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Andrea Frilling

Publications and source records attributed to Andrea Frilling.

At least 19 recordsLinked to original sources
PubMed2006

Liver transplantation and incidentally found hepatocellular carcinoma in liver explants: need for a new definition?

BACKGROUND: "Incidentally" identified hepatocellular carcinoma (iHCC) in liver explants after liver transplantation (LTx) is a frequently reported finding, which is characterized with a good prognosis. The purpose of this study was to evaluate the outcome of patients with these tumors in our series and in literature reports, and to compare their prognosis to that of HCC diagnosed preoperatively. METHODS: From April 1998 to December 2003, 432 patients underwent deceased-donor LTx at our center for nonmalignant indications. An additional 31 patients with a preoperative known HCC (pkHCC) received deceased-donor grafts. A literature search was performed intending to estimate the incidence of iHCC in liver explants and the outcome after LTx. RESULTS: iHCC was found in 5 of the 432 patients. All five patients are currently alive without evidence of tumor recurrence after a median follow-up of 43 months. On the other hand, in the group of the 31 patients with pkHCC, 22 of them are at the moment alive in a median follow-up of 28 months. When comparing the two groups, no difference in survival could be found (P=0.1419 in log-rank test). Literature reports of 705 instances with iHCC over the past 20 years showed a statistical "better survival" in only 24 cases. CONCLUSION: Literature reports showed a remarkable "deviation" of the expected tumor characteristics for the iHCC. Obviously, this is because of a widely characterization of iHCC, including also tumors which are rather undetected HCC during the waiting time to LTx. A more precise definition for the iHCC is needed.

Carcinoma, Hepatocellular↗
PubMed2006

Living donor liver transplantation for hepatocellular carcinoma: a single-center preliminary report.

Liver transplantation (LT) is the treatment of choice for early hepatocellular carcinoma (HCC) in patients with end-stage liver disease but is limited by the availability of donor organs. Living donor liver transplantation (LDLT) represents an alternative therapeutic option for patients with disease confined to the liver. Between April 1998 and December 2003, 537 patients underwent liver transplantation in our center. Thirty patients with HCC and associated terminal cirrhosis and 4 patients with tumor recurrence after liver resection who underwent LDLT were reviewed. Nineteen patients (55.8%) met the Milan criteria for LT, whereas 15 patients (44.2%) "exceeded" them. The overall survival rates at 1 and 2 years were 68% and 62%, respectively, with a median follow-up of 41 months (range, 17-64 months). Five patients (14.7%) died in the first 30 days after LDLT. Hospital mortality was significantly correlated with age > 60 years. Four patients developed recurrence between 6 and 35 months after LDLT. Recurrence was significantly related to the presence of more than 3 tumor lesions in our series. In conclusion, LDLT is a promising treatment option for patients with HCC. Even longer follow-up and bigger patients' series are needed to fully assess the benefits of LDLT for HCC patients exceeding the Milan criteria.

Adolescent↗
PubMed2006

"Hepar divisum"--as a rare donor complication after intraoperative mortality of the recipient of an intended living donor liver transplantation.

In this study, we present our experience with 4 healthy donors having the rare condition of "hepar divisum" after the intraoperative death of the recipient of an intended right adult living donor liver transplantation (LDLT). The study included 4 donors and 4 intended right LDLT recipients affected by neuroendocrine tumor (n = 2), hepatocellular carcinoma (n = 1), and cryptogenic cirrhosis (n = 1). All 4 recipients died intraoperatively. At the time of recipient death, the dissection of the donor liver parenchyma was complete, the vessels intact, and the hepatic duct(s) already divided. In each case, reconstruction of the donor biliary tract was performed: hepaticojejunostomy (HJ) in 2 cases, each with 3 ducts, and duct-to-duct anastomosis in 2. Of the donors receiving the HJ, 1 had a cut surface bile leak and the other experienced an anastomotic leak, treated by percutaneous drainage and reoperation, respectively. The latter patient experienced recurrent HJ stenosis at 44 months and 50 months after the operation and was treated by percutaneous balloon dilatation. One duct-to-duct reconstruction was complicated by early stenosis (postoperative day 6) and treated with endoscopic stenting. In conclusion, in the case of intraoperative death of the recipient of an intended LDLT, when the parenchyma and the hepatic duct of the donor have already been divided, the options are completion of the donor hepatectomy or the status of "fegatum divisum" with reconstruction of biliary tract. The high incidence of biliary complication, however, is of concern. When more than 1 hepatic duct is present, the donor hepatectomy should be completed and the graft reallocated according to the policy of the transplant institution.

Adult↗
PubMed2005

Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro.

AIM: To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs) in vitro. METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot. RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 mug/L, respectively. However, the expression of CK19 by BECs was not changed. CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Aged↗
PubMed2005

High frequency of loss of heterozygosity in imprinted, compared with nonimprinted, genomic regions in follicular thyroid carcinomas and atypical adenomas.

CONTEXT: Many mammalian genes that are imprinted regulate cell growth, differentiation, and apoptosis. Because imprinting silences one of the two alleles, resulting in functional haploinsufficiency, we hypothesized that loss of heterozygosity (LOH) at an imprinted locus may result in the deletion of the only functional copy of an imprinted tumor suppressor gene. OBJECTIVE: The goal of this study was to specifically address this hypothesis that in thyroid neoplasias loss of imprinted loci becomes enriched during oncogenesis. DESIGN: In total, thyroid tissue was obtained from 72 patients with thyroid neoplasias comprising 34 follicular thyroid carcinomas (FTCs) and 38 follicular adenomas. We performed PCR-based LOH analysis of DNA from paired normal-tumor samples using 18 markers mapped to imprinted regions (IR) and 13 markers in nonimprinted regions (NIR). RESULTS: Overall LOH frequencies for the IR markers were 26% for the adenomas and 38% for the carcinomas. In the NIR, the overall LOH frequency was 23 and 26% for adenomas and FTCs, respectively. The difference in LOH frequencies between IR and NIR was statistically significant only for the carcinomas (P = 0.001), although there was a similar trend for the atypical adenomas (ATY, P = 0.06). CONCLUSIONS: Our observations suggest that IRs are more prone to genomic instability in FTCs. The fact that the ATY trended toward differential IR/NIR LOH, similar to FTC, may suggest that loss of IR might be instrumental in the adenoma-carcinoma sequence in thyroid carcinogenesis and that ATY could be an important intermediate in this pathway.

Adenoma↗
PubMed2005

Liver transplantation for hepatocellular carcinoma in cirrhosis within the Eurotransplant area: an additional option with "livers that nobody wants".

BACKGROUND: Liver transplantation is recognized as the treatment of choice for small hepatocellular carcinomas (HCC) in patients with end-stage liver failure. However, because of limited organ availability, not all those who qualify can benefit from it. METHODS: Over a 3-year period, we accepted and subsequently transplanted 10 deceased donor liver allografts allocated through Eurotransplant. These organs had been officially offered to and rejected by other transplant centers a total of 40 times due to medical or logistical reasons prior to our acceptance. They were implanted into patients in the waiting list with HCC and cirrhosis. Recipients without HCC transplanted with such "undesirable" grafts were not included in this study. RESULTS: Two patients had initial poor graft function but subsequently recovered. There was one arterial complication requiring reintervention. Median intensive care unit and hospital stays were 6 and 28 days respectively. One patient developed renal insufficiency, but recovered after 3 months. One patient developed HCC recurrence in the allograft and underwent a successful atypical liver resection 23 months after transplantation. All patients are currently alive, with follow-up periods ranging from 5 to 36 months. CONCLUSIONS: Liver transplantation with such "livers that nobody wants" constitutes an additional option for patients with HCC and cirrhosis. The risk-benefit ratio in these instances should be evaluated on a case-by-case basis.

Adult↗
PubMed2005

Effectiveness of a new carrier-bound fibrin sealant versus argon beamer as haemostatic agent during liver resection: a randomised prospective trial.

BACKGROUND AND AIMS: A new carrier-bound fibrin sealant, TachoSil, is expected to be efficacious and safe as a haemostatic treatment in hepatic resection. DESIGN: A prospective, randomised, open and controlled multicentre trial with intraoperative as well as postoperative assessment of efficacy and a 1 month follow-up period. SETTING: Tertiary care centres. PATIENTS/METHODS: One hundred and twenty-one patients requiring secondary haemostasis during planned liver resection. Patients with coagulation disorders and patients with persistent major bleeding after primary haemostatic measures were excluded. INTERVENTION: Application of either carrier-bound fibrin sealant (n=59) or argon beamer (argon beam coagulator) (n=62) as secondary haemostatic treatment. MAIN OUTCOME MEASURE: Time to intraoperative haemostasis. RESULTS: There was a significant superiority of TachoSil over argon beamer with regard to time to haemostasis (3.9 min, median 3.0, range 3-20 min vs 6.3 min, median 4.0, range 3-39 min) (P=0.0007). Haemoglobin concentration of drainage fluid was significantly lower on day 2 after surgery in TachoSil patients (1.1 mmol/l) than in argon beamer patients (2.3 mmol/l) (P=0.012). Overall, the frequency and causality of adverse events did not differ between the two treatment groups. CONCLUSION: TachoSil is superior to argon beamer in obtaining effective and fast intraoperative haemostasis. The safety data show TachoSil to be tolerable and safe for haemostatic treatment in liver resection.

Drug Carriers↗
PubMed2005

Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination.

Thyroid carcinoma is a common endocrine cancer with a favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate follicular carcinomas from benign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses should be explored. We conducted a microarray-based study to reveal the genetic profiles unique to FTC and follicular adenomas (FAs), to identify the most parsimonious number of genes that could accurately differentiate between benign and malignant follicular thyroid neoplasia. We confirmed our data by quantitative RT-PCR and immunohistochemistry in two independent validation sets with a total of 114 samples. We were able to identify three genes, cyclin D2 (CCND2), protein convertase 2 (PCSK2), and prostate differentiation factor (PLAB), that allow the accurate molecular classification of FTC and FA. Two independent validation sets revealed that the combination of these three genes could differentiate FTC from FA with a sensitivity of 100%, specificity of 94.7%, and accuracy of 96.7%. In addition, our model allowed the identification of follicular variants of papillary thyroid carcinoma with an accuracy of 85.7%. Three-gene profiling of thyroid nodules can accurately predict the diagnosis of FTC and FA with high sensitivity and specificity, thus identifying promising targets for further investigation to ultimately improve preoperative diagnosis.

Adenocarcinoma, Follicular↗
PubMed2005

Hepatic venous outflow reconstruction in right live donor liver transplantation.

The increasing experience with live donor liver transplantation has allowed for the identification of potential morbidities associated with technical considerations. Technical graft failure can be associated with both inflow and outflow vascular compromise. Although the latter has not always been given the relevance of the former, evidence pointing to its pivotal role continues to mount. We believe that impaired venous outflow was a cause of previously unexplained graft failures during our initial experience. Based on this observation, we developed a technique to prevent the "choking" of the graft at the outflow anastomosis with the inferior vena cava (IVC). The enhanced outflow via a cloaca maximum is achieved by reconstructing the graft vessels with preserved veins or arteries (usually iliac vessels are used) from a blood-group-identical or blood-group-compatible deceased organ donor. Alternatively, hepatic vein or portal vein obtained from the resected native liver can be used. The reconstructed common outflow is anastomosed to a triangular opening of the IVC. Such enhanced outflow provides optimal venous drainage, especially during the early phase of growth of the graft.

Anastomosis, Surgical↗
PubMed2005

Preoperative donor liver biopsy for adult living donor liver transplantation: risks and benefits.

The role of liver biopsy (LB) in donor selection for adult living donor liver transplantation remains controversial, since the procedure is associated with additional potential risks for the donor. From April 1998 to August 2004, 730 potential living donors for 337 adult recipients underwent our multistep evaluation program. In 144 candidates, LB was performed. LB was obtained in a percutaneous ultrasound-guided fashion by means of Menghini needle (32 cases) or Tru-cut needle (112 cases). The biopsy specimen was preserved in 5% formalin and processed with hematoxylin & eosin-stained sections. Thirty-one (21%) of 144 candidates who underwent an LB had a positive finding at histological examination that induced their exclusion from donation, of whom 21 had liver steatosis of varying kind and grade (10%-80%) and 10 had a nonsteatotic hepatopathy (non-A-D hepatitis in 6 cases, diffuse granulomatosis in 2, schistosomiasis in 1, fibrosis in 1). The only observed major complications related to LB were 2 intraparenchymal haematomas, both of which resolved spontaneously within a few months. In conclusion, based on these findings, we believe that preoperative LB in the donor selection for adult LDLT is necessary, once the initial donor screening and noninvasive evaluation is complete. Because other screening modalities can be unreliable, without preoperative LB a fraction of potential donors will be operated on inappropriately, risking both donor and recipient. The main objective of LB should be to ensure the donor's safety more than the preservation of the graft function.

Adult↗
PubMed2004

Silencing of the maternally imprinted tumor suppressor ARHI contributes to follicular thyroid carcinogenesis.

The two most common subtypes of thyroid cancer, follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma, have been extensively studied, but our fundamental understanding of the molecular events in thyroid epithelial oncogenesis is still limited. Unreported data from our previous published global gene expression analysis revealed that the tumor suppressor gene aplysia ras homolog I (ARHI) is frequently underexpressed in FTCs. In this study, we elucidated the frequency and mechanism of ARHI silencing in benign and malignant thyroid neoplasia. We demonstrated that underexpression of ARHI occurs principally in FTCs (P = 0.0018), including its oncocytic variant (11 of 13), even at minimally invasive stage but not classic papillary thyroid carcinoma (two of seven) or follicular adenoma (FA) (three of 14). FTCs show strong allelic imbalance with reduction in copy number/loss of heterozygosity (LOH) in 69%, compared with less than 10% for FAs. In combination with our LOH data, bisulfite sequencing in a subset of samples revealed that FA displays a symmetric methylation pattern, likely representing one unmethylated allele and one presumptively imprinted allele, whereas FTC shows a virtually complete methylation pattern, representing LOH of the nonimprinted allele with only the hypermethylated allele remaining. Furthermore, we showed that pharmacologic inhibition of histone deacetylation but not demethylation could reactivate ARHI expression in the FTC133 FTC cell line. Therefore, our data suggest that silencing of the putative maternally imprinted tumor suppressor gene ARHI, primarily by large genomic deletion in conjunction with hypermethylation of the genomically imprinted allele, serves as a key early event in follicular thyroid carcinogenesis.

Adenocarcinoma, Follicular↗
PubMed2004

Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets.

Increased levels of interleukin (IL)-10 have been described as a negative prognostic indicator for survival in patients with various types of cancer. IL-10 exerts tolerogenic and immunosuppressive effects on dendritic cells, which are crucial for the induction of an antitumor immune response. Blood dendritic cell antigen (BDCA)-2 and BDCA-4 are specifically expressed by CD123(bright) CD11c- plasmacytoid dendritic cells; whereas BDCA-1 and BDCA-3 define 2 distinct subsets of CD11c+ myeloid dendritic cells. In this study, the T-helper cell (Th)1/Th2 cytokine serum profile of 65 hepatocellular carcinoma patients was assessed. We found that serum levels of IL-10 were substantially increased in hepatocellular carcinoma patients as compared with controls. Peripheral blood mononuclear cells from healthy volunteers were exposed to recombinant human (rh)IL-10 in vitro to additionally characterize its impact on distinct blood dendritic cell subsets. A dramatic decrease of all myeloid dendritic cell (MDC) and plasmacytoid dendritic cell (PDC) subsets was detectable after 24 hours of continuous rhIL-10 exposure. Moreover, the expression of HLA-DR, CD80 and CD86, was significantly reduced on rhIL-10-treated dendritic cell subsets. Direct ex vivo flow cytometric analysis of various dendritic cell subpopulations in peripheral blood from hepatocellular carcinoma patients revealed an immature phenotype and a substantial reduction of circulating dendritic cells that was associated with increased IL-10 concentrations in serum and with tumor progression. These findings confirm a predominantly immunosuppressive role of IL-10 for circulating dendritic cells in patients with hepatocellular carcinoma and, thus, may indicate novel aspects of tumor immune evasion.

Adult↗
PubMed2004

Volumetric and functional recovery of the liver after right hepatectomy for living donation.

Our objective was to study the kinetics of recovery of the liver volume and liver function after right hepatectomy (RH) for living donation, comparing conventional and quantitative liver function tests, i.e., galactose elimination capacity (GEC). A total of 27 donors underwent RH averaging 61% of the whole liver volume. The conventional and quantitative liver function tests, as well as magnetic resonance imaging volumetric studies, were performed preoperatively at postoperative day (POD) 10, 90, 180, and 360. Mean residual volume increased by 88% within 10 days from RH and thereafter did not show any significant variation. After 1 year, only 83% of the original volume was reached. GEC per milliliter of liver volume expressed in percent of initial value (GEC/mL) showed a decrease of 25% at POD10, an increase up to 125% at POD 180, and returned to normal values at POD 360. Liver biochemistries, International Normalized Ratio (INR), and bilirubin returned to normal in 10 days. Cholinesterase showed a similar course like GEC. In conclusion, within 10 days of 61% loss of its initial volume, the liver is capable of regenerating a volume necessary to its function, although it corresponds to only 74% of the initial one. It takes only 10 days to normalize liver biochemistries, while cholinesterase and albumin recover over 90 days. However, a direct measure of the cytosolic liver function obtained by GEC shows that functional recovery occurs much more gradually than the recovery of volume and liver biochemistries.

Adult↗
PubMed2004

Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center.

Adequate selection of donors is a major prerequisite for living donor liver transplantation (LDLT). Few centers report on the entire number of potential donors considered or rejected for living donation. From April 1998 to July 2003, a total of 111 living donor liver transplantations were performed at our institution, with 622 potential donors for 297 adult recipients and 78 potential donors for 52 pediatric recipients evaluated. In the adult group, only 89 (14%) potential donors were considered suitable, with a total of 533 (86%) potential donors rejected. Of these, 67% were excluded either at initial screening or during the first and second steps of the evaluation procedure. In 31% of all cases, the evaluation of donors was canceled because of recipient issues. In the pediatric group, 22 (28%) donors were selected, with the other 56 (72%) rejected. Costs of the complete evaluation process accounted for 4,589 Euro (Euro) per donor. The evaluation of a potential living donor is a complex and expensive process. We present the results on the evaluation of the largest group of potential donors for adults reported in the literature. Only 14% of potential donors in our series were considered suitable candidates. It has not yet been established who should cover the expenses of the evaluation of all rejected donors. In conclusion, all efforts should be made in order to develop an effective screening protocol for the evaluation of donors with the aim of saving time and resources for a liver transplantation program.

Adolescent↗