Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation

Urinary thromboxane B₂ (u-TXB₂) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB₂ levels exceeded 3.0g/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB₂ levels exceeded 3.0g/mmol creatinine. In 6 episodes of acute rejection, the TXB₂ levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB₂ values were between 3.0 and 4.9g/mmol creatinine. In 2 episodes of liver necrosis the TXB₂ value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB₂ level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB₂ showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0g/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB₂ of 5.0g/mmol creatinine. These results indicate that the serial determination of u-TXB₂ is a useful diagnostic means for predicting acute rejection after liver transplantation.     

肝移植术后巨细胞病毒感染的防治研究

目的探讨肝移植患者术后巨细胞病毒 (CMV)感染情况及其与急性排斥反应的关系。方法应用PCR和ELISA方法检测 78例肝移植受体手术前后、78例供体及 70例接受上腹部手术的非肿瘤患者血清中的CMV DNA和CMV抗体 ,用免疫组织化学方法检测肝组织中CMV抗原。结果供、受体术中肝脏活体组织学检查的CMV早期抗原 (EA)和晚期抗原 (LA)全部为阴性。术前CMV DNA或CMV IgM阳性的受体术后均为阳性 ;术前CMV DNA或CMV IgM阴性的受体术后CMV DNA或CMV IgM转为阳性的分别有 2 6 %和 10 %。 78例受体CMV DNA阳性率由术前的 5 %增加到术后的 31% ,两者比较差异有显著意义 (P <0 0 5 )。 2 6例患者发生了 33次急性排斥反应 ,16次 (49% )CMV DNA检测阳性、11次 (33% )CMV IgM检测阳性 ,而在术后常规检测血CMV DNA和CMV IgM的阳性率分别不超过 13%和 9% ,两者比较差异有显著意义 (P <0 0 5 )。 2 6例发生急性排斥患者肝脏活体组织学检查CMV EA和CMV LA阳性者均为 9例 (2 7% ) ,与术后的常规肝脏穿刺结果比较差异有显著意义 (P <0 0 5 )。结论 1.肝移植术后CMV感染率明显升高。 2 .CMV感染可能是发生急性排斥反应的危险因素。 3.发生急性排斥反应时 ,应使用抗CMV药物 ;未感染CMV的受体接受感染供体的肝脏时应预防用药。     

The use of fine-needle aspiration biopsy in detection of acute rejection in children after liver transplantation

Diagnosis of acute rejection after liver transplantation is based mainly on clinical signs and the liver core biopsy findings. In this study we retrospectively analyzed our data on the routine use of fine-needle aspiration biopsy (FNAB) after 63 pediatric liver transplantations. A total of 824 FNABs was taken during the postoperative hospitalization, with a mean of 13 biopsies per patient. Forty-nine acute rejection episodes were diagnosed and treated after 39 transplantations (62%). The FNAB analysis detected rejections often before clinical signs. At the time of rejection diagnosis, fever was present in 38% of the patients, and serum bilirubin and alanine aminotransferase were elevated in only 19% and 13%, respectively. The rejections responded well to oral methylprednisolone, and lymphoglobulins were needed in only two episodes (4%). The results indicate that FNAB is a safe and sensitive method for the diagnosis and follow up of acute cellular rejection in pediatric liver recipients.     

Evaluation of Calprotectin Level in Intestinal Content as an Early Marker for Graft Rejection

Introduction

The diagnosis of rejection after intestinal transplantation is still performed by endoscopic biopsy monitoring. Less invasive diagnostic procedures are desirable, although they are not available so far. Calprotectin, a stable cytosolic granulocyte protein, which previously was used as a marker of inflammatory processes, has been proposed to be a biochemical marker for rejection. The aim of the present work was to analyze the concordance between calprotectin levels in intestinal content and the presence of graft rejection after small bowel transplantation.

Methods

Calprotectin level was measured using a commercial ELISA kit on 137 samples of intestinal content randomly collected during endoscopies performed on 11 intestinal transplantation patients during 2 years' follow-up. Calprotectin determinations were correlated with histological and clinical findings. The cut-off level was determined retrospectively by receiver-operator curve analysis.

Results

Based on histological findings and clinical records, samples were discerned as rejection positive (37 of 137), versus negative (35 of 137) samples or those with no clinical, endoscopic, or histological findings (65 of 137 samples). A cut-off value of 65 μg of calprotectin/g of intestinal content provided the best assay parameter according to the clinical findings: a 76% sensitivity and a 47% specificity. False positive results corresponded to patients with gastrointestinal infections (13%), systemic infections (13%), ulcers (10%), or nonspecific histological alterations of the mucosa (15%). The other false positive cases corresponded to postsurgical samples (4%), or patients with concomitant gastrointestinal symptoms (2%). Most false negative results (78%) were observed during recovery from severe acute rejection episodes, among successfully treated patients. In these cases, epithelial reconstitution and no mucosal infiltration was observed. If the latter group were discarded, sensitivity rose to 93%, and specificity, to 50% with a 96% negative predictive value. Furthermore, a weak correlation was observed between calprotectin levels and the severity of rejection.

Conclusions

This study confirmed the results obtained by other groups: fecal calprotectin dosage showed a good sensitivity but low specificity for the diagnosis of intestinal rejection because high calprotectin levels can also be observed in other clinical conditions. Nevertheless, it might be used as a first line for continuous evaluation of intestinal transplantation status, like other biochemical parameters that are used in kidney or liver transplantation, before considering the need for a biopsy.     

抗白细胞介素2受体单克隆抗体在肝移植中的应用

目的 探讨抗白细胞介素2受体单克隆抗体(抗IL—2R单克隆抗体)的不同给药时间对肝移植后排斥反应的影响。方法 将21例肝移植患者分为两组，均于手术当天及术后第4d分别应用20mg的抗IL—2R单克隆抗体，不同的是前10例患者的首次剂量于移植肝恢复血流后给予(术中组)，而后11例患者在移植术开始前2h给予(术前组)。两个组术后均同时使用环抱素A和激素。术后随访3个月。结果 经活检病理证实的急性排斥反应，术中组的发生率为5／10(50％)，术前组为3／11(27％)；术中组还有3例急性排斥反应未经病理证实，但抗排斥治疗有效，而术前组无类似病例，若综合考虑，则术前组急性排斥反应发生率(3／11)明显低于术中组(8／10，P＜0．05)。在抗IL—2R单克隆抗体应用的过程中没有发现明显的不良反应。结论 术前2h给予抗IL—2R单克隆抗体预防急性排斥反应的效果优于移植肝恢复血流后用药。     

Is blood eosinophilia an effective predictor of acute rejection in living donor liver transplantation?*

Summary The association of blood eosinophilia with acute cellular rejection (ACR) after living donor liver transplantation has not been examined yet. The subjects were the 167 recipients who underwent liver biopsy (314 times). The blood eosinophil counts in the preoperative period (n = 167), 3 days before (n = 314) and on the day of biopsy (n = 314) were compared among the groups stratified by severity of ACR. Among 314 biopsy specimens, the 140 biopsy specimens were diagnosed with ACR. In the 140 ACR episodes, eosinophil counts before and after therapy was compared between the episodes that responded to therapy (n = 80) and those not (n = 60). The sensitivity and specificity of preoperative eosinophilia (eosinophil counts >130 mm(3)) to predict ACR was 33% and 65%, respectively. The eosinophil counts >400 mm(3) 3 days before and on the day of biopsy was associated with the severity of ACR (P < 0.0001). The sensitivity to predict ACR was 26% and 33%, and the specificity, 94% and 93%, respectively. There was no significant difference in changes of eosinophil counts between the steroid-responders versus the nonresponders. The present results suggested the limited role of eosinophilia as a predictor of ACR after living donor liver transplantation.     

Serum levels of interleukin-9 during acute rejection in liver transplantation

Introduction

Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection.

Methods

IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy.

Results

The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation.

Conclusions

These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection.     

An increase in myeloid-related protein serum levels precedes acute renal allograft rejection

Upon interaction with activated endothelium, monocytes and neutrophils form complexes of myeloid-related protein 8 (MRP8) (S100A8) and MRP14 (S100A9), two members of the calcium-binding S100 family that are secreted during transendothelial migration. In a pilot study of 20 renal transplant recipients and a validation study of 36 renal transplant recipients, MRP8/14 serum levels were measured with an enzyme-linked immunosorbent assay for 28 d, associated with C-reactive protein and creatinine serum levels, and grouped according to biopsy-proven acute rejection. Serum levels of MRP8/14 but not C-reactive protein were significantly increased for several days during the first 2 wk for the acute rejection groups in both studies (P < 0.005, on day 6 after transplantation). As determined by using receiver operating characteristic curves, the optimal cutoff for 100% specificity and high sensitivity (67%) for acute rejection on day 6 after transplantation was calculated to be 4.2 microg/ml for MRP8/14 in the pilot study; this value was confirmed in the validation study. Positive MRP8/14 serum levels preceded acute rejection episodes by a median of 5 d. A 3-d course of intravenous methylprednisolone therapy reduced prerejection MRP8/14 serum levels from 5.7 microg/ml to 3.3 microg/ml (P < 0.05). All MRP8/14 serum levels were below the cutoff during urinary tract infections, delayed graft function, or cytomegalovirus infections, and these values did not differ significantly from control values. It is concluded that the MRP8/14 complex is a very early serum marker suitable for monitoring of acute rejection with high sensitivity and specificity.     

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients

Long-term success of human lung transplantation has been hindered by the lack of an effective and repeatable method of obtained tissue from the transplanted lung for histology. Management of patients is complicated by the difficulty in distinguishing clinically between opportunistic infection of the lung and rejection. As a result, a large number of patients in recent reports develop chronic disabling obliterative bronchiolitis, believed to be the consequence of "chronic" rejection. Twenty-one patients have undergone heart-lung transplantation in our institute since 1984. During fiberoptic bronchoscopy, 43 transbronchial lung biopsies were performed in 15 patients. Twenty episodes of rejection occurred in 11 patients, from whom 16 sets of biopsies showed the typical changes of perivascular infiltrate and mucosal inflammation. Three biopsies were falsely negative; six routine biopsies performed when patients were well were all normal. Overall sensitivity was 84% and specificity 100%. By contrast, the sensitivity of the chest radiograph was only 40%. Opportunistic lung infection in 8 patients was diagnosed by transbronchial biopsy with a sensitivity of 38% and specificity of 100%. In no patient with opportunistic infection were the histologic features of rejection seen. Transbronchial lung biopsy offers a safe and repeatable method to obtain tissue from heart-lung transplants for histology. It has enabled the management of the lung transplant patient to be equivalent to that of the kidney, liver, and heart transplant patient.     

Treatment of antibody-mediated rejection with high-dose immunoglobulins in ABO-incompatible liver transplant recipient

ABO-incompatible liver transplantation (LT) entails high risk of antibody-mediated rejection (AMR) and poor graft survival. Different treatment modalities have been reported, but none with use of a 2-week course of high-dose polyclonal i.v. immunoglobulins (IVIg) associated with plasmapheresis without the use of steroid pulses or monoclonal antibody. A 60-year-old male patient with blood-group O, Caucasian, underwent urgent LT for acute liver failure after hepatectomy for HCV-related hepatocellular carcinoma. He was grafted with a 66-year-old, blood-group A, HCV-positive liver graft. Pretransplant conditioning consisted of plasmapheresis and immunosuppression was triple with tacrolimus (TAC), steroids, and mycophenolate mofetil with anti-IL2-R monoclonal antibodies, plasmapheresis if hemagglutinin level >1:8, and extracorporeal photopheresis. After reduction of liver function tests to baseline, the patient presented a tenfold increase in alanine aminotransferases (ALT) levels 7 days post-transplantation. AMR was confirmed on histology. Treatment consisted of IVIg (1.5 g/Kg/daily for the first 7 days, and 1 g/Kg/daily from day 8 to 14) with a 14-day course of plasmapheresis. No side effect was observed and daily blood IgG levels ranged between 24.4 and 36.4 g/l. At the end of the scheduled course ALT returned to baseline. A control liver biopsy 55 days after LT showed no rejection and replacement of necrosis with fibrous strands. This case may support the role of high-dose IVIg for treatment and/or prophylaxis of severe AMR.     

Noninvasive assessment of cardiac transplant rejection. A critical look at the approach to acute rejection.

The diagnosis of acute rejection remains a key issue in the management of the heart transplant recipient. Myocardial biopsy for tissue examination is the basic step for screening and diagnosis of acute rejection. Although endomyocardial biopsy is reliable, it is an inefficient approach to screening after transplantation and yielded only a 14% rate of positive results in the author's experience, from 1983 to 1990, of 568 biopsies. A reliable noninvasive method for screening acute rejection is therefore needed. Numerous noninvasive methods have been studied to monitor the systemic immune process against the allograft or to evaluate the effect of rejection on graft function and status. For 13 methods of evaluating immune process against the allograft the sensitivity and specificity ranged from 13% to 95% and 19% to 94% respectively. For nine methods of evaluating allograft function, sensitivity and specificity ranged from 60% to 93% and 65% to 97% respectively. Overall, methods monitoring allograft function and status have better results in predicting acute rejection. Nevertheless, the author estimated that 15 episodes of acute rejection would have been missed by these monitoring methods in his group of patients.     

Der Wert der Duplexsonographie nach der orthotopen Lebertransplantation Erfahrungen an 44 Patienten

Zusammenfassung In einer prospektiven Untersuchung wurde an 44 Patienten (33 Männer, 11 Frauen) riach einer elektiven orthotopen Lebertransplantation die Duplexsonographie 196ma1 angewendet. Ziel der Untersuchung war es festzustellen, inwieweit and in welchem zeitlichen Zusammenhang sich die Parameter pulsatiler FluBindex (PFI) und Dämpfungsindex (DI) bei Komplikationen wie Abstoung und Cholangitis verändern. Der Duplex-Doppler-Ultraschall wurde im Mittel 5mal pro Patient durchgeführt. Die letzte Sonographie erfolgte am Entlassungstag. Bei den Messungen fiber der Leberarterie, der Pfortader und den Lebervenen wurden jeweils der PFI und der DI bestimmt. Die Ergebnisse der Indexuntersuchungen wurden mit dem klinischen Verlauf (Abstoung, Cholangitis) sowie mit den Resultaten von 88 Biopsiepräparaten der Lebertransplantate in Beziehung gesetzt. Bezüglich einer histologisch gesicherten AbstoBung ergab der PFI (über der Leberarterie gemessen) eine Sensitivität von 69,4 % and eine Spezifitdt von 72,2 %, der DI (über den Lebervenen gemessen) eine Sensitivität von 89,4% und eine Spezifitdt von 89,1 %. Wenn auch die einfach und beliebig oft anwendbare Untersuchungstechnik die bioptische Sicherung einer Rejektion nicht ersetzen kann, so ist sie in hohem Mae in der Lage, Indikationen zur Biopsie frühzeitig stellen zu lassen und ein Ansprechen auf eine Therapie kurzfristig und mit holier Genauigkeit anzuzeigen.

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Duplex sonography after orthotopic liver transplantation: findings in 44 patients

In a prospective study, 44 patients (11 women, 33 men) who had received orthotopic liver transplants underwent a total of 196 consecutive duplex Doppler ultrasound examinations. The aim of the study was to evaluate the correlation between the pulsatile flow index (PFI) and the damping index (DI) as far as complications as rejection or cholangitis were concerned. The patients were examined five times each on average. The PFI and DI were measured in the hepatic artery, the portal vein and the hepatic veins. The findings were compared with the clinical course (cholangitis, rejection) and the histomorphological diagnosis as determined in biopsy specimens. In biopsy-proven rejection episodes, the sensitivity of the PFI in the hepatic artery was 69.4%, the specificity 72.2%. The sensitivity of the DI in the hepatic vein was 89.4%, the specificity 89.1 %. Combining the two, specificity was more than 90%. PFI and DI in the portal vein bore no apparent relation to clinical course or histomorphological diagnosis. We found duplex Doppler ultrasound extremely beneficial in determining the timing and indication for liver biopsy. In addition, this simple examination, which can be performed as often as desired, accurately shows the transplanted liver's response to measures taken to counter rejection.

     

Tacrolimus for steroiD-resistant liver rejection in children

Abstract Eighteen pediatric liver transplant recipients were converted from cyclosporine-based immunosuppression to tacrolimus for refractory rejection episodes affecting 21 grafts. Before conversion, steroid boluses were applied to all episodes followed by OKT3 monoclonal antibodies in 3 of them. Baseline biopsy showed cellular rejection in 18 patients and ductopenia in 3 cases. Thirteen episodes initiated within the first 2 postoperative weeks, and 8 occurred beyond the 21st day. A previous steroiD-responsive episode of rejection was noted in 4 patients. Tacrolimus was administered by the oral route to obtain trough blood levels in the range 6–15 ng/ml. Reversal of rejection was obtained in 15 patients (71.4%). Complete normalization of liver function tests was achieved in 10 out of 12 patients who were followed for more than 6 months. A refractory evolution affected 6 patients (28.5 %). Significant factors predictive for tacrolimus-resistant rejection were identified as ductopenia on baseline biopsy, previous episodes of acute rejection, late onset rejection (beyond 21st posttransplant (day), and a longer time of evolution of rejection prior to conversion.     

Day-5 protocol liver allograft biopsies document early rejection episodes and are predictive of recurrent rejection.

METHODS. The day-5 posttransplant protocol biopsy specimens and clinical courses of 27 consecutive orthotopic liver transplant recipients followed up at least 6 months were reviewed. RESULTS. Twelve (44%) of 27 patients had histologic evidence of rejection on the day-5 biopsy; 8 (67%) of these 12 patients required OKT3 for reversal of the rejection. No significant differences in biochemical liver test results, bile output, or cyclosporine levels were observed between this group and the 15 patients (56%) without histologic evidence of rejection on day 5. Eight (67%) of the 12 patients with rejection had recurrent rejection episodes, with one recurrence each in six patients, two recurrences in one patient, and three recurrences in one patient. Of the 15 patients without rejection on day 5, nine (60%) subsequently had rejection at 10 days, 14 days, and 1 1/2, 3 1/2, 4, 5, and 11 months after transplantation. Only one (11%) of these nine patients had a recurrent rejection episode. There were no differences in the incidence of posttransplant cytomegalovirus infections between the two groups. Two cases of posttransplant lymphoma were seen; they developed in two patients without rejection on the day-5 biopsy. No patients or allografts were lost to acute or chronic rejection. No complications occurred as a result of the day-5 protocol biopsy. CONCLUSION. The day-5 protocol biopsy is useful in detecting rejection episodes that may not otherwise be clinically apparent.     

The accuracy of aspiration cytology in the diagnosis of rejection following orthotopic liver transplantation

Abstract. The role of aspiration cytology (AC) and the total corrected increment (TCI) in the diagnosis of hepatic rejection was assessed in 30 patients following 36 liver transplants. A total of 174 AC specimens were "blindly" evaluated. Patients underwent protocol AC twice weekly and when biochemical or clinical parameters suggested rejection. Hepatic rejection was only confirmed when clinical and biochemical changes were accompanied by positive histological diagnosis. In all, 103 specimens were matched against histology, the remainder assessed against retrospective clinical and biochemical diagnoses. There were 80 cytological diagnoses of rejection, confirmed in 69 specimens, and 94 diagnoses of no rejection, confirmed in 73 specimens. These figures give a sensitivity of 76.7%, a specificity of 86.9% and a positive predictive value of 86.3%. Overall, 39.7% of specimens taken more than 2 months after grafting proved to be incorrectly diagnosed. However, the accuracy was higher in 145 specimens taken within 8 weeks of transplantation, with a sensitivity of 81.3%, a specificity of 90%, a positive predictive value of 89.7% and an accuracy of 85.5%. Although histology remains the gold standard in the diagnosis of acute rejection after hepatic grafting, AC using a TCI with a positive predictive value of 86.3% may prove to be of value in monitoring liver transplant patients in the first 2 months after grafting.     

Soluble interleukin-2 receptor level as an indicator of liver allograft rejection

We studied the serum levels of soluble interleukin-2 receptors (SIL-2R) in liver allograft recipients: a control group without rejection or CMV disease, a group with only rejection episodes, and a group with only cytomegalovirus disease. Rejection was diagnosed by the presence of compatible laboratory and histologic abnormalities and absence of other causes of graft dysfunction. CMV disease was diagnosed by isolation of CMV in blood or liver specimen cultures or identification of cytomegalic inclusions in the liver biopsy specimen. Of 82 consecutive recipients treated with cyclosporine and prednisone, 12 were in the control group, 20 in the rejection group, and 5 in the CMV disease group. The remaining 45 had other or multiple complications. In the control group the SIL-2R levels (determined by an ELISA) decreased by a mean of 4% per day after transplantation; in the rejection group the levels increased by a mean of 17% per day in the 10 days prior to the diagnosis of rejection; in the CMV disease group the levels tended to increase prior to the diagnosis of CMV disease. The rejection group had significantly higher SIL-2R levels than the control group at comparable times. Thus, SIL-2R levels were significantly increased at the time of allograft rejection compared with levels in a control group, and recipients with CMV disease had increased levels of SIL-2R but they were not as high as in recipients with rejection episodes.     

Urinary polyamines as markers of cardiac allograft rejection. A clinical evaluation

Histologic evaluation of endomyocardial biopsy specimens is the current method of monitoring rejection after cardiac transplantation. Unfortunately, this technique gives a discontinuous evaluation of the recipient immunologic status. A noninvasive marker of immunologic activation and of allograft rejection that would permit a more continuous monitoring than the biopsy technique would be clinically useful. Urinary polyamine excretion reflects cellular proliferation or degeneration and, as a marker of cellular metabolic activity, may also reflect lymphocyte proliferation and organ rejection. From July 1985 to December 1986, urinary polyamines were studied in 18 patients during hospitalization for heart and heart-lung transplantation. Endomyocardial biopsy was performed twice a week and histologic rejection was characterized by standard criteria. Urinary specimens were collected daily and analyzed for polyamines by high-pressure liquid chromatography. Concentrations of acetylputrescine and total urinary polyamines were significantly higher before the 20 rejection episodes than before the 80 biopsies yielding negative results. So that their clinical usefulness could be evaluated, an elevation of polyamines and a daily level variability of 28% or more was chosen to indicate increased metabolic cellular activity and to predict rejection in the next 8 days. On the basis of these definitions, the sensitivity of polyamine assays to predict rejection was 85%, the specificity 88%, and the positive predictive value 79%. Therefore, serial measurements of urinary polyamines may provide daily information on the recipient's immunologic status after cardiac transplantation.     

Plasmacytic hyperplasia--the early form of posttransplant lymphoproliferative disorder--with atypical morphology and clinical course in patient after liver transplantation: a case report

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation.     

Combined liver-kidney transplantation: long-term follow up in 18 patients

Abstract Since August 1992, 18 patients underwent combined liver and kidney transplantation. Eight patients had lymphocytotoxic antibodies pretransplant and 5 of these patients (27.7%) had a positive crossmatch. Fifteen patients received cyclosporine-based immunosuppression and 3 patients were treated with a tacrolimus-based immunosuppressive protocol. One patient died in the postoperative course due to intractable bleeding episodes after 96 days and one kidney graft was lost due to technical complications. The 1-year survival rate of patients with combined transplantation was 95% vs 87% in patients with liver transplantation alone. None of the patients with a positive crossmatch experienced a hyperacute rejection of the kidney. The long-term patient and graft survival was not impaired in patients with a positive crossmatch. These results suggest that combined liver-kidney transplantation is a safe treatment for enD-stage liver and renal disease. A positive crossmatch or positive lymphocytotoxic antibodies are not contraindications for a combined transplantation.     

Endomyocardial biopsy in heart transplantation: schedule or event?

Background

Endomyocardial biopsy is the gold standard to identify rejection after heart transplantation. Due to its invasiveness, discomfort, and difficult vascular access, some patients are not willing to accept routine scheduled biopsies years after heart transplantation. The purpose of this study was to identify whether there was a difference in outcomes among the scheduled versus event biopsy groups.

Methods

We studied 411 patients who underwent heart transplantation from 1987 to 2011, reviewing biopsy results and pathology reports. There were 363 patients who followed the scheduled biopsy protocol, and 48 patients who were assigned to the event biopsy group. We extracted data on biopsy results, rejection episodes, rejection types, and survival time.

Results

The 2481 reviewed biopsies over 24 years, showed most rejection episodes (86.4%) to occur within 2 years after heart transplantation. The rejection incidence was low (2.1%) at 3 years after transplantation. The major reason for an event biopsy was poor vascular access, such as tiny central vein or congenital disease without a suitable central vein. Event biopsy group patients were younger than schedule biopsy patients (19.7 years old vs 47.6 years old; P < .05). The 10-year survival rates were 64% among the event versus 53% among the scheduled biopsy group (P = .029). The 10-year rates of freedom from rejection were similar.

Conclusions

The rejection rate was low after 3 years; episodes occurred within 2 years. Although the long-term survival in the event group was better, they had a younger man age. The rejection and freedom from rejection rates were similar. As the rejection rate was low at 3 years after transplantation, we suggest that the event principle could be applied for biopsy at 3 years after heart transplantation.