Enhancement of Sphingomyelinase-Induced Endothelial Nitric Oxide Synthase-Mediated Vasorelaxation in a Murine Model of Type 2 Diabetes.

Sphingolipids are important biological mediators both in health and disease. We investigated the vascular effects of enhanced sphingomyelinase (SMase) activity in a mouse model of type 2 diabetes mellitus (T2DM) to gain an understanding of the signaling pathways involved. Myography was used to measure changes in the tone of the thoracic aorta after administration of 0.2 U/mL neutral SMase in the presence or absence of the thromboxane prostanoid (TP) receptor antagonist SQ 29,548 and the nitric oxide synthase (NOS) inhibitor L-NAME. In precontracted aortic segments of non-diabetic mice, SMase induced transient contraction and subsequent weak relaxation, whereas vessels of diabetic (Leprdb/Leprdb, referred to as db/db) mice showed marked relaxation. In the presence of the TP receptor antagonist, SMase induced enhanced relaxation in both groups, which was 3-fold stronger in the vessels of db/db mice as compared to controls and could not be abolished by ceramidase or sphingosine-kinase inhibitors. Co-administration of the NOS inhibitor L-NAME abolished vasorelaxation in both groups. Our results indicate dual vasoactive effects of SMase: TP-mediated vasoconstriction and NO-mediated vasorelaxation. Surprisingly, in spite of the general endothelial dysfunction in T2DM, the endothelial NOS-mediated vasorelaxant effect of SMase was markedly enhanced.

Our initial experiences with mpMRI-ultrasound fusion-guided prostate biopsy / Kezdeti tapasztalataink az mpMR fúziós ultrahangvezérelt prosztatabiopsziával

Introduction: The past decade has seen some major changes in the diagnostics of prostate cancer. Progress in MR imaging has allowed us to better visualise prostate cancer and thus perform targeted biopsies of tumour suspect lesions. mpMRI-ultrasound fusion-guided prostate biopsy is a precise and cost-effective method to diagnose prostate cancer. Objective: The purpose of this study was to summarise our results in mpMRI-ultrasound fusion biopsy between 2017 and 2019 and compare them with the findings in the current literature. Method: Between 2017 and 2019, fully 40, mpMRI-ultrasound fusion biopsies were performed transperineally using the BioJet fusion system at Semmelweis University Urology Clinic. The MRI evaluations were done in line with the PI-RADS v2 guidelines. It was analysed whether the PI-RADS score, the location of the tumour, lesion size, the signs of extraprostatic extension, PSA/PSAD density and prostate volume have an influence on the outcome of mpMRI-ultrasound fusion biopsy. Results: Prostate cancer was diagnosed in 80% of the cases during targeted biopsies. The detection rate was 91%, 85%, and 20% for PI-RADS 5, 4 and 3 lesions, respectively. The detection rate was significantly higher for lesions located at the peripheral zone compared to the ones in the transitional zone (khi2(1) = 6.555, p = 0.010, Fisher-exact p = 0.017, V = 0.355). Signs of extraprostatic extension and higher PSAD correlated with better detection rate (khi2(1)= 7.704, p = 0.006, Fisher-exact p = 0.004, V = 0.355; and 0.47 ± 0.50 ng/ml2 vs. 0.18 ± 0.17 ng/ml2; Z = 3.447, p<0.001, respectively). The size of the lesions did not influence the outcome. The analysis showed a significant correlation between large prostate volumes and negative biopsies (50.9 ± 18.8 ml vs. 119.6 ± 91.6 ml; Z= ­3.505, p<0.001). Conclusions: The detection rate of prostate cancer with targeted biopsies was higher than the data found in the international literature. The PI-RADS score, the location of the tumour, MRI signs of extraprostatic extension, PSAD and prostate volume had an influence on the detection rate. Our findings may promote a better selection of the best candidates for targeted biopsies in the future.

Oncological Screening of Kidney Transplant Patients: The Role of Ultrasound Examination.

INTRODUCTION: Immunosuppressive therapy used after organ transplantation represents a considerable oncological risk. Abdominal ultrasound examinations play an essential role in the oncological screening of organ transplant patients. Our aim was to study the effectiveness of the ultrasound screening protocol currently used in our clinic. METHODS: Reports of screening abdominal ultrasound examinations of kidney transplant recipients were processed at the Department of Transplantation and Surgery of Semmelweis University from January 2012 to December 2015. RESULTS: In 1478 studies, 14 patients were diagnosed with a malignant tumor, 11 of which were formed in the native shrunken kidney. The mean age for tumor diagnosis was 55.6 ± 12.6 years, and 80% of the patients diagnosed with tumor were male. On average, 7.5 ± 4.6 years passed between the transplantation and recognition of the tumor. All of the kidney tumors were diagnosed at an early stage: histologic examination of removed kidneys showed 73% pT1a- and 17% pT1b-stage tumors. CONCLUSION: In our study, early stage shrunken kidney cancers were outstandingly the most common post-transplant malignancies found by ultrasound screening. Annual ultrasound examinations as part of our current screening protocol allowed the detection of tumors at an early stage in kidney transplant recipients.

Liver Transplant for Metastatic Neuroendocrine Tumors: A Single-Center Experience in Hungary.

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher. METHODS: We performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months. RESULTS: Ten liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence. CONCLUSION: Patient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.

Diagnosis and Management of a De Novo Urothelial Carcinoma in a Kidney Allograft: A Case Report.

INTRODUCTION: Following renal transplantation, the incidence of malignancies is 3-5 times higher than that of healthy individuals. Among other type of cancers, the risk of urological tumors is also elevated. However, only a few cases of de novo transitional cell carcinomas occurring in renal allografts have been reported. CASE REPORT: A 63-year-old tertiary transplanted male patient was urgently hospitalized for a painless macroscopic hematuria. Ultrasonography revealed pyelectasis and a hematoma in the renal pelvis. A percutaneous nephrostomy tube was inserted. An anterograde pyelography was performed later, where a filling defect was still observable in the location of the previously reported hypoechoic mass. Contrast-enhanced ultrasonography showed enhancement of the lesion. An ultrasound-guided percutaneous biopsy was performed. The histologic evaluation revealed a high-grade transitional cell carcinoma. A whole-body staging computed tomography scan did not show signs of metastatic disease. The renal allograft was surgically removed. No disease progression was observed during the 21-month follow-up period. CONCLUSIONS: Painless hematuria and asymptomatic hydronephrosis occurring after kidney transplantation should raise the possibility of urothelial carcinoma in the kidney graft. Contrast-enhanced ultrasound should be considered as a first-line diagnostic modality because it is easily accessible and does not raise concerns about nephrotoxicity or radiation burden.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

[Thermoablation therapy in the treatment of benign lesions]. / Thermoablatiós lehetoségek a benignus térfoglaló képletek gyógyításában.

INTRODUCTION: Depending on their size and location, some benign tumors can cause prolonged discomfort and even rupture and fatal bleeding in severe cases. Hitherto the therapeutic strategies for such lesions were observation, surgery and in selected cases transarterial embolization. AIM: Our aim was to present the possibilities of thermoablation for treating lesions. METHOD: Here we present interventions of four patients in Semmelweis University Department of Transplantation and Surgery. A thyroid adenoma and a kidney angiomyolipoma were treated with radiofrequency ablation. Two patients with a liver haemangioma were treated with microwave thermoablation technique. RESULTS: Complications were not observed in any of the cases. In most cases, the size of the treated lesions decreased. The mean decrease in volume was 32.7%. The contrast enhancement of the lesions also decreased, the mean reduction in contrast enhancing volume was 75.3%. CONCLUSIONS: Thermoablational procedures for the benign tumors presented above are safe. The therapy shows excellent cosmetic results, a shorter hospital stay and quicker recovery. Orv. Hetil., 2016, 157(51), 2040-2047.

Confined compression experiments on bovine nucleus pulposus and annulus fibrosus: sensitivity of the experiment in the determination of compressive modulus and hydraulic permeability.

The biphasic material properties for nucleus pulposus tissue in confined compression have not been reported previously, and are required for a better understanding of intervertebral disc function and to provide material properties for use in finite-element models. The aims of this study were to determine linear and non-linear material properties for nucleus pulposus and annulus fibrosus tissues in confined compression, to define the influence of swelling conditions on these properties, and to determine the changes in the compressive modulus and hydraulic permeability induced by the repetition of the stress-relaxation experiment after a return to swelling pressure equilibrium. Specimens from caudal bovine nucleus and annulus were tested in confined compression stress-relaxation experiments and analyzed to quantify the compressive modulus and hydraulic permeability using linear and non-linear biphasic models. Our results suggested the use of confined swelling pre-test condition and non-linear biphasic model, which provided the material parameters with lowest relative variance and water content most representative of physiological conditions. Smaller compressive modulus and higher hydraulic permeability were obtained for the nucleus (H(A0)=0.31+/-0.04 MPa, k(0)=0.67+/-0.09 x 10(-15)m(4)/Ns) than for the annulus (H(A0)=0.74+/-0.13 MPa, k(0)=0.23+/-0.19 x 10(-15)m(4)/Ns), with relatively weak non-linearities. Strains up to 20% resulted in material properties that were significantly altered upon retesting. These altered material properties are an effort to quantify non-recoverable damage that occurs in disc tissue and suggest that in vivo exposure of disc tissues to low strain-rate and high-deformation loading conditions which outpace biological repair may result in altered mechanical behaviors.