Impossible Yet Possible-Orthotopic Liver Transplantation in a Patient With Complete Portal Vein Thrombosis: A Case Report and Literature Review.

This case study presents a liver transplantation (LT) in a patient with incidentally, intraoperatively detected complete portal vein thrombosis (PVT), classified as YERDEL stage 4, challenging traditional surgical boundaries. The patient's resilience and the innovative approach adopted by the surgical team exemplify the evolving complexities of LT in the context of advanced PVT. This report underscores the significance of detailed case documentation in medical literature, especially for complex transplant scenarios. It contributes to a broader understanding of surgical techniques and patient-centered approaches in LT. The narrative highlights the dynamic interplay between surgical advancements and vascular complications, advocating for the refinement of surgical methods and a reevaluation of conventional perspectives in transplantation. This case is pivotal in illustrating medical progress and the persistent pursuit of better outcomes in complex transplant situations.

Resection of Biliary Cystadenoma in a Pregnant Woman: A Case Report With Five Years of Follow-Up.

Biliary cystadenomas (BCAs), rare cystic tumors occurring in the biliary system, account for fewer than 5% of cystic lesions in the liver. This case details successful resection in a 29-year-old pregnant woman at seven weeks gestation. Urgent left hemihepatectomy and cholecystectomy removed a mucinous hepatobiliary cystadenoma. Postoperatively, a healthy newborn was delivered by cesarean section. Five-year follow-up showed no recurrence. BCAs present diagnostic challenges due to nonspecific symptoms, and surgical intervention, preferably complete resection, is recommended for potential malignancy, after weighing benefits against complications in critical hepatic vessel lesions.

Hepatic Hemangioma: Review of Imaging and Therapeutic Strategies.

Hepatic hemangiomas are the most common benign liver tumors. Typically, small- to medium-sized hemangiomas are asymptomatic and discovered incidentally through the widespread use of imaging techniques. Giant hemangiomas (>5 cm) have a higher risk of complications. A variety of imaging methods are used for diagnosis. Cavernous hemangioma is the most frequent type, but radiologists must be aware of other varieties. Conservative management is often adequate, but some cases necessitate targeted interventions. Although surgery was traditionally the main treatment, the evolution of minimally invasive procedures now often recommends transarterial chemoembolization as the treatment of choice.

Transarterial Bleomycin-Lipiodol Chemoembolization for the Treatment of Giant Hepatic Hemangiomas: An Assessment of Effectiveness.

This study evaluates the effectiveness of superselective transcatheter arterial chemoembolization (TACE) using a bleomycin-lipiodol emulsion in treating giant hepatic hemangiomas. A retrospective review included 31 patients with a mean age of 53 ± 10.42 years who underwent TACE from December 2014 to October 2022, with follow-up imaging examinations to assess outcomes. Technical success was defined as successful embolization of all feeding arteries, and clinical success was defined as a reduction in hemangioma volume by 50% or more on follow-up imaging. This study observed a 100% technical success rate. Post-embolization syndrome was common, and two cases of asymptomatic hepatic artery dissection were noted. Clinical success was achieved in 80.6% of patients, with significant volume reduction observed in the majority. Conclusively, superselective transcatheter arterial chemoembolization with bleomycin-lipiodol emulsions is presented as a viable and effective treatment option for giant hepatic hemangiomas. With no procedure-related mortality and significant volume reduction in most cases, this method offers a promising alternative to surgical intervention. This study's findings suggest a need for further exploration and validation in larger-scale prospective studies.

Safety and Feasibility of Transarterial Bleomycin-Lipiodol Embolization in Patients with Giant Hepatic Hemangiomas.

Giant hepatic hemangiomas present a significant clinical challenge, and effective treatment options are warranted. This study aimed to assess the safety and feasibility of transarterial bleomycin-lipiodol embolization in patients with giant hepatic hemangiomas. A retrospective analysis was conducted on patients with giant hepatic hemangiomas (>5 cm). Transarterial chemoembolization (TACE) was performed using 7-20 cc of lipiodol mixed with 1500 IU of bleomycin. Safety outcomes, including post-embolization syndrome (PES), hepatic artery dissection, systemic complications, and access site complications, were evaluated. Radiation doses were also measured. Feasibility was assessed based on the achieved hemangioma coverage. Seventy-three patients (49 female, 24 male) with a mean age of 55.52 years were treated between December 2014 and April 2023. The average hospitalization duration was 3.82 days, and 97.3% of lesions were limited to one liver lobe. The average bleomycin dose per procedure was 1301.5625 IU, while the average lipiodol dose was 11.04 cc. The average radiation dose was 0.56 Gy. PES occurred after 45.7% of TACE procedures, with varying severity. Complications such as hepatic artery dissection (three cases), access site complications (two cases), and other complications (one case) were observed. No treatment-related mortality occurred. Hemangioma coverage exceeding 75% was achieved in 77.5% of cases. The study results suggest that transarterial bleomycin-lipiodol embolization is a safe and feasible treatment option for a heterogeneous group of patients with giant hepatic hemangiomas. This approach may hold promise in improving outcomes for patients with this challenging condition.

Comparison of Perfusion Pressure in Aorta Using High-Pressure Perfusion and Gravity Perfusion During the Kidney Transplant Procedure.

Organ perfusion is an element of organ donation aimed at cooling the organ, washing out morphotic elements, and creating favorable conditions for the storage and transport of organs. Depending on the method used, perfusion is performed under gravity perfusion (GP) or perfusion under high pressure (HPP). This study aimed to measure the pressure of the perfusion fluid in the abdominal aorta during the use of GP and HPP. The study was performed during 35 organ procurements from deceased donors. The direct proportional increase of pressure in the aorta, depending on the applied perfusion method, was observed. GP was on average 37.8 mm Hg; using a pressure of 50 mm Hg in the HPP, an average of 57 mm Hg was obtained, and using a pressure of 200 mm Hg, 99.4 mm Hg was obtained. The study found that during the application of GP, the pressure generated in the abdominal aorta is low, which may lead to inadequate perfusion of organs. HPP is a faster method that leads to a proper perfusion of the procured organs and is also a safe method because, despite the use of high pressure, no damage to the transplanted kidneys was observed.

Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) constitute a promising tool in regenerative medicine and can be isolated from different human tissues. However, their biological properties are still not fully characterized. Whereas MSCs from different tissue exhibit many common characteristics, their biological activity and some markers are different and depend on their tissue of origin. Understanding the factors that underlie MSC biology should constitute important points for consideration for researchers interested in clinical MSC application. AIM: To characterize the biological activity of MSCs during longterm culture isolated from: bone marrow (BM-MSCs), adipose tissue (AT-MSCs), skeletal muscles (SM-MSCs), and skin (SK-MSCs). METHODS: MSCs were isolated from the tissues, cultured for 10 passages, and assessed for: phenotype with immunofluorescence and flow cytometry, multipotency with differentiation capacity for osteo-, chondro-, and adipogenesis, stemness markers with qPCR for mRNA for Sox2 and Oct4, and genetic stability for p53 and c-Myc; 27 bioactive factors were screened using the multiplex ELISA array, and spontaneous fusion involving a co-culture of SM-MSCs with BM-MSCs or AT-MSCs stained with PKH26 (red) or PKH67 (green) was performed. RESULTS: All MSCs showed the basic MSC phenotype; however, their expression decreased during the follow-up period, as confirmed by fluorescence intensity. The examined MSCs express CD146 marker associated with proangiogenic properties; however their expression decreased in AT-MSCs and SM-MSCs, but was maintained in BM-MSCs. In contrast, in SK-MSCs CD146 expression increased in late passages. All MSCs, except BM-MSCs, expressed PW1, a marker associated with differentiation capacity and apoptosis. BM-MSCs and AT-MSCs expressed stemness markers Sox2 and Oct4 in long-term culture. All MSCs showed a stable p53 and c-Myc expression. BM-MSCs and AT-MSCs maintained their differentiation capacity during the follow-up period. In contrast, SK-MSCs and SM-MSCs had a limited ability to differentiate into adipocytes. BM-MSCs and AT-MSCs revealed similarities in phenotype maintenance, capacity for multilineage differentiation, and secretion of bioactive factors. Because AT-MSCs fused with SM-MSCs as effectively as BM-MSCs, AT-MSCs may constitute an alternative source for BM-MSCs. CONCLUSION: Long-term culture affects the biological activity of MSCs obtained from various tissues. The source of MSCs and number of passages are important considerations in regenerative medicine.

Assessment of immunologic, proangiogenic and neurogenic properties of human peripheral nerve epineurium for potential clinical application.

The epineural sheath is a promising naturally occurring material for enhancement of peripheral nerve regeneration. Based on a literature search there is a limited number of reports on the biological and immunological properties of human epineurium. The goal of this study was to assess, using immunocytochemical methods, the immunological (HLA class I and II antigens, T lymphocytes, macrophages), proangiogenic (VEGF, CD31), and neurogenic (GFAP, S-100) properties of human epineurium isolated from ilioinguinal nerves (n=19) taken from deceased donors, and from sciatic nerves (n=12) taken from limbs amputated due to critical ischemia. Our studies confirmed reduced expression of HLA class II antigens on the infiltrating cells, a reduced number of T lymphocytes, and greater vessel density in the epineurium obtained from deceased organ donors. Macrophages were more abundant in the epineurium isolated from the amputated limbs. We found that the epineurium harvested from peripheral nerves of the deceased donors showed negligible immunogenic and increased proangiogenic properties compared to the epineurium of nerves taken from amputated limbs. These findings support the rationale to use human epineurium obtained from deceased donors as a new biological material for enhancement of peripheral nerve repair for potential clinical application in regenerative medicine.

Incidental gallbladder cancer after cholecystectomy: 1990 to 2014.

INTRODUCTION: Cancer of the gallbladder is a serious diagnostic and therapeutic problem. According to the literature, 30% of cases are not confirmed before surgery. Other cases are detected incidentally by histopathology. Clinical trials and meta-analyses show that incidental gallbladder cancer (iGBC) occurs in 0.19%-2.8% of patients after cholecystectomy. The aim of this study was to analyze the incidence and severity of iGBC in cholecystectomy procedures performed in the surgical department at the 4th Military Teaching Hospital in Wroclaw during the years 1990-2014. PATIENTS AND METHODS: In the years 1990-2014, a total of 7,314 cholecystectomies were performed in the surgical department because of cholecystolithiasis: 6,145 were performed using the laparoscopic approach (84.02%), 867 were performed as open surgery (11.8%), and 302 cases required conversion (5.1%). In this group, 5,214 of the patients were females (71.3%) and 2,100 were males (28.7%), with an average age of 54.7 years. RESULTS: We found 64 iGBC cases which were confirmed by histopathology. This represented 0.87% of all cases. In this group, 50 patients were females (78.1%) and 14 were males (21.8%), with an average age of 67.1 years. Of this group, 40 patients underwent a classic cholecystectomy, while 24 underwent laparoscopic procedures, out of which 13 cases ultimately required traditional surgery. The histopathology showed 15 carcinomas that were classified as G1 (23.4%), 28 were G2 (43.75%), and 21 were G3 (32.8%). CONCLUSION: iGBC detected after a cholecystectomy due to cholecystolithiasis is a rare disease. We found iGBC in 0.87% of cases, which is on a comparable scale to the world literature. In the case of cancer, we frequently found it necessary to convert to an open surgical procedure. This cancer is more common in females and in people over 60 years of age.

Transplantology: Challenges for Today.

Clinical transplantology in Poland had its 50th anniversary this year. With the early and long results comparable to the best achieved in the world leading centers, we face old and completely new challenges for this medical speciality. Main and growing challenge is insufficient number of available organs. With less than 15 donors/mln population/year Poland stay in the lower row of European countries in this measurement of transplant activity. Donation system is not efficient enough and we lose a big number of potential donors still. Living donation (with the exception for the fragments of the liver) remains low despite of different initiatives made so far on the national and local levels. Donation after cardiac death is possible from the point of Polish juridical regulations, but since last 3 years had not showed real impact on country donation rates (only three procedures done). Methods of tissue typing remain slow and cause relatively long times of cold ischemia for kidney programs. Second main challenge is chronic rejection causing loss of organs in the long-term follow-up and no efficient treatment employed. The emerging possibility of tolerance induction despite of plenty of new protocols proposition in the publications does not show up a clinical everyday practice in work. The same is with xenotransplantation promises; even we were informed recently that till 2030 such genetically modified porcine organs will be available. The next challenge is production of organs and tissues from own recipients cells installed on the different scaffolds or 3D printed. Other challenge is the personnel working in this field. We observe like in the other European countries lack of new candidates for work in this field together with serious problems of nursing staff, being a catastrophic perspective in country medical service in general, not only in transplant centers. The last but not least challenge is financial side of transplant programs.

Adrenal cortical carcinoma with extension into the inferior vena cava--case report and literature review.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an incidence rate of 1 to 2 per million person-years. ACC most commonly arises sporadically, but may be associated with familial tumour syndromes. Clinical symptoms are mainly related to an excess of steroid hormones. We present an unusual case of adrenocortical carcinoma in a 27-year-old male who complained of non specific mass-effect related symptoms of slowly growing intensity differing from others described in literature because of the patient's age and the sudden deterioration of the clinical course. The tumour was resected with the left kidney with an extension into the inferior vena cava. Histological examination revealed morphological features characteristic of an adrenal cortical tumour. The immunohistochemical results (positive reactions for vimentin, CD56, inhibin, melan A, synaptophysin, bcl-2, calretinin) confirmed the diagnosis. According to the most widely used modified Weiss criteria and the Van Slooten system, a diagnosis of adrenal cortical carcinoma was strongly confirmed. The postoperative condition was poor. Reoperation was conducted, including abdominal aorta thrombectomy and aortic prosthesis implantation. The patient died two days after the second operation. Autopsy revealed a metastatic tumour in the left lung and morphological symptoms of acute circulatory collapse due to a massive haemorrhage into the abdominal cavity, which was the direct cause of death. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1602226377106882.

Nogo-B expression, in arterial intima, is impeded in the early stages of atherosclerosis in humans.

Nogo-B (Reticulon 4B) is considered to be a novel vascular marker, which may have a protective role in injury-induced neointima formation and atherosclerosis. Nogo A/B is found to be crucial for monocyte/macrophage recruitment in acute inflammation and it is expressed in CD68 + macrophages. We hypothesize that macrophage infiltration in atherosclerosis is not dependent on Nogo-B expression in arterial wall. We have assessed Nogo-B expression and macrophage accumulation in the iliac arteries of healthy organ donors and organ donors with cardiovascular risk factors. Paraffin sections of 66 iliac arteries, from 44 deceased organ donors (17 women and 27 men), were studied. The healthy and cardiovascular risk (CVR) subgroups were created. With regard to staging of the atherosclerotic process, the thickness of arterial intima was measured in digitalized images of H+E stained tissue sections. Immunohistochemical reactions (Nogo-B and CD68) were carried out in all arteries (66 samples). Western blotting (WB-19 samples) and real-time PCR (27 samples) were performed on selected arteries. Significantly higher Nogo-B expression was demonstrated in the intima of the healthy subjects' subgroup, using immunohistochemistry. WB and real-time PCR revealed a trend toward lower Nogo-B expression in the adventitia of the CVR subgroup. Furthermore, the thickness of the intima was found to negatively correlate with the expression of Nogo-B in the intima and media (r = -0.32; p < 0.05; r = -0.32; p < 0.05). Macrophage infiltrates were more prominent in intima of CVR subjects (0.65 vs 3.52 a.u.; p < 0.01). Macrophage density in intima increased with atherosclerosis progression (r = 0.37; p < 0.01). CD68 macrophages density in adventitia was lower in CVR arteries than in healthy arteries. The expression of Nogo-B, in arterial intima, is impeded in the early stages of atherosclerosis. Accumulation of arterial intimal CD68 macrophages has been shown to progress; however, the overall macrophage density in the adventitia is reduced in arteries shown to have intimal thickening. Macrophage infiltration is not accompanied by Nogo-B expression in atherosclerotic arteries.

Successful embolization of the peripheral branches of the superior mesenteric artery performed because of tuberculosis-associated acute bleeding in a patient after a renal transplant.

We report a renal transplant recipient infected with Mycobacterium tuberculosis who presented with severe intestinal bleeding. The bleeding was the result of an injured vessel of mesenteric artery distal branches diagnosed by traditional arteriography and computed tomography angiography. As the patient's condition was serious, the only considered rescue therapy was endovascular treatment. The endovascular procedure was successful because the bleeding stopped. Embolization of a small intestinal artery may be a successful rescue treatment of intestinal bleeding in a patient after renal transplant.

Malignancy after renal transplantation in the new era of immunosuppression.

BACKGROUND: This retrospective single-center study was undertaken to assess the occurrence of de novo neoplasms in renal transplant recipients according to the immunosuppressive regimen and time after transplantation. MATERIAL/METHODS: Observation encompassed 1028 patients transplanted between the years 1983-2006 and followed for 0.5-23 years. Patients with skin cancer other than melanoma were excluded due to incomplete data collection. RESULTS: Malignancy appeared in 4.8% (49) of the patients after the period of 5.8 ± 4.7 years at the age of 54 ± 13 years. The most common malignancies were urinary tract tumors (22%) and non-Hodgkin lymphoma with post-transplant lymphoproliferative disease (PTLD) (16%). Malignancy occurred in 5.2% of patients on cyclosporine (CSA), azathioprine (AZA) and prednisone (P); in 3.4% of patients on mofetil mycophenolate (MMF) with CSA and P; in 3.3% of patients on MMF with tacrolimus (TAC) and P; and in 2 of 20 patients (10%) receiving AZA with P 15 years after transplantation. The regimen consisting of CSA, AZA with P could be distinguished by the higher risk of malignancy occurrence. The occurrence of malignancy was significantly earlier on MMF+TAC+P compared to other regimens (p<0.05). The highest incidence of malignancy on AZA with P could be attributed to the longer observation period. CONCLUSIONS: In the new era of immunosuppression, despite lower occurrence, malignancy tends to appear earlier after the transplantation.

The increased risk of post-transplant diabetes mellitus in peritoneal dialysis-treated kidney allograft recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication in kidney allograft recipients, significantly contributing to the elevated cardiovascular morbidity after renal transplantation and increased risk of chronic transplant dysfunction. The aim of the present investigation was to evaluate the factors influencing PTDM development. Under particular consideration were the elements, existing before the transplantation, especially the modality of dialysis treatment significance, i.e. haemodialysis (HD) versus peritoneal dialysis (PD). METHODS: Three hundred and seventy-seven consecutive outpatients who underwent renal transplantation (RTx) in our institution between January 2003 and December 2005 were analysed. PTDM was diagnosed according to the current American Diabetic Association/World Health Organization criteria. Statistical inference was conducted by means of univariate methods (one factor versus PTDM) and multivariate methods in frames of generalized linear model. RESULTS: In the study group, 72 patients (23.4%) developed PTDM after RTx (55 HD and 17 PD patients). PTDM incidence at 3, 6 and 12 months was 15.9%, 22.1% and 23.4%, respectively. The mean interval from transplantation to the onset of PTDM was 3.08 ± 2.73 months. In univariate analysis, the factors associated with the elevated risk of PTDM appearance were older recipient age, positive family history of diabetes, hypertensive nephropathy as end-stage renal disease cause, higher body mass index at transplantation, treatment by PD, and the graft from an older donor. In multivariate verification, statistical significance remained: older recipient age (P < 0.001), positive family history of diabetes (P = 0.002), and treatment by PD (P = 0.007). CONCLUSIONS: Treatment by PD appears to be a possible novel factor, not yet reported, which may increase the risk of PTDM development.

First Polish forearm transplantation - final report (outcome after 4 years).

BACKGROUND: Hand transplantation (HTx) presents an exceptional reconstructive solution for hand amputees. Relatively few patients qualify for such an operation - generally healthy patients suffering from a serious disturbance of body integrity. CASE REPORT: We present a patient 48 months after unilateral transplantation of an allogenic forearm. Clinical course, laboratory results, function of the graft, and quality of life of the patient are analyzed. These findings are compared with those achieved by 2 other patients - recipients of allograft forearm transplanted on the same zone in Lyon 2002, and Louisville 2001. The patient suffered no post-transplantation infections, had 1 episode of rejection - I degrees . Except for mild diabetes, no disturbances of internal organs were observed. Total active motions of fingers (TAM) equaled 53% of fingers of unaffected hand. The functional evaluation by SF 36 is 53; by DASH - 92; Chen's score system rates our patient as II (good); CFSS score system - 84 points (excellent result). His functional result is similar to that achieved by 2 others mid-forearm recipients. CONCLUSIONS: The upper limb transplant performed on a functionally unfavorable zone of the mid-forearm has greatly increased patient's quality of life.

The influence of CTLA-4 gene polymorphism on long-term kidney allograft function in Caucasian recipients.

The aim of the study was to examine whether CTLA-4 (CD152) and CD28 gene polymorphisms affect the outcome of kidney transplantation (KTx). Polymorphisms of the CTLA-4 gene (-318 C>T, +49 A>G, and the microsatellite polymorphism in the 3'UTR of exon 4 (AT)(n)) and a CD28 gene (IVS3 +17T>C) were investigated in 314 allograft recipients with a mean age of 41.9+/-12 years. The median time since KTx was 97.5 months. The genotypes of the SNPs were determined by SSP-PCR and (AT)(n) genotype by PCR and capillary electrophoresis (ABI Prism 310). In general, no relationship was found between the allele variants and acute rejection or graft function. Univariate and multivariate analyses showed no influence of CTLA-4 or CD28 polymorphism on graft/patient survival. In the individuals bearing the combination of the homozygous variant of low AT repeat number (82 bp) and the homozygous variant A (adenine) in CTLA-4 +49 A>G, higher eGFR was observed at one year after KTx, which was also maintained at 10 years. In summary, 24.2% of the studied patients carrying the "favorable" CTLA-4 genotype exhibited significantly higher allograft function than the 16.9% recipients with the "unfavorable" genotype up to 10 years post transplantation.

Plasma and urine leukocyte elastase-alpha1protease inhibitor complex as a marker of early and long-term kidney graft function.

BACKGROUND: Neutrophils are mediators of ischaemia/reperfusion (I/R) injury following kidney transplantation (kTx). Leukocyte elastase (LE) complex with alpha(1)protease inhibitor (LE-alpha(1)PI) is a marker of neutrophil degranulation. The aim of this study was to evaluate LE-alpha(1)PI as a marker of I/R kidney damage and to search for correlations between leukocyte activation and post-transplant complications. METHODS: Plasma and urine LE-alpha(1)PI were estimated in 55 deceased-donor kidney graft recipients on postoperative days (POD) 1, 3 and 7, as well as in the late post-transplant period. RESULTS: The plasma LE-alpha(1)PI level peaked on POD 1 after kTx, and the urine LE-alpha(1)PI peaked on POD 3. On POD 1 and POD 3, the urine LE-alpha(1)PI levels were higher in delayed graft function (DGF) patients than in patients with immediate graft function (IGF: P < 0.001 and P < 0.003, respectively). Urine LE-alpha(1)PI excretion on POD 1 was significantly higher in patients with longer cold ischaemia time (CIT) than in patients with shorter CIT, P < 0.002. Multivariate regression model revealed two factors influencing the occurrence of early acute rejection-urine LE-alpha(1)PI complex on POD 3 and human leukocyte antigen (HLA) mismatches. There was a significant association between the plasma LE-alpha(1)PI on POD 3 and serum creatinine level 6 and 12 months after kTx (r(2) 0.24; P < 0.005 and 0.19; P < 0.005, respectively). CONCLUSIONS: This study is the first presentation of a simple, non-invasive measurement of neutrophil activation after kTx. It also demonstrates a strong correlation between the early post-transplant LE-alpha(1)PI complex level and kidney graft function.

Benzylpenicillin, acetylcysteine and silibinin as antidotes in human hepatocytes intoxicated with alpha-amanitin.

Fatalities due to mushroom poisonings are increasing worldwide, with high mortality rate resulting from ingestion of amanitin-producing species. Intoxications caused by amanitin-containing mushrooms represent an unresolved problem in clinical toxicology since no specific and fully efficient antidote is available. The objective of this study was a comparative evaluation of benzylpenicillin (BPCN), acetylcysteine (ACC) and silibinin (SIL) as an antidotes in human hepatocytes intoxicated with alpha-amanitin (alpha-AMA). All experiments were performed on cultured human hepatocytes. Cytotoxicity evaluation of cultured cells using MTT assay and measurement of lactate dehydrogenase (LDH) activity was performed at 12, 24 and 48h of exposure to alpha-AMA and/or antidotes. The significant decline of cell viability and significant increase of LDH activity were observed in all experimental hepatocyte cultures after 12, 24 and 36h exposure to alpha-AMA at concentration 2microM. Exposure of the cells to alpha-AMA resulted also in significant reduction of cell spreading and attachment. However, addition of tested antidotes to experimental cultures significantly stimulated cell proliferation and attachment. In cell cultures exposed simultaneously to alpha-AMA and tested antidotes cytotoxic parameters (MTT and LDH) were not significantly different from control incidences. The cytoprotective effect of all antidotes was not dose-related, which reflects a high efficacy of all these substances. Administration of studied antidotes was not associated with any adverse effects in hepatocytes. The administration of ACC, BPCN or SIL to human hepatocyte cultures showed a similar strong protective effect against cell damage in alpha-AMA toxicity.

Impact of sirolimus treatment in kidney allograft recipients with prolonged cold ischemia times: 5-year outcomes.

OBJECTIVES: Sirolimus, an effective and non-nephrotoxic immunosuppressant, may have an antiproliferative effect on renal tubular cells and increase their apoptosis, thus hindering the recovery of an injured kidney. The aim of this study was to evaluate the impact of combined sirolimus and cyclosporine therapy on the incidence and duration of delayed graft function and long-term graft function. MATERIALS AND METHODS: The study group consisted of 23 renal transplant recipients treated with a sirolimus-cyclosporine-prednisone regimen (sirolimus group). The reference group was composed of 23 patients treated with azathioprine-cyclosporine-prednisone. Because of a long cold ischemia time, all the patients were at high risk of developing delayed graft function. RESULTS: There was an equal frequency of delayed graft function in the sirolimus group compared with the reference group (39% vs 34.8%). The duration of delayed graft function was longer in sirolimus group compared with the reference group (21.2 +/- 12.2 days vs 6.8 +/- 2.5 days) (P < .004). The serum creatinine level at the 12th month was higher in patients with delayed graft function than it was in the remaining patients, independent of the immunosuppression protocol. One and 5-year graft survival rates were 100% and 87% in the sirolimus group, and 95% and 74% in the reference group. The 5-year patient survival rate was 100% in both groups. CONCLUSIONS: Sirolimus significantly retards the recovery from posttransplant renal failure, but it does not increase the incidence of delayed graft function. Sirolimus therapy should be initiated after recovery from posttransplant renal failure. Sirolimus treatment is beneficial for long-term graft survival.