Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications. PATIENTS AND METHODS: Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2-10 mmHg, n = 28), target IAP group (10-20 mmHg, n = 71), and high IAP group (20-34 mmHg, n = 16) as well as with CBT as a continuous variable. RESULTS: 115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035). CONCLUSIONS: IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

New onset diabetes after kidney transplantation is associated with increased mortality-A retrospective cohort study.

OBJECTIVE: Clinical outcomes in individuals with new onset diabetes after transplantation (NODAT) and the optimal treatment for this complication are poorly characterized. This study was intended to better define these issues. METHODS: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in the study. Clinical outcomes were compared between those who developed NODAT and those who did not. In those who developed NODAT, oral therapy was compared with insulin based therapy. RESULTS: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Using Cox multivariate analysis adjusted for age and gender, hazard ratio for overall mortality among patients with NODAT versus those without NODAT was 2.69 (95% CI 1.04-7.01). Among patients who developed NODAT, 29 patients (40%) were treated with an insulin-based regimen. At the end of follow-up, no difference was found in mean HbA1c, and therapy regimen was not associated with greater mortality. CONCLUSIONS: New onset diabetes in kidney transplanted patients is associated with increased mortality compared with kidney transplanted patients without NODAT.

The impact of the israeli transplantation law on the socio-demographic profile of living kidney donors.

The Israeli transplantation law of 2008 stipulated that organ trading is a criminal offense, and banned the reimbursement of such transplants by insurance companies, thus decreasing dramatically transplant tourism from Israel. We evaluated the law's impact on the number and the socio-demographic features of 575 consecutive living donors, transplanted in the largest Israeli transplantation center, spanning 5 years prior to 5 years after the law's implementation. Living kidney donations increased from 3.5 ± 1.5 donations per month in the pre-law period to 6.1 ± 2.4 per month post-law (p < 0.001). This was mainly due to a rise in intra-familial donations from 2.1 ± 1.1 per month to 4.6 ± 2.1 per month (p < 0.001). In unrelated donors we found a significant change in their socio-demographic characteristics: mean age increased from 35.4 ± 7.4 to 39.9 ± 10.2 (p = 0.001), an increase in the proportion of donors with college level or higher education (31.0% to 63.1%; p < 0.001) and donors with white collar occupations (33.3% to 48.3%, p = 0.023). In conclusion, the Israeli legislation that prohibited transplant tourism and organ trading in accordance with Istanbul Declaration, was associated with an increase in local transplantation activity, mainly from related living kidney donors, and a change in the profile of unrelated donors into an older, higher educated, white collar population.

Consequences of treated versus untreated asymptomatic bacteriuria in the first year following kidney transplantation: retrospective observational study.

Asymptomatic bacteriuria (AB) is frequent among kidney transplant patients during the first year post transplantation. Currently, there are no clear guidelines for the antibiotic treatment of AB among these patients. We examined the outcomes of treatment versus no treatment of AB in kidney transplant patients during the first year post transplantation. A retrospective cohort study including adults >16 years of age transplanted in one center between 1/2004 and 12/2010 was undertaken. The primary outcome was a composite of hospitalization for symptomatic urinary tract infection (UTI) or more than 25 % reduction in the estimated glomerular filtration rate (eGFR) 30 days after the documentation of AB. Secondary outcomes included symptomatic UTIs following the episode of AB, persistent recurrent AB, total days in hospital, mortality, adverse events, and resistance development. A total of 112 patients with AB fulfilled the inclusion criteria. Twenty-two patients received antibiotic treatment (19.6 %), while 90 patients did not. The primary outcome occurred in 4/22 (18.2 %) of the treated patients versus 5/90 (5.6 %) of the untreated patients [odds ratio (OR) = 3.78, 95 % confidence interval (CI) 0.9-15]. The risk of developing symptomatic UTI after AB was almost three times higher (p < 0.05) and the total number of hospitalization days at 6 months post AB was also significantly higher (p < 0.026) in the treated group. No patient died during the study period. UTI caused by bacteria resistant to the antibiotic used for the treatment of AB occurred in 36 % of the treated patients. We observed no benefit for the antibiotic treatment of AB in the short- and long-term follow-up. A prospective observational study is needed.

Mucormycosis in a liver allograft: salvage re-transplantation and targeted immunosuppressive management.

Zygomycetes infection is associated with a high mortality in transplant populations. We describe a child with liver allograft Rhizopus oryzae infection who was salvaged by liver re-transplantation. A 10-year-old child presented with anastomotic bile leak that was repaired. A combined antibiotics and voriconazole regimen was introduced for Escherichia coli and Candida krusei growth in the peritoneal fluid. Despite broad antibiotic and antifungal coverage, the patient continued to have an ongoing infection. A follow-up computed tomography scan 8 weeks later showed 2 liver abscesses infiltrating the stomach and the diaphragm, with splenic infarcts and pericardial effusion. Aspirated samples from the liver abscess and the pericardial fluid revealed R. oryzae. Immunosuppression was discontinued and an antifungal regimen combining amphotericin B, posaconazole, and caspofungin was introduced. After 3 weeks of treatment with control of the systemic signs of infection, a positron emission tomography showed the fluorescence stain limited to the liver. With infection confined to the liver, the child underwent liver re-transplantation, splenectomy, and partial gastrectomy. Immunosuppression was reintroduced with recovery of the immune response observed by the CD4 cells adenosine triphophate release (Cylex(™) ImmuKnow(®) assay) and posaconazole was continued for another year. At 3-year follow-up, the child maintained normal graft function. We conclude that discontinuation of immunosuppression combined with a modern antifungal regimen may allow salvage re-transplantation in patients with liver mucormycosis.

Impact of "critical lesions" on outcomes following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. METHODS: Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). RESULTS: Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. CONCLUSIONS: Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.

A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study.

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.

Magnetic resonance cholangiopancreatography for the accurate diagnosis of biliary complications after liver transplantation: comparison with endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography - long-term follow-up.

Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.

Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D- recipients and for six months in R-/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant-related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P-NS). Time-to-onset of CMV infection was comparable in both groups (P-NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R-/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.

Prolongation of survival of rat cardiac allografts by T cell vaccination.

Administration of attenuated, activated autoimmune T lymphocytes to syngeneic mice and rats has been shown to prevent or induce remission of experimental autoimmune diseases specific for the autoimmune T cells. The process has been termed "T cell vaccination." In a recent study, T cell vaccination was done using T cells sensitized to rat alloantigens. The procedure produced a significant reduction of the mixed lymphocyte reaction (MLR) against allogeneic cells. The reduction in MLR was not specific: Vaccination with T cells specific for stimulator cells of one allotype led to a reduced MLR stimulated by cells of another allotype. The present study was undertaken to examine whether T cell vaccination can induce tolerance to transplantation antigens in vivo. We used the model of heterotopic cardiac transplantation in rats. We now report that vaccinating rats with syngeneic, activated, alloantigen-primed T lymphocytes significantly prolonged survival of rat cardiac allografts. The effect of T cell vaccination was most evident when the T cells had been obtained from rats specifically sensitized against the donor rats: Brown-Norway (BN) allografts in control Wistar rats survived 8.5 +/- 0.4 d while BN allografts survived 29.2 +/- 7.1 d in Wistar rats that had been vaccinated with Wistar anti-BN cells. Vaccination of Wistar rats with Wistar anti-hooded T cells prolonged survival of BN heart allografts to a lesser but significant degree (13.0 +/- 1.1 d). Thus, T cell vaccination of recipients can prolong survival of allografts.

Twin pregnancy: not only a medical event.

AIM: Twin pregnancies are at greater risk of obstetrical and perinatal adverse outcome compared to singletons. In addition, expecting twins can have particular psychological consequences on both parents. The aim of our study was to interview women with a twin pregnancy and their partners in order to assess their feelings and emotions related to the twins and to evaluate the opportunity to activate an information group about the theme of twin pregnancy, and a development of twins and family management. METHODS: Twenty patients with an uncomplicated twin pregnancy and their partners answered 9 questions in a semistructured interview, set on the basis of the psychological and social issues reported in the literature on couples expecting twins. Emerging themes and key words were extracted from the interviews and analysed. RESULTS: Quantitative analysis showed that women were, in most cases, shocked at the time of the diagnosis of twinning, while men tried to minimize the worries of their partners. Women reported some fears related to the practical management of the future life, but they declared to feel not different from women expecting singleton, confirming the data reported in the literature. Seventy percent of the women were interested in meeting other parents with twins. Qualitative analysis frequently indicated the defence mechanism of rationalisation and negation of the worries concerning the pregnancy risks and the future care of their babies. Their answers seem to hide fears and doubts that are confessed with difficulty. CONCLUSION: Our study suggests the importance for hospital staff to create an atmosphere of calm and to demonstrate empathy and understanding, with the aim to help and allow the mothers to express their fears.

Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome.

A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was converted to FK506 with a complete response. Compared with 315 acute rejection episodes ([AR] occurring less than 6 months posttransplant), patients with late rejection episodes had an equivalent response to steroids (63.2% AR reversed vs. 71% LR reversed) but a lower response rate to OKT3 (91.5% AR reversed vs. 62.5% LR reversed). There was, therefore, a higher rate of persistent rejection (61% AR episodes vs. 15.4% LR episodes) but no increase in the incidence of chronic rejection (7% AR episodes vs. 7.7% LR episodes). We conclude that LR is a relatively common occurrence following liver transplant, which is most often associated with low cyclosporine levels. Many of these episodes are due to noncompliance, but biliary problems must also be investigated. The incidence of resistant rejection is higher in this group of patients but is not associated with a concurrent increase in chronic rejection.

Association of lamivudine resistance in recurrent hepatitis B after liver transplantation with advanced hepatic fibrosis.

BACKGROUND: Orthotopic liver transplantation (OLT) in patients with hepatitis B virus (HBV) infection is known to be associated with a high recurrence rate and poor prognosis. Lamivudine, a nucleoside analogue, is a potent inhibitor of HBV replication, but it is associated with a 14-39% rate of resistance. METHODS: We report on four patients who underwent OLT for HBV infection. In all cases, the HBV infection recurred in the grafted liver and was treated with lamivudine (100 mg daily) on a compassionate-use basis. The patients were monitored closely for serum liver enzymes, hepatitis B surface antigen and HBV DNA (by hybridization). Liver biopsy was performed before and after lamivudine therapy. HBV DNA was amplified from serum for each patient and sequenced through a conserved polymerase domain, the tyrosine-methionine-aspartate-aspartate (YMDD) locus. RESULTS: All four patients exhibited lamivudine resistance 9-20 months after initiation of the drug. In all patients with a clinically mild disease, liver histology findings (12-24 months after lamivudine therapy) showed progressive fibrosis as compared to biopsies performed before lamivudine therapy, with a significant increase (> or =2 points) in the Knodell score in three patients. Moreover, two patients exhibited worsening of the necroinflammatory process. A mutation at the YMDD motif of the HBV polymerase gene was detected in all cases. CONCLUSIONS: Lamivudine resistance frequently occurs in patients with recurrent HBV infection after OLT and is associated with advanced hepatic fibrosis and necroinflammatory process. A combination of antiviral therapies may be necessary.

Beneficial effect of lamivudine in recurrent hepatitis B after liver transplantation.

Orthotopic liver transplantation (OLT) in patients infected with hepatitis B virus (HBV) is known to be associated with a high recurrence rate and poor prognosis. Interferon treatment in these patients offers little benefit and may lead to further complications. Lamivudine, the (-)enantiomer of 3'-thiacytidine, a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in patients with chronic HBV infection. Three HBV-positive OLT patients were administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks, in an open, compassionate-use basis. All three patients were HBV DNA-negative before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9 months) after OLT, in spite of adequate immunoprophylaxis. All three patients had high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and histologic evidence of recurrent HBV infection of the grafted liver, and HBV DNA was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV DNA disappeared from the serum of all patients (detected by hybridization); by the 10th week, HBV DNA was also negative by polymerase chain reaction in two out of three patients. Interestingly, the one patient who was HBV DNA positive by polymerase chain reaction still has mildly elevated ALT levels, whereas the other two patients have normal ALT levels. We also noted that on the 5th week there was a transient elevation of serum ALT levels in two patients. No adverse effects or rejection episodes were noted. In conclusion, lamivudine is a beneficial and well-tolerated therapy in OLT patients with recurrent HBV infection. We are studying the effect of lamivudine in other patients and for a longer period of time.

Prolonged preservation in University of Wisconsin solution associated with hepatic artery thrombosis after orthotopic liver transplantation.

Hepatic artery thrombosis (HAT) after liver transplantation (LTx) usually mandates retransplantation. Prolonged preservation with Eurocollins solution has been associated with HAT. We reviewed our experience with 359 LTx patients to identify risk factors for HAT. All grafts were preserved in University of Wisconsin solution. HAT developed in 12 patients (3%) within 50 days. Seven patients were asymptomatic; four presented with biliary sepsis and 1 with poor graft function. Two patients had suffered acute rejection; another 2 had severe preservation injury. Technical problems accounted for 4 cases; in the remaining 8, no etiology was found. Diagnosis was at a mean 14.7 days after LTx. One patient maintains normal graft function 3 years after LTx without intervention. Eight underwent re-LTx, 3 of whom died. Routine surveillance via duplex enabled early diagnosis and revascularization in 3 patients; in all 3, no biliary complications occurred between 6 and 20 months. Overall graft and patient survival after HAT were 33.3% and 75%, respectively. Cold ischemic time (CIT) averaged 813 min in patients with HAT and 669 min in those without HAT (P < .05). HAT occurred in 7/165 patients with CIT > 12 hr, and in 3/234 patients with CIT < 12 hr (P = 0.0699). By avoiding CIT > 12 hr, we have recently avoided HAT in 78 consecutive patients. We conclude that CIT > 12 hr may increase the risk of HAT. When HAT is diagnosed before biliary sepsis develops, flow can often be restored and retransplantation averted.

OKT3 rescue for steroid-resistant rejection in adult liver transplantation.

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8%) and SR in 86 (32.4%), and OKT3 was given for persistent rejection in 71 (26.8%). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P < 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P < 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6% for NR, 79.8% for SR, and 67.6% for OKT3. The 1-year patient survival rate was 85.2% for NR, 83.7% for SR, and 84.5% for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed lymphoproliferative disorder, and only 1 survived in response to drastic reduction of immunosuppression. In conclusion, OKT3 was effective as rescue therapy for adult liver transplant steroid-resistant rejection. Because of the associated morbidity and expense, OKT3 should be used in a selective fashion. Failure to respond to OKT3 is a serious complication, and should not be managed by prolonged or repeated courses, but rather by alternative means.

Successful use of an enhanced immunosuppressive protocol with plasmapheresis for ABO-incompatible mismatched grafts in liver transplant recipients.

Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompatible allografts. Quadruple immunosuppression consisted of OKT3, Cytoxan, cyclosporine, and steroid taper; prostaglandin E-1 was administrated intravenously the first week. All patients underwent perioperative plasmapheresis to maintain hemagglutinin levels < 1:16. Patient survival was 80%; graft survival was 60% at 140-505 days. The rejection rate was 90%. Three recipients (A1-->O) lost their grafts to severe rejection at 5, 12, and 30 days after transplantation. All 3 had pretransplantation hemagglutinin levels > or = 1:100. Elevated hemagglutinin levels preceded the diagnosis of severe acute cellular rejection; plasmapheresis failed to lower anti-A titers in these 3 patients. We conclude that in an urgent setting, lowering of preformed hemagglutinins via plasmapheresis in combination with quadruple induction immunosuppression allows liver transplantation across ABO barriers. In patients with high baseline levels of preformed hemagglutinins, the risk of subsequent graft loss may be increased and transplantation with an ABO-incompatible graft may serve as a lifesaving intermediate step.

Obviation of prereperfusion rinsing and decrease in preservation/reperfusion injury in liver transplantation by portal blood flushing.

Liver allografts are traditionally rinsed with cold lactated Ringer's (LR) prereperfusion to clear K(+)-rich preservation solution from the hepatic vasculature. LR has been shown, however, to be injurious to the graft. By restoring portal blood flow without rinsing and discarding the initial blood traversing the liver (PB flush), we sought to eliminate rinsing without inducing hyperkalemia. Between August 1988 and December 1992, 481 OLTx were performed in 412 pts. Four rinsing methods were used sequentially: group 1 (157 pts)--low-flow-rate cold LR rinse (500 ml, 100 ml/min via standard i.v. tubing at 100 cm H2O [LFLR]) during lower caval anastomosis; Group 2 (120 pts)--LFLR as in group 1, at reperfusion, 500 ml PB flush via IVC catheter; group 3 (66 pts)--high-flow-rate LR rinse (500 ml, 1 L/min using large-bore tubing with 100 cm H2O rinsing pressure [HFLR]), PB flush as in group 2; Group 4 (62 pts)--no LR rinse; PB flush as in groups 2 and 3. Poor early graft function (PEGF) was defined as peak ALT or AST > 2500 U or PT > 16 sec (on POD 2); PEGF causing re-OLTx or death within 14 days was called primary nonfunction (PNF). Group 1 and Group 3 had high PEGF rates. Group 4 had significantly less PEGF than Group 1, with a trend toward a significant difference from Group 3. In Group 1, 3 pts. had intraoperative hyperkalemic cardiac arrest; this did not occur when PB flush was performed. PB flush without prior rinsing optimizes graft function without risk of hyperkalemia. LR rinse, alone or followed by PB flush, is unnecessary and may be deleterious.

Defibrotide for the treatment of veno-occlusive disease after liver transplantation.

BACKGROUND: Veno-occlusive disease (VOD) after liver transplantation is associated with acute rejection and poor outcome. The use of antithrombotic and thrombolytic agents is limited by their toxicity. Defibrotide is a polydeoxyribonucleotide with thrombolytic and antithrombotic properties and no systemic anticoagulant effect. METHODS: Defibrotide, 35-40 mg/kg/day, was administered intravenously for 21 days on a compassionate-use basis to two patients aged 66 and 49 years. VOD had developed 6 weeks and 4 months after orthotopic liver transplantation for hepatitis C and hepatitis B infection, respectively. VOD was diagnosed clinically by findings of weight gain (8.5% and 16%), ascites, jaundice (serum bilirubin 5.4 mg/dl and 21.7 mg/dl), and severe coagulopathy (in one patient), and histologically by the presence of hemorrhagic centrilobular necrosis and fibrous stenosis of the hepatic venules. One of the patients had received azathioprine as part of the immunosuppressive regimen. There was no evidence of acute cellular rejection histologically. RESULTS: After 3 weeks of defibrotide administration, the first patient showed complete clinical resolution of the VOD, and serum bilirubin level normalized. He is alive 6 months after transplantation. The second patient, treated at a later stage of disease, showed marked improvement in the coagulopathic state, but there was no resolution of the VOD. He died 2 months later of multiorgan failure due to Escherichia coli sepsis. Neither patient had side effects from the drug. CONCLUSIONS: Defibrotide is a promising drug for the treatment of VOD after liver transplantation and needs to be evaluated in large, prospective studies.