Optimizing Survival for Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Report and Current Perspectives.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options. METHODS: We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed. RESULTS: A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

Graft Arterial Dissection and Thrombosis After Kidney Transplantation With Undiagnosed Fibromuscular Dysplasia From a Deceased Donor: Case Report and Review.

BACKGROUND: Fibromuscular dysplasia (FMD), a relatively frequent arterial deformity with an estimated prevalence of 2% to 6% has been sporadically reported during deceased donor kidney donations. Only 8 case reports are available in the previous literature. CASE PRESENTATION: In our work, implantation of 2 kidneys from the same deceased donor with macroscopically evident and later histologically confirmed FMD are presented, one of which ended up as acute arterial complication. Renal arteries were cut short to allow safe implantation, but arterial dissection and thrombosis led to graft loss in the early perioperative period in the latter case. CONCLUSIONS: Although resection of the arterial segments affected by FMD as a routine may allow implantation, macroscopically healthy-looking arteries might still be affected and thus carry elevated postoperative risk. The aim of our case report is to make proposal for an onsite diagnosis of FMD in case of clinical suspicion.

Evolution of liver transplant waiting list in Hungary between 1995 and 2019. / Májvárólista 1995-2019: a hazai adatok nemzetközi összehasonlítása.

Összefoglaló. Bevezetés: A májtranszplantációs program részeként 1995 óta létezik folyamatosan vezetett várólista Magyarországon. Célkituzés: A legfontosabb várólista-paraméterek megállapítása és nemzetközi összehasonlítása. Módszer: A szerzok az 1995. január 1. és 2019. december 31. között elso májátültetés céljából várólistára helyezett betegek adatait elemezték. Eredmények: Összesen 1722 beteget helyeztek várólistára, 1608 felnottet, 114 gyermeket. A férfiak aránya 51,2%, az átlagéletkor 45,6 év. Az évente regisztrált új jelöltek száma 25 év során közel az ötszörösére emelkedett. A listára helyezés leggyakoribb indikációja a víruseredetu cirrhosis volt (n = 451). Ezt követte a cholestaticus (n = 314) és az alkoholos májbetegség (n = 264). Rosszindulatú daganat, 82%-ban hepatocellularis carcinoma miatt 215 beteget regisztráltak. Krónikus betegségekben az átlagos Model for End-Stage Liver Disease pontszám a regisztráláskor 13,5 volt. A 2018. december 31-ig listára helyezettek (n = 1618) 61%-a részesült májátültetésben, 24%-a várakozás közben meghalt, 7%-a a mutétre alkalmatlanná vált. A mutét elotti medián várakozási ido 248 nap volt a krónikus és 2 nap az akut betegek listáján. A transzplantált tumoros betegek (n = 132) szignifikánsan rövidebb ideig vártak mutétre (medián 115,5 nap), mint a többi krónikus beteg (n = 803, medián 282 nap). Az Eurotransplanthoz való csatlakozás utáni idoszakban (2013. július 1. és 2018. december 31. között) a transzplantációs arány növekedett (67%), a várólista-halálozás (meghaltak + mutétre alkalmatlanná váltak) 24%-ra csökkent. Megbeszélés: A várólista folyamatos bovülése hozzájárult a hazai májátültetési program fejlodéséhez. A hazai várólista diagnózis szerinti összetétele a mások által közöltekkel nagyrészt egyezik. A transzplantáltak aránya a nemzetközi átlagnak megfelelo. A várólista-halálozás és a mutét elotti várakozási ido a magyarországinál alacsonyabb donációs aktivitású vagy jelentosen nagyobb várólistával rendelkezo országokéhoz hasonló. Következtetés: Várólista-paramétereink javításához a transzplantációk számának további növelése szükséges. Orv Hetil. 2022; 163(8): 301-311. INTRODUCTION: The Hungarian liver transplant program including waiting list started in 1995. OBJECTIVE: Evaluation of the wait-list parameters and comparing them with those in the literature. METHOD: Data of patients listed for primary liver transplantation between 1995 and 2019 were analyzed. RESULTS: A total of 1722 recipient candidates were registered on the liver transplant waiting list: 1608 adults (51.2% men) with mean age of 45.6 year and 114 patients aged <18 year. Virus-induced cirrhosis was the leading indication of listing (n = 451) and cholestatic liver diseases (n = 314) and alcoholic cirrhosis (n = 264) thereafter. The mean Model for End-Stage Liver Disease score was 13.5 for those with chronic disease. 61% of 1618 patients listed before December 31, 2018 underwent liver transplantation and 31% were removed from the wait-list for death or clinical deterioration. After joining Eurotransplant (period of 01. 07. 2013-31. 12. 2018), the transplant rate was 67%, the waiting list removal due to death/too sick for operation decreased to 24%. The median waiting time till transplantation was 248 days for those on elective and 2 days on acute list. Patients grafted with malignancy (n = 132) waited significantly shorter time than those with chronic non-malignant liver disease (median 115.5 versus 282 days). DISCUSSION: The composition of our waiting list by primary liver disease was similar to that of countries with large burden of hepatitis C. Transplant rate was average, wait-list mortality and waiting time were in line with those observed in low-donation countries or in the case of large volume waiting list. CONCLUSION: Listing of increasing the number of patients contributed to evolution of our liver transplant program. To improve our parameters, increasing transplant activity is warranted. Orv Hetil. 2022; 163(8): 301-311.

Outcomes of first versus third kidney transplantations: propensity score matching and paired subgroup analysis-a single-centre experience.

BACKGROUND: In the Eurotransplant, 12.6% of kidney transplantations are a repeat procedure. Third transplants are significantly more complex than first and second ones. We compared the results of first (PRT) versus third (TRT) transplantations. METHODS: Between 2011 and 2016, we performed 779 deceased donor adult kidney transplantations, 14.2% out of them were second, 2.6% (20) third, and 0.3% fourth. We compared the pre-, intra-, and postoperative data, kidney function, and survival rate. RESULTS: Recipients of TRT were younger (53.4 vs. 47.3 p = 0.02). HCV infection rate (20%, p = 0.00) is ten times higher. The operation time is longer (132 vs. 152 min, p = 0.02), and delayed graft function is much more frequent (22.4% vs. 60%, p = 0.00). Induction therapy was given to every TRT (7.9% vs.100%), but as a result, the rejection rate was the same (~ 15%). Hospital stay is a week longer. Patient's survival at 1, 3, and 5 years for PRT is 96.4%, 93.9%, and 91.2% and for TRT is 90%, 85%, and 78.4%, respectively (p = 0.023). TRT's odds ratio of fatal outcome is 4.35 (1.5-12.5). Graft survival at 1, 3, and 5 years for PRT is 93.1%, 91.4%, and 90.3% and for TRT is 75%, 75%, and 75%, respectively (p = 0.020). TRT's odds ratio of graft loss is 3.14 (1.1-8.9). Of PRT 85.76%, out of PRT 85.76%, while out of TRT 60% live with a functioning graft, p=0.00149. CONCLUSION: In a third transplant, both graft and patient survival are significantly inferior to primer ones. Careful selection is required to minimize the patient risk and graft loss.

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.

[Volume-based haemostasis reserves in blood product free liver transplantations]. / Térfogatalapú haemostasistartalékok vérmentes májtranszplantációk során.

Introduction: During liver transplantation, haemostasis is typically assessed by means of standard laboratory tests and viscoelastic tests, while dynamic monitoring of coagulation factor specific blood losses is an unusual, yet established approach. Aim: Our aim was to evaluate the volume-based haemostasis reserves in blood product free liver transplants in the first perioperative 48 hours, in association with the Child-Pugh score. Method: Data of 59 blood product free liver transplanted patients' coagulation factor levels, viscoelastic parameters and coagulation factor specific blood losses according to Gross methodological, baseline and 'coagulopathic' trigger levels were analysed. The haemostasis reserves were estimated according to the Child-Pugh classification. Laboratory tests and the calculation of haemostasis reserves were carried out before liver transplantation (T1), at the end of the surgery (T2) and also 12-24-48 hours postoperatively (T3-T4-T5). The viscoelastic tests were performed before liver transplantation (T1) and at the end of the surgery (T2). Results: Fibrinogen levels decreased by 1.2 g/L. Factor II, V, VII, X levels decreased by 26-40%. From T2 to T4, fibrinogen increased by 0.9 ± 0.6 g/L over 24 h (p<0.001). Factor II, V, VII, X levels increased by 12-30% between T3 to T5 (p<0.001). The viscoelastic parameters remained in the normal range during liver transplantation (T1-T2). Haemostasis reserves decreased by 61% at the end of surgery (p<0.001), but reached 88% of the preoperative value on the second postoperative day. The initial reserves of Child B and C groups were 36-41% lower than Child A, nevertheless, these differences were not significant at 48 hours. Conclusion: The volume-based haemostasis approach supplements the standard laboratory and viscoelastic tests. This unusual approach dynamically indicates the actual reserve of haemostasis and shows the 'weakest link' within the system. Orv Hetil. 2020; 161(7): 252-262.

[The start of the Hungarian lung transplantation program and the first results]. / A magyar tüdotranszplantációs program indulása és elso eredményei.

The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859-1868.

Effect of fulvic and humic acids on iron and manganese homeostasis in rats.

The objective of this study was to investigate the effects of fulvic acid (FA) and humic acid (HA) as the two main compounds of humic substances, separately on Fe and Mn homeostasis. Seventy-two male Wistar rats were randomly divided into 9 experimental groups. The control diet (AIN-93G formula) and diets supplemented with 0.1%, 0.2%, 0.4% and 0.8% HA or FA were fed for 26 days. Fe and Mn concentrations of the large intestinal content, liver, kidney, femur and hair were determined. No significant differences were observed in the production parameters. The effects of FA and HA on iron homeostasis were significantly different. FA proved to be a good iron source, and slightly increased the iron content of liver and kidney, but - up to a dietary iron level of 52.7 mg/kg - it did not influence the efficiency of iron absorption. Above a dietary iron level of 52.7 mg/kg down-regulation of Fe absorption can be assumed. HA significantly stimulated the iron uptake and there was no down-regulation of Fe absorption up to 0.8% dietary HA supplementation level (61.5 mg Fe/kg diet). In the HA groups the iron content of the liver and kidney decreased significantly, suggesting that in spite of the better Fe absorption, the HA-Fe complex does not provide iron to the investigated organs. Neither FA nor HA supplementation influenced the Fe content of the femur and hair and slightly decreased the Mn concentration in the large intestinal content. This effect was significant (with a 22.7% Mn concentration decrease) only at the HA supplementation rate of 0.8%. Neither FA nor HA influenced significantly the Mn concentrations of the liver, kidney and femur. The Mn concentration of the hair in rats receiving FA- or HA-supplemented diets was higher than in the control rats; however, this result needs further confirmation.

Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500µM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.

Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb.

The most severe complication of ischemia-reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.

Substance use in Roma and non-Roma adolescents.

Little data have been published on specific health indicators for Roma, especially on substance use and related problems, and to our knowledge no data are available for Roma adolescents. The objective was to assess substance use of Roma as compared with non-Roma adolescents. Prevalence of tobacco and illicit drug use, and alcohol intoxication were examined in 225 Roma and 182 non-Roma adolescents. Relationship between substance use and potential risk factors, and ethnicity, was investigated by logistic regression analyses. A matched sample of Roma and non-Roma subjects was also used for additional confirmatory conditional regression analyses. Results indicated a significant association between Roma ethnicity and higher lifetime prevalence of tobacco use, alcohol intoxication, and illicit drugs use. Roma girls as compared with non-Roma girls evidenced a disproportionately higher prevalence of smoking as compared with the difference between Roma and non-Roma boys. Chi square analyses showed for both Roma parents a higher level of tolerant attitude to smoking. The inequalities of the health status in substance use behaviors of the Roma versus non-Roma population, expressed in a more pronounced way in the female Roma population, emerge at an early age, based on our data; they are observable already in the early adolescent and adolescent age groups.

The interaction between resistance modifiers such as pyrido[3,2-g]quinoline, aza-oxafluorene and pregnane derivatives with DNA, plasmid DNA and tRNA.

Various resistance mechanisms such as complex formation with DNA, tRNA and MDR1 p-glycoprotein were modified in bacteria and cancer cells in presence of pregnane, pyridoquinoline, and aza-oxafluorene derivatives. Interaction between the compounds, plasmid DNA and tRNA was shown and compared to the interaction with calf thymus DNA. Complex formation with MDR1 p-glycoprotein and drug accumulation increased in cancer cells. Both plasmid DNA and p-gp complex formation were related to the chemical structures of the resistance modifiers.

Single-layer continuous suturing for end-to-end colonic anastomosis using a modified closed-bowel technique.

We describe our modified technique of performing one-layer continuously sutured colonic anastomosis, which we introduced in 1995. We also present the preliminary results of performing end-to-end intra-abdominal colonic anastomosis constructed by single-layer continuous suturing using the closed-bowel technique in 106 patients. Mortality was 2.8%, the incidence of early postoperative surgical complications was 3.8% [including anastomotic leakages (1.9%)], and the rate of reoperation for infective complications was 2.8%. These positive results show that this is an effective method of performing end-to-end colonic anastomosis. We think that our technical modification provides advantages for one-layer continuously sutured colonic anastomosis.

Large gastrointestinal stromal tumor presenting as an ovarian tumor. A case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract localized mostly in the upper or medial part of the digestion tract. CASE: A colonic GIST in a young woman extended to the pelvis, giving the impression of an ovarian tumor. CONCLUSION: In the case of a pelvic mass, especially if other unusual anamnestic data and signs are present, the possibility of other than a gynecologic tumor has to be considered. Every effort should be made to identify the origin of the tumor and related anatomic structures, especially the ovaries.