Biomedical subjects

A Katalinic

Publications and source records attributed to A Katalinic.

At least 37 records · Page 2Linked to original sources

PubMed2002

Safety aspects of gonadotrophin-releasing hormone antagonists in ovarian stimulation procedures: ovarian hyperstimulation syndrome and health of children born.

The safety of ovarian stimulation procedures or the procedure of assisted reproduction in general can be estimated by various parameters. Two of the most important are the health of children born after the procedure and the incidence of ovarian hyperstimulation syndrome (OHSS). The latter is important because it is the most severe, potentially life-threatening complication of any stimulation procedure. The use of gonadotrophin-releasing hormone (GnRH) antagonists in ovarian stimulation protocols has had no impact on the health of children born. This was proven in 227 children born after the use of cetrorelix and in 73 children born after the use of ganirelix. To analyse the incidence of OHSS and the impact of GnRH antagonists on clinical pregnancy rates compared with the long protocol, a meta-analysis was done. This showed a reduction of OHSS with the use of cetrorelix. Furthermore, when compared with the long protocol, clinical and ongoing pregnancy rates were not significantly reduced with the use of cetrorelix. Taken together, the use of GnRH antagonists are safe with regard to children's health. The incidence of OHSS does not increase with ganirelix, and a reduction can be expected with cetrorelix.

Female↗

PubMed2002

Normal values of fetal ductus venosus blood flow waveforms during the first stage of labor.

OBJECTIVE: To present normal values of fetal ductus venosus blood flow waveforms during the first stage of labor during and between contractions. MATERIALS AND METHODS: Seventy-eight women between the 37th and 41st weeks of gestation were included in the study. At distinct stages of cervical dilation, blood flow velocity waveforms of the fetal ductus venosus during and between contractions were visualized in fetuses with a normal non-stress test. The pulsatility index for veins, peak velocity index for veins and fetal heart rate were calculated off-line. The means +/- standard deviations (SD) during and between contractions were compared using the Wilcoxon test. RESULTS: Ductus venosus blood flow velocity waveforms were visualized during 331 contractions and 375 episodes of uterine quiescence in 74 of 78 fetuses (95%) during normal labor. The mean +/- standard deviation values of pulsatility and peak velocity indices for veins during contractions were 1.66 +/- 0.85 (median: 1.56, range: 0.29-4.69) and 1.46 +/- 0.65 (median: 1.34, range: 0.26-3.13), respectively. Between contractions the values were 0.48 +/- 0.19 (median: 0.46, range: 0.14-1.00) for the pulsatility index and 0.44 +/- 0.18 (median: 0.42, range: 0.14-1.00) for the peak velocity index for veins. These differences during and between contractions were highly significant (P-value < 0.0001), whereas the fetal heart rate showed no significant differences. CONCLUSION: There are significant differences in fetal ductus venosus blood flow waveforms during and between labor contractions. Further studies should evaluate whether these normal values of the fetal ductus venosus are beneficial for risk evaluation in fetuses with an abnormal non-stress test and/or intrauterine growth restriction.

Adult↗

PubMed2002

Doppler assessment of the uterine circulation in the second trimester in twin pregnancies: prediction of pre-eclampsia, fetal growth restriction and birth weight discordance.

OBJECTIVE: To compare singleton nomograms of the uterine circulation with previously established twin nomograms in the prediction of pre-eclampsia, fetal growth restriction (FGR), and birth weight discordance > or = 20% in twin gestations. METHODS: This was a retrospective analysis of maternal and perinatal data obtained from 256 dichorionic twin pregnancies. The mean uterine artery resistance index was calculated from both sides and the presence and absence of notching was recorded. Cut-off levels for abnormal flow parameters were the 95th centile of reference ranges of either singleton or twin nomograms. RESULTS: According to twin reference values, 14.0% of patients were screen positive, compared to only 3.1% when singleton reference values were used. The sensitivity of abnormal uterine artery Doppler results defined by twin nomograms vs. singleton nomograms was 36.4% vs. 18.2% for pre-eclampsia, 26.7% vs. 9.7% for FGR, 28.9% vs. 7.9% for birth weight discordance > or = 20%, and 26.5% vs. 10.3% for any adverse outcome, respectively. CONCLUSION: Despite using specially constructed twin nomograms, uterine artery Doppler studies in twin gestations had an overall low sensitivity in predicting adverse obstetric outcome. Negative predictive values of uterine Doppler studies in twin gestations are lower compared to those reported in unselected singleton pregnancies, i.e. maternal and fetal complications occur more frequently despite normal uterine artery waveforms. This suggests that there is an additional pathomechanism, causing pre-eclampsia and FGR in twin gestations, that is unrelated to uteroplacental insufficiency.

Adult↗

PubMed2002

Tailoring the GnRH antagonist cetrorelix acetate to individual patients' needs in ovarian stimulation for IVF: results of a prospective, randomized study.

INTRODUCTION: This study was performed to evaluate whether a tailored approach to the administration of the GnRH antagonist cetrorelix acetate according to follicular size leads to a reduction in the amount of Cetrotide vials used and/or an increased number of monitoring visits. METHODS: Sixty patients were prospectively randomized (using sealed envelopes) to receive either the fixed multiple dose antagonist protocol starting on day 6 of stimulation (group 1), or an individualized protocol with the time of antagonist start according to follicle size (14 mm, group 2), or an individualized single dose protocol (group 3). Recombinant human (rh)FSH was used. The primary endpoints were the number of Cetrotide vials and number of monitoring visits. Statistical power for the parameter Cetrotide vials was 80%. RESULTS: Patients in group 1 needed significantly more Cetrotide vials (6.81 +/- 1.61) than patients of group 2 (4.59 +/- 1.65; P < 0.01). The number of monitoring visits was similar between the three groups. Surprisingly, the number of retrieved oocytes was significantly higher in the individualized groups as compared with group 1. Despite a significantly lower total amount of rhFSH used, estradiol levels were significantly higher in group 2 as compared with group 1. CONCLUSION: Tailoring of GnRH antagonist protocols leads to an optimization of ovarian stimulation with more oocytes retrieved despite less rhFSH used, and the same number of monitoring visits.

Adult↗

PubMed2001

INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas.

The INK4a-ARF (CDKN2A)- locus on chromosome 9p21 encodes for two tumour suppressor proteins, p16(INK4a) and p14(ARF), that act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in tumorigenesis of hepatocellular carcinoma (HCC), we analysed the alterations of p14(ARF), p16(INC4a) and p53. After microdissection, DNA of 71 hepatocellular carcinomas was analysed for INK4-ARF inactivation and p53 mutation by DNA sequence analysis, methylation-specific PCR (MSP), restriction-enzyme related polymerase chain reaction (RE-PCR), mRNA expression and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INC4a) were assessed by differential PCR. Inactivation of p14(ARF) was found in 11/71 cases (15%), alterations of p16(INK4a) occurred in 47/71 carcinomas (66%), which correlated with loss of mRNA transcription. Five tumours (7%) had homozygous deletions of the INK4a-ARF locus. We failed to detect specific mutations of both exons. P16(INK4a) methylation with an unmethylated p14(ARF) promotor appeared in 39 cases. Mutations of p53 were found in 30 of 71 HCC (42%), and only one of them harboured p14(ARF) inactivation. We failed to establish alterations of the INK4a-ARF locus or p53 status as independent prognostic factor in these tumours. Our data indicate, that p14(ARF) methylation occurs independently of p16(INK4a) alterations in a subset of HCC together with wild type p53. The INK4a-ARF-/p53-pathway was disrupted in 86% of HCC, either by p53 mutations or by INK4a-ARF inactivation, and may have co-operative effects in hepatocarcinogenesis.

Adult↗

PubMed2001

The effect of bowel resection on survival in advanced epithelial ovarian cancer.

OBJECTIVE: FIGO stage III ovarian cancer is further categorized according to the size of tumor, but not according to the organs affected. In this study we evaluated the outcome of patients with and without macroscopic bowel involvement in stage III ovarian cancer. METHODS: This retrospective study analyzed the outcome of 194 ovarian cancer patients with FIGO III with and without bowel involvement who were operated on in our institution between 1985 and 1994. RESULTS: The study demonstrated that maximum tumor reduction without remaining macroscopic cancer offered the best overall survival times in FIGO III ovarian cancer patients. However, whenever the bowel was involved, even maximum bowel resections did not prolong survival compared to patients with remaining tumor after surgery. CONCLUSIONS: This retrospective study demonstrated that bowel involvement in ovarian cancer had a bad prognosis and that survival in these patients could not substantially be prolonged when the affected parts of bowel were resected. To further substantiate these findings, future studies on advanced ovarian cancer should differentiate between patients with and without bowel involvement.

Epithelial Cells↗

PubMed2001

Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta-analysis.

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.

Chorionic Gonadotropin↗

PubMed2001

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.

Abruptio Placentae↗

PubMed2001

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

BACKGROUND: A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). METHOD: All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). RESULTS: Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. CONCLUSION: Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

Administration, Intravaginal↗

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

Radiation therapy for benign diseases: patterns of care study in Germany.

BACKGROUND: Radiotherapy of benign diseases is controversial and rarely applied in Anglo-American countries, whereas in other parts of the world it is commonly practiced for several benign disorders. Similar to a European survey, a patterns of care study was conducted in Germany. METHOD: Using a mailed questionnaire, radiation equipment, treatment indication, number of patients, and treatment concepts were assessed in 1994, 1995, and 1996 in 134 of 152 German institutions (88%): 22 in East and 112 in West Germany; 30 in university hospitals and 104 in community hospitals. Average numbers of each institution and of all institutions were analyzed for frequencies and ratios between regions and among institutions. Radiation treatment concepts were analyzed. RESULTS: A mean of 2 (range 1-7) megavoltage and 1.4 (range 0-4) orthovoltage units were available per institution; 32 institutions (24%) had no orthovoltage equipment. A mean of 20,082 patients were treated annually: 456 (2%) for inflammatory diseases (221 hidradenitis, 78 local infection, 23 parotitis; 134 not specified) 12,600 (63%) for degenerative diseases (2711 peritendinitis humeroscapularis, 1555 epicondylitis humeri; 1382 plantar/dorsal heel spur; 2434 degenerative osteoarthritis; 4518 not specified); 927 (5%) for hyperproliferative diseases (146 Dupuytren's contracture, 382 keloids; 155 Peyronie's disease; 244 not specified); 1210 (6%) for functional disorders (853 Graves' orbitopathy; 357 not specified); and 4889 (24%) for other disorders (e.g., 3680 heterotopic ossification prophylaxis). In univariate analysis, there were geographic (West vs. East Germany) differences in using radiation therapy (RT) for inflammatory and degenerative disorders, and institutional differences (university versus community hospitals) in using RT for hyperproliferative and functional disorders (p < 0.05). The prescribed dose concepts were mostly in the low dose range, <10 Gy but varied widely and inconsistently within geographic regions and institutions. CONCLUSION: Radiation therapy is a well-accepted and frequently practiced treatment for several benign diseases in Germany; however, there are significant geographic and institutional differences. As the number of orthovoltage units decreases, an increasing patient load will demand more megavoltage units, which may compromise the cost-effectiveness of this treatment. Only 4% of all clinical institutions have been involved in controlled clinical trials. To maintain a high level of RT service to other disciplines, RT treatment guidelines, quality control, and continuing medical education are required.

Disease Management↗

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

Analysis of the risk factors associated with endoscopic sphincterotomy techniques: preliminary results of a prospective study, with emphasis on the reduced risk of acute pancreatitis with low-dose anticoagulation treatment.

BACKGROUND AND STUDY AIMS: The aim of the present study was to analyze the risk factors associated with complications of endoscopic sphincterotomy (ES). PATIENTS AND METHODS: In all consecutive endoscopic sphincterotomies carried out between September 1994 and December 1996, the possible risk factors (12 patient-related factors and 12 procedure-related ones), as well as the concomitant medical treatment, indications, techniques, and success of endoscopic sphincterotomy were evaluated prospectively. Risk factors were analyzed on an exploratory basis using univariate methods. "Potential risk factors" (univariate, P<0.1) underwent multivariate analysis to determine independent "risk factors" (multivariate, P<0.05). In addition, the complication rate was calculated according to the number of potential risk factors present. RESULTS: A total of 438 patients who underwent ES were analyzed. Complications occurred in 7.5% (n = 33; acute pancreatitis 4.3%, hemorrhage 2.3 %, cholangitis 0.9%, technical 0.2%). Statistical analysis of the complications identified three independent risk factors (coagulopathy, patient age (< or =60 years, pancreas divisum), and one protective factor (pancreatic duct obstruction). The frequency of acute pancreatitis was increased by two independent risk factors (pancreas divisum, ES frequency <40 procedures/year) and was reduced if low-dose anticoagulation (unfractionated heparin or low molecular weight heparin) was administered (0.9%, one of 115 vs. 5.8%, 18 of 313; P<0.05). The effect of anticoagulation was not confounded by the presence or absence of other potential risk factors for acute pancreatitis. Neither the risk nor the severity of hemorrhage were increased by low-dose anticoagulation. Due to the low number of events, only potential risk factors for hemorrhage were identified (coagulopathy, intensive-care treatment). The overall complication rate and the incidence of pancreatitis and hemorrhage increased significantly depending on the number of simultaneous potential risk factors present (P<0.0001). CONCLUSIONS: Patients at risk for complications after endoscopic sphincterotomy can be identified by risk factor analysis. These data suggest the hypothesis that low-dose anticoagulation prior to endoscopic sphincterotomy reduces the risk of acute pancreatitis after sphincterotomy.

Acute Disease↗

PubMed2000

Experience with the elective transfer of two embryos under the conditions of the german embryo protection law: results of a retrospective data analysis of 2573 transfer cycles.

The German embryo protection law (Embryonenschutzgesetz, ESchG) does not allow embryo selection. Therefore, only as many oocytes at the pronuclear stage (PN), as are planned to be transferred, are allowed to be cultured. It is not known whether, under these conditions, it is possible to reduce the number of embryos for transfer without a corresponding reduction of the overall pregnancy rate (PR). We retrospectively analysed 2573 consecutive transfer cycles following either in-vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection. Out of these cycles, 234, 329 and 792 were performed with one, two, and three embryos respectively, because only that number was available (non-elective transfer). Another 123 and 1095 transfer cycles were performed with two and three embryos, respectively, which were selected from a higher number of PN oocytes (elective transfer). The clinical ongoing PR were 3.9, 9.1 and 17.7% respectively for the groups with non-elective transfer of 1, 2 and 3 embryos, and 22.0 and 22.5% for the groups with elective transfers with two and three embryos, respectively. There was no statistically significant difference in PR between the two elective embryo transfer groups up to the age of 40 years. The multiple pregnancy rate was reduced by 7.9%. The reduction of the number of embryos transferred from three to two can be performed even under the conditions of the ESchG without an effect on the overall PR.

Abortion, Spontaneous↗

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↗

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↗

PubMed1999

Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma.

The prognosis of patients with resectable hepatocellular carcinoma depends mainly on the anatomical 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 and that parameters of cell loss (usually, but not exclusively, due to programmed cell death) are biologically relevant, the identification and quantitation of proliferative capacity and apoptosis may be of prognostic importance. In this study four different methods have been used to assess proliferation in a series of 193 curatively (R0) resected hepatocellular carcinomas: mitotic count, immunohistochemical assessment of MIB-1 (Ki-67), proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNORs). Apoptosis was assessed using the in situ-end labelling (ISEL) technique in combination with morphological criteria. Patients who received liver transplantation were excluded. The results obtained were compared with histopathological stage (according to UICC), Edmondson grade, several other histopathological factors, and survival rate. Significant statistical correlations were seen between the 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 factors influencing patients' survival. On multivariate Cox survival analysis, mitotix index, concomitant cirrhosis, Edmondson grade, and patient age were the only significant independent prognostic factors. Apoptosis was not related to prognosis or to other parameters examined. These results indicated that mitotic index is an additional prognostic parameter which could provide auxiliary information for patients' outcome. MIB-1 and PCNA immunostaining and AgNORs showed a good correlation among themselves. Apoptosis did not predict prognosis in hepatocellular carcinoma.

Apoptosis↗

PubMed1999

[Radiotherapy of benign diseases: a pattern of care study in Germany].

BACKGROUND: Radiation therapy of benign diseases is controversially discussed and rarely applied in Anglo-American countries, while in other parts of the world, especially Central and East Europe, it is commonly practised for several benign disorders. Similar to the European Society of Therapeutic Radiology and Oncology survey, a patterns of care study was performed in Germany. METHOD: A questionnaire was mailed in 3 years (1994, 1995, 1996) to all radiation facilities in Germany, which assessed equipment, indications, number of patients and treatment concepts. A total of 134 (88%) institutions returned all requested data: 22 in East and 112 in West Germany; 30 in university and 104 in community/private hospitals. The average data of each institution and of all institutions were analyzed for frequencies and ratios between different regions and institutions. RESULTS: A mean of 2 (range 1 to 7) megavoltage (Linac/Cobalt 60) and 1.4 (range 0 to 4) orthovoltage units were available per institution; 32 (24%) institutions had no orthovoltage equipment. A mean of 20,082 patients were treated per year: 456 (2%) for inflammatory diseases (221 hidradenitis, 78 nail bed infection, 23 parotitis, 134 not specified), 12,600 (63%) for degenerative diseases (2,711 peritendinitis humeroscapularis, 1,555 epicondylitis humeri, 1,382 heel spur, 2,434 degenerative osteoarthritis, 4,518 not specified), 927 (5%) for hypertrophic diseases (146 Dupuytren's contracture, 382 keloids, 155 Peyronie's disease, 244 not specified), 1,210 (6%) for functional disorders (853 Graves' orbitopathy, 357 not specified), and 4,889 (24%) for other disorders (e.g. 3,680 heterotopic ossification prophylaxis). In univariate analysis, there were significant geographical (West vs East Germany) differences in the use of radiotherapy for inflammatory and degenerative disorders and institutional differences (university vs community/private hospitals) in the use of radiotherapy for hypertrophic and functional disorders (p < 0.05). The prescribed dose concepts were mostly in the low dose range (< 10 Gy), but varied widely and inconsistently within geographic regions and institution types. CONCLUSION: Radiotherapy is a well accepted and frequently practised treatment for several benign diseases in Germany, however, there are significant geographical and institutional differences. As the number of orthovoltage units decreases, an increasing patient load is in demand of more megavoltage units, which may compromise the cost-effectiveness of this treatment. Only 4% of all clinical institutions are involved in controlled clinical trials. To maintain a high level of radiotherapy service to other disciplines, radiotherapy treatment guidelines, quality control and continuing medical education are required.

Dose Fractionation, Radiation↗