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Melinda Látos,1 György Lázár,1 Zoltán Horváth,1 Victoria Wittmann,1 Edit Szederkényi,1 Zoltán Hódi,1 Pál Szenohradszky,1 Márta Csabai2 1Department of Surgery, Faculty of Medicine, 2Psychology Institute, University of Szeged, Szeged, Hungary Abstract: Interdisciplinary studies suggest that the mental representations of the transplanted organ may have a significant effect on the healing process. The objective of this study was to examine the representations of the transplanted organ and their relationship with emotional and mood factors, illness perceptions, and the functioning of the transplanted organ. One hundred and sixty-four kidney transplant patients were assessed using the Spielberger Anxiety Inventory, the Beck’s Depression Scale, the Posttraumatic Growth Inventory, the Brief Illness Perception Questionnaire, and the Transplanted Organ Questionnaire. Medical parameters were collected from the routine clinical blood tests (serum creatinine and estimated glomerular filtration rate levels) and biopsy results. Our most outstanding results suggest that kidney-transplanted patients’ illness representations are associated with health outcomes. The Transplanted Organ Questionnaire “psychological rejection” subscale was connected with higher serum creatinine and estimated glomerular filtration rate levels. Logistic regression analysis showed that psychological rejection subscale, Brief Illness Perception Questionnaire, and Posttraumatic Growth Questionnaire total scores were associated with graft rejection. These results may serve as a basis for the development of complex treatment interventions, which could help patients to cope with the bio-psycho-social challenges of integrating the new organ as part of their body and self. Keywords: anxiety, depression, illness representations, posttraumatic growth, psychological rejection, renal transplantation

Infected pancreatic necrosis and sepsis are the leading causes of mortality in necrotizing pancreatitis. A review has been undertaken of the results of the past two decades relating to different surgical treatments of infected pancreatic necrosis. During the period 1978-85, the surgical treatment of necrotizing pancreatitis and its complications in our department consisted of the `conventional' therapy (resection of the involved pancreatic tissue, or necrosectomy and drainage) in 61 patients, with a mortality rate of 36% (22 patients died). Since 1986, we have performed necrosectomy and other surgical interventions combined with continuous widespread lavage in 142 patients with infected pancreatic necrosis. The overall mortality decreased significantly to 6.3% (9 patients died). This result was achieved by means of aggressive surgical treatment, continuous, prolonged washing and suction drainage and supportive therapy, including immunonutrition, modifying the cytokine production and adequate antibiotic and antifungal medication. This surgical strategy provides the possibility for recovery in cases of necrotizing pancreatitis with septic complications. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the FAN1 gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a FAN1 mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous FAN1 mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous FAN1 mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for FAN1 mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.

Introduction: The risk of cutaneous malignancies is significantly higher in immunosuppressed patients compared to the general population. These high-risk skin tumors tend to be aggressive, multiplex, rapidly growing lesions. It is common to see local recurrence after surgical excision. Multiplex tumors are difficult to treat, especially in the head/neck region., Objective: Amongst the standard treatment options, electrochemotherapy can be a suitable option. Our aim was to evaluate the efficacy of electrochemotherapy in immunocompromised patients., Method: In 9 immunosuppressed patients, 118 (average: 13, n = 5-27) non-melanoma skin tumors were treated with electrochemotherapy with intravenous administration of bleomycin, according to the ESOPE criteria., Results: The median follow-up was 15 months. 6 months after the treatment, the objective response rate was 96%. We observed complete response in 88%, partial response in 8% and progressive disease in 2% of the treated lesions. In 2%, the response was not evaluable., Conclusion: In immunocompromised patients, electrochemotherapy is an effective and safe therapeutic option for non-melanoma skin tumors. In order to provide more ideal management for this special sub-group, prevention, multidisciplinary approach and optimized immunosuppressive therapy is essential. Orv Hetil. 2023; 164(37): 1462-1468.

Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved. In addition, due to the vectorial transport of ions and fluid the intraluminal pressure in the organoids is elevated, which may hinder the study of physiological processes. To overcome these, we developed an advanced culturing method for human pancreatic organoids based on the removal of the extracellular matrix that induced an apical-to-basal polarity switch also leading to reversed localization of proteins with polarized expression. The cells in the apical-out organoids had a cuboidal shape, whereas their resting intracellular Ca 2+ concentration was more consistent compared to the cells in the apical-in organoids. Using this advanced model, we demonstrated the expression and function of two novel ion channels, the Ca 2+ activated Cl - channel Anoctamin 1 (ANO1) and the epithelial Na + channel (ENaC), which were not considered in ductal cells yet. Finally, we showed that the available functional assays, such as forskolin-induced swelling, or intracellular Cl - measurement have improved dynamic range when performed with apical-out organoids. Taken together our data suggest that polarity-switched human pancreatic ductal organoids are suitable models to expand our toolset in basic and translational research., (© 2023. The Author(s).)

Regardless of its aetiology, sustained intracellular Ca 2+ overload is a well-known hallmark of acute pancreatitis (AP). Toxic Ca 2+ elevation induces pancreatic ductal cell damage characterized by impaired ion and fluid secretion - essential to wash out the protein-rich fluid secreted by acinar cells while maintaining the alkaline intra-ductal pH under physiological conditions - and mitochondrial dysfunction. While prevention of ductal cell injury decreases the severity of AP, no specific drug target has yet been identified in the ductal cells. Although Orai1, a store-operated Ca 2+ influx channel, is known to contribute to sustained Ca 2+ overload in acinar cells, details concerning its expression and function in ductal cells are currently lacking. In this study, we demonstrate that functionally active Orai1 channels reside predominantly in the apical plasma membrane of pancreatic ductal cells. Selective CM5480-mediated Orai1 inhibition impairs Stim1-dependent extracellular Ca 2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. Furthermore, prevention of sustained extracellular Ca 2+ influx protects ductal cell secretory function in vitro and decreases pancreatic ductal cell death. Finally, Orai1 inhibition partially restores and maintains proper exocrine pancreatic secretion in in vivo AP models. In conclusion, our results indicate that Orai1 inhibition prevents AP-related ductal cell function impairment and holds the potential of improving disease outcome. KEY POINTS: Sustained intracellular Ca 2+ overload in pancreatic acinar and ductal cells is a hallmark of biliary and alcohol-induced acute pancreatitis, which leads to impaired ductal ion and fluid secretion. Orai1 is a plasma membrane Ca 2+ channel that mediates extracellular Ca 2+ influx upon endoplasmic reticulum Ca 2+ depletion. Results showed that Orai1 is expressed on the luminal plasma membrane of the ductal cells and selective Orai1 inhibition impaired Stim1-dependent extracellular Ca 2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. The prevention of sustained extracellular Ca 2+ influx protected ductal cell secretory functions in in vitro models and maintained exocrine pancreatic secretion in in vivo acute pancreatitis models. Orai1 inhibition prevents the bile acid- and alcohol-induced damage of the pancreatic ductal secretion and holds the potential of improving the outcome of acute pancreatitis., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Introduction. The rate of graft failure after kidney transplantation is 7–10% in the first year and 3–5% in subsequent years. The indication and exact timing of graftectomy is a matter of debate in some cases, particularly in the case of asymptomatic grafts that are no longer functioning. Methods. Data of patients who underwent kidney transplantation at the Transplantation Unit, Department of Surgery, Szeged, Hungary between January 1, 2015 and December 31, 2020 were analyzed. We reviewed the indications, timing and complications of graftectomies and compared early and late graftectomies. Results. 294 kidney transplants were performed during the study period. 37 patients (13%) of them underwent graftectomy. The most common indications were bleeding 11 (30%), arterial circulatory disorders 8 (22%), v. renal thrombosis 7 (19%), mixed active antibody and ongoing cellular rejection 7 (19%), and acute humoral rejection 4 (10%). Graftectomies were performed in 26 cases with inoperative and in 11 cases with functional graft. Comparing early and late graftectomies, 15 cases (40%) underwent early graftectomy within 30 days after transplantation and 22 cases (60%) underwent late graftectomy. Conclusions. The most common cause of graftectomies in the study period was acute bleeding, which is also due to disturbed homeostasis in chronic renal failure. In the case of the early ones, emergency surgery and in the vast majority of late graftectomies, elective surgery was performed.

Introduction: Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible., Method: A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges., Result: The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96., Conclusion: Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Following kidney transplantation (KT), new-onset diabetes mellitus (NODM) is one of the most common complications. NODM usually occurs early after KT, and is diagnosed according to the general guidelines relevant for general diabetes mellitus patients. Arterial stiffness is a surrogate marker of cardiovascular risk. According to the literature, a successful KT has only limited and late beneficial effects on aortic elastic properties. The present study aimed to assess whether NODM has any additive value on the worsening of echocardiography-derived aortic elastic properties in transplanted patients., Methods: We have included 28 nondiabetic post-KT patients in the study, older than 18 years (mean age: 48.2 ± 6.9 years; 13 men, 15 women). After an oral glucose tolerance test, 8 patients were diagnosed with NODM, and their results were compared to 23 age-, sex-, and risk factor-matched controls (mean age: 54.9 ± 11.0 years; 9 men, 14 women). All post-KT patients and matched controls underwent a complete transthoracic 2-dimensional Doppler echocardiography, together with an assessment of echocardiographic aortic elastic properties. The assessments included aortic strain, aortic distensibility, and aortic stiffness index., Results: Aortic elastic properties showed alterations in post-KT patients compared to matched controls (aortic strain: .084 ± .039 vs .057 ± .032, P  <  .05; aortic distensibility: 2.36 ± 1.09 cm 2 /dynes 10 -6 vs 1.83 ± 1.18 cm 2 /dynes 10 -6 , P = .07; aortic stiffness index: 7.15 ± 3.58 vs 11.2 ± 6.1, P <  .05). Further deterioration in the aortic stiffness index (14.8 ± 7.6 vs 9.68 ± 4.88, P <  .05) was detected in the presence of NODM., Conclusions: NODM following successful KT facilitates aortic stiffening., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The first kidney transplantation was performed in Hungary by András Németh in 1962. It was a living donor procedure. After many years of silence, organized cadaveric programs were established in Budapest (1973), Szeged (1979), Debrecen (1991), and Pécs (1993). The heart program was initiated by Professor Zoltán Szabó in 1992 and the liver transplant program by Professor Ferenc Perner in 1993. The pancreas transplantation program was started in Pécs in 1998 by Károly Kalmár-Nagy, followed another in Budapest by Robert Langer in 2004. The lung transplant program was started in cooperation with Vienna in 1996. This fruitful collaboration continues today, even though that the national Hungarian program was established by Ferenc Rényi-Vámos and Professor György Lang in 2015, as it is detailed in this special issue. As a framework, the Hungarian Society of Organ Transplantation was founded in 1997 to give a scientific background for the transplant professionals. The coordination and organ allocation from deceased donors is carried out in collaboration with Eurotransplant. Usually more than 200 potential cadaveric donors are reported yearly, and 168 actual donation after brain death (DBD) donors (17.17 pmp) were utilized in 2018. The multiorgan donor rate was 65.5% among all DBDs in 2018; 505 organs were donated for transplant purposes. To date, more than 10,000 organ transplantations have been performed. The living related kidney transplant program was established in all transplant centers, led by Budapest. In this paper the authors summarize the activity of the Hungarian transplant community and of the Society over the last few decades., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular disease is the major cause of deaths after transplantation, with diabetes mellitus being the main risk factor in development., Aim: The aim of our study was to assess the prevalence of new onset diabetes mellitus in connection with the cardiovascular risk predicted by the HEART Score., Method: 44 patients were involved in our study; after overview of baseline data, OGTT was performed, followed by patient classification into the following groups: normal, impaired fasting glucose/impaired glucose tolerance, and new onset diabetes mellitus. Insulin resistance and kidney function were also assessed., Results: Concerning baseline data, cold ischemic time (p = 0.016), body weight (p = 0.035), BMI (p = 0.025), and HbA 1C (p = 0.0024) proved to be significantly different between normal and diabetic patients. Significant difference was found based on HOMA IR between the two groups 1.69±0.51 vs 6.46±1.42; p = 0.0017). Based on the HEART Score, patients with new onset diabetes mellitus were put into Group 3, which also reflects the risk which diabetes carries for the development of cardiovascular diseases., Conclusion: Cardiovascular risk can be decreased with increased allograft survival by early diagnosis and management of diabetes. Orv Hetil. 2017; 158(38): 1512-1516.

The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTC circ ). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTC circ value was 3 layers. In contrast, the strict threshold-adopted by the Banff 2013 classification-displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTC circ was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTC circ (2.6 layers vs 4.5 layers in moderate-to-severe TG; p < 0.0001). Amongst the various criteria, the permissive criterion was associated most frequently with mild TG, and had prognostic relevance. Because of this, we propose its usage as a marker of early cABMR-induced PTCBML if non-alloimmune causes of PTCBML can be ruled out.

Introduction: Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria., Aim: The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation., Method: Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys., Results: Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation., Conclusion: Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Little is known about the morphology and clinical relevance of arteritis in renal allograft biopsies with transplant glomerulopathy. We retrospectively reviewed the morphologic findings and clinical course of 59 patients with cg, 16 of which featured concurrent arteritis (fibrosing intimal arteritis with luminal narrowing in 15, and acute intimal arteritis in 1 case). Fifteen out of the 16 cases with arteritis fulfilled the morphological diagnostic criteria for chronic active antibody-mediated rejection, and 11 cases with arteritis showed morphological evidence of concurrent, ongoing T-cell-mediated alloimmune response (acute T-cell-mediated rejection in 5, borderline changes in 6 cases). Further, the Banff grades of interstitial inflammation in scarred and nonscarred cortex, total cortical inflammation, and arterial luminal narrowing were significantly higher in biopsies with arteritis. By immunohistochemistry, T-lymphocyte predominance over macrophages was found in the intimal infiltrates in 14 out of 16 cases, and cytotoxic T-lymphocytes were identified among intimal mononuclears in 10 cases. Patients with arteritis demonstrated a significantly shorter renal survival (7.5 vs. 29 months). In conclusion, T-cell-mediated mechanisms could play a role in the development of arteritis concurrent with cg. However, this finding does not exclude the possibility that antibody-mediated rejection can also contribute to the evolution of the lesion. Importantly, the lesion carries negative prognostic value likely via severe arterial luminal narrowing.

The aim of this study was to explore the role of body image, posttraumatic growth, and emotional state in recovery after transplantation. A total of 53 kidney transplant patients were assessed using our Self-Test and Organ Drawing Test, the Spielberger Anxiety Inventory, the Beck Depression Inventory, and the Posttraumatic Growth Inventory in a 3-year follow-up. Logistic regression analysis showed that lower levels of integrity of the body image and posttraumatic growth, and higher pre-discharge serum creatinine levels were significant predictors of graft rejection. Our results suggest that the integrity of the body image and posttraumatic growth might contribute to better health outcomes in organ transplantation., Competing Interests: Conflicts of Interest: None declared.

Introduction: New-onset diabetes is one of the most common complications after kidney transplantation., Aim: The aims of the authors were to examine the frequency of new-onset diabetes mellitus in kidney transplanted patients receiving cyclosporine A (n = 95) and tacrolimus (n = 102) and to analyze the occurrence of T-cell mediated rejection in these two groups of patients., Method: Age, laboratory results, renal function and histological findings were evaluated one year after kidney transplantation. Histological evaluation was performed according to the 2007 modification of the Banff 1997 classification., Results: New-onset diabetes developed in 12% of patients receiving cyclosporine A-based immunosuppression and in 24% of patients taking tacrolimus (p = 0.002). Uric acid level (p = 0.002) and the age of the recipient (p = 0.003) were significantly different in the new-onset diabetic and non-diabetic groups, while renal function showed no significant difference. Evaluation of tissue samples revealed a significant difference in T-cell mediated rejection between the new-onset diabetic and non-diabetic groups (13 vs. 8 patients; 37% vs. 6%; p = 0.001)., Conclusions: The results indicate an early development of the pathological effect of new-onset diabetes after kidney transplantation on the morphology of the renal allograft.

The first Hungarian kidney transplantation was performed by András Németh in Szeged in 1962, approximately 50 years ago. A preliminary agreement with Eurotransplant was signed in 2011, and special patient groups gained benefit from this cooperation in 2012, wnich lead to a full membership to Eurotransplant. This event inspired the authors to review the history of Hungarian kidney transplantation of the past 50 years, from the first operation to recent via the specific cornerstones of the transplant program. The donor of the first Hungarian kidney transplantation was the brother of the recipient. The operation itself was technically successful, but the lack of immunosuppression caused graft rejection, and the patient died after 79 days. His brother, the donor, is still healthy, after 50 years, and he encourages everybody to donate organs. Organized kidney transplant program started more than 10 years later, such as 1973, in Budapest. The program was supported by the Ministry of Health. New centers joined the program later, Szeged in 1979, Debrecen in 1991 and Pécs in 1993. These four transplant centers work currently in Hungary, and 6611 kidney transplantation has been performed up to the end of year 2012.

Unlabelled: Transplant patients' attitudes and representations related to their illness, their body, and the healing process have a significant impact on their recovery., Aims: The study involved 51 patients from the Department of Surgery, University of Szeged, Hungary. The primary aim was to examine the possible connections between emotional and mood factors, illness and body representations, and the successful onset of renal functions after surgery., Methods: Patients were tested with a combination of 4 instruments: Spielberger's anxiety scale and Beck depression scale, self and organ drawings, and a questionnaire designed by the authors., Results: Our data suggest that high distress correlates with kidney disfunction after transplantation. Patients with higher anxiety drew the kidney larger in their projective drawing test. It was a remarkable result that post-transplant blood test on Day 10 showed significantly lower creatinine and urea levels in those patients who had drawn the kidney smaller in their projective drawing test. This might indicate that the organ's normal intrapsychic integration and the related kidney functions are disturbed., Conclusions: The results of this study provide useful information about the psychological background, which has received relatively little attention so far. It can also give important clues for further research on clinical health psychology in supporting the healing process.

Background: Cyclosporin A, sirolimus, tacrolimus, and everolimus are immunosuppressive drugs used for therapy after organ transplantation. There are several analytical procedures for monitoring the drug level in blood, e.g. immunological methods and high-performance liquid chromatography combined with mass spectrometry (MS). From external quality assessment schemes, it became evident that the analytical results show high dispersion and further standardization is required., Methods: Liquid/liquid extraction of the drugs from whole blood samples was performed using ammonium acetate buffer, pH 9.5, and tert-butylmethyl ether/ethyl acetate (1:1 v/v). Separation of the immunosuppressive drugs was achieved by HPLC using a phenyl-hexyl-RP column with a ternary gradient elution profile, consisting of water, methanol, and acetonitrile containing 0.1% v/v formic acid and 0.1 mmol/L Cs+. Quantification of immunosuppressive drugs was performed by isotope-dilution mass spectrometry using [2H12]-Cyclosporin A [13C, 2H3]-Rapamycin, [13C, 2H2]-Tacrolimus, and [13C2, 2H4]-42-O-(2-Hydroxyethyl)rapamycin as internal standards., Results: The recovery of the new procedure was determined by analysis of spiked blood samples. The recovery in spiked EDTA whole blood samples was 100.8 - 102.5% for cyclosporin A, 101.6 - 103.0% for sirolimus, 100.0 - 101.2% for tacrolimus, and 99.5 - 102.4% for everolimus. The imprecision of the new measurement procedure, expressed as the coefficient of variation (CV), was 1.17 - 2.60% for cyclosporin A in the concentration range between 8.1 and 979 microg/L, 0.92 - 1.72% for sirolimus in the concentration range between 2.1 and 33.2 microg/L, 0.44 - 1.06% for tacrolimus in the concentration range between 2.0 and 30.8 microg/L and 0.82 - 4.34% for everolimus in the concentration range between 2.1 and 31.4 microg/L., Conclusions: An isotope dilution LC-MS/MS procedure for determination of four immunosuppressive drugs was developed to provide a basis for further development toward a reference measurement procedure.

Objectives: Authors present a case of successful surgical treatment of a ureter diverticulum observed 3 months after kidney transplantation., Methods: The fluid collection was detected by ultrasound. Percutaneous drainage was performed, after that the excretion of 4 litres of fluid was observed during 12 hours. This finding clearly indicated the connection with the urinary system. This fact was proved and precisely localised by contrast filling of the lesion under fluoroscopic control., Results: Resection of the ureter diverticulum was performed, and the patient recovered fully, there was no change observed in the graft function during the whole procedure., Conclusion: The ureter diverticulum is a rare complication after kidney transplantation: the present case is the only one observed among more then 600 kidney transplantations performed during 20 years in our centre.

Pancreatic necrosis associated with septic conditions is the leading cause of mortality in acute pancreatitis. Since 1986, 155 patients with infected pancreatic necrosis have been treated. The mean APACHE II score was 18.5 (range 11-32). In all cases, the infected pancreatic necrosis was combined with retroperitoneal abscesses. The surgical treatment was performed on average 18.5 days (range 8-25 days) after the onset of acute pancreatitis. The operative management consisted of wide-ranging necrosectomy in the total affected area, combined with widespread lavage and suction drainage. In 69 of the 155 cases (45%), some other surgical intervention (distal pancreatic resection, splenectomy, cholecystectomy, sphincteroplasty or colon resection) was also performed. Following surgery supportive therapy was applied in all patients, which also consisted orf immunonutrition (glutamine and arginine supplementation) and modification of cytokine production by petoxyfillin and dexamethasone from 1992. TNF and IL-6 serum levels were measured by ELISA and in vitro stimulation of leukocytes were induced by E. coli LPS. Following surgery, continuous lavage and suction drainage were applied for an average of 41.5 days (range 21-90 days), with an average of 9.5 (range 5-20) litres of saline per day. The bacteriologic findings revealed mainly enteral bacteria, but Candida infection was also frequently detected. The incidence of fungal infection was 20%. Thirty-two patients (21%) had to undergo reoperation. The cytokine production capacity (TNF and IL-6) was shown to correlate with the prognosis. As a consequence of pentoxifyllin and dexamethasone therapy, the TNF production generally dropped to the normal level. The overall hospital mortality was 6.4% (10 patients died). In our experience, infected pancreatic necrosis responds well to aggressive surgical treatment, continuous, long-standing lavage and suction drainage, together with supportive therapy consisting of immunonutrition and modification of cytokine production, combined with adequate antibiotic and antifungal medication.

Several complications can occur during both the early and late postoperative periods after kidney transplantation. The methods used to follow up 575 kidney transplanted patients, (transplantations performed between October 1979 and November 1997) in the early (within 6 weeks) and late postoperative periods have been assessed. The diagnostic value of core biopsies and ultrasound examinations, the prevalence of complications, and the applicability of the diagnostic tools in the evaluation of the graft status and viability were analyzed. In the early postoperative period, graft rupture occurred more frequently after biopsy than in the late period (7.4% vs 0.82%), this leading graft loss in 18 of 20 cases. The sonographically diagnosed morphologic and functional changes were also analyzed. Sonography proved a very accurate method for the detection of perirenal fluid collections and masses and severe vascular complications. The data demonstrated that biopsy is indicated in the early postoperative period when the result of sonography is doubtful. In the late postoperative period, biopsy should be performed in every case.

The authors present the case of a 47 year old male patient with acute necrotizing pancreatitis complicated with widespread mesenteric necrosis and abscess. The critically ill patient (APACHE score: 28.5) underwent on seven operations and required 50 days of intensive care. The authors analyse the conditions of successful treatment and emphasize the importance of new available therapeutic approaches and instruments.