PubMed Health⌕ Search

Biomedical subjects

Andrea Frilling

Publications and source records attributed to Andrea Frilling.

At least 19 recordsLinked to original sources
PubMed2006

Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.

Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.

Aged↗
PubMed2006

Optimizing preoperative imaging in primary hyperparathyroidism.

BACKGROUND: Scintigraphy of the hyperfunctioning parathyroid glands using technetium 99m ((99m)Tc)-methoxyisobutylisonitrile ((99m)Tc-MIBI) is an established and highly sensitive preoperative localization tool whose importance has been further increased by advances in minimally invasive surgery . The goal of the present prospective study was to determine the benefit of optimized imaging in a consistent patient population. METHODS: Eighty-four patients with first presentations of primary hyperparathyroidism were investigated with (99m)Tc-MIBI scintigraphy, thyroid scintigraphy, and cervical ultrasonography. The evaluation algorithm consisted of (a) evaluation of the planar images alone, (b) additional evaluation of single-photon emission computed tomography (SPECT), (c) additional evaluation of thyroid gland scintigraphy, and (d) additional evaluation of ultrasound. All patients subsequently underwent parathyroidectomy. The intraoperative and the histologic findings were correlated with the results of the scintigraphic imaging. RESULTS: The sensitivity of planar parathyroid scintigraphy was 74% and could be increased to 91% by the additional investigations. The difference was statistically significant (p<0.05). At the same time, a small increase in specificity from 96% to 99% was seen. CONCLUSIONS: Prior to minimally invasive treatment of hyperparathyroidism, we recommend combined localization studies consisting of sequential (99m)Tc-MIBI scintigraphy, additional SPECT plus thyroid gland scintigraphy, plus high-resolution cervical ultrasonography.

Adult↗
PubMed2006

Liver transplantation with "rescue organ offers" within the eurotransplant area: a 2-year report from the University Hospital Essen.

Liver transplantation (LTx) is the only treatment for patients with end-stage liver failure. This report focuses on 45 deceased donor liver allografts allocated through Eurotransplant as "rescue offers," which were accepted and subsequently transplanted at our center over a two-year period. These organs had been officially offered to and rejected by other transplant centers a total of 162 times prior to our acceptance. Primary nonfunction was observed in six patients. Two of them died and four were retransplanted. Overall patient survival was 84.4%. LTx with such "rescue organs" constitutes an additional transplant option and a safe mechanism to "rescue" organs within Eurotransplant.

Adult↗
PubMed2006

Left hepatic trisectionectomy for hepatobiliary malignancies.

BACKGROUND: Left hepatic trisectionectomy is the most extended hepatic resection. To date, few data are available on longterm outcomes after this operation. STUDY DESIGN: Between June 1998 and July 2004, a total of 52 patients underwent left trisectionectomy for primary or secondary hepatobiliary tumors at our institution. Data were analyzed with regard to patient characteristics, intraoperative details, pathologic findings, perioperative morbidity and mortality, and outcomes as determined by survival. RESULTS: Left trisectionectomy was combined with caudate lobectomy and hilar lymph node dissection in 29 and 35 patients, respectively. In addition, 43 procedures were performed in 31 patients: resection of hilar bifurcation (n = 15), bile-duct revision (n = 5), wedge resection of segment VI/VII (n = 10), gastrectomy (n = 1), and resection or reconstruction of hepatic vessels or the inferior vena cava (n = 12). Operative morbidity and mortality were 50% and 11.9%, respectively. By multivariate analysis, additional operative procedures constituted the only positive predictor of postoperative morbidity. One-, 3-, and 5-year survival rates were 65%, 52%, and 33%, respectively. After R0 resection (n = 37), 1-, 3-, and 5-year survival rates were 78%, 68%, and 44% compared with 38%, 15%, and 7% after R1 resection (p = 0.0004). Survival corresponding to the four most frequent tumor types (hepatocellular carcinoma, cholangiocellular carcinoma, hilar cholangiocarcinoma, and colorectal metastases) was comparable with survival data reported in the literature after less-extensive resections. CONCLUSIONS: Left trisectionectomy provides acceptable survival rates in both locally advanced primary hepatobiliary malignancies and large metastatic liver tumors. Despite major progress in surgical technique and perioperative management, left trisectionectomy is still associated with higher operative mortality and morbidity than less-extensive resections. Because selection criteria for this type of procedure are not clearly defined, particular attention should be focused on the oncologic benefits when considering this operation.

Adult↗
PubMed2006

Surgery for hepatocellular carcinoma arising in hereditary hemochromatosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a well-known complication of hereditary hemochromatosis. The benefit of surgical therapy in this clinical entity is not well documented. The purpose of this study was to evaluate the outcome of such patients both in our own experience as well as in the published literature. METHODS: 320 patients with a diagnosis of HCC were evaluated at our institution to undergo either surgical resection (n = 262) or liver transplantation (n = 58) during the 4- year period from January 2001 to December 2004. We identified 5 patients with HCC arising in the setting of hemochromatosis. A literature search was performed to estimate resectability rates as well as outcomes after liver transplantation for HCC arising in hemochromatosis. RESULTS: HCC was multifocal in 4 instances and solitary in 1 case. The liver was cirrhotic in all but 1 case. Three patients underwent an exploratory laparotomy, 1 an exploratory laparoscopy, and 1 underwent transplantation. HCC was unresectable in all cases. The patient with a solitary tumor and cirrhosis underwent 5 sessions of transarterial chemoembolization and is alive 37 months after surgical exploration. The 3 patients with multifocal tumors who underwent exploratory laparotomies died within 6 months after the intervention. The fifth patient who underwent a deceased donor split liver transplantation for multifocal tumor is alive without recurrence 3 years after transplantation. These results are similar to those in the literature that concur with the low resectability rate and the favorable outcome after liver transplantation. CONCLUSION: Resectability rates of HCCs arising in hemochromatosis are extremely low, given that tumors are usually multifocal and the livers cirrhotic in the majority of the instances. Early detection of hemochromatosis as well as intensive tumor screening of cirrhotic patients with hemochromatosis could possibly optimize the role of surgery or accelerate the decision to proceed with liver transplantation.

Aged↗
PubMed2006

A limited set of human MicroRNA is deregulated in follicular thyroid carcinoma.

CONTEXT: Although the pathogenesis of follicular thyroid carcinoma (FTC) and its relation to follicular adenoma (FA) remains unclear, detailed understanding of FTC carcinogenesis would facilitate addressing the scientific and clinical challenges, given that there are morphological and molecular similarities between FTC and the frequently occurring FA. Micro-RNAs (miRNAs) are a new class of small, noncoding RNAs implicated in development and cancer and may lend novel clues to FTC genesis. For the latter process, a deregulated miRNA can orchestrate the aberrant expression of several hundred target genes. OBJECTIVE: The objective of the study was to identify deregulated miRNAs in FTC. DESIGN: We used two high-density expression arrays to identify miRNAs and their target genes that are differentially expressed between FTC and FA. Validation was done by quantitative RT-PCR. We further functionally characterized the effect of deregulated miRNAs in vitro using HEK293T, FTC133, and K5 cell lines. PATIENTS: In total, 45 primary thyroid samples (23 FTC, 20 FA, four normal control thyroid) were analyzed. RESULTS: Two specific miRNAs, miR-197 and miR-346, were significantly overexpressed in FTC. In vitro overexpression of either miRNA induced proliferation, whereas inhibition led to growth arrest. Overexpression of miR-197 and miR-346 repressed the expression of their predicted target genes in vitro and in vivo. CONCLUSIONS: Our observations show that miR-197 and miR-346 contribute to FTC carcinogenesis. Both miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference, which could potentially normalize the deregulated profile of many downstream target genes.

Adenocarcinoma, Follicular↗
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↗
PubMed2006

Liver transplantation for patients with metastatic endocrine tumors: single-center experience with 15 patients.

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.

Adult↗
PubMed2006

Quality of life and psychiatric complications after adult living donor liver transplantation.

We investigated the psychosocial effects of a right hepatectomy on donors for adult living donor liver transplantation (ALDLT). Questionnaires were sent to 66 actual donors, who had undergone ALDLT between August 1998 and September 2003, as well as to 139 potential donors, who had been examined as possible candidates for ALDLT; the latter had been excluded and had not undergone surgery. All actual donors reported full recovery within an average period of 14.41 (standard deviation = 8.86) weeks; all had returned to their preoperative employment. In preparation for ALDLT, they had received significantly more support from their families in the decision-making process than the potential donors had (t = 2.02; degree of freedom = 79; P = 0.047); they also felt better informed about donation than the potential donors (t = 2.04; df = 64; P = 0.045). Psychiatric problems occurred in 6 (14%) female donors in the perioperative period, mostly in connection with unrealistic outcome expectations. Donors with severe postoperative complications (n = 3) demonstrated higher scores of psychiatric symptoms (chi-square = 6.39; df = 2; P = 0.041). When we compared potential and actual donors, a significant difference in emotional quality of life was not demonstrated (t = 0.41; df = 76; P = 0.684), and it corresponded to that of the normative sample. For donors, perceived emotional quality of life did not depend on the course of recovery of the recipients. Six to 9 months after donation, potential donors reported a significantly higher physical quality of life than actual donors (t = 2.20; df = 56; P = 0.032). In conclusion, female donors, donors with their own major complications, or donors with unrealistic outcome expectations should be provided with adequate psychosocial care. With regard to the psychosocial outcome, ALDLT is a safe intervention for the donor.

Adult↗
PubMed2006

Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors.

BACKGROUND: Treatment with (90)Y- or (177)Lu-DOTATOC has recently been introduced in the palliative treatment of somatostatin receptor-expressing neuroendocrine tumors (NETs). The aim of the study was to present clinical experience with (90)Y- and (177)Lu-DOTATOC therapy in the management of NET. METHODS: To prove suitability for treatment each patient underwent scanning with (111)In-DTPAOC or (68)Ga-DOTATOC positron emission tomography/computed tomography. All patients received [(90)Y-DOTATOC] as initial treatment. In case of disease relapse the treatment was repeated. To avoid side effects of repeated [(90)Y] applications, a switch to [(177)Lu-DOTATOC] was carried out. Clinical, biochemical, and radioimaging responses were documented. RESULTS: Twenty patients with metastatic nonresectable NETs (15 pancreas NETs, 2 midgut NETs, 1 gastrinoma, 1 paraganglioma, 1 NET of unknown primary origin) were included. In 8 patients the treatment was repeated more than once (mean, 3 times; range, 2-5 times). After [(90)Y] treatment moderate toxicity was observed in 8 patients. No serious adverse events were documentable. After restaging, a partial remission was found in 5 patients, stable disease in 11 patients, and tumor progression in 4 patients. CONCLUSIONS: Peptide receptor-targeted radionuclide therapy is a promising, safe, and feasible approach in the palliative therapy of patients with NET.

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↗