David P. Foley

Surgical Management of Hilar Cholangiocarcinoma

Objective:To assess the surgical management of hilar cholangiocarcinoma over a time period when liver resection was considered standard management. Summary Background Data:Hilar cholangiocarcinoma remains a difficult challenge for surgeons. An advance in surgical treatment is the addition of liver resection to the procedure. However, liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased mortality. Methods:Between 1997 and 2004, 80 patients with hilar cholangiocarcinoma having surgery were reviewed. Fifty-three patients had attempted curative resections, 14 patients had palliative bypasses, while 13 patients had findings that precluded any further intervention. Twenty-three patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. Results:Patients undergoing resection had a 9% operative mortality, with morbidity of 40%. Patients who demonstrated lobar hypertrophy preoperatively due to tumor involvement of the contralateral liver or induced with portal vein embolization (PVE) had a significantly lower operative mortality than those patients without hypertrophy. Median overall survival in patients resected was 40 months, with 5-year survival of 35%. Negative margins were achieved in 80% of cases and were associated with improved survival. Five-year survival in patients undergoing resection with negative margins was 45%. Conclusion:Combined liver and bile-duct resection can be performed for hilar cholangiocarcinoma with acceptable mortality, though higher than that for liver resections performed for other indications. The use of PVE in cases where hypertrophy of the remnant liver has not occurred preoperatively may reduce the risk of operative mortality.

Donation After Cardiac Death: The University of Wisconsin Experience with Renal Transplantation

Owing to the shortage of organ donors, there is renewed interest in donation after cardiac death (DCD), formerly referred to as nonheart‐beating donation. From January 1984 until August 2000, 382 renal transplants were performed from DCD donors. These were compared with 1089 renal transplants performed from donation after brain death (DBD) donors. The mean warm ischemic time in DCD donors was 16.5 min. There was no statistical difference in cold ischemic time, rate of primary nonfunction, or graft loss in the first 30 days after transplantation. The rate of delayed graft function (DGF) was higher for DCD donors (27.5% vs. 21.3%; p = 0.016) and discharge creatinine was higher in DCD donors (1.92 mg/dL vs. 1.71 mg/dL; p = 0.001). There was no statistical difference in the 5‐, 10‐, or 15‐year allograft survival when DCD donors were compared with DBD donors (64.8%, 44.8%, 27.8% vs. 71.3%, 48.3%, 33.8%; p = 0.054). Likewise, no statistical difference in the rate of technical complications was seen. Our long‐term data indicate that the results of renal transplantation from DCD donors are equivalent to long‐term allograft survival from DBD donors despite an increase in the rate of DGF. Organ procurement organizations, transplant centers, and hospitals should work to expand the implementation of DCD policies.

Are We Frozen in Time? Analysis of the Utilization and Efficacy of Pulsatile Perfusion in Renal Transplantation

Preservation techniques are crucial to deceased donor kidney transplantation (DDTx), but the efficacy of pulsatile perfusion (PP) versus cold storage (CS) remains uncertain. We describe patterns of PP use and explore four fundamental questions. What kidneys are selected for PP? How does PP affect utilization of donated kidneys? What effect does PP have on outcomes? When does PP appear to be most efficacious? We examined rates of PP in DDTx in the United States from 1994 to 2003. We generated models for organ utilization, delayed graft function (DGF) and for the use of PP. We analyzed the long‐term effect of PP with multivariate Cox models. The utilization rates for non‐expanded criteria donors (ECDs) were similar by storage type, but for ECDs there was a significantly higher utilization rate with PP (70% with PP vs. 59% with CS, p < 0.001). Use of PP was widely variable across transplant centers. DGF rates were significantly lower with PP (27.6% vs. 19.6%). PP was associated with a mild benefit on death censored graft survival (adjusted hazard ratio = 0.88, 95% CI 0.85–0.91). Reduced DGF and significantly lower discard rates of ECDs associated with PP suggest an important utility of PP in renal transplantation. Additional evidence of improvement in graft survival, particularly in more recent years, provides further encouraging evidence for the use of PP.

Preemptive retransplantation for BK virus nephropathy: successful outcome despite active viremia.

BK virus nephropathy (BKVN) is now recognized as a major cause of renal allograft loss. Recent reports suggest that retransplantation in patients with graft loss due to BKVN is safe after return to dialysis. Since early transplantation is associated with improved outcomes, it would be advantageous if this procedure could be performed prior to ultimate graft loss. However, little data are available regarding the safety of this approach during active viremia. In this report, we describe successful preemptive retransplantation with simultaneous allograft nephrectomy in two patients with active BKVN and viremia at the time of surgery. With 21‐ and 12‐month follow‐up, respectively, both patients have stable allograft function and no evidence for active viral replication. We conclude that preemptive retransplantation can be considered in patients with failing allografts due to BKVN.

Effect of sirolimus withdrawal in patients with deteriorating renal function.

Sirolimus has been an important addition to immunosuppressive regimens utilized in kidney transplantation. However, sirolimus can potentiate calcineurin inhibitor (CNI) nephrotoxicity by some still uncertain mechanisms. Studies have demonstrated that withdrawal of a CNI under sirolimus immunosuppression can improve renal function. However, it has yet to be demonstrated that withdrawal of sirolimus from such a regimen can also improve renal function and reverse progressive functional deterioration. We studied 17 patients who developed deterioration of renal function while on a CNI and sirolimus. Once an established deterioration in renal function was noted, sirolimus was withdrawn from the regimen and replaced with mycophenolate mofetil. Out of 17 patients with a negative slope in 1/cr, 15 demonstrated a positive treatment effect (change to a positive slope). On aggregate, renal function improved by 18% (creatinine 2.75–2.24 mg/dL), LDL cholesterol improved, as did hematocrit values after withdrawal. The majority of patients on a CNI and sirolimus regimen who experience deterioration in renal function demonstrate improvement in renal function after withdrawal of sirolimus. This strategy may be particularly useful in those patients where CNI withdrawal is considered to be of high immunologic or metabolic risk.

Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia

Murine total hepatic ischemia (THI) followed by reperfusion without shunting of the portal vein induces significant lethality in rodents due to intestinal congestion. Two methods have been promulgated to study THI and reperfusion in mice without intestinal congestion: subcutaneous splenic transposition which creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30% hepatectomy, which creates a portosystemic shunt via the small remnant of remaining caudal lobe. We compared outcome, inflammatory response and hepatic injury due to THI and reperfusion in these two models. Female C57BL/6 mice underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic ischemia followed by 60 min of reperfusion. Survival, surgical complications, serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were identified by morphological criteria. Complication rates for the ST and caudal shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal shunt, respectively. Both groups had elevated serum AST/ALT concentrations. However, in mice undergoing caudal shunt, AST/ALT levels were also significantly increased even without THI. The number of apoptotic hepatocytes after THI and reperfusion in mice following caudal shunt was significantly higher compared with those of ST (P<0.001). Both ST and caudal shunt can be used in models of THI and reperfusion to prevent significant lethality due to intestinal congestion. However, ST is a simple, safe and suitable model, whereas caudal shunt requires manipulation of the liver, and is associated with significant hepatic injury and morbidity.

Major hepatectomy induces phenotypic changes in circulating dendritic cells and monocytes.

IntroductionPatients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the phenotype of effector cells may predispose these patients to infectious sequelae.MethodsTo better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4 expression.ResultsMajor hepatectomy increased the numbers of activated CD16bright blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells. Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious outcomes.

The influence of pancreas after kidney transplantation on patient survival and kidney allograft function

Purpose of reviewPancreas transplantation after kidney transplantation improves the quality of life of kidney transplant recipients by removing the exogenous need for insulin and decreasing the number of hypoglycemic events. Recent studies have raised concern, however, over the potential negative impact of pancreas after kidney transplantation. This paper reviews the influence of pancreas after kidney transplantation on patient survival and kidney allograft function. Recent findingsTwo recent retrospective reviews examined the effects of pancreas after kidney transplantation on patient survival. A survival disadvantage was reported for recipients of pancreas after kidney transplants at both 1 and 4 years compared with those on the waiting list for a pancreas transplant. Another study examined the survival benefit of pancreas after kidney transplantation in a recent cohort of patients with current follow-up and found neither a survival advantage nor disadvantage between recipients of pancreas after kidney transplants and wait-listed patients. Other researchers demonstrated that pancreas after kidney transplantation had a negative impact on preexisting renal allograft function. SummaryDespite improving quality of life, pancreas after kidney transplantation also increases the short-term mortality rate, although this risk is eliminated with long-term follow-up. In addition, pancreas after kidney transplantation can be detrimental to the survival and function of the kidney allograft, but judicious selection of patients with adequate renal function for the pancreas after kidney transplantation procedure seems to void this risk.

Psychosocial support after simultaneous pancreas and kidney transplantation

We read with interest the article by Otte on the review of pediatric liver transplantation based on 20 years of experience [1]. In this article, psychological and mental impact of pediatric liver transplantation was discussed. Likely, the similar situation may occur after simultaneous pancreas and kidney transplantation (SPK), as SPK is indicated exclusively for patients with uremic type I diabetes with long-standing disease history from younger age. We recently experienced a case of SPK transplant who required the removal of both kidney and pancreas allografts for organ failure secondary to hypochondriasis-induced medication noncompliance. A 36-year-old female with type I diabetes and diabetic nephropathy was referred to our hospital as a candidate for SPK. The durations of diabetes treatment and dialysis were 26 years and 3.5 months, respectively. She was unmarried and lived with her mother. Her social history includes dropout from the college at second grade. She underwent uneventful SPK, received standardized immunosuppression including daclizumub, mycophenolate mofetil and tacrolimus. Her postoperative course was complicated by only minor gastrointestinal symptoms such as constipation, diarrhea and appetite loss; however, she claimed immediate nursing attention more than necessary during days and nights, and sometimes threatened discharge against medical advice. She was discharged on postoperative day 16 with normal blood glucose and good renal function. During her outpatient follow-up visits, she became malnourished and was admitted to the hospital with severe abdominal pain. Work-up showed no apparent cause of the pain, and the patient recovered without any intervention. Renal function and blood glucose level were within normal limits. During subsequent outpatient follow-up visits, she showed worsening nutritional status, and she also presented with severe recurrent abdominal pain. Blood trough levels of tacrolimus were unmeasurable, and the diagnosis of acute rejection secondary to non-compliance was made. She underwent removal of kidney and pancreas grafts on the day 42 after transplantation. Histological examination revealed massive necrosis of kidney and pancreas allografts secondary to severe acute rejection. She returned to insulin therapy and hemodialysis. Psychosocial background of SPK patients is often complicated due to long-standing disease history. The adverse psychosocial consequences come from dependency on parents and medical personnel, unrelenting lack of respite from illness and continuous need for treatment, restricted diet and fluid intake, and multiple losses (disability, financial insecurity, loss of self-esteem, delayed independence, etc.) [2,3]. Additionally, psychosocial morbidity in transplant patients is common as the incidence of major depression and anxiety neurosis are 2–16% and 2–14%, respectively [2]. The patients sometimes develop poor coping and social skills that ultimately leads to frustration. These inappropriate behaviors may eventually lead to postoperative noncompliance and the loss of transplanted organs. Unfortunately, it is difficult to predict postoperative compliance as preoperative compliance does not necessarily reflect postoperative compliance [2,4–6]. So, it is important for physicians, transplant coordinators and other team members to recognize the signs of psychosocial morbidity in these patients. Addressing these issues earlier may prevent subsequent noncompliance and transplant organ loss.