Stress (Takotsubo) Cardiomyopathy During Liver Transplantation: Case Study and Literature Review.

A case of stress (takotsubo) cardiomyopathy (TC) that occurred intraoperatively during liver transplantation surgery was identified by transesophageal echocardiography. Only a few cases of TC occurring during liver transplantation have been reported to date. Unlike other cases reported, TC occurred during the anhepatic stage of the liver transplantation, with subsequent complete recovery. Notwithstanding the large number of cases of TC in the perioperative settings reported worldwide, the exact reasons of this syndrome occurring intraoperatively as well as precipitating factors and conditions remain mostly unknown.

Coloduodenovesical Fistula After Simultaneous Pancreas-Kidney Transplant: Case Report and Review of the Literature.

BACKGROUND: Complicated diverticulitis after transplantation occurs in as many as 3.5% of cases and carries a 25% mortality rate. Diagnosis of complicated diverticulitis in this population can be challenging because of abnormal presentations caused by immunosuppression. Only 4 cases of fistulization after kidney transplantation are described in the literature; none occurred after simultaneous pancreas-kidney transplant. METHODS: We present a first case of a coloduodenovesical fistula in a patient 9 years after simultaneous pancreas-kidney transplant. The patient presented with intermittent episodes of elevated creatinine and recurrent urinary tract infection. The presence of fistula was strongly suspected in cystoscopy, but, despite extensive investigation, a fistula tract could not be identified. RESULTS: The patient ultimately underwent surgical exploration for positive cystoscopy examination, continuation of urinary complaints, and presence of multiple colonic diverticula in computed tomography scan. At surgical exploration, a fistula track was identified between the sigmoid colon and duodenal stump of the pancreas allograft. Subsequently, sigmoidectomy, bladder repair, and enteric conversion of the pancreas transplant were performed. CONCLUSIONS: Complications of diverticulitis should be considered in organ transplant recipients presenting with recurrent urinary infection and elevated creatinine, and surgical exploration might be indicated even if unable to well-define the fistula tract.

Liver Transplantation for Urea Cycle Disorders: Analysis of the United Network for Organ Sharing Database.

BACKGROUND: Urea cycle disorders (UCD) are caused by rare inherited defects in the urea cycle enzymes leading to diminished ability to convert ammonia to urea in the liver. The resulting excess of circulating ammonia can lead to central nervous system toxicity and irreversible neurologic damage. Most cases are identified in children. However, UCDs can also be diagnosed in adulthood, and liver transplant is occasionally required. METHODS: We examined the UNOS database to evaluate outcomes in adult and pediatric patients who underwent liver transplant as treatment for a UCD. We identified 265 pediatric and 13 adult patients who underwent liver transplant for a UCD between 1987 and 2010. RESULTS: The majority (68%) of these patients were transplanted before age 5 years. Ornithine transcarbamylase (OTC) deficiency was the most common UCD in both adults and children who underwent transplant. UCD patients who underwent liver transplant were younger, more likely to be male (67%), had lower pediatric end-stage liver disease/model for end-stage liver disease scores, and were more likely to be Caucasian or Asian compared with all other patients transplanted during the same time period. UCD patients did not have an increased utilization of living donor transplantation in this US cohort. Univariate and multivariate risk factor analyses were performed and did not reveal any significant factors that were predictive of post-transplant death or graft loss. CONCLUSIONS: Excellent outcomes were seen in both children and adults with UCDs who underwent transplant with overall 1-, 5-, and 10-year survivals of 93%, 89%, and 87%, respectively.

Liver transplantation in the United States, 1999-2008.

Changes in organ allocation policy in 2002 reduced the number of adult patients on the liver transplant waiting list, changed the characteristics of transplant recipients and increased the number of patients receiving simultaneous liver-kidney transplantation (SLK). The number of liver transplants peaked in 2006 and declined marginally in 2007 and 2008. During this period, there was an increase in donor age, the Donor Risk Index, the number of candidates receiving MELD exception scores and the number of recipients with hepatocellular carcinoma. In contrast, there was a decrease in retransplantation rates, and the number of patients receiving grafts from either a living donor or from donation after cardiac death. The proportion of patients with severe obesity, diabetes and renal insufficiency increased during this period. Despite increases in donor and recipient risk factors, there was a trend towards better 1-year graft and patient survival between 1998 and 2007. Of major concern, however, were considerable regional variations in waiting time and posttransplant survival. The current status of liver transplantation in the United States between 1999 and 2008 was analyzed using SRTR data. In addition to a general summary, we have included a more detailed analysis of liver transplantation for hepatitis C, retransplantation and SLK transplantation.

Orthotopic, but reversed implantation of the liver allograft in situs inversus totalis-a simple new approach to a difficult problem.

Situs inversus totalis is a rare congenital anomaly in which the heart and abdominal organs are oriented in a mirror image of normal. It provides a unique challenge as there is no established technique for liver transplantation in these patients. Employing two major alterations from our standard technique, a liver was transplanted in the left subphrenic space of a patient with situs inversus totalis. First, the liver was flipped 180 degrees from right to left (facing backward). Second, a reversed cavaplasty (anterior, not posterior, donor suprahepatic caval incision) was performed. Otherwise, it was standard, with end-to-end anastomoses of the portal vein, hepatic artery and bile duct. Three years after the entirely uneventful transplant, the recipient continues to enjoy the benefits of a normally functioning liver. The described technique prevented torsion, kinking and tension on the anastomosed structures by allowing the liver to sit naturally in an anatomical position in the left hepatic fossa. As it required no special measurements or maneuvers, the technique was easy to execute and required no donor liver size restrictions. This novel technique, with a reversed cavaplasty and a 180 degrees right-to-left flip of the liver into a left-sided hepatic fossa, may be ideal for situs inversus totalis.

A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for long-term liver allograft survival in recipients transplanted for hepatitis C.

UNLABELLED: Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a major barrier to survival of the transplanted liver. While cyclosporine (CsA) in vitro has been shown to suppress HCV replication, an effect is not seen with tacrolimus (Tac). Evidence is inconsistent whether or how this translates to clinical practice. To expand the evidence on this issue, we analyzed graft survival and histological outcomes after liver transplantation for HCV hepatitis. METHODS: Using our longitudinal database (1991 onward) graft outcomes for all liver transplant recipients with HCV were evaluated (105 grafts in 97 patients). Severe activity, severe fibrosis, and graft survival were analyzed. All liver biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15, 14%). Comparisons of outcomes using CsA versus Tac therapy were done using survival analysis via the log-rank test. RESULTS: Graft survival was significantly better in the CsA group. Although there was no apparent difference in severe activity (grade 2), there was a statistically significant difference in graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained response to antiviral therapy was twice as high in the CsA group, 50% versus 22% (P = 0.16; NS). CONCLUSIONS: Graft survival in liver transplant recipients with HCV may be greater with CsA-based immunosuppression. There may also be a lower rate of fibrosing cholestatic hepatitis in this group.

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.

Endourologic therapy of bladder calculi in simultaneous kidney-pancreas transplant recipients.

OBJECTIVES: To identify the incidence and the success of endourologic therapy for symptomatic bladder-related calculi in simultaneous kidney-pancreas (SPK) transplant patients with bladder drainage. METHODS: A retrospective review of 300 SPK transplant patients with bladder drainage, treated at the University of Wisconsin, Madison from December 1985 to November 1995, is presented. A 3% incidence of bladder calculi was identified. All patients underwent cystolitholapaxy using electrohydraulic lithotripsy and endoscopic suture removal. Follow-up ranged from 15 to 86 months. RESULTS: A 100% stone-free rate was achieved after cystolitholapaxy and endoscopic suture removal. Two patients (22%) developed postprocedural urinary tract infections. No pancreaticoduodenocystotomy leaks or further complications were identified. CONCLUSIONS: SPK transplant patients with nonabsorbable sutures used for the duodenocystotomy anastomosis are at an increased risk for bladder calculi. Cystolitholapaxy with electrohydraulic lithotripsy is a safe and effective treatment for these suture-related stones.

Infant pediatric liver transplantation results equal those for older pediatric patients.

METHODS: From July 1984 to July 1995, 99 pediatric patients underwent 127 orthotopic liver transplants (OLT) at the University of Wisconsin Children's Hospital. The patients were divided into four groups according to age at time of transplant: group I, 0 to 6 months (n = 20); group II, 6 to 12 months (n = 18); group III, 1 to 2 years (n = 10); and group IV, 2 to 18 years (n = 51). A retrospective analysis was performed to compare these four groups with regard to preoperative indications and demographics, intraoperative technique, complications, and survival. All patients were followed up for 2 to 13 years. RESULTS: Biliary atresia was the most common indication for OLT in all four groups. The average waiting period varied from 19+/-18 days for group I to 44+/-64 days for group IV. Reduced-size liver transplant (I, 41%; II, 52%; III, 28%; IV, 21%), split-liver transplant (I, 0%; II, 7.4%; III, 17%; IV, 2.9%), or whole-liver transplant techniques were used. Although postoperative Intensive Care Unit stay was longer for the 0- to 6-month-old patients (I, 20+/-64; II, 7.6+/-9; III, 13+/-17; IV, 6.8+/-14 days), the total hospital stay (I, 43+/-63; II, 33+/-34; III, 32+/-20; IV, 29+/-31 days) was similar for all patients. The incidence of hepatic artery thrombosis (I, 19%; II, 19%; III, 27%; IV, 16%), biliary tract complications (I, 4.8%; II, 15%; III, 20%; IV, 14%), and retransplantation (I, 9.5%; II, 41%; III, 33%; IV, 14%) were not significantly different between the four groups. Portal vein thrombosis (I, 9.5%; II, 11%; III, 6.6; IV, 0%) and primary nonfunction (I, 9.5%; II, 7.4%; III, 0%; IV, 3.1%) occurred more frequently in the 0- to 6-month and 6- to 12-month groups, however, the 1-, 5-, and 10-year survival rate for patients (I, 85%, 79%, 79%; II, 89%, 74%, 74%; III, 80%, 80%, 80%; IV, 84%, 75%, 75%, respectively) and primary liver allografts (I, 69%, 69%, 69%; II, 72%, 72%, 63%; III, 70%, 70%, 70%; IV, 71%, 57%, 57%, respectively) were not significantly different (P = .98 and P = .83). CONCLUSION: These results demonstrate that OLT can be effectively performed on infants of all ages and that OLT should not be delayed because of age.

Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection.

Mycophenolate mofetil (the morpholinoethyl ester of mycophenolic acid) inhibits de novo purine synthesis via the inhibition of inosine monophosphate dehydrogenase. Its selective lymphocyte antiproliferative effects involve both T and B cells, preventing antibody formation. Mycophenolate mofetil has immuno-suppressive effects alone, but is used most commonly in combination with other immunosuppressants. Mycophenolate mofetil, in combination with cyclosporin and corticosteroids, has been studied in large, randomised clinical trials involving nearly 1500 renal allograft transplant recipients. These trials demonstrated that mycophenolate mofetil is significantly more effective in reducing treatment failure and acute rejection episodes than placebo or azathioprine. Additionally, mycophenolate mofetil may be able to reduce the occurrence of chronic rejection. Mycophenolate mofetil is relatively well tolerated. The most common adverse effect reported is gastrointestinal intolerance; haematological aberrations have also been noted. The reversible cytostatic action of mycophenolate mofetil allows for dose adjustment or discontinuation, preventing serious toxicity or an overly suppressed immune system. Cytomegalovirus tissue invasive disease and the development of malignancies are concerns that merit evaluation in long term follow-up studies. Mycophenolate mofetil does not cause the adverse effects typically associated with other commercially available immunosuppressant medications such as nephrotoxicity, hepatotoxicity, hypertension, nervous system disturbances, electrolyte abnormalities, skin disorders, hyperglycaemia, hyperuricaemia, hypercholesterolaemia, lipid disorders and structural bone loss. Based on preliminary information, a positive benefit-risk ratio has been demonstrated with the use of mycophenolate mofetil in the prophylaxis of rejection in cadaveric renal allograft transplantation. Data from studies in other types of organ transplants are promising, but are too limited to draw clear conclusions. Long term follow-up studies are required to confirm these observations. Although mycophenolate mofetil is expensive, the beneficial effects on the reduction of rejection, treatment failure and related expenses suggest that it is most likely to be cost effective.

Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis.

BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS: These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.

The influence of native nephrectomy on the incidence of recurrent disease following renal transplantation for primary glomerulonephritis.

Factors influencing the incidence of recurrent glomerulonephritis following renal transplantation are poorly understood. Bilateral pretransplant native nephrectomy has been advocated to reduce the likelihood of recurrence after renal transplant. However, there is significant morbidity of native nephrectomy in the uremic population. Therefore, we sought to determine the effect of pretransplant native nephrectomy on the incidence of recurrent primary glomerulonephritis and the attendant risk of graft failure due to recurrent disease. Three hundred sixty-four consecutive cadaveric (n = 214), living-related (n = 137), and living-unrelated (n = 13) renal transplants were performed in 319 patients with a diagnosis of primary glomerulonephritis. Specific diagnoses included were focal segmental glomerulosclerosis (FSGS), rapidly progressive glomerulonephritis/idiopathic crescentic glomerulonephritis (RPGN/ICG), IgA nephropathy (IgA), mesangioproliferative glomerulonephritis, type I and II (MPG), anti-glomerular basement membrane nephritis (anti-GBM), and membranous glomerulonephritis (MGN). Rates of recurrence and graft loss were compared between patients treated with bilateral native nephrectomy (n = 61) and those who were not (n = 303). Bilateral nephrectomy did not prevent or delay the onset of recurrent glomerulonephritis in the renal allograft. In fact, there was a significantly increased five- and ten-year risk of recurrence in patients undergoing pretransplant nephrectomy vs. no nephrectomy (25.2% and 42% vs. 13.9% and 19.4%, P < 0.02, respectively). The increased rate of recurrence was evident in the CAD/LUD recipients, but not in recipients of LRD transplants. Of the specific diseases, FSGS and MGN recurred more commonly (20.2% and 20.3%, respectively). A detrimental effect of pretransplant nephrectomy on recurrence rates and incidence of graft loss due to recurrent disease independent of other variables could be demonstrated only for FSGS patients. Based on these findings, we no longer recommend native nephrectomy in the prospective renal transplant recipient at high risk for developing recurrent glomerulonephritis.

Simultaneous pancreas--kidney transplantation: recent experience at the University of Wisconsin.

After a decade of rapid development, simultaneous pancreas--kidney (SPK) transplantation has become routine at the University of Wisconsin (UW). Since developing the concept of direct drainage of pancreas allograft exocrine secretions into the urinary bladder at UW in 1982, we performed 381 SPK transplantations in this technique. Patient and graft survival following SPK transplantation has increased significantly from our early experience to the recent time. The one- and five-year patient survival rates for the entire series of 381 SPK transplantations were 96% and 88% respectively. The actuarial one- and five-year kidney allograft survival rates in these patients were 87% and 78%. The pancreas allograft survival rates were similar at 86% and 74%. Several changes are responsible for our current high level of success. UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications.

Simultaneous pancreas-kidney transplantation at the University of Wisconsin.

After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications. The critical modifications in surgical technique have included the avoidance of systemic heparinization, complete mobilization of the iliac vein for a tension-free anastomosis between an unmodified donor portal vein and the recipient iliac vein, oversewing of the revised duodenal staple lines and meticulous hemostasis. The most important recent improvement in immunosuppression is the use of mycophenolate mofetil, which has dramatically reduced rejection. Finally, PDC leaks, the principal and potentially most devastating complication of SPK transplantation, are rapidly diagnosed and treated expeditiously.

Dynamics of normal and ischemic canine papillary muscles.

This investigation was designed to elucidate the dynamics of the left ventricular (LV) papillary muscles. Miniature tantalum myocardial markers were placed on the tip and base of each papillary muscle in six dogs. Markers were also implanted into the LV myocardium to define two orthogonal equatorial diameters and the long-axis dimension. Two weeks later, after recovery from thoracotomy, markers were visualized by biplane fluoroscopy, and video images were recorded during control conditions, after autonomic blockade, after inotropic stimulation with calcium, after methoxamine infusion (to increase afterload), and after blood volume augmentation (to increase preload). Two days later, radiographic recordings were made before and after occlusion of the left circumflex coronary artery. Computer-aided analysis of the video recordings was used to determine three-dimensional coordinates of the markers. It was found that before circumflex coronary occlusion, the dynamics of both papillary muscles closely mimicked the dynamics of the LV as a whole. The papillary muscles shortened during ejection and lengthened during diastole. Their lengths changed minimally during the isovolumic periods, and this behavior was not altered by any of the interventions except coronary occlusion. During circumflex coronary artery occlusion, the ischemic posterior papillary muscle lengthened during isovolumic contraction and most of ejection and shortened only when LV pressure began to fall. Hence, we believe that previous studies demonstrating papillary muscle lengthening during isovolumic contraction and shortening during isovolumic relaxation may have been confounded by coexistent myocardial ischemia or stunning.

Annuloplasty with flexible or rigid ring does not alter left ventricular systolic performance, energetics, or ventricular-arterial coupling in conscious, closed-chest dogs.

Eighteen dogs were randomly chosen to undergo mitral annuloplasty with either a Carpentier-Edwards rigid ring (n = 6 in each group) or a Duran-Medtronic flexible ring or to undergo a sham procedure with an operation, but no ring. Tantalum markers were inserted to measure left ventricular volume and geometry. After 1 and 6 weeks, biplane videofluoroscopic images were obtained during steady-state conditions and during vena caval occlusion. Global and regional systolic function was assessed with load-insensitive indexes. Comparison of all three groups and both times (1 and 6 weeks) showed no significant differences among the three groups in global or regional (basal, equatorial, and apical) left ventricular systolic performance. Furthermore, neither type of annuloplasty ring significantly affected left ventricular pump efficiency, ventricular-arterial coupling ratio, or systolic circumferential contraction and rotation of the basal left ventricular sites.

Arterial and venous blood flow: noninvasive quantitation with MR imaging.

Quantitative measurements of arterial and venous blood flow were obtained with phase-contrast cine magnetic resonance (MR) imaging and compared with such measurements obtained by means of implanted ultrasound (US) blood flow probes in anesthetized dogs. The US flowmeter was enabled during a portion of each MR imaging sequence to allow virtually simultaneous data acquisition with the two techniques. MR imaging data were gated by means of electrocardiography and divided into 16 phases per cardiac cycle. The rates of portal venous blood flow measured with MR imaging and averaged across the cardiac cycle (710 mL/min +/- 230 [standard deviation]) correlated well with those measured with the flowmeter and averaged in like fashion (751 mL/min +/- 238) (r = .995, slope = 1.053). The correspondence in arterial blood flow was almost as good. No statistically significant difference existed between the paired measurements of blood flow obtained with MR imaging and the implanted probe. It is concluded that, as a noninvasive means of accurate quantification of blood flow, phase-contrast MR imaging may be especially useful in deep blood vessels in humans.