Dual Organ Research Articles

OP180: Mucosal malignancy with solid organ transplantation

Purpose 1. Measure the prevalence of mucosal head and neck squamous cell carcinoma (HNSCC) using a large database of solid organ transplant recipients. 2. Assess the risk of malignancies considering organ type, age at transplant and use of immunosuppressive medications. 3. Investigate the impact of on overall survival of each patient subset. Methods A database containing all solid organ transplant recipients at UMHS was used, and medical records from 4125 patients transplanted from 1996 to 2006 were queried using EMERSE (Electronic Medical Record Search Engine), with a bundle of search terms designed to screen for target malignancies. Once cases were identified, analysis of differences in incidence based on transplant site and age was performed using a generalized linear model with transplant organ and age at transplant as predictors. For all patients transplanted in the year 2002, medication usage history and survival data were gathered for subgroup analysis of these endpoints. Results The transplant recipient cohort consisted of 59% kidney, 22% liver, 8% lung, 10% heart and 5% receiving dual organ transplant. Head and neck cancer (HNSCC) was diagnosed in 0.6% of patients (n = 26). The mean age (std., range) at transplant was 44 years (17, Conclusion Transplant recipients carry an elevated risk of mucosal malignancies. Older age is correlated with increased risk of malignancy and shorter post-transplant interval. There is a trend towards worse prognosis in HNSCC patients with solid organ transplant.

Transplantation for Inherited Metabolic Disorders of the Liver

Inherited metabolic diseases that affect the liver are a frequent cause of liver failure in children, but other disorders more commonly cause liver failure in adulthood where they may present with chronic liver disease and, less frequently, with acute liver failure. The identification of the underlying genetic defect for many of these inherited disorders has improved our understanding of their pathophysiology and impacted on the indications for and timing of liver transplant, yielding better outcomes. Screening for disease and genetic counseling of family members may help prevent adverse outcomes in relatives of affected individuals. Timely liver transplantation offers correction of the inherited metabolic defect and restores liver function when medical therapy is not possible or when complications of liver disease arise. Some inherited metabolic diseases have their defect based in the liver and lead not to liver disease, but to other end organ damage. Earlier detection of these disorders may prevent pathological injury by treatment of the underlying disease or by pre-emptive liver transplant. In some instances where damage of other organs has already occurred, dual organ transplant with liver and another organ may be needed. Improvement in the technical aspects of performing liver transplantation and posttransplant care has led to better outcomes for those with inherited metabolic disorders of the liver.

490 Change in Renal Function and Association With Acute Hospitalization in Chronic Ambulatory Heart Failure Patients

Acute deteriorations in renal function are common in hospitalized heart failure patients and associated with a worse prognosis. The relationship between small, serial fluctuations in renal function and prognosis in ambulatory heart failure patients remains unclear. Cardiorenal syndrome is a new and emerging classification for dual organ dysfunction occurring in the heart failure population and there is significance in identifying prognostic factors for its onset and progression. We set out to evaluate the rates of change in three measures of renal function: cystatin C (a serine protease inhibitor that appears to be a more sensitive approximation of renal GFR) , creatinine and estimated glomerular filtration rate (eGFR) and their association with acute hospitalization in an ambulatory cohort of heart failure patients. A total of 140 patients (83% male, mean EF 24.8±7.0%) were prospectively followed for up to 24 months (median 333 days (IQR 192-457) in a tertiary care heart failure clinic. Laboratory values and clinical outcomes were measured every 3 months. eGFR was calculated by the MDRD equation. Mixed and ordinary linear regression models were employed to determine the association of rates of renal function change and hospitalization. During the study period there were a total of 84 (range 0-9; 60%) hospitalizations in the study population. In general, renal function decreased in the population over the study period (eGFR 0.28mls/min/m2 per month (95% CI -0.43 to -0.14, p<0.0001); creatinine 0.62 μmol/L per month (95% CI 0.27-0.96, p<0.0001). The rates of change of serum creatinine and eGFR were highly associated with acute hospitalizations; eGFR -1.07 (95% CI -1.83 to -0.32, p=0.005), creatinine 0.56 (95% CI 0.23-0.89, p=0.001). Changes in cystatin C were not associated with hospitalizations (0.003 95% CI -0.004 to 0.010, p=0.4). Serial changes in serum creatinine and eGFR, but not cystatin C, are associated with an increased risk of hospitalization in chronic stable ambulatory heart failure patients.

Renal allografts in plasma cell myeloma hematopoietic cell graft recipients: on the verge of an explosion?

Renal dysfunction is a common complication of plasma cell myeloma (PCM) that may be severe enough to necessitate hemodialysis. Although high-dose chemotherapy and hematopoietic cell transplant (HCT) appears superior to conventional chemotherapy in likelihood of achieving CR and is associated with improvement in and, at times, reversal of renal dysfunction, many patients remain dialysis-dependent presenting the challenge of renal transplantation in this population. We reviewed the published literature and summarize the outcomes on dual organ (HCT and renal allograft) transplantation in patients with PCM and dialysis-dependent renal failure. In a literature review of 14 reports, 26 of 166 dialysis-dependent patients became dialysis-independent. Our review includes a very heterogenous patient population but suggests that HCT and renal allograft may be feasible in a subset of PCM patients with dialysis-dependent renal failure. Although there is a concern for renal allograft rejection upon withdrawal of immunosuppression, data suggest that resumption of antirejection therapy leads to stable renal function. Bortezomib potentially can be used as maintenance treatment in patients who have not achieved a CR while preventing renal allograft rejection. The literature that describes dual transplants has included patients with long-term follow-up (>7 years in some patients). It is possible, however, that there may be publication bias with only favorable results being reported. More research is necessary to further delineate the subset of PCM patients most likely to benefit from renal transplant. A special registry for data collection for long-term follow-up may be useful to improve future patient survival.

The Complex Exocrine–Endocrine Relationship and Secondary Diabetes in Exocrine Pancreatic Disorders

The pancreas is a dual organ with exocrine and endocrine functions. The interrelationship of the endocrine-exocrine parts of the pancreas is a complex one, but recent clinical and experimental studies have expanded our knowledge. Many disorders primarily of the exocrine pancreas, often solely in the clinical realm of gastroenterologists are associated with diabetes mellitus (DM). Although, the DM becoming disorders are often grouped with type 2 diabetes, the pathogenesis, clinical manifestations and management differ. We review here data on the association of exocrine-endocrine pancreas, the many hormones of the pancreas and their possible effects on the exocrine functions followed by data on the epidemiology, pathogenesis, and management of DM in chronic pancreatitis, cystic fibrosis, pancreatic cancer, and clinical states after pancreatic surgery.

P83 Combined liver and kidney transplantation: a single centre experience

IntroductionCombined liver kidney transplantation (CLKT) is an accepted approach to management of patients with dual organ pathology, but may be associated with significant additional post-operative morbidity and mortality in comparison...

217 Risk-Stratification of Heart Transplant (HTX) Candidates with Advanced Liver Dysfunction

Purpose: HTX candidates frequently have liver dysfunction. Identification of patients who may proceed to heart transplant or need dual organ transplant is difficult. Models of End-Stage Liver Disease (MELD) score has been shown to predict outcomes in HTX patients. Whether MELD score, liver biopsy, hemodynamics or echocardiography differentiates these patients was investigated. Methods and Materials: Retrospective chart review of all patients evaluated for HTX at Columbia University from 1/00-10/10 identified 37 patients with liver disease who underwent liver biopsy. Echo, right heart cath and MELD were available in all patients; 22 patients had liver hemodynamics. Results: 25 patients were listed for HTX, and 12 patients were rejected secondary to advanced liver disease. Etiology of liver disease was: HCV (11), alcohol (5), amiodarone toxicity (5), congestive hepatopathy (15) and infiltrative disease (1). 15 patients were transplanted: 14 male, age 56 6 years. 75% had mod-severe RV dysfunction, mean RA 14.4 6.6 mmHg, mean hepatic wedge 21.7 7 and MELD 14 4.4. Liver pathology showed 2 with cirrhosis, 2 with moderate and 11 with minimal fibrosis. One and 5 year survival was 94%, and 85%. Of the remaining 10 listed patients, 9 died prior to HTX. Hemodynamics, pathology and MELD were similar to those transplanted (MELD 13.3 5.5). Of the rejected patients, 80% were male, age 52 14 years. 75% had mod-severe RV dysfunction, mean RA 19 7, mean hepatic wedge 22.7 4.5 and MELD 17 7.3. Liver pathology showed 5 with cirrhosis, 4 moderate and 3 with minimal fibrosis. 9 of 12 patients died. MELD score for all 37 patients did not correlate with liver fibrosis severity. Conclusions: Rejected candidates had modestly worse hemodynamics and MELD when compared to accepted candidates, with more advanced liver pathology. Liver pathology identifies patients who might benefit from dual organ transplant, whereas MELD might identify their surgical risk. High mortality on the transplant waitlist reflects organ shortage and inability to offer device therapy to these patients.

249 Strongyloides Stercoralis Infection After Simultaneous Pancreas and Kidney Transplant; A Case Report in Survival

STRONGYLOIDES STERCORALIS INFECTION AFTER SIMULTANEOUS PANCREAS AND KIDNEY TRANSPLANT; A CASE REPORT IN SURVIVAL Ameena Bagree, Amber Podoll, University of Texas Health Science Center, Houston, Texas USA Strongyloides stercoralis hyperinfection has been described rarely in single solid organ transplant patients but never in dual organ transplants to date. It is associated with a very high mortality rate (80-90%). We present a 50 year old Canadian-born male 4 months status post simultaneous pancreas kidney (SPK) transplant that was maintained on prograf, mycophenolic acid and low dose prednisone. He had several months of indolent symptoms of nausea and diarrhea with no identifiable source and multiple negative stool cultures. He, then, acutely represented with diarrhea, vomiting, larva currens abdominal rash, and acute respiratory failure with no readily identifiable exposures. Mycophenolic acid was discontinued. Extensive Strongyloides larval infiltration was detected by duodenal biopsy with massive shedding in nasogastric and respiratory secretions. An initial regimen of enteric Ivermectin 15mg daily and Albendazole 400mg BID was started. His Ivermectin was titrated to three times daily. The patient improved clinically and was extubated 10 days after initiation of therapy. Ivermectin was discontinued following negative larval samples from stool, tracheal, and gastric aspirates but had to be resumed due to one episode of recurrence of larva. Once the larval samples cleared, the ivermectin dosing was eventually minimized to the lowest possible dose and tapered off along with albendazole. The main concern during his therapeutic course was diminished responsiveness and neurotoxicity from ivermectin. The patient has now begun to make a slow neurologic recovery and long term outcomes remain to be determined. His renal and pancreatic grafts remained fully functional throughout his illness. This unique case highlights the importance of aggressive, early diagnosis and proposes a potential treatment regimen that can reduce this infection’s high mortality.

Cystatin C, NT-proBNP, and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome

Background: Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed.Methods and results: Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n = 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (β = 0.39, P < 0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (β = 0.26, P < 0.0001) and IL-10 (β = 0.15, P < 0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2–2.9, P = 0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP.Conclusion: Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart–kidney interactions.

Dual Transplantation of Marginal Kidneys From Nonheart Beating Donors Selected Using Machine Perfusion Viability Criteria

Viability testing can be used to avoid the transplantation of nonheart beating donor organs that are likely to have primary nonfunction. Such testing also identifies a second group of kidneys which, although unsuitable for solitary transplantation, may be considered for dual transplantation. In kidneys in this group solitary transplants would be unlikely to produce a sufficient glomerular filtration rate to support the recipient. However, if used together as a dual transplant, they have the potential to produce sufficient renal function in 1 patient. The group at our unit has performed 23 dual nonheart beating donor renal transplants from 2003 to date. Using 3 and 12-month post-transplantation recipient glomerular filtration rates as primary end points we compared our dual transplant group with our series of 115 single nonheart beating donor transplants from 1998 to 2006. At 3 and 12 months mean glomerular filtration rates in the dual group were 46.2 and 45.5 ml per minute per 1.73 m(2), respectively. These values were not significantly different from the mean glomerular filtration rates of 40.7 and 43.0 ml per minute per 1.73 m(2), respectively, in the single transplant group. We have observed that a subset of nonheart beating donor kidneys that do not satisfy the viability criteria for single organ transplantation may become successful dual organ grafts, thus, avoiding unnecessary organ nonuse and maximizing organ resources.

In this issue

In this issue

Mechanical Circulatory Support as a Bridge to Combined Dual Organ Transplantation in Children

The use of mechanical circulatory support as a bridge to cardiac transplantation is now an accepted therapeutic option. Also, as the criteria for organ transplantation have broadened, multi-organ transplantation has become more feasible. We report the cases of 2 children with end-stage heart failure and renal failure who were successfully bridged to combined, single-donor heart and kidney transplantation with mechanical circulatory support.

Long-term Analysis of Combined Liver and Kidney Transplantation at a Single Center

To analyze use of combined liver and kidney transplantation (CLKT) for patients with chronic primary diseases of both organs and for patients with hepatorenal syndrome. Retrospective case series. Multiorgan transplantation service in a large university medical center. A total of 98 patients underwent 99 CLKTs during a 16-year period; 76 had primary renal diseases, and 22 had hepatorenal syndrome. Patients receiving isolated liver and kidney transplants were analyzed for comparison. Patient and graft survival, rejection rates, and need for hemodialysis before and after transplantation. Overall patient survival was 76%, 72%, and 70% at 1, 3, and 5 years, respectively; liver graft survival was 70%, 65%, and 65%; and kidney graft survival was 76%, 72%, and 70%. No risk factors analyzed for recipients or donors were associated significantly with early posttransplantation mortality or graft loss. In 28 patients who received monoclonal antibody induction therapy with interleukin 2 blockers, there were significantly fewer episodes of acute liver rejection. For patients with hepatorenal syndrome, CLKT did not confer a survival advantage over liver-only transplantation (1-year patient survival was 72% vs 66%; P = .88). The 1-year acute kidney rejection rate in the adult CLKT group was 14% vs 23% in a 5-year cadaveric renal transplantation cohort (P<.01). First, CLKT is indicated in patients with dual organ disease and achieves excellent results. Second, CLKT for hepatorenal syndrome is indicated in patients receiving hemodialysis for longer than 8 weeks and confers advantages in patient survival and use of hospital resources. Third, the liver is immunoprotective for the kidney.

Retrieval of abdominal organs for transplantation

Organ retrieval and donor management are not yet standardized. Different transplant centres apply various techniques, such as single or dual organ perfusion, dissection in the cold or warm, and single or en bloc organ removal. These different approaches may cause inconvenience, especially when more than one organ retrieval team is involved. Cochrane Library, Medline and PubMed were searched for publications on multiorgan donor/donation, retrieval technique and procurement. Levels of evidence and grades of recommendation were evaluated based on current advice from the Oxford Centre for Evidence-Based Medicine. Multiorgan donation itself does not compromise the outcome of individual organ transplants. Dissection of abdominal organs for transplantation is best performed after cold perfusion. Abdominal organs should be removed rapidly, en bloc, and separated during back-table dissection in the cold, particularly if pancreas or intestine is included. Perfusion itself should be carried out after single cannulation of the aorta with an increased pressure. Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. Nevertheless, optimized donor treatment and organ retrieval should increase the number and quality of cadaveric donor organs and improve graft function and survival.

Aspirin reduces platelet aggregation during high-energy excimer laser

Excimer laser is used clinically in arterial revascularization procedures. This study evaluated the efficacy of aspirin in reducing platelet aggregation during high-energy excimer lasing. Platelet rich plasma (PRP) from seven rabbits was circulated in a dual organ chamber with aspirin added to one and the other was control. PRP was irradiated using an excimer laser (308 nm; 45 mJ/mm(2); 25 Hz; 5 minutes) via a 2.0 mm laser catheter. Platelet aggregation (particle volume) was measured by laser-light scattering. Morphology was evaluated by phase contrast and electron microscopy. Baseline platelet volume was 3.4 microm(3) for both control and aspirin groups. Following lasing, platelet volume peaked at 102.2 +/- 18.5 microm(3) for control compared to 43.1 +/- 49.2 microm(3) for aspirin-treated PRP (P < 0.0001). Aspirin reduces large platelet aggregates but not small aggregates by 58% during lasing of PRP.

Are liverworts imitating mycorrhizas?

Are liverworts imitating mycorrhizas?

Concurrent focal hepatic and splenic lesions: a pictorial guide to differential diagnosis.

Although medical literature and differential diagnoses discussions tend to be organ specific, systemic diseases more commonly manifest with multi-organ involvement. Detection of dual organ involvement combined with clinical history narrows the differential to provide a more specific diagnosis. Two organs closely linked are the liver and the spleen. Many processes affect both of these organs through their common denominator, the reticuloendothelial system (RES). This pictorial essay reviews the wide spectrum of benign and malignant pathologies to be considered when computed tomography (CT) demonstrates concurrent focal disease in the liver and spleen.

Renal failure in the recipients of nonrenal solid organ transplants.

The increased success and availability of transplantation of solid organs other than kidneys has resulted in a large number of patients at risk for the usual medical complications of long-term immunosuppressive therapy. Acute and chronic renal failure play a critical role in the success of these

Renal and biliary abnormalities in a new murine model of autosomal recessive polycystic kidney disease

Current models of autosomal recessive polycystic kidney disease (ARPKD) fail to demonstrate biliary abnormalities in association with renal cysts. We therefore studied a new murine model of ARPKD in which dual renal tubular and biliary epithelial abnormalities are present. Affected homozygous animals typically die 1 month postnatally in renal failure with progressively enlarged kidneys. Renal cysts shift in site from inner cortical proximal tubules at birth to collecting tubules 20 days later, as determined by segment-specific lectin binding. Increased numbers of mitosis were demonstrated in proximal and collecting tubular cysts. In addition, epithelial hyperplasia was demonstrated morphometrically in the intra- and extrahepatic biliary tract of affected animals. The number of intrahepatic biliary epithelial cells was increased by 50% on postnatal day 5 and by 100% on postnatal day 25 (P < 0.01). Despite an increased frequency of "chaotic" portal areas in mice with renal cysts, no intrahepatic cysts or shape abnormalities of the biliary lumen were detected using biliary casts and morphometry. Additionally there was nonobstructive hyperplastic dilatation of the extrahepatic biliary tract which was linked in all animals to the presence of renal cysts. The hyperplastic abnormalities in both renal and biliary epithelium make this new mouse strain a good model for the study of the dual organ cellular pathophysiology of ARPKD.

Time sequence of the infection process eucalypt ectomycorrhizas

SUMMARYThe paper‐sandwich technique for simultaneous inoculation of populations of root apices, was used to produce numbers of synchronously developing ectomycorrhizas, and to permit direct time‐sequencing of stages in the infection process in eucalypts. After one day there was evidence of chemical interaction between fungus and host. By two days, sheath formation had started in the cap region, cap cells were invaded by fungus, and apical root tissues commenced to swell. By four days all the anatomical features of an ectomycorrhiza were present, including the Hartig net. Thereafter, mycorrhizal features were merely enhanced and perpetuated by subsequent acrogenous development of the fungus‐root dual organ. The process of mycorrhizal perpetuation involved the same sequence of events (sheath development at the apex associated with invasion of cap cells, modification of other root tissues, then finally formation of Hartig net) as did the initial infection process.