Interpretation of LDH Values after Kidney Transplantation.

Kidney transplantation is the gold-standard therapy for end-stage renal disease. However, in the early postoperative period following allograft kidney transplantation, insufficient graft function presents a diagnostic challenge to clinicians. Ischemic damage to the graft and/or an early autoimmune rejection may cause a decrease in function. Ischemic damage is a benign and transient condition, while acute immune rejection requires immediate therapy. A kidney graft ultrasound may produce a false negative result, and graft biopsy is invasive and slow to return results. Serum lactate dehydrogenase (LDH) is under examination as a possible tool for differential diagnosis between ischemic damage and immune rejection. Herein, we analyze the continuous lab results of four patients in the early post-transplantation period, showing patterns correlating with different clinical outcomes and prognoses. In our experience, a persistent elevated LDH accompanies ischemic damage. Immune rejection was, however, associated with a decrease in LDH. Hemodialysis was not a confounding factor, while packed red blood cell transfusion caused severe diagnostic problems.

[Tacrolimus therapy after renal transplantation. Current questions of concentration/dose ratio]. / Takrolimuszterápia vesetranszplantáció után. A koncentráció/dózis arány aktuális kérdései.

Tacrolimus is an important part of immunosuppressive therapy after solid organ transplantation. The therapeutic range of the drug from the calcineurin inhibitor group is narrow. Adjustment of the blood concentration can be very complicated but to be able to avoid the occurrence of side effects or ineffective immunosuppression it is inevitable. This article summarizes the properties of tacrolimus pharmacokinetics, pharmacogenetics and pharmacodynamics. We will focus on individual variations of cytochrome enzymes. In the following part, a new method for screening high risk patients will be introduced. We will present the publications of the determination of the concentration/dose (C/D) ratio. By determining the C/D ratio, researchers identify fast and slow metabolizing patient groups. Fast metabolizers require higher doses in general and the occurrence of complications is also more frequent in this group. Long-term results are lagging behind the slow metabolizing group. The long-term results of renal transplantation nowadays contribute to the postoperative period and the later years rather than the surgery itself. It includes the proper management of previous illnesses (e.g., hypertension, diabetes, endocrinological problems), detection of complications (e.g., infections, malignancies), and the precise regulation of immunosuppressive therapy. Orv Hetil. 2019; 160(30): 1178-1183.

[Antibody-mediated rejection: challenge of the treatment in kidney transplantated patients]. / Antitestmediált rejekció: kihívás a veseátültetett betegek kezelésében.

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

[Rare bile duct anatomy variant - Right bile duct intraparenchymal junction into the left bile duct]. / Az epeutak ritka anatómiai variánsa − A jobb ductus hepaticus intraparenchymalis csatlakozása a bal oldali ductus hepaticusba.

The authors present a case of a 67-year-old male patient, who previously had been diagnosed with a malignant liver tumor localized in segment II. He underwent bisegmentectomy (II and III) and partial IV segmentectomy. After the primary surgery jaundice developed, the level of bilirubin increased and after several imaging modalities reoperation was indicated. During the surgery a rare bile duct anatomy variant was found. The right hepatic duct joined the left duct in the parenchyma of the left lobe, and was ligated at the resection. As the liver hilum was not explored, the absence of the right duct was not discovered. Reconstruction of the biliary system was accomplished by a Roux-en-Y loop.

PARP inhibition attenuates acute kidney allograft rejection by suppressing cell death pathways and activating PI-3K-Akt cascade.

BACKGROUND: Novel immunosuppressive therapy facilitates long term allograft survival, but acute tubular necrosis and ischemia-reperfusion during transplantation can compromise allograft function. These processes are related to oxidative stress which activates poly- (ADP-ribose) polymerase (PARP) contributing to the activation of cell death pathways. Here we raised the possibility that PARP inhibition curbs cell death pathways and shifts kinase signaling to improved graft survival. METHODS FINDINGS: In an acute rat kidney rejection model, we provided evidence that the PARP inhibitor 4-hydroxy-quinazoline (4OHQ) attenuates rejection processes initiated oxidative/nitrosative stress, nuclear poly-ADP-ribosylation and the disintegration of the tubulo-interstitial structures. The PARP inhibitor attenuated rejection processes induced pro-apoptotic pathways by increasing Bcl-2/Bax ratio and suppressing pro-apoptotic t-Bid levels. In transplanted kidneys, the cell death inducing JNK1/2 is normally activated, but PARP inhibition suppressed this activation with having only modest effects on ERK1/2 and p38 MAP kinases. In untreated transplanted kidneys, no significant alterations were detected in the cytoprotective PI-3K-Akt pathway, but the PARP inhibitor significantly activated Akt (by S473 phosphorylation) and suppressed GSK-3ß, as well as activated acute NF-kappaB activation contributing to graft protection. CONCLUSION: These data show the protective role of PARP inhibition on graft survival by attenuating poly-ADP-ribosylation, oxidative stress, suppressing pro-apoptotic and increasing anti-apoptotic protein level, and by shifting MAP kinases and PI-3-K-Akt pathways to cytoprotective direction. Thus, addition of PARP inhibitors to standard immunosuppressive therapies during kidney transplantation may provide increased protection to prolong graft survival.

[Role of simultaneous pancreas-kidney transplantation in the treatment of diabetes mellitus]. / Szimultán hasnyálmirigy-vese transzplantáció helye a diabetes mellitus kezelésében.

The life expectancy of patients with type 1 diabetes mellitus is inferior to that of patients with some malignancies. Simultaneous pancreas-kidney transplantation is the procedure providing the best survival results among all options of renal replacement therapy. The operative techniques and immunosuppresion have been standardized in the last decade. Although the number of transplantable organs falls behind the need, simultaneous pancreas-kidney transplantation is the method of choice for the eligible patients. The results of the two Hungarian simultaneous pancreas-kidney transplantation programs are in accordance with data published in the international literature.

[From the surgical field to the microscope. A new tool to identify the lymph node specimens in oncologic surgery]. / A mutotol a mikroszkópig. A rendszerezett nyirokcsomóminták azonosításának új eszköze a ráksebészetben.

Oncologic surgery and pTNM staging require systemic removal of the locoregional lymphnodes. While the optimal extent and therapeutical and/or prognostic value of the lymphadenectomy/sampling are debated organ by organ and (sub)speciality by (sub)speciality, relevance of the lymphnode sytem-tumor concept itself is beyond doubt. Loss of information and existence of traps on the "surgical field-microscope" pathway is an international phenomenon, calling for solution. An integrated sterile and disposable lymphnode tray system is presented here for applications in the different fields of cancer surgery of the upper GI tract, retroperitoneum (gynecology, urology) and ear-nose-throat surgery.

[Clinical study of non-melanoma skin cancer following human organ transplantation]. / A szervtranszplantációt követo non-melanoma bortumorok klinikai vizsgálata.

INTRODUCTION: Increasing evidence suggests that non-melanoma skin cancers (NMSC) are the most frequent tumours in transplanted patients. In this study, we present the first Hungarian dermatological screening program to establish the incidence of NMSC after organ transplantations. PATIENTS AND METHODS: 116 adult, "Caucasian" (white skin) transplanted (kidney, simultaneous-pancreas-kidney) patients (70 male and 46 female) of the Surgical Department of Pécs University were enrolled from September 2008. All patients underwent a a full skin examination by a dermatologist for NMSC as well as a standardized questionnaire was filled in to assess risk factors. RESULTS: Screening resulted in 16 NMSC (13.8%, median age: 49.3 years, male : female = 1 : 1) diagnoses with a median duration from transplantation of 4.1 years. Histology showed 13 basal cell carcinoma (BBC), 3 squamous cell carcinoma (SCC), with a 4 : 1 ratio of BCC : SCC. Incidence of NMSC was significantly higher on patients who were treated with cyclosporine as immunosuppressant, who had more than 2 sunburns prior to transplantation, or had outdoor workplace ( p < 0.05). CONCLUSIONS: These data confirm the importance of skin cancer surveillance in transplant recipients via a close cooperation between Transplantation and Dermatological Centres. Our results reflect the international data, except for the BCC : SCC ratio. Further studies needed to elucidate this difference.

[Surgical treatment of primary leiomyosarcoma of the inferior vena cava]. / Primer vena cava inferior leiomyosarcoma (VCI-LMS) sebészi kezelése.

CASE REPORT: pLMS in the wall of the inferior vena cava is an extremely rare form of retroperitoneal malignancies. A case in a young female patient is presented; clinical symptoms, pre- and postoperative diagnosis and surgical treatment are discussed. A retroperitoneal mass detected by imaging was found to be a large tumor mass located at the middle segment of the IVC on exploration. The tumour was successfully excised and the IVC was reconstructed with a synthetic graft. Eight years later, this patient needed a repeat surgery due to local recurrence. This time tumour was attached to the left renal vein. A re-resection of the IVC was performed with subsequent synthetic graft reconstruction and the distal end of the left renal vein was reimplanted into a lower segment of IVC. DISCUSSION: Primary leiomyosarcoma of the inferior vena cava (pLMS-IVC) is an extremely rare form of retroperitoneal malignancies. The tumour arises from the medial layer of the venous wall and can grow either intraluminally, or extraluminally or in both directions, as well. It can be localized in the first segment of IVC (above the hepatic veins), in the second segment between hepatic and renal veins and finally in the third segment between the right common iliac vein and renal veins. Therefore, the tumour can infiltrate both hepatic and/or renal vessels. Upper segment tumours can cause Budd-Chiari syndrome (hepatomegaly, abdominal pain, jaundice and ascites) with a bad prognosis. Middle segment tumours usually present with right upper quadrant pain, or may mimic biliary tract disease with a much better prognosis. Accumulating experience suggests that radio-chemotherapy alone seems to be less effective than "en bloc" resection with clear margins including loco-regional lymph nodes. Therefore, our choice of treatment was the latter. Although radical resection can be carried out in most of cases, 50% of patients develop a late recurrence yet.

Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation.

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.

[Surgical treatment of pulmonary metastases of colorectal cancers]. / A colorectalis tumorok tüdô metastasisainak sebészi kezelése.

INTRODUCTION: Results of a retrospective study of patients who underwent pulmonary metastasectomies after colorectal surgery in the last five years are reported here. Prognostic factors are evaluated and analyzed in the context of current literature. MATERIAL AND METHODS: 37 lung resections were performed in 33 patients between 2001 and 2006, the male:female ratio was 19:14. The average age was 61.3 years (49-76). We analyzed the extent of lung resections, disease free intervals (DFI), laterality of the tumours, number and locations of metastases, lymph node involvements and the incidence of resection of hepatic metastases. Altogether, 20 solitary lung metastases were removed and 17 multiple resections were performed. 25 sublobar resections, 11 lobectomies and one pneumonectomy were carried out. 18 patients had right sided, eight patients had left sided and six patients had bilateral disease. 6 of the 33 patients underwent either synchronous or metachronous liver resection for hepatic metastases. RESULTS: Survivals were calculated by the Kaplan-Meier method. The average DFI was 27.6 months. When all patients were considered, the average survival was 28 months. 52% of the patients had a 3-year postoperative survival, if lung metastases were present only. CONCLUSIONS: Patients benefit from surgical removal of lung metastases of colorectal cancer. There were no differences in survival rates between patients who underwent resection of solitary or multiple lung metastases up to seven deposits. However, the average survival was 12 months shorter if hilar/mediastinal lymph nodes were involved. Furthermore, the average survival of six patients with hepatic metastases was 10 months shorter than the rest of the group. There was no benefit of DFI over 24 months. None of the other prognostic factors showed significant difference.

Association between carcinosarcoma and the transplanted kidney.

BACKGROUND: Renal carcinosarcoma is a rare tumor with 12 reported cases in the world literature. To our knowledge, carcinosarcoma of a renal allograft has not been reported to date. CASE REPORT: A multifocal urothelial carcinosarcoma of a transplanted kidney in a 49-year-old woman is described. Genomic analysis of the extracted nuclei of all the neoplastic cells showed uniformly XY genotype proving the transplant origin of the tumor. RESULTS: The carcinogenic role of immunosuppressive medications in kidney-transplanted patients is reported in the literature. In this case, immunosuppression may have promoted the carcinosarcoma. CONCLUSION: Renal transplant patients should be monitored for the development of malignancy in the allograft and elsewhere.

Pulmonary embolization as primary manifestation of hepatocellular carcinoma with intracardiac penetration: a case report.

Intracardiac manifestation of hepatocellular carcinoma (HCC) is a rare condition and an uncommon finding even at autopsy. Pulmonary tumor embolism as a presenting feature of HCC has been published only twice previously. In our case report, a 63-year-old man presented with high fever and six episodes of recurrent pneumonias during the last half year. Echocardiography was performed, a solid mass was found in the right atrium. Transesophageal echocardiography proved a tumor mass in the inferior vena cava (IVC) extending into the right atrium, abdominal ultrasound revealed tumor mass in the IVC and a solid tumor in the liver. Combined liver and heart surgery was attempted in order to remove the tumor mass from both the liver and the right atrium. Acute cor pulmonale occurred during tumor removal from the right atrium and the patient expired. In addition to local factors the possibility of embolization should arise in the background of recurrent pneumonia. Occult carcinoma must be included in possible causes of recurrent pulmonary embolism. Searching for primary malignancy should include HCC as frequent cause of hypercoagulability. In case of HCC, echocardiography is suggested because of the possibility of expansion in IVC or right atrium and tumor-embolization.

Gastrointestinal stromal tumours in a single institute: is there an association to other gastrointestinal malignancies?

Our knowledge of Gastrointestinal Stromal Tumours (GIST) has been broadened in the last few years by the discovery of the key function of c-kit tyrosine kinase mutation in their pathogenesis. A single institution database is presented and a hypothesis is examined regarding probable connection between GIST and other gastrointestinal malignancies. Between 2000 and 2004 20 patients were admitted to our department with GIS tumour. With the addition of three cases detected between 1991 and 2000, and proved to be GIST retrospectively, 23 cases are followed. Mean age was 64.52 years, male to female ratio 11:12. Ten tumours originated from the stomach, ten from small bowel, one from rectum and two from mesenterium. All patients underwent surgery, 16 operations were completed with R0 radicality, one R1 and four R2 resections were performed. Follow-up ranged from 1 to 157 months. Five out of 23 patients died (21.7%), six patients live with metastatic disease, twelve are disease free. Amongst patient-, tumour- and treatment-related factors the prognostic significance of Fletcher's risk and radicality of resection was demonstrated (p<0.05). Significantly more synchronous or metachronous gastrointestinal malignancies were found is this population of GIST patients, when compared to the prevalence of malignancies in normal Hungarian population (p<0.001).

[Results of 300 kidney transplantations]. / 300 vesetranszplantáció eredményei.

Kidney transplantation is a widely used method for the treatment o fend-stage renal disease. Between September 3, 1993 and December 2002 a total of 300 kidney transplantations were performed at the Department of Surgery at the Medical University of Pécs. In 24 patients simultaneous kidney and pancreas transplantation was performed. The mean age of the 189 male and 111 female patients was 42 years. The HLA B, Dr tissue antigen mismatches was 1.63. The average cold ischemic time was 1199 minutes whereas the average anastomotic time was 43 minutes. Early surgical complications happened to 16 patients. In spite of the immunosuppressive treatment 26 acute steroid resistant rejection have occurred, 9 of which were irreversible. In our opinion the meticulous surgical technique is as important as the postoperative care is. The early and late complications of 300 renal transplants are reviewed by the authors.

[Effects of ischemic preconditioning on the oxidative stress in small bowel autotransplantation]. / Vékonybél autotranszplantációt megelózó ischemiás prekondícionálás hatása az oxidatív stressz kialakulására.

One determining factor in intestinal transplantation is the bowel's extreme sensitivity to ischemia-reperfusion injury. This study was meant to investigate the effect of ischemic preconditioning prior to autotransplantation. Total orthotopic intestinal autotransplantation was performed in 40 mongrel dogs. Four groups (GI-GIV) were established. In GI and GII grafts were stored in 4 degrees C Euro Collins and University of Wisconsin solutions. In GIII and GIV before preservation IPC was induced by 4 cycles (5-min ischemia + 10-min reperfusion). Three hours of preservation was followed by 1 hour of reperfusion. We determined oxidative stress markers in bowel tissue [reduced glutathione (GSH), superoxide dismutase (SOD)], oxygen free radicals (OFRs) (confocal microscopy), NF-kappa B (gel electrophoretic mobility shift assay), DNA damage (TUNEL). Cold preservation could not prevented against oxidative stress and resulted decrease of SOD activity significantly during reperfusion. In the preconditioned groups the elevated GSH and better preserved SOD activity indicated development of protection. Production of OFRs increased during reperfusion in non-preconditioned groups. Activation of NF-kappa beta was peaking by 1-3 hours following preconditioning. We detected more cells suffered DNA strand breaks in preconditioned groups. Our findings confirm that ischemic preconditioning prior to preservation can moderate the severity of oxidative stress and activate the endogenous celluar adaptation in bowel tissue.

The effects of preconditioning on the oxidative stress in small-bowel autotransplantation.

BACKGROUND: One determining factor in intestinal transplantation is the extreme sensitivity of the small bowel to ischemia-reperfusion injury. This study investigated the effect of ischemic preconditioning prior to autotransplantation. METHODS: Total orthotopic intestinal autotransplantation was performed in 40 mongrel dogs. In 4 groups (GI-GIV), grafts were stored for 3 hours in cold Euro Collins (GI,GIII) and University of Wisconsin (GII,GIV) solutions. In GIII and GIV, before preservation, preconditioning was induced by 4 cycles (5-min ischemia + 10-min reperfusion). Bowel samples were collected after laparotomy (control), at the end of preservation and reperfusion periods. We determined oxidative stress markers (reduced glutathione [GSH], superoxide dismutase [SOD]), production of oxygen free radicals, activity of nuclear factor-kappaB (NF-kappaB), and DNA damage. RESULTS: In the non-preconditioned groups, GSH concentration increased slightly, while SOD activity decreased significantly during reperfusion. In the preconditioned groups, GSH increased markedly, and better preservation of SOD was observed. The number of oxygen free radicals increased during reperfusion mainly in non-preconditioned groups. Activation of NF-kappaB peaked by 1 hour, and decreased 3 hours after preconditioning. We observed DNA-damaged cells in all groups. CONCLUSIONS: Our findings confirm that preconditioning prior to preservation can moderate the severity of oxidative stress and activate the endogenous cellular adaptation in bowel tissue.