János Fazakas

Epidural Anesthesia? No of Course

Although the contraindications for thoracic epidural anesthesia (TEA) are well defined, the debate continues about whether TEA improves outcomes. Pro and con trials and a metaanalysis in the past have yielded equivocal results; they did not deal with new vascular intervention or drugs. The benefit of TEA in surgery is to provide analgesia. In subgroups, TEA can decrease the mortality and morbidity. In contrast, the cost can increase in the situation of a complication that is opposite to the side effects is rare, but the impairment caused by them is out of proportion to the benefits. Primary or secondary prophylaxis with antithrombotic drugs is increasing in developed countries because of the increasing cardiovascular interventions and aging of the population. The neuroaxial guidelines are useful, but the changing of the coagulation profile after hepatectomy is not included in them. The decision to use TEA in liver surgery must be individualized with steps planned from the beginning. TEA suitability is based on an evaluation of the contraindications, comorbidities, coagulation profiles, hepatic reserve, and balance of benefits and risks. The insertion or withdrawal of the epidural catheter should be made with care according to the neuroaxial guidelines and in the presence of a normal TEG. The decreasing level of prothrombin content and platelet counts after hepatectomy should be closely monitored every 2 to 5 days.

Sepsis: From Pathophysiology to Individualized Patient Care

Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review.

Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience

Abstract: Background: Cytomegalovirus (CMV) presents a serious threat to CMV‐seronegative recipients (R−), who have received an organ from a seropositive donor (D+).

The use of autologous rectus facia sheath for replacement of inferior caval vein defect in orthotopic liver transplantation

Occasionally, during liver transplantation, vascular reconstructions have to be performed. Donor vessels can be harvested for this purpose. However, when these are lacking, alternatives should be available. A possible alternative can be the use of autologous rectus fascia sheath, folded as a tube with the mesothelium on the inside. Earlier experimental studies from our centre showed the successful use of the rectus fascia sheath graft in vascular defects in animal experiments. This report describes the first use of this autologous tubular graft for replacement of the inferior caval vein interponate during liver transplantation in men.

Relationship Between Hepatitis C Virus Recurrence and De Novo Diabetes After Liver Transplantation: The Hungarian Experience

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively (P=.011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P=.017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P=.039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P=.019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.

New-onset diabetes mellitus after liver transplantation

A de novo diabetes mellitus a majatultetes gyakori szovődmenye. Celkitűzes: A de novo diabetes gyakorisagat, jelentőseget es a kockazati tenyezők szerepet vizsgaltuk. Modszer: 1995 es 2009 kozott 310 majatultetett beteg adatait dolgoztuk fel retrospektiv modszerrel. De novo diabetest allapitottunk meg, ha az ehomi vercukor a 3. posztoperativ honapon tul ismetelten >6,8 mmol/l volt, es/vagy a majatultetes utan tartos, a 3. posztoperativ honapot meghaladoan is fenntartott antidiabetikus terapia indult. Eredmenyek: De novo diabetes a betegek 20%-anal (63 beteg) alakult ki. A de novo es a kontrollcsoport kozott az alabbiakban talaltunk kulonbseget. Donor-testtomegindex (24±3 vs. 22,4±3,6 kg/m 2 , p = 0,003), ferfi nem (58% vs. 33%, p = 0,002). Recipienseletkor (47,6±7,2 vs. 38,3±14,6 ev, p<0,001), -testtomegindex (26,7±3,8 vs. 23,3±5,6 kg/m 2 , p<0,001), ferfi nem (60% vs. 44%, p = 0,031). A de novo diabetesesek csoportjaban a betegek 66%-at HCV talajan kialakult cirrhosis miatt transzplantaltak, a kontrollcs...UNLABELLED New-onset diabetes is a common complication after liver transplantation. AIM We aimed to analyze the incidence and rate of known risk factors and the impact of new-onset diabetes mellitus on postoperative outcome. METHODS We retrospectively evaluated the files of 310 patients who underwent liver transplantation between 1995 and 2009. Definition of new-onset diabetes included: repeated fasting serum glucose >6.8 mmol/l and/or sustained antidiabetic therapy that was present 3 months after transplantation. RESULTS New-onset diabetes occurred in 63 patients (20%). Differences between the new-onset and the control group were the donor body mass index (24+/-3 vs. 22.4+/-3.6 kg/m 2 , p = 0.003), donor male gender (58% vs. 33%, p = 0.002), and recipient age (47.6+/-7.2 vs. 38.3+/-14.6 year, p<0.001), body mass index (26.7+/-3.8 vs. 23.3+/-5.6 kg/m 2 , p<0.001), male gender (60% vs. 44%, p = 0.031). The 66% of patients with new-onset diabetes were transplanted with cirrhosis caused by hepatitis C virus infection, while in the control group the rate was 23% (p<0.001). Cumulative patient survival rates at 1, 3, 5 and 8 year were 95%, 90.6%, 88% and 88% in the control group, and 87%, 79%, 79% and 64% in the de novo group, respectively (p = 0.011). Cumulative graft survival rates at 1, 3, 5 and 8 year in the control group were 92%, 87%, 86% and 79%, in the de novo diabetes group the rates were 87%, 79%, 79%, 65%, respectively (p = NS). In case of early recurrence (in 6 months), majority of patients developed new-onset diabetes (74% vs. control 26%, p = 0.03). More patients had more than 10 times higher increase of the postoperative virus titer correlate to the preoperative titer in the de novo diabetes group (53% vs. 20%, p = 0.028). Mean fibrosis score was higher in new-onset group one year after the beginning of antiviral therapy (2.05+/-1.53 vs. 1.00+/-1.08, p = 0.039). CONCLUSIONS Risk factors for new-onset diabetes after transplantation are older age, obesity, male gender and cirrhosis due to hepatitis C infection. The early recurrence, viremia and more severe fibrosis after antiviral therapy have an impact on the occurrence of new-onset diabetes in hepatitis C positive patients.

Biliary complications following orthotopic liver transplantation. The Hungarian experience

INTRODUCTION The authors summarize the characteristics of biliary complications following liver transplantation in the Hungarian liver transplant program. Aims were to analyze the frequency and the types of biliary complications as well as their effect on the patient and graft survival. The authors observed the known risk factors in the Hungarian practice, and they also try to find unknown risk factors for biliary complications. They review the therapy of biliary complications. METHOD In the retrospective study, patients were divided into two groups, with and without biliary complication after liver transplantation. These two groups were compared with many factors, and with the survivals. The biliary complication group was divided into two parts: those who had an early and those with a late biliary complication. These two new groups were also compared with the controls. The results are summarized in tables and statistical figures. Categorical variables are evaluated by chi 2 -test, continuous ones are with Levine Test (for homogenicity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis. RESULTS Biliary complication appeared in 25% of the patients. The most frequent complications were stenosis (18%), biliary leakage (9%), biliary necrosis (6%), and ischaemic type of biliary lesions (3%). The 5-year survival is worse when biliary complications were diagnosed (55%) than without such a complication (66%). In the biliary complication group the retransplantation rate was higher (15%). The most frequent treatments were interventional radiologic methods (69%), surgical methods (17%), and the ERCP. CONCLUSIONS The rate of biliary complications met the international reviews. Risk factors for biliary complications were cholangitis, hepatic artery thrombosis and stenosis, high rate of intraoperative blood transfusions, and acute rejection. Biliary complications frequently associated with the initial poor function of the transplanted graft. Early biliary complications have a negative impact on patient survival, while late complications influence a decreased quality of life. Biliary complications were treated mostly by interventional radiologic procedures.

The recurrence of hepatitis C virus after liver transplantation

A hazai majatultetesi programban magas a hepatitis C-virus (HCV) okozta vegstadiumu majbetegseg miatt vegzett majatultetesek aranya. Celkituzes: A szerzok dolgozatukban elemzik a C-hepatitis miatt majatultetesen atesett betegek adatait. Modszer: Az 1995 ota vegzett 295 primer majatultetes adatainak retrospektiv elemzese: donor- es recipiens-, valamint perioperativ es tulelesi adatok, szerumvirus-RNS-titer, percutan majbiopsziak szovettani eredmenyei. Eredmenyek: A mutet 111 betegnel tortent HCV-fertozes miatt, ez az elvegzett majatultetesek 37,6%-a. A vizsgalt 111 beteg kozul 22 beteg (20%) a posztoperativ idoszakban, a virus kiujulasanak eszlelese elott, egyeb okbol meghalt. A 89 beteg kozul 16 esetben (18%) a virus visszatereset meg nem eszleltek, 73 betegnel (82%) azonban a virus kiujulasa szovettanilag igazolhato volt. Negyven betegnel (56%) a C-virus okozta hepatitis kiujulasat egy even belul eszleltek, kozuluk 28 esetben (39%) 6 honapon belul, 12 esetben hat honapon tul, de 1 even belul (17%), es 32 betegnel (44%) egy even tul. A vegstadiumu C-cirrhosis miatt majatultetett betegek kumulativ 1, 3, 5 es 10 eves tulelese 73%, 67%, 56% es 49% volt. A HCV-negativ, majatultetett betegeknel ezek az ertekek 80%, 74%, 70% es 70%, a kulonbseg szignifikans. A majgraft kumulativ tulelese HCV-pozitiv betegeknel 72%, 66%, 56% es 49% volt, mig HCV-negativ betegeknel 76%, 72%, 68% es 68%, itt nem szignifikans a kulonbseg. Korai kiujulas eseten szignifikansan magasabb szerumvirus-RNS-titert mertek az elso 6 honapban majatultetes utan. A majatultetes utan 6 honappal vett protokollbiopszia korai kiujulas eseten magasabb Knodell-pontszamot eredmenyezett, mint kesoi kiujulaskor. A fibrosisindex eseteben ez forditva volt. A majatultetestol az elso antiviralis kezelesig eltelt ido 1995–2002 kozott atlagosan 20 honap volt, 2003 ota 8 honap. Kovetkeztetesek: Az idosebb donorokbol szarmazo, marginalis majgraftok magasabb vertranszfuzio-igeny mellett torteno beultetese elorevetiti a hamarabb bekovetkezo virusrekurrenciat. Ezt a tendenciat erositi a posztoperativ akut rejectio es az emiatt adott szteroid boluskezeles. A kombinalt antiviralis kezeles protokollja kulonbozik az altalanosan alkalmazottol: az un. „stopszabaly” nem ervenyes. Virusnegativva a betegek csak kevesebb mint 10%-a valik, melynek a fenntartott immunszuppresszio az oka. A majatultetes utan koran, akar fel even belul elkezdett antiviralis kezeles a beteg- es grafttulelest pozitivan befolyasolja, es feltehetoen csokkenti a HCV-reinfekcio miatti retranszplantaciok szamat. A masodik majatultetesnel akkor varhatok jo eredmenyek, ha idoben tortenik, a recipiens meg megfelelo fizikai allapota mellett. Ennek megiteleseben a MELD-score segit. Kulcsszavak: majatultetes, hepatitis C-virus, interferon, rekurrencia, retranszplantacio, tuleles The recurrence of hepatitis C virus after liver transplantation. The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. Aim: Authors present the results of liver transplantations performed due to HCV infection. Method: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. Results: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recur

HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients

BACKGROUND Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection. METHODS Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types. RESULTS We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences were not significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction. CONCLUSIONS HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and was not influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference was not significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

Surgical aspects of pediatric liver transplantation. Living donor liver transplant program in Hungary

Because of the long waiting time for pediatric liver transplantation, new techniques of liver transplantation were invented. Split and living-donor related liver transplantation are common today and the Kaplan-Meier (3 years) overall survival is over 80%. By splitting the liver, two recipients can be transplanted. In general, the left lobe is used for the pediatric, the right lobe for the adult recipient. There are a lot of combinations depending on the donor and recipient weight. The accepted liver volume is approx. 1% of the recipient body weight. The results of the Hungarian pediatric program improve, 27 transplantations were done using 14 partial liver grafts and living donor program was started. Using strict protocols and improving surgical skills, the overall pediatric survival was over 80% in the last 5 years.