Rick Selby

Abdominal organ cluster transplantation for the treatment of upper abdominal malignancies

Ten patients with primary malignant tumors of the biliary tract, duodenum, or stomach and with secondary involvement of the liver underwent removal of most or all of the stomach, liver, pancreas, spleen, duodenum, proximal jejunum, terminal ileum, and ascending and transverse colon. The void in the upper abdomen was filled with an organ cluster graft consisting of the liver, pancreas, duodenum, and variable segments of proximal jejunum. Eight of the ten patients are alive after 3 to 9 months, all with good liver and pancreas function, and most with satisfactory function of the gastrointestinal tract. One of the surviving patients was in the hospital for 4 months because of multiple enteric fistulas and infections; the other seven survivors were discharged after an average of 43 +/- 17.61 (SD) days. Recurrent tumor has not been proved in any of the surviving recipients and is suspected in only one. The study of such cases should provide insight and guidelines applicable to other visceral transplantation procedures that may be attempted in the future.

Intestinal transplantation in composite visceral grafts or alone.

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.

Does an infected peripancreatic fluid collection or abscess mandate operation

OBJECTIVE To assess the treatment of peripancreatic fluid collections or abscess with percutaneous catheter drainage (PCD). SUMMARY BACKGROUND DATA Surgical intervention has been the mainstay of treatment for infected peripancreatic fluid collections and abscesses. Increasingly, PCD has been used, with mixed results reported in the literature. METHODS A retrospective chart review of 1993 to 1997 was performed on 82 patients at a tertiary care public teaching hospital who had computed tomography-guided aspiration for suspected infected pancreatic fluid collection or abscess. Culture results, need for subsequent surgical intervention, length of stay, and death rate were assessed. RESULTS One hundred thirty-five aspirations were performed in 82 patients (57 male patients, 25 female patients) with a mean age of 40 years (range 17-68). The etiologies were alcohol (41), gallstones (32), and other (9). The mean number of Ransons criteria was four (range 0-9). All patients received antibiotics. Forty-eight patients had evidence of pancreatic necrosis on computed tomography scan. Cultures were negative in 40 patients and positive in 42. Twenty-five of the 42 culture-positive patients had PCD as primary therapy, and 6 required subsequent surgery. Eleven patients had primary surgical therapy, and five required subsequent surgery. Six patients were treated with only antibiotics. The death rates were 12% for culture-positive patients and 8% for the entire 82 patients. CONCLUSIONS Historically, patients with positive peripancreatic aspirate culture have required operation. This series reports an evolving strategy of reliance on catheter drainage. PCD should be considered as the initial therapy for culture-positive patients, with surgical intervention reserved for patients in whom treatment fails.

Renal cell carcinoma metastatic to the pancreas: a single-institution series and review of the literature.

OBJECTIVES To present a series of 5 patients with solitary metastatic renal cell carcinoma (RCC) to the pancreas after radical nephrectomy at our institution and review the published reports of this rare event. METHODS A retrospective review of the records of 5 patients with histologically confirmed RCC metastatic to the pancreas after radical nephrectomy was performed. A total of 5 patients (4 men, 1 woman) with a median age of 56 years (range 54 to 68) underwent radical nephrectomy for primary RCC. The pathologic stage was Robson I (n = 3) or Robson III (n = 2), with a left-sided tumor occurring in 3 patients and a right-sided tumor in 2 patients. The median interval from nephrectomy to the diagnosis of the pancreatic metastasis was 12 years (range 4 to 15). All patients were symptomatic at presentation, including weight loss (n = 3), abdominal pain (n = 3), early satiety (n = 1), steatorrhea (n = 1), and/or hemosuccus pancreaticus (n = 1). RESULTS All pancreatic metastases were hypervascular on imaging studies, and surgical removal was accomplished by pancreaticoduodenectomy (n = 3), partial pancreatectomy (n = 1), or subtotal pancreatectomy (n = 1). One patient died of disseminated disease 12 months after pancreatic resection. Two other patients had recurrences in the lung (n = 1) at 5 months or the pancreas/liver (n = 1) at 48 months. Both of these patients underwent a second resection and were disease free at 2 and 12 months afterward. The two remaining patients were disease free at 7 and 24 months after pancreatic resection. CONCLUSIONS RCC is an unpredictable tumor that may demonstrate very late metastases even from early-stage lesions. Aggressive surgical management of isolated pancreatic lesions offers a chance of long-term survival.

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

Background. There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). Methods. Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. Results. Renal half-life of KALT allografts was shorter than CLKT group (6.6±0.9 vs. 11.7±1.3 years, P<0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P<0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P<0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P<0.001). Conclusion. Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.

Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome†

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End‐Stage Liver Disease–based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post‐LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End‐Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT. Liver Transpl, 2012.

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation.

Background. Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. Methods. From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. Results. Graft and patient survival rates were lower among LKT recipients compared with KAT (P <0.001) and PKT recipients (P <0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P =0.005 vs. KAT, P =0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P <0.0001). Conclusions. Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.

Progressive neurologic disability in methylmalonic acidemia despite transplantation of the liver

Abstract. Methylmalonic acidemia unresponsive to cobalamin is often fatal in infancy. Patients have been considered candidates for hepatic transplantation and experience has been that the procedure eliminates the life-threatening episodes of ketoacidosis that characterize this disease. Conclusion: experience with a 24-year-old patient treated with hepatic transplantation indicates that this procedure does not prevent progressive renal failure and neurologic dysfunction.

Liver transplantation for type IV glycogen storage disease

Type IV glycogen storage disease is a rare autosomal recessive disorder (also called Andersen’s disease1 or amylopectinosis) in which the activity of branching enzyme alpha-1, 4-glucan: alpha-1, 4-glucan 6-glucosyltransferase is deficient in the liver as well as in cultured skin fibroblasts and other tissues.2,3 This branching enzyme is responsible for creating branch points in the normal glycogen molecule. In the relative or absolute absence of this enzyme, an insoluble and irritating form of glycogen, an amylopectin-like polysaccharide that resembles plant starch, accumulates in the cells. The amylopectin-like form is less soluble than normal glycogen, with longer outer and inner chains and fewer branch points. The clinical onset of the disease is insidious, with nonspecific gastrointestinal symptoms at first, followed by progressive hepatosplenomegaly, portal hypertension, ascites, and hepatic failure. Children with this disorder usually die of hepatic cirrhosis by the age of two to four years. 4–8 In exceptional cases, cardiomyopathy,5–7,9 neurologic syndromes — including tremors, seizures, and dementia10,11 — or variable manifestations of myopathy5,12,13 have been reported. In patients with these unusual symptoms, the clinical onset is frequently later than in typical cases, and death most often results from cardiac failure. Liver transplantation for Type IV glycogen storage disease was attempted in 1972; the recipient died 110 days later after the rejection of the first liver transplant and attempted re transplantation.14 Liver transplantation was first performed successfully in September 1984 in Patient 1 of this series; since that time we have treated six more such patients. Our experience with these seven patients forms the basis of this report.

Live donor liver transplantation without blood products: strategies developed for Jehovah's Witnesses offer broad application.

Objective:Developing strategies for transfusion-free live donor liver transplantation in Jehovahs Witness patients. Summary Background Data:Liver transplantation is the standard of care for patients with end-stage liver disease. A disproportionate increase in transplant candidates and an allocation policy restructuring, favoring patients with advanced disease, have led to longer waiting time and increased medical acuity for transplant recipients. Consequently, Jehovahs Witness patients, who refuse blood product transfusion, are usually excluded from liver transplantation. We combined blood augmentation and conservation practices with live donor liver transplantation (LDLT) to accomplish successful LDLT in Jehovahs Witness patients without blood products. Our algorithm provides broad possibilities for blood conservation for all surgical patients. Methods:From September 1998 until June 2001, 38 LDLTs were performed at Keck USC School of Medicine: 8 in Jehovahs Witness patients (transfusion-free group) and 30 in non-Jehovahs Witness patients (transfusion-eligible group). All transfusion-free patients underwent preoperative blood augmentation with erythropoietin, intraoperative cell salvage, and acute normovolemic hemodilution. These techniques were used in only 7%, 80%, and 10%, respectively, in transfusion-eligible patients. Perioperative clinical data and outcomes were retrospectively reviewed. Data from both groups were statistically analyzed. Results:Preoperative liver disease severity was similar in both groups; however, transfusion-free patients had significantly higher hematocrit levels following erythropoietin augmentation. Operative time, blood loss, and postoperative hematocrits were similar in both groups. No blood products were used in transfusion-free patients while 80% of transfusion-eligible patients received a median of 4.5+/− 3.5 units of packed red cell. ICU and total hospital stay were similar in both groups. The survival rate was 100% in transfusion-free patients and 90% in transfusion-eligible patients. Conclusions:Timely LDLT can be done successfully without blood product transfusion in selected patients. Preoperative preparation, intraoperative cell salvage, and acute normovolemic hemodilution are essential. These techniques may be widely applied to all patients for several surgical procedures. Chronic blood product shortages, as well as the known and unknown risk of blood products, should serve as the driving force for development of transfusion-free technology.