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Biomedical subjects

A Pfleiderer

Publications and source records attributed to A Pfleiderer.

At least 19 recordsLinked to original sources

Cytogenetic analysis of an adenoid cystic carcinoma of the Bartholin's gland. A rare, semimalignant tumor of the female genitourinary tract.

Cytogenetic analysis has been performed on short-term cultures from a 56-year-old woman suffering from an adenoid cystic carcinoma of Bartholin's gland. Beside a normal female karyotype, the tumor revealed an abnormal cell line with complex chromosome changes involving the chromosomes 1, 4, 6, 11, 22, and 14. The mainly structural and nonbalanced rearrangements led to the loss of the chromosome segments 1p31----qter, 4q22----q28, 6p12----qter, 11p11.2----pter, 14q24----qter, and 22q13----qter. Clonal numerical aberrations were not observed. To our knowledge, such a tumor has to-date not been cytogenetically investigated.

Bartholin's Glands

HPV 16 DNA in autopsy material of a metastatic cervical carcinoma.

Human papillomavirus (HPV) DNA has been regularly detected in primary cervical carcinomas and in some metastatic lesions. Using Southern blot hybridization on autopsy material we found HPV 16 DNA in a primary cervical carcinoma and in multiple metastases therefrom.

Carcinoma, Squamous Cell

Steroid receptors in ovarian carcinoma: immunohistochemical determination may lead to new aspects.

87 nonpretreated stage III/IV ovarian common epithelial carcinomas were studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunohistochemistry (IHC) and biochemical (DCC) analysis. While the DCC assay showed tumors to be receptor-positive in 62% (ER) and 66% (PR), receptor-positive malignant epithelial cells were only detected in 38% (ER) and 31% (PR) by IHC. There was only a low correlation between the semiquantitative results of ER and PR IHC and the corresponding values of DCC receptor determination. The finding of steroid receptor-positive stromal cells without any evidence of hormone receptor-positive epithelial tumor cells offers a possible explanation for discrepant results in numerous cases with obviously "false positive" results of DCC analysis. Since the considerable heterogeneity of steroid receptor expression present in many ovarian neoplasms can only be detected by IHC, it seems to be the appropriate method of ER and PR determination. Most patients were treated by both radical cytoreductive surgery (n = 76) and a platinum-based chemotherapy (n = 79). ER was not shown to be of significant prognostic value. However, survival was significantly better in patients with PR positive tumors (IHC and DCC) on univariate analysis. Residual tumor after primary surgery was the only remaining significant prognostic factor after multivariate analysis. Further studies are needed to clarify the biological function of steroid receptor-positive stromal cells in ovarian carcinomas.

Adult

Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin-pretreated patients: a study with ondansetron.

Vomiting and nausea are the most distressing side-effects of cancer chemotherapy. With standard antiemetic regimens (e.g. metoclopramide based combinations) sufficient antiemetic control is achieved in 50-70% of cisplatin treated patients. Ondansetron, a selective 5-HT3-receptor antagonist has shown efficacy in cisplatin-induced emesis. In the present study, we evaluated the safety and efficacy of ondansetron in cisplatin pretreated patients who had suffered from severe emesis in spite of antiemetic prophylaxis. Complete antiemetic control was reached in 43.5% on the day of treatment and in 27.2% of the patients regarding a worst day analysis. 25% of the patients suffered from severe cisplatin-induced emesis (greater than 5 emetic episodes per 24 h). We try to characterise risk-factors for cisplatin-induced emesis by performing a multivariate analysis. Sex, cisplatin dose, and combination therapy with cisplatin plus anthracyclines seem to be independent risk-factors for vomiting on day 1 and on worst day. Delayed emesis occurred less often when sufficient antiemetic protection from acute vomiting had been obtained. Female sex, cisplatin dose and recurrent disease seem to influence the probability for occurrence of delayed vomiting.

Adult

Oncogene and growth factor expression in ovarian cancer.

The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c-myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern

Conservative management of acoustic neuromas.

The results of this study and others document the biologic behavior of acoustic neuromas. In view of the evidence presented, which describes both variable rates of individual tumor growth and spontaneous regression in size, it would seem prudent that before selecting a nonsurgical treatment modality, the growth rate for the particular tumor in question should be established. To date, none of the literature that addresses the use of focused irradiation has attempted to do so. Our study as well as those of others suggests that the growth rate of acoustic neuromas becomes predictable over time. Based on this observation, a conservative (nontumor excision) management strategy is proposed for selected individuals. Patients to whom this management philosophy has been recommended or who themselves have chosen this option are seen twice yearly. Each visit consists of a thorough neurotologic examination as well as high-definition CT or MRI. Careful comparison of the clinical course as well as calculation of the tumor size is carried out in each instance. If the clinical course and rate of tumor growth remain unchanged over a 3-year follow-up, annual assessments are recommended. In the event of tumor enlargement, surgery may or may not be recommended, depending on the rate of growth and the age of the patient. Our experience suggests that a rate of growth equal to or exceeding 0.2 cm per year constitutes an indication for tumor removal.

Age Factors

[Surgical therapy of progressive or recurrent malignant ovarian tumors].

Out of a total of 120 patients operated on for recurrent ovarian cancer, two at the very best, but possibly not even one, will have a definitive chance of cure. Despite the poor long-term prognosis, as well as the lengthy operation and postoperative treatment involved, it does not seem justified to withhold surgery for recurrent disease totally. In some cases, symptoms can be treated with surgery, such as tumour pain or an impending ileus. In other cases, patients live for 10 years and longer, after multiple operations for relapse, without suffering severe physical symptoms. These are mainly patients with circumscribed, solitary, and very slowly growing tumours, in which cases, it is possible to remove the tumour again and again by surgery. The most relevant prognostic factors include the size of the residual tumour left at the primary operation, the time between the primary operation and the recurrence of the tumour, the type of growth of the recurrent tumour, as well as the extent of the tumour size reduction achieved at the first recurrence operation.

Abdominal Neoplasms

[Therapy of endometrial cancer].

Surgical-pathological categorising of endometrial carcinoma makes it possible to treat this cancer in a more differentiated way. In clinical stage I, 6% of the adnexes, 10% of the pelvic lymph nodes and 5% of the paraaortic lymph nodes are affected. There is a direct correlation between depth of invasion and pelvic and paraaortic lymph node metastases. The new surgical-pathological categorising of endometrial carcinoma requires extensive surgery. Lymphadenectomy, which is necessary for categorisation means over-treatment for 2 thirds of all cases. Today, low-risk endometrial cancers can be distinguished from high risk ones by vaginal sonography as well as NMR permits the detection of invasion preoperatively and curettage to determine the unfavorable subtypes (seropapillary, clear-cell), hormonal receptors and ploidy. In low-risk cases, hysterectomy (with adnexes) and careful revision of the abdomen is sufficient. No further adjuvant therapy is necessary. In high-risk cases, an extended pelvic and, in the case of metastases, an para-aortic lymphadenectomy is imperative. Percutaneous X-ray therapy is not necessary in low-risk cases postoperatively. In high-risk cases, its effectiveness is not established and is probably not superior to the operative removal of metastases. Radiation of the vaginal cuff is necessary and successful in high-risk cases. In low-risk cases, side-effects are minimal. Adjuvant therapy with gestagens in low-risk cases is not indicated, because of their side-effects and does not reduce recurrence rate. Recurrent and metastasizing endometrial carcinomas respond to gestagens in about 15% of cases. Response is receptor dependent. High dose is not more effective. Endometrial carcinoma responds to chemotherapy. Most effective is adriamycin with a response rate of 35%. Combination therapies did not show greater effect in randomized studies. Recurrence free interval is only 6 to 8 months, however. An adjuvant chemotherapy is only indicated in the case of a serous carcinoma.

Combined Modality Therapy

[Recurrent theca cell tumor].

Thecomas are considered to be benign ovarian tumours. Whether there are malignant thecomas, is a subject of controversy in literature. This contribution describes a case of recurrent thecoma with a clinically malignant course and histological signs of malignant dedifferentiation. The particular diagnostic and therapeutic consequences of this rare disease are discussed with emphasis on the need for radical surgical intervention.

Adult

A new approach to the management of acute epistaxis.

A new approach to the management of acute epistaxis is described using suction with the operating microscope to define the bleeding point prior to the application of hot wire cautery. This technique was shown to be completely successful in stopping haemorrhage in 82% of acute referrals in a prospective series of 33 patients. It resulted in a significant reduction both in the use of nasal packing and in the length of hospital stay compared with a group of controls treated by traditional means. It is proposed that in most cases of acute epistaxis the bleeding point is accessible to cautery and nasal packing should be reserved for a minority of refractory cases. This avoids unnecessary patient discomfort and the complications of prolonged nasal packing and hospitalization.

Acute Disease

Endometrial malignancy.

This article reviews published papers on endometrial carcinoma from August 1989 to July 1990. The hypothesis of two different pathogenic types of endometrial carcinoma, which are well correlated with favorable and unfavorable prognosis, has been established. The prognosis for patients under 21 years of age with well-differentiated endometrial carcinoma is excellent; for them, a conservative, fertility-preserving treatment is possible. The characteristics of carcinomas with unfavorable prognoses are also discussed. These prognostic factors are measurable in tissue from preoperative curettage. Measurement of myometrial invasion by vaginal sonography and nuclear magnetic resonance imaging is possible with a high degree of safety preoperatively as well. At least intraoperatively, an exact measurement of depth of invasion can be obtained by frozen-section diagnosis. In an optimal preoperative examination, it should be possible to select patients with a high rate of metastases for intraoperative lymphadenectomy. For adjuvant postoperative therapy, percutaneous radiotherapy is indicated in high-risk patients in whom no optimal lymphadenectomy has been done. Vaginal irradiation, however, used in all cases up until now, is known to bring about more local complaints. Adjuvant progestagen treatment in low-risk patients is dangerous because it can cause a higher rate of cardiovascular disease and does not reduce death by recurrent disease. The profit for high-risk patients seems very small. Analysis of endometrial carcinoma tissue shows a high rate of receptors for luteinizing hormone-releasing hormone and analogues. Adjuvant chemotherapy in high-risk patients until now has been without measurable effect.

Female

In situ distribution of transforming growth factor alpha in normal human tissues and in malignant tumours of the ovary.

The distribution of transforming growth factor alpha (TGF-alpha) in human normal tissues from the uterus, Fallopian tube, ovary, small and large intestine, lung, spleen, kidney, and skin was studied by immunohistochemistry. TGF-alpha was found in epidermis, bronchial epithelium, intestinal mucosa, renal tubules, endo- as well as in exocervical and endometrial epithelium, and in the serous epithelium of the Fallopian tube. No TGF-alpha was detected in the stromal components of any of the tissues nor in any of the pre- and post-menopausal ovaries studied. Twenty-nine ovarian tumours including 23 ovarian carcinomas, one malignant mixed Mullerian tumour, two ovarian metastases of gastrointestinal carcinomas, one dysgerminoma, one sarcoma, and one fibroma were studied for TGF-alpha by the same immunohistochemical method. In 25 cases, specific cytoplasmic staining for TGF-alpha of epithelial tumour cells could be demonstrated. The pattern and intensity of the TGF-alpha immunostain varied among the TGF-alpha-positive tumours. No TGF-alpha was found by immunohistochemistry in the remaining four cases nor in the stromal tumour components of any of the lesions studied. Northern blot analysis for TGF-alpha mRNA was performed on 12 of the tumours. While the immunohistochemistry and blotting results correlated well in ten cases, discordant results were obtained in two lesions.

Blotting, Northern

Estrogen and progesterone receptors in endometrial cancer and their prognostic relevance.

Three hundred and nine malignant endometrial tumors were biochemically analyzed with respect to estrogen (ER) and progesterone (PR) receptors. Fifty-seven percent of endometrial carcinomas were ER and PR positive (greater than or equal to 50 fmole/mg of cytosol protein); 24% were negative for both receptors. Five sarcomas and 16 of 21 mixed müllerian tumors were receptor negative. Receptor status correlated with clinical stage and grade of histological differentiation, but not with myometrial invasion. Anamnestic data on patients showed no differences between those with receptor-negative and receptor-positive tumors. Five-year survival rate (stage I) and median survival time (stages II-IV, recurrences) for patients with ER+/PR+ and ER-/PR+ endometrial cancer were significantly better than for ER-/PR- and ER+/PR- patients. A multivariate analysis demonstrated progesterone receptor as a significant prognostic factor next to clinical stage. Estrogen receptor had no significant prognostic relevance. A retrospective analysis of gestagen treatment and progesterone receptor status confirms the importance of PR, possibly independent of hormonal treatment.

Adenocarcinoma

[Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F].

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.

Adult

Human papillomavirus DNA in invasive carcinoma of the vagina.

The presence of human papillomavirus (HPV) DNA in invasive carcinomas of the vagina, in their lymph node metastases, and in corresponding normal tissue was investigated by Southern blot hybridization with 32P-labeled HPV DNA. Tumor tissue from ten of 18 patients with vaginal carcinoma contained HPV DNA. Three of the 18 patients had a history of cervical neoplasia more than 14 years before the diagnosis of vaginal carcinoma. Five of 15 primary squamous cell carcinomas, one primary adenocarcinoma, and a vulvar recurrence of a vaginal squamous carcinoma contained HPV 16. A primary squamous carcinoma yielded HPV-related sequences. The HPV copy number varied from 0.5 to 50 per cellular genome. Four histologically positive inguinal lymph nodes from three patients contained HPV DNA. In six tumor-free control tissues from four patients, no HPV DNA was detected. No relationship was established between HPV positivity, HPV type, or copy number of the tumor and the grade of differentiation or keratinization or the clinical stage. After a median follow-up of 13 months, five of nine HPV-positive patients were alive without recurrence, whereas all seven HPV-negative patients had died because of disease. The results of this study indicate a possible major role of HPV in the development of vaginal cancer.

Adult