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Andrea Frilling

Publications and source records attributed to Andrea Frilling.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2004

Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is expressed by many tumors, including hepatocellular carcinoma (HCC) and is involved in tumor angiogenesis. Little is known about its role for HCC infiltration into normal liver parenchyma. METHODS: The effects of VEGF on the integrity of tight junctions were studied in HepG2 cells and human HCC by means of confocal laser scanning microscopy. RESULTS: VEGF induced within 45 min a marked loss of pseudocanaliculi and disruption of occludin-delineated tight junctions. This effect of VEGF was mimicked by phorbol-12-myristate-13-acetate (PMA) and was sensitive to protein kinase C (PKC) inhibition by Gö6850. VEGF induced within 15 min the translocation of the PKC alpha-isoform to the plasma-membrane, but had no effect on the activity of Erks and p38(MAPK). Sections from surgically removed HCC showed expression of VEGF in the tumor and occludin disassembly in normal liver parenchyma next to the tumor. CONCLUSIONS: VEGF induces disruption of tight junctions in a PKC-alpha dependent manner. In addition to its known angioneogenic properties, VEGF may promote HCC spreading into normal liver parenchyma. The data may provide another rationale for the use of VEGF antagonists for tumor therapy.

Carcinoma in Situ↗
PubMed2004

Hepatoma--resection or transplantation.

The most frequent tumors of the liver originate from the hepatocytes, bile duct epithelium, and endothelial cells. Hepatocellular carcinoma accounts for 80% to 90% of primary liver cancer. Cholangiocarcinoma, a neoplasm that arises from the biliary tree, is the second most common primary hepatic malignancy. This article deals with the epidemiology and clinical presentation and the diagnostic confirmation and classification of both conditions, and with the use of liver resection and transplanation treatment for both.

Bile Duct Neoplasms↗
PubMed2004

Importance of adrenal incidentaloma in patients with a history of malignancy.

BACKGROUND: Adrenal incidentaloma presents a frequent finding in patients with a history of malignancy. This study was carried out to determine whether imaging techniques can discriminate between a malignant and a benign adrenal tumor and subsequently select candidates for adrenal surgery. METHODS: Beginning in July 1995, oncologic patients with adrenal incidentaloma underwent abdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and [ 18 ]fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET). Consecutively in all patients adrenalectomy was performed. Histologic findings were compared with the imaging results. RESULTS: In 42 patients, 33 to 79 years old (mean age, 58 years), 44 adrenal lesions were detectable. Two patients presented with bilateral adrenal masses. At operation, 43 adrenal resections and 3 biopsies were performed. Histologic examination revealed 31 metastases (71%) and 13 adrenal adenomas (29%). In metastases the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 66%, 81%, 100%, and 100%, respectively. For adrenal adenoma, the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 46%, 39%, 100%, and 54%, respectively. CONCLUSIONS: In oncologic patients with indeterminate adrenal tumors MRI and 18-FDG-PET provide accurate differentiation between metastases and benign adenomas. Positive results of these 2 imaging modalities are highly suggestive for metastatic disease. In cases of negative MRI and 18-FDG-PET results the adrenal lesion corresponds to a benign adenoma that needs no surgical intervention.

Adenoma↗
PubMed2004

Latest development in split liver transplantation.

Currently, orthotopic liver transplantation (LT) represents the treatment of choice for most end-stage liver diseases. Advances in surgical techniques and immunosuppressive therapy have markedly increased its success. However, the main obstacle in LT remains the lack of donor organs with a current mortality rate for patients on the waiting list of up to 20%. This chapter focuses on developments in SLT techniques and living-donor LT to alleviate this problem. SLT yields a net gain of organs, in that it uses one organ to save either an adult and a child, or two adults. The initially used technique of ex-situ splitting is being replaced progressively by the in-situ splitting technique, which yields better preserved grafts. The latest step has been the introduction of living-donor segmental LT. The systematic combination of both techniques may lead to a further reduction of mortality for patients on the waiting list for LT.

Female↗
PubMed2003

Prophylactic thyroidectomy in multiple endocrine neoplasia: the impact of molecular mechanisms of RET proto-oncogene.

BACKGROUND: Multiple endocrine neoplasia (MEN) type 2, a cancer syndrome inherited in the dominant fashion, is defined by the occurrence of medullary thyroid carcinoma (MTC), either as a singular lesion (familial medullary thyroid carcinoma, FMTC) or with the variable expression of pheochromocytoma, hyperparathyroidism (MEN 2A), ganglioneuromas, buccal neuromas and Marfanoid-like phenotype (MEN 2B). DISCUSSION: Germline mutations of the RET proto-oncogene, localized on chromosome 10q11.2, have been identified as the underlying genetic cause of the disorder. In the majority of patients with MEN 2A/FMTC missense mutations at exon 10 or exon 11 are identifiable. Cysteine to arginine exchange at codon 634 is the mutation most frequently found. In MEN 2B approximately 95% of patients present with a mutation at codon 918 (exon 16). Additionally, less frequent mutations in other codons have been found in both syndromes. The DNA-based genotype analysis enables the identification of gene carriers at risk of developing MTC and offer them prophylactic thyroidectomy prior to development of any thyroid pathologies. Prophylactic surgery is generally recommended for MEN 2A/FMTC gene carriers at the age of 4-6 years. Due to the aggressiveness of the MEN 2B syndrome gene carriers should be operated by the age of 1 year. Presumably some less virulent mutations allow postponement of the prophylactic treatment to the second to fourth decade of life. CONCLUSIONS: Compared to standard presymptomatic biochemical screening, genetic testing and consecutive prophylactic treatment contribute to better outcome of individuals at risk for MTC.

Genotype↗
PubMed2003

Hepatitis B virus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape.

Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from patients with chronic hepatitis B virus (HBV) infection are functionally impaired. In our present study MoDC from healthy subjects were propagated in vitro and inoculated with HBV particles to investigate the precise mechanisms that underly MoDC dysfunction. T-cell proliferation assays revealed an impaired allostimulatory capacity of HBV-inoculated MoDC (HBV-MoDC) as well as a lower potential of stimulating autologous T cells against a recall antigen in comparison to control-MoDC. Interleukin-2, tumour necrosis factor-alpha and interferon-gamma production by T cells in proliferation assays with HBV-MoDC was significantly lower than with control-MoDC and correlated with lower IL-12 production in HBV-MoDC cultures. The presence of the nucleoside analogue lamivudine (3TC), an inhibitor of HBV replication, restored impaired allostimulatory function of HBV-MoDC and up-regulated major histocompatibility complex class II expression. These results show that HBV infection compromises the antigen-presenting function of MoDC with concomitant impairment of T helper cell type 1 responses. This may play an important role for viral immune escape leading to chronic HBV infection. However, 3TC treatment can overcome HBV-MoDC-related T-cell hyporeactivity and this underscores its important role in enhanced immune responses to HBV.

Adult↗
PubMed2003

Histidine-tryptophan-ketoglutarate versus University of Wisconsin solution in living donor liver transplantation: results of a prospective study.

The grafts obtained from a living donor hepatectomy are perfused on the back table with either University of Wisconsin solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK). The efficacy and safety of these solutions have been studied in cadaveric liver transplantation, however, there is no study comparing the two solutions in adult-to-adult living donor liver transplantation. In this study, UW and HTK were used in the perfusion of right living donor grafts. The grafts were perfused with a predetermined sequence and volume of one of the solutions. Liver biochemistries, complications, and graft and patient survival were analyzed. From January 2001 to September 2002, 30 grafts were alternately perfused with either UW (UW group) or HTK (HTK group). The perfusion was performed first via the artery and then via the portal vein with a predetermined volume. At a mean follow-up of 13 +/- 7 months, no significant statistical difference between groups UW and HTK in posttransplantation liver biochemistries, complications, or patient and graft survival (84% and 80%, respectively) was observed. In conclusion, UW and HTK are equally effective and safe in the perfusion of the living donor liver grafts. HTK has a slight practical advantage over UW because it does not need to be flushed away before reperfusion of the graft and is less expensive.

Adenosine↗