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A Tannapfel

Publications and source records attributed to A Tannapfel.

At least 91 records · Page 5Linked to original sources
PubMed2000

Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma.

Reduced expression of the cyclin-dependent kinase inhibitor p27 has previously been correlated with fatal clinical outcome in some tumors, including gastric, breast, and prostate cancers. For hepatocellular carcinoma, the findings are equivocal. In situ hybridization and immunohistochemistry were performed on a series of 203 curatively (R0) resected hepatocellular carcinomas and in corresponding non-cancerous liver tissue to detect p27. Patients receiving liver transplantation were excluded. The results were correlated with histopathological stage according to the UICC system, Edmondson grade, several other histopathological factors of possible prognostic significance, and finally patient survival. Whereas p27 mRNA was expressed homogeneously in all carcinomas examined, the p27 protein was found in various amounts. The labeling index of p27 protein was significantly lower in advanced stages of the disease (P < 0.001, chi(2) = 28.1). We observed decreased p27 protein in higher pT categories (P < 0.001, chi(2) = 24.7) and in multiple tumor nodules (P < 0.001, chi(2) = 9.3). Multivariate Cox survival analysis identified age, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. We conclude that evaluation of p27 in hepatocellular carcinoma is useful to predict stage of disease and may have clinical significance, e.g., in predicting optimal therapeutic regimes.

Adult↗
PubMed2000

p53 mutation pattern in hepatocellular carcinoma in workers exposed to vinyl chloride.

BACKGROUND: Vinyl chloride (VC) is a known animal and human carcinogen that is associated with liver angiosarcoma and most likely also with hepatocellular carcinoma (HCC) in humans. METHODS: The authors examined the presence of p53 gene mutations in 18 HCC specimens from patients with known exposure to VC (median, 8883 parts per million-years; median duration, 245 months). In all cases, other risk factors for the development of HCC (hepatitis B virus and hepatitis C virus infections, alcohol consumption, and metabolic or autoimmune disorders) were excluded. Three patients had concomitant cirrhosis. The p53 gene was examined by direct sequencing of exons 5-9. RESULTS: Mutations of the p53 gene were found in 11 of 18 HCCs examined. The point mutations detected were comprised of five transversions and five transitions. Five of 11 mutations (codons 175, 245, 248, 273, and 282) occurred at CpG sites. Histopathologic liver alterations (mild sinusoidal dilatation, [portal] fibrosis, and centrilobular siderosis) in tumor surrounding nonneoplastic liver confirmed exposure to VC. CONCLUSIONS: The results of the current study indicated a relation between VC exposure and the development of HCC. The mutation pattern of p53 with a nearly equal rate of incidence of transitions and transversions and a high rate of incidence of mutations at CpG sites may reflect endogenous mechanisms (e.g., deamination of 5-methylcytosine) rather than exogenous carcinogens.

Aged↗
PubMed2000

Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival.

Median survival time of nonresectable hilar bile duct cancer is only 4 to 6 months owing to tumor spread in the biliary tree, refractory cholestasis, and sepsis or liver failure. We explored whether local photodynamic therapy of nonresectable bile duct cancer could improve survival. A sample size of 23 patients is required to detect an increase in 6-month survival rate from less than 50% to greater than 70% in a single-arm phase-II trial with a statistical power of 80% (Fleming's single step procedure; alpha = 0.05). Twenty-three consecutive patients (8 women, 15 men; 67 +/- 14 years) with nonresectable bile duct cancer (Bismuth type III n = 2, type IV n = 21) were treated with photodynamic therapy and biliary endoprosthesis. Photofrin (QLT Pharmaceuticals, Vancouver, Canada) (2 mg/kg body weight intravenously) was photoactivated after 1 to 4 days with laser light (630 nm; 242 J/cm(2)) via endoscopic retrograde access. The 6-month survival rate was 91% after diagnosis and 74% after start of photodynamic therapy (30-day mortality rate was 4%) at a median follow-up time of 10.3 months after diagnosis. Causes of death were tumor progression (n = 9) and bacterial infections (n = 4). The median rate of local tumor response was 74%, 54%, 29%, and 67% after the first, second, third, fourth, and fifth photodynamic therapy. Time to progression ranged from 3 to 8 months. All patients, except 1 with diffuse liver metastases, improved in cholestasis, performance, and quality of life. Photodynamic therapy can prevent tumor occlusion of hilar bile ducts. The apparent benefit in survival time should be confirmed in a controlled trial versus palliation by endoprosthesis only.

Adenocarcinoma↗
PubMed2000

[Treatment concept of adenomas of Vater's ampulla].

INTRODUCTION: The most common benign ampullary tumors are adenomas (80%). They are considered as premalignant lesions with a transformation rate to carcinoma of up to 30%. METHODS: From 1 January 1997 to 28 February 1999 we treated 11 patients with adenoma of the ampulla of Vater. An ampullectomy was performed in 10 cases. One poor-risk patient could not be operated on. RESULTS: No operative mortality occurred. In two patients a pT1 adenocarcinoma was diagnosed postoperatively. One of the two patients with a high-risk carcinoma underwent a second operation, a Whipple pancreatoduodenectomy. Nine of 10 patients had no recurrence with a median follow-up of 12 months. CONCLUSION: One patient died of glioblastoma. We would therefore recommend ampullectomy as the first-line treatment for benign tumors of the ampulla of Vater. In low-risk pT1 carcinoma (G1/G2, L0) and R0 resection, local excision is acceptable. In high-risk pT1 carcinoma (G3 and/or L1) Whipple pancreatoduodenectomy is mandatory.

Adenocarcinoma↗
PubMed2000

Evaluation of ultracision in lung metastatic surgery.

BACKGROUND: There are very few studies on the histological outcome of lung metastatic surgery using the Ultracision particularly in deeper areas of the lung. METHODS: In a prospective study, we resected 24 lung metastases from 18 patients using the Ultrasonic scalpel (Ethicon Endo-Surgery, Norderstedt, Germany). We analyzed the risk of bleeding and air leakage as well as the histopathological features of the resection area. RESULTS: There was no intraoperative bleeding and, in 72%, no intraoperative air leakage. The resection surface was closed with a suture. In 8 cases, the metastases were located deeply, near the hilus of the lobe which did not necessitate a lobectomy. Histologically, occluded blood vessels as well as occluded small bronchioli under 0.1 cm were observed. There was no evidence of deep tissue destruction. No postoperative complications occurred. CONCLUSIONS: Ultracision in metastatic lung surgery is an appropriate method of treatment with minimum risk of bleeding or air leakage. This procedural approach allows for adequate resection of lung metastases while sparing a generous amount of healthy lung tissue.

Adult↗
PubMed2000

Effect of venous drainage site on insulin action after pancreas transplantation in the rat--is there insulin resistance and a risk for atherosclerosis?

The aim of the present study was to determine the influence of the venous drainage site on insulin homeostasis and the possible risk for atherosclerosis development after pancreas transplantation. We studied inbred rats that received pancreas transplants with either systemic (STX) or portal (PTX) venous drainage after prior induction of diabetes with streptozotocin and sham-operated controls. The observation period was 6 months. Fasting plasma glucose and insulin levels were similar in all 3 groups, but fasting plasma glucagon levels were elevated in STX (mean +/- SEM, 282+/-35 ng/L) in comparison to PTX rats (119+/-9 ng/L, P < .05), although the difference versus the control group (191+/-31 ng/L) was insignificant. Glucose utilization and hepatic glucose production (HGP), assessed by a dose-response euglycemic-hyperinsulinemic clamp in combination with tritiated glucose infusion, were similar in all 3 groups. The groups were also similar with respect to the molar ratio of plasma C-peptide and insulin during basal steady state and the metabolic clearance rate (MCR) of insulin during the clamp studies, suggesting an unchanged hepatic insulin extraction (HIE) after transplantation with either technique. Factors known to be related to atherosclerosis, ie, blood pressure, intracellular magnesium, and fasting levels of plasma cholesterol, triglycerides, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, were similar in all 3 groups. Light microscopy of the aorta showed a slightly thicker intima in STX rats (24.3+/-0.5 microm, P < .05) versus PTX rats (21.4+/-0.7 microm) and control (21.4+/-0.6 microm); however, atherosclerosis-like lesions were absent in all 3 groups. In conclusion, in a rat model with streptozotocin-diabetes and pancreas transplantation but no need for immunosuppression, both systemic and portal venous drainage avoid peripheral and hepatic insulin resistance; also, there is no increased risk for atherosclerosis.

Animals↗
PubMed2000

Neoadjuvant photodynamic therapy before curative resection of proximal bile duct carcinoma.

BACKGROUND: Hilar bile duct carcinoma has an 80% probability of local recurrence after curative resection, which might be reduced if neoadjuvant photodynamic therapy is feasible. CASE AND TREATMENT: After intravenous injection of sodium porfimer we treated an adenocarcinoma of the proximal common bile duct (T2 N0 M0, Bismuth type II) in a 72-year-old man with red laser light (applied from the lumen at a dose 250 Joules/cm2), and the adjacent right and left hepatic and common bile duct at a dose of 125 Joules/cm2. After 23 days the tumor was completely resected (adenocarcinoma pT2 pNO; G2). RESULTS: In the lumenal, 4-mm-thick layer the bile duct specimen exhibited complete tumor necrosis with pigmentation of photodegraded porfimer and no viable tumor cells, while in the outer layer of the wall (at 5-8-mm depth) viable cancer cell nests without degraded porfimer were seen. The bile duct tissue showed little damage. Eighteen months after surgery, neither tumor recurrence nor stricture formation was found at the pretreated bilioenteric anastomoses. CONCLUSIONS: a) Photodynamic therapy with sodium porfimer seems to be confined to the superficial 4-mm layer of bile duct cancer. b) Neoadjuvant photodynamic therapy is feasible for hilar bile duct carcinoma.

Adenocarcinoma↗
PubMed2000

Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver.

This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0-) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4-9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a G-->C and C-->T transition, changing the hot spot amino acid determined by exons 4-8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.

Apoptosis↗
PubMed2000

Description of an intraperitoneal tumour xenograft survival model in the pig.

AIMS: Experimental animal studies are necessary if the results of minimally invasive oncological surgery are to be improved. In particular the influence of surgical technique on tumour implantation needs further assessment. Small animals such as rodents are inappropriate for such laparoscopic surgical studies. There is a requirement for another animal tumour model with animals greater in size. METHODS: Accordingly we developed an intraperitoneal tumour xenograft survival model using the domesticated pig. After creating a 12 mmHg pneumoperitoneum, 10(7)human HeLa cells were injected into the peritoneal cavity of nine non-syngeneic animals to induce tumour xenograft. Resection of the sigmoid colon using four trocars and a transanal double-stapling technique was performed. The mean operating time was 69 min. No signs of post-operative pain symptoms were observed, and all the animals survived the procedure and gained weight. After 4 weeks, the animals were sacrified and all incision sites and anastomoses were excised. RESULTS: Immunohistochemical staining with antihuman pancytokeratin antibodies confirmed tumour implants in 25 out of 36 port-sites (63.8%). No peritoneal carcinosis nor tumour implants at anastomosis sites were observed. CONCLUSION: This intraperitoneal xenograft tumour model in the pig can be applied in survival studies to check the quality of surgical techniques and its influence on tumour implantation following laparoscopy for cancer.

Animals↗
PubMed2000

Acute rejection of hepatic allografts from HLA-DR13 (Allele DRB1(*)1301)-positive donors.

Acute rejection of hepatic allografts does not show consistent association with the number of mismatches of HLA classes I and II. Therefore, we investigated the relation between specific donor or recipient HLA antigens and the occurrence of acute rejection. HLA typing of 35 liver transplant recipients and donors was performed by serological standard technique, with confirmation and subtyping by polymerase chain reaction with sequence-specific primers. HLA class I antigens were not associated with the occurrence of acute rejection. The graft was positive for HLA-DR13 in 8 of 13 transplant recipients (62%) with acute rejection, but only 4 of 22 recipients (18%; P =.024; P(Bonferroni-corrected) =.33, not significant) without rejection. The graft was positive for DRB1*1301 in 7 of 13 recipients (54%) with acute rejection, but only 1 of 22 recipients (5%) without rejection (P =.002; P(Bonferroni-corrected )=.028). This patient had experienced long-lasting bacterial sepsis, which markedly reduced the risk for acute rejection. We speculate that the expression of donor DRB1*1301 (if mismatched) may increase the risk for acute hepatic allograft rejection.

Acute Disease↗
PubMed2000

Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver.

BACKGROUND: Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies. AIMS: To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver. METHODS: The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Hypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients. CONCLUSION: These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.

Bile Duct Neoplasms↗
PubMed2000

Cyclical endometrial steroid hormone receptor expression and proliferation intensity in the mare.

The aims of this study were to investigate the steroid hormone receptor expression and the proliferation intensity during the equine endometrial cycle by immunohistological methods, established for routine examination of formalin-fixed, paraplast-embedded specimens. Endometrial biopsy specimens were obtained during one cycle from 7 mares. In comparison with the blood steroid hormone levels the quantity and distribution of oestrogen (ER) and progesterone receptors (PR) and the proliferation marker Ki-67 antigen expression were investigated. Rising 17beta-oestradiol concentrations in preoestrus induce a synchronous expression of ER, PR and Ki-67 antigen in stromal cells. In the early dioestrus 17beta-oestradiol levels decrease and progesterone levels reach their maxima. This correlates with an intense proliferation activity and the highest hormone receptor expression in epithelial cells. In accordance to the morphological features of asynchronous glandular differentiation in fibrotic areas (endometrosis) their epithelial hormone receptor expression is out of phase.

Animals↗
PubMed2000

[Prognostic significance of proliferation markers in hepatocellular carcinoma (HCC)].

BACKGROUND: The prognosis of patients with curatively resectable hepatocellular carcinoma depends mainly on anatomic extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas, identification and quantitation of proliferative capacity may be of prognostic importance. METHODS: We have compared four different methods to assess proliferation in a series of 193 curatively (R0-) resected hepatocellular carcinomas: Mitotic count, immunohistochemical assessment of the MIB-1- (Ki-67-), Antigen Proliferating Cell Nuclear Antigen (PCNA) and silverstained nucleolar organiser regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), Edmondson Grade and with survival rate. RESULTS: In each carcinoma, we could demonstrate mitotic figures, MIB-1, PCNA and AgNOR dots in variable proportions. Significant statistical correlations were seen between Mitotic Index, the rate of nuclear positivity for MIB-1 and PCNA and the number of AgNOR dots. In univariate survival analysis tumour stage and Edmondson Grade, Mitotic Index, MIB-1 and PCNA Index and mean AgNOR-number were significant patients' survival influencing factors. Performing multivariate Cox survival analysis, Mitotic Index, concomitant cirrhosis, Edmondson Grade and patient age were the only significant independent prognostic factors. CONCLUSION: These results indicated that Mitotic Index is an additional prognostic parameter which could provide auxiliary information for patients' outcome.

Adult↗
PubMed2000

[Isolated tumor cells in primary malignant liver tumors].

The failure to reduce the mortality of patients with malignant liver tumors (hepatocellular carcinoma, cholangiocarcinoma) is probably a result of the early dissemination of cancer cells to secondary sites, which is usually missed by conventional diagnostic procedures used for tumor staging. Recent developments in the field of molecular biology enable us to detect tumor cells at a submicroscopic level. Therefore, over the past 10 years, sensitive assays have been developed to detect individual carcinoma cells disseminated to regional lymph nodes or distant organs. In contrast to colorectal and also breast cancer where disseminated tumor cells may be of additional prognostic value, few data exist for hepatocellular carcinomas. Until now, no relevant studies have been reported for cholangiocarcinoma. Alpha-fetoprotein and also albumin mRNA have been used for the detection of circulating micrometastatic tumor foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. If hepatocyte-specific mRNAs are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells. The literature about the incidence of "micrometastases" and specificity of different assays for hepatocellular carcinomas varies tremendously. This clearly indicates the need for uniformity in protocols. For hepatocellular carcinoma, mRNA for alpha-fetoprotein and albumin is not a specific marker of circulating micrometastases, but may serve for treatment monitoring. Nevertheless, PCR-based techniques are a powerful tool in the therapeutical monitoring of hepatocellular carcinoma and will find their way into the daily practice of diagnostic histopathologists in the near future.

Bile Duct Neoplasms↗
PubMed2000

[Indications for liver biopsy in liver tumors].

Significant progress has been made in the assessment of liver dysfunction by application of non-invasive physical and biochemical test procedures. However, liver biopsy remains an important tool for diagnosis, evaluation and prognosis of chronic liver diseases and hepatic neoplasms. Liver biopsy results are most useful when the biopsy is performed for well-defined indications following a complete work-up of the patient. In case of lesions highly suspicious for hepatocellular carcinoma, a biopsy should be performed in case surgical (curative) treatment is no option. Thus for the planning of a surgical intervention, biopsy of the tumor is not necessary. In case of concomitant liver cirrhosis, a biopsy taken from the non-neoplastic (cirrhotic) liver may help to assess the functional capacity or to clarify the etiology. Metastases of the liver with unknown primary tumor should be biopsied to obtain information of the primary tumor and the potential for cytostatic therapy. In case of hemangioma or focal nodular hyperplasia, diagnosed and confirmed by radiology or ultrasound, biopsy is usually not necessary. Concern has been expressed about seeding of the needle tract with malignant cells. Indeed, such instances have been recorded with various carcinomas, but they remain rare events and are seldom of clinical importance. With the use of needles with diameter < 1.3 mm to minimise also the risk of bleeding, the procedure is simple, safe and painless.

Biopsy, Needle↗
PubMed2000

[Hepatocellular carcinoma: resection versus transplantation].

For decision of adequate surgical therapy and comparison of results differentiation of hepatocellular carcinomas (HCC) in cirrhotic and noncirrhotic livers is important. Liver resection is the treatment of choice for HCC in noncirrhotic liver. Between 4/94 and 8/99 we treated 54 patients with hepatocellular carcinoma (HCC) by subtotal hepatic resection (n = 40) and orthotopic liver transplantation (n = 14). Overall 1- and 3-year survival rates of the resection group were 45 and 25% (median follow up: 3.5 years). One-year survival in the transplantation group was 72% (median follow up: 2.2 years). In patients with HCC in cirrhosis in UICC stage I to III the optimal therapy is a controversial issue. In these patients the results after liver resection are poor due to high operative mortality and recurrence (3-year recurrence-free survival: 30%). Regarding the literature, liver transplantation is the treatment of choice in small (< 3-5 cm, < or = 2 tumors) HCCs arising in cirrhosis with better outcome compared to resection. The data in the literature report 3-year-survival rates after liver transplantation of 60-80%. However, consequent patient selection is necessary for this treatment modality. Due to the limited donor resources liver transplantation is rarely justified in advanced tumors.

Carcinoma, Hepatocellular↗
PubMed1999

Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma.

BACKGROUND: The protein p73, the first identified homologue of the tumor suppressor gene p53 (also known as TP53), has been shown to induce apoptosis (programmed cell death), but its function in tumor development has not been established. This study was undertaken to investigate the expression of p73 in liver tissue of patients with hepatocellular carcinoma (HCC) and to determine whether this expression has any impact on prognosis. METHODS: In situ hybridization and immunohistochemistry for the detection of p73 RNA transcripts and protein, respectively, were performed in tissues from 193 patients with curatively (R0-) resected HCC. Patients receiving liver transplantation were excluded. The results obtained were analyzed with respect to their association with pathohistologic stage, Edmondson grade, p53 expression status and several histopathologic factors of possible prognostic value, and, finally, with patient survival. RESULTS: RNA transcripts encoding p73 were detected by in situ hybridization in tumor cells but not in stromal, endothelial, or inflammatory cells or in cholangiocytes. Transcripts were also found occasionally in non-neoplastic hepatocytes. By immunohistochemistry, we detected p73 protein in 61 (32%) of the 193 carcinomas examined. Positive immunohistochemical staining was confined to the cell nucleus. Univariate survival analysis showed that p73 expression status was statistically significantly related to prognosis (two-sided P<.0001). Patients with p73-positive tumors had a poorer prognosis than those with p73-negative carcinomas. Multivariate Cox survival analysis identified the age of the patient, p73 expression status, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. CONCLUSION: The protein p73 is overexpressed by a subset of HCCs and could serve as a useful indicator of prognosis in patients with this disease.

Apoptosis↗