Biomedical subjects

S Wellek

Publications and source records attributed to S Wellek.

At least 37 records · Page 2Linked to original sources

PubMed1995

Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II.

In a multicentre randomised clinical trial 364 children with biopsy proven medulloblastoma were randomly assigned to receive or not pre-radiotherapy chemotherapy. Children with total or subtotal removal of the tumour, no evidence of invasive brain stem involvement, and no evidence of metastatic disease either within or without the cranium were designated "low risk", those with gross residual tumour, evidence of invasive brain stem involvement or metastases in the central nervous system were designated "high risk". All children were prescribed 55 Gy to the tumour bearing area. "Low risk" children could be randomised to "standard" radiotherapy 35 Gy to the craniospinal axis or "reduced" dose 25 Gy to the craniospinal axis. Chemotherapy consisted of vincristine, procarbazine, and methotrexate given in a 6-week module before radio-therapy, and for "high risk" children, vincristine and CCNU given after radiotherapy. No benefit for the receipt of pre-radiotherapy chemotherapy could be demonstrated for any group. In addition, a negative interaction was observed between the receipt of the chemotherapy and reduced dose radio-therapy with a particularly poor outcome being observed in this group of children.

Adolescent↗

PubMed1995

[Orbital diameter, inner and outer orbital distance. A growth model of fetal orbital measurements].

AIM: Aim of this study was to establish a growth model for the intrauterine growth of the following fetal parameters: orbital diameter, interorbital and biocular diameters. METHOD: Data were measured in a prospective cross-sectional study with real-time ultrasound. The study group consisted of 1090 healthy fetuses between 12 and 41 weeks gestation. For curve standardisation a growth model for all parameters was used. RESULTS: Using this growth model growth profiles (5., 50., and 95. percentiles) were established. All orbital parameters showed a nonlinear growth. CONCLUSION: Since ocular and orbital malformations (anophthalmia, microphthalmia, hypo- and hypertelorism) are often principal signs of generalised syndromes, orbital biometry is helpful for a detailed prenatal investigation of the fetal face. This is demonstrated in 2 cases with an orbital malformation (orbital hypoplasia, hypotelorism).

Cephalometry↗

PubMed1995

[Normal ultrasound curves of the fetal osseous thorax and fetal lung].

Over and above the evaluation of fetal standard data, chest and lung measurements were performed in a prospective cross-sectional study with real-time ultrasound. The study group consisted of 610 patients between 12 and 41 weeks' gestation. Only uncomplicated pregnancies with carefully documented gestational age were included. Patients with multiple pregnancy, fetal anomalies, intrauterine growth retardation or macrosomia and patients with oligohydramnios were excluded. Transversal (BTTD) and sagittal (BTSD) diameter of the bony fetal thorax were measured as an outer-outer-measurement at the level of the atrioventricular valves; the thorax should be as circular as possible and at right angles to the fetal spine. Lung measurements (LD) were performed in the same plane in the direct extension of the long axis of the fetal heart. The circumference of the bony thorax (BTC) was calculated from the two thoracic diameters according to the formula BTC = (BTTD+BTSD)/2 x 3.142. For all parameters growth curves with 5., 50. and 95. percentiles were established. Growth of the bony thorax as well as the lung diameter was shown in a nonlinear function. Lung diameter and thoracic circumference were used to calculate the ratio of these two parameters with reference to the gestational age.

Anthropometry↗

PubMed1995

Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience.

A total of 83 patients with nonorgan-confined bladder cancer with or without lymph node metastases (tumor stages pT3b, pT4a and/or pN1, pN2) was evaluated in November 1993 for relapse-free and overall survival. All patients underwent radical cystectomy between 1987 and 1991, 38 underwent adjuvant polychemotherapy with methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC). Of the 83 patients 49 had entered a prospective randomized trial comparing adjuvant to no adjuvant treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of the 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log-rank test for relapse-free survival curves). Preliminary data were published in 1992. Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC, 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. The update of patient followup obtained in November 1993 continues to demonstrate a significant improvement in progression-free survival in favor of patients randomized for adjuvant chemotherapy (p = 0.0005). Followup of patients living free of disease ranged from 38 to 78 months. In a second analysis of actual treatment, the total collective of 83 patients treated from 1987 to 1991 was reviewed: 38 who had actually undergone adjuvant M-VAC/M-VEC (18 during the prospective trial and 20 in 1991 as the routinely recommended therapy) were compared with 45 without adjuvant M-VAC/M-VEC (7 refused to participate in the adjuvant trial, 8 randomized for but did not undergo adjuvant M-VAC/M-VEC, 23 belonged to the control group of the trial, and 7 underwent cystectomy in 1991 and remained without adjuvant treatment). This analysis again revealed a significant prognostic advantage in favor of the patients treated with adjuvant M-VAC/M-VEC. We conclude that adjuvant chemotherapy with M-VAC/M-VEC leads to a significant prolongation of relapse-free survival and to an improvement of the definitive cure rates after radical cystectomy for locally advanced transitional cell carcinoma of the bladder.

Adult↗

PubMed1995

Age-related reference ranges for growth parameters.

We propose an approach to the computation of age-related reference ranges which guarantees that the proportion of sampled data points covered by the reference band has an arbitrarily specified value. Unlike other approaches in the literature, this method does not have to rely on parametric distributional assumptions. The boundaries of the bands are given by smooth curves, and for modeling the mean as a function of age, a sufficiently flexible class of monotonically increasing functions is used, since in the applications all measured variables are biological growth parameters. The width of the reference band is allowed to be proportional to any suitably fixed function of age which we propose in practice to be taken linear. The approach is illustrated by examples from a large-scale study of the distribution of fetal size measurements obtained by routine prenatal sonography.

Age Factors↗

PubMed1994

Factors influencing survival after resection of pancreatic cancer. A DNA analysis and a histomorphologic study.

BACKGROUND: The influence of DNA content on prognosis in stomach cancer has been investigated rarely, and the results are controversial. METHOD: The prognostic relevance of the DNA content and histomorphologic parameters was evaluated in 41 patients after resection of pancreatic cancer. RESULTS: In the univariate analysis, the DNA content, tumor size, lymph node status, tumor stage, nuclear grade, and type of resection had a statistically significant influence on the prognosis. No association was found between the DNA content and the histomorphologic features. Apart from the operative procedure, the DNA content was the strongest indicator of prognosis in the multivariate analysis. CONCLUSIONS: Further investigations are necessary to find out if DNA analysis can be performed preoperatively on material obtained by fine-needle aspiration.

Cell Nucleus↗

PubMed1994

Intraocular thymoxamine or acetylcholine for the reversal of mydriasis.

In a placebo-controlled prospective study, thymoxamine 0.02% or acetylcholine 1.0% or thymoxamine 0.01% plus acetylcholine 0.5% were used intraocularly to reverse mydriasis during cataract surgery. Prior to surgery, pupils were dilated with scopolamine 0.25%, tropicamide 1%, and phenylephrine 10%. At the end of surgery, 228 eyes were randomly assigned to 1 of 4 different treatments: 57 eyes each received intracamerally thymoxamine 0.02%, acetylcholine 1%, a combination of both drugs, or placebo. At 5 min posttreatment, there was a significant mean pupillary constriction of 1.86 +/- 0.67 mm following acetylcholine administration and 1.53 +/- 0.80 mm following thymoxamine application as compared with the placebo group, in which the pupillary diameter remained almost constant. For the combination of acetylcholine plus thymoxamine the effect was fully additive, with a pupillary constriction of 3.42 +/- 0.98 and 4.04 +/- 1.02 mm being observed at 5 and 10 min posttreatment, respectively. No drug-related side effect was detected. We conclude that thymoxamine can be useful during surgery as an intraocular miotic to reverse mydriasis and can considerably enhance miosis when given in combination with acetylcholine.

Acetylcholine↗

PubMed1994

Epidemiology of hepatocellular carcinoma. Evaluation of viral and other risk factors in a low-endemic area for hepatitis B and C.

To assess whether hepatocellular carcinoma (HCC) in patients with cirrhosis of the liver is associated with particular risk factors, a retrospective, case-control study was performed. Eighty-six patients with HCC (90% had underlying cirrhosis of the liver) were compared with 86 controls who had cirrhosis but not hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and to hepatitis C virus (anti-HCV) were evaluated; and alcohol and nicotine abuse were assessed by history. The prevalence of HBsAg and anti-HBc was similar in both, case and control patients. Antibodies to hepatitis C virus were detected more frequently among patients with HCC and cirrhosis (37%) compared to cirrhosis alone (22%). Alcohol abuse was found more frequently in patients with cirrhosis alone. Smoking habits were comparable between the two groups. None of the tested variables were related to an increased risk for HCC. Using an ordinary logistic regression approach, none of the variables could be identified as an independent risk factor for HCC. However, the combination of hepatitis B virus infection and hepatitis C virus infection was more prevalent in the patients with hepatocellular carcinoma and cirrhosis (48%) when compared to patients with cirrhosis alone (13%) (odds ratio 6.364; CI 1.149-35.229). In conclusion, we failed to identify independent risk factors for the development of HCC in Germany. However, the combination of hepatitis B and C virus infection increases the risk for liver cancer. Molecular analyses have to be performed to elucidate viral hepatocarcinogenesis.

Aged↗

PubMed1993

Prognostic value of DNA analysis in colorectal carcinoma.

BACKGROUND: Reported experiences regarding the prognostic significance of DNA content in colorectal carcinoma have been a matter of controversy. METHODS: DNA analysis with image cytometry was performed in 137 patients with colorectal cancer. Only patients who had resection without tumor residual and who did not die postoperatively as a consequence of the operation were entered in the study. At the time of DNA analysis, neither the histomorphologic data nor the relapse-free survival time of the patients were known. RESULTS: In this investigation the DNA content of tumor cells had no univariate or multivariate influence on the relapse-free survival time. The prognosis was dependent on the tumor localization, depth of tumor infiltration, lymph node metastasis, and grade. CONCLUSIONS: DNA content provides no additional prognostic information in colorectal carcinoma.

Adult↗

PubMed1993

[The role of M-VAC polychemotherapy in the treatment of advanced urothelial carcinoma of the bladder].

Over the last seven years, M-VAC combination chemotherapy has been used for: the treatment of transitional cell carcinoma with metastases (palliative indication) or to reduce operable T4a tumours (inductive, initial or preliminary indication), or before or after t for bladder cancers (neoadjuvant and adjuvant indications). The authors present their experience of 17 cases of stage T4a transitional cell carcinoma transformed into an operable stage by M-VAC. Those patients with regression of the tumour to a non-invasive stage at operation (patients with a good response) had a good prognosis. In contrast those patients with residual invasive tumour all died from their disease. A prospective comparative study was performed between total cystectomy alone and cystectomy completed by adjuvant M-VAC in patients with a worrying histology. This study was based on 49 cases up until December 1990. A significant improvement in the prognosis was observed in patients receiving adjuvant M-VAC. The recurrence-free survival was considerably prolonged in this second group (study suspended in November 1992). When metastases developed, palliative M-VAC only rarely prolonged survival.

Adult↗

PubMed1993

A log-rank test for equivalence of two survivor functions.

We consider a hypothesis testing problem in which the alternative states that the vertical distance between the underlying survivor functions nowhere exceeds some prespecified bound delta > 0. Under the assumption of proportional hazards, this hypothesis is shown to be (logically) equivalent to the statement [beta[ < log(1 + epsilon), where beta denotes the regression coefficient associated with the treatment group indicator, and epsilon is a simple strictly increasing function of delta. The testing procedure proposed consists of carrying out in terms of beta (i.e., the standard Cox likelihood estimator of beta) the uniformly most powerful level alpha test for a suitable interval hypothesis about the mean of a Gaussian distribution with fixed variance. The computation of the critical constant of this test is very easy in practice since it admits a representation as the root of the alpha th quantile of a noncentral chi-square distribution with a single degree of freedom.

Biometry↗

PubMed1993

[Value of image analysis DNA cytometry in cancer of Vater's ampulla].

In 27 patients who underwent partial duodenopancreatectomy due to cancer of the ampulla of Vater, in addition to the TNM classification and usual morphologic criteria, the paraffin-embedded material underwent deparaffinization, was rehydrated, and was mechanically and enzymatically processed into a single-cell solution. For evaluating the DNA histogram this was analyzed with the help of automatic single cell cytophotometric study. At the time of DNA analysis the histomorphological data and the survival time of the patients were not known. In the univariate analysis the 5-year survival rate of patients with diploid or hypotriploid tumors (n = 12) was 69% of patients with diclonal (diploid-triploid n = 7, triploid-tetraploid n = 1) tumors was 62.5% and no patient with a triploid or hypertriploid tumor (n = 7) survived 5 years. No association could be found between the known prognostic criteria and the DNA content. The multivariate analysis shows that beside the lymph node status, the DNA content of tumor cells had a strong and independent influence on the prognosis in cancer of the ampulla of Vater.

Adenocarcinoma↗

PubMed1992

DNA image cytometry in stomach carcinoma. Its relation to histomorphologic parameters and its influence on prognosis.

BACKGROUND: The influence of DNA content on the prognosis in stomach cancer is controversial. METHOD: After curative resection of stomach carcinomas (adenocarcinomas [n = 58]; signet ring cell carcinomas [n = 24]; undifferentiated carcinomas [n = 21]), the influence of the DNA content and histomorphologic parameters on the prognosis was examined. RESULTS: In the multivariate regression analysis, the prognosis depended on the lymph node status (P = 0.0009), pT stage (P = 0.02), tumor localization (P = 0.03), and histologic type (P = 0.05). The prognosis was independent of the DNA content. Furthermore, the degree of differentiation, operative procedure, safety distance, size of the tumor, and sex and age of the patient also did not influence the prognosis. CONCLUSIONS: The DNA content of the tumor cells in stomach carcinoma does not influence prognosis.

Adenocarcinoma↗

PubMed1992

[Image cytometric DNA analysis in the evaluation of the risk of recurrence after resection of rectal carcinoma].

Prognostically relevant factors derived from re-operative endoluminal US examination or the histopathological work-up of the surgical specimen in carcinoma of the rectum are well known. We investigated the question as to whether the DNA content of tumor cells is an independent influencing factor of prognosis after resection of rectal carcinoma. In 68 patients who underwent resection for rectal carcinoma, in addition to the TNM classification and the usual morphological evaluation, the paraffin-embedded tumor material was de-paraffinized, rehydrated and treated mechanically and enzymatically prior to application to microscope slides. These smears were analysed with the aid of automatic single cell cytometry, and DNA measurements were performed. In contrast to flow cytometry, this technique permits, on the basis of electronic selection criteria, selective analysis of the tumor cells, while artefacts, stroma and inflammatory cells can be excluded. Using DNA cytometry, we were able to differentiate between diploid, polyploid and aneuploid tumors. The best prognosis was associated with a diploid tumor, the poorest with aneuploid tumor. Regression analysis, however, showed that the DNA content of tumor cells is of only secondary significance.

Cytological Techniques↗

PubMed1992

[Comparison of DNA analysis with histomorphologic parameters in stomach cancer].

After curative resection of stomach carcinomas (adenocarcinomas: n = 58, signet ring cell carcinomas: n = 24, undifferentiated carcinomas: n = 21) the DNA content of the tumor cells was compared with the histomorphological parameters. There was a correlation between the DNA content and the histomorphological parameters. The DNA analysis had no additionally prognostic influence. In the multivariate regression analysis the prognosis depended on lymph node status (p = 0.0009), pT-stage (p = 0.02), tumor localization (p = 0.03) and the histological type (p = 0.05). The prognosis was independent of the DNA content. Furthermore, neither did the degree of differentiation, the operative procedure, the safety distance, the size of the tumor, the sex nor the age of the patient have any influence on the prognosis.

Adenocarcinoma↗

PubMed1992

DNA image cytometry: a prognostic tool in rectal cancer?

In 68 patients the DNA content of tumor cells was measured by image cytometry after resection of the rectum because of cancer. In the DNA histogram a differentiation between diploid (n = 19), polyploid (n = 24), hypotriploid (n = 17), and hypertriploid (n = 8) tumors was possible. The best relapse-free survival time was found in patients with diploid tumors. The prognosis worsened from polyploid to hypotriploid and was worse in hypertriploid tumors. Testing for a prognostic advantage of diploid over aneuploid tumors without adjustment for additional factors simply by means of the log-rank statistic gave a (one-sided) P of 0.1013. In a multivariate analysis the degree of differentiation turned out most important. Again, an appropriate test for prognostic relevance of DNA content failed to be significant (P = 0.3264).

Adult↗

PubMed1992

Advanced bladder cancer (stages pT3b, pT4a, pN1 and pN2): improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy. Results of a controlled prospective study.

A total of 49 bladder cancer patients with tumor stages pT3b, pT4a and/or pelvic lymph node involvement without microscopic or macroscopic evidence of residual tumor was randomized into 2 comparative groups: the chemotherapy group was to receive 3 adjuvant cycles of methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC) after radical cystectomy. The control group received no additional treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log rank test for relapse-free survival curves). Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC (3 cycles in 16 patients and 2 cycles in 2). Of the remaining 8 patients 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. An update of the patients in August 1991 revealed a further increase in the prognostic difference between the 2 trial arms (p = 0.0012). Of 18 patients who received treatment with M-VAC or M-VEC only 3 have had tumor progression to date compared to 18 of 23 patients in the control group. Further statistical analysis of the data was performed on the basis of Cox's regression model, incorporating various criteria as explanatory variables, including patient sex and age, pT stage and number of involved lymph nodes. This multivariate analysis revealed a significant decrease in the risk of tumor recurrence (p = 0.0007, 2-sided) after adjuvant chemotherapy. The number of lymph nodes involved was also of prognostic significance (p = 0.0028, 1-sided). The results indicate that the survival time after radical cystectomy can be prolonged considerably by adjuvant polychemotherapy in cases of locally advanced bladder carcinoma. Fortunately, all of these conclusions are not affected by switching from an intent-to-treat analysis to an analysis of the therapy actually performed. The p values obtained from the latter are 0.0005 (log rank test) and 0.0001 (Cox model with the same set of additional regressors).

Adult↗

PubMed1991

[Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography].

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.

Adult↗