatment is examined. A review of the patient’s chart was performed along with a review of the literature using a Medline search. Translations were performed whenever necessary. There are 23 reports of 29 patient cases of pancreatic schwannomas in English and European literature and one report of 10 patient cases in the Japanese literature. The mean age was 57.75 years (range 32–89) and the male-to-female (M:F) ratio was 17:23. The mean reported size was 8.79 cm. The lesion was located in the head in 16 patients (40%), the body in 8 patients (20%), the body and tail in 8 patients (20%), the tail in 6 patients (15%), the head and body in 1 patient (2.5%), and the location was not specified in 1 patient (2.5%). Of the English and European patients, 11 out of 30 patients (36.7%) exhibited solid tumors and 14 out of 30 patients (46.7%) exhibited cystic tumors. The majority of the tumors (35 out of 40) were benign, but there were.ve reported malignancies. There were no deaths or recurrences reported with a follow-up of 18.68 months ± 24.09 (range 3–108 months). Pancreatic schwannomas are rare, and the preoperative diagnosis is difficult. Intraoperative frozen section can confirm the diagnosis of a benign schwannoma. Enucleation of the tumor from the surrounding parenchyma is recommended, if possible. Patients undergoing resection indicate an excellent long-term prognosis.

Older living donors provide excellent quality kidneys: a single center experience (older living donors).

Abstract:  Background:  The role of advanced age live donors remains controversial because of decline in glomerular filtration rate and perceived increased risks of perioperative complications.

Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma

Background: Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. Methods: Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The CyberknifeTM stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. Results: 34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. Conclusions: SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma.