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Biomedical subjects

E Petru

Publications and source records attributed to E Petru.

At least 109 records · Page 6Linked to original sources

Feasible model for locoregional and systemic longterm administration of drugs and concomitant blood sampling in Sprague-Dawley rats.

This methodological study describes three surgical procedures for locoregional and systemic drug administration, which are based on a similar experimental design. Cannulation of the arterial and portal access to the liver in comparison to the general venous system, and arterial access to the large intestine through a permanently implantable system, suitable for serial bolus injections and infusions in unrestrained rats, is presented (experiment I). Furthermore, an infusion system for longterm administration (experiment II) and a method for blood sampling during locoregional or systemic infusion procedures (experiment III) have been developed. The positioning and free flow of the catheters were checked by means of scintigraphy, administration of fluorescein under UV light and angiography in animals of experimental series I. After 7 days, no obstruction was detected. On day 15 and 30 following implantation 73.3% and 58.3% of the animals, respectively, showed unimpeded flow through the catheter system. The methods described here were well tolerated by the animals without alteration of their general condition and are currently in use in a series of chemotherapeutic and pharmacokinetic investigations.

Animals↗

Therapeutic ratio of mono or combination bacterial lipopolysaccharide therapy in methylnitrosourea-induced rat mammary carcinoma.

Four experiments investigating the antitumor activity of bacterial lipopolysaccharide (LPS) against the autochthonous methylnitrosourea-induced mammary carcinoma are summarized. Administration of LPS alone i.v. caused distinct regression of small tumors following its first injection. This therapeutic effect, however, was short-lived and could not be maintained by administering a second dose. The observed antineoplastic activity of LPS was dose-related, whereas no dose-response relationship was observed with respect to its toxicity. A series of experiments in which LPS was combined with other compounds to possibly exploit its activity while reducing the toxicity were performed. Neither the combination with cytotoxic drugs such as 4'-(9-acridinylamino)-methansulfone-m-aniside or cyclophosphamide nor that with 1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine or hexadecylphosphocholine showed sufficient anticancer activity at acceptable toxicity. In all experiments promising efficacy was observed at high dosages but also high toxicity. When the dosages were reduced, diminished antineoplastic activity was found together with overproportionally high mortality. It might therefore be concluded that the active dose range of LPS cannot be reached clinically because of its inherent toxicity.

Animals↗

Influence of perinatal nicotine administration on transplacental carcinogenesis in Sprague Dawley rats by N-methylnitrosourea.

The administration of nicotine during the perinatal stages of life resulted in a significant decrease in tumours occurring after transplacental induction by N-methylnitrosourea (MNU). The overall tumour incidence following p.o. application of MNU to dams was 85% in rats of the F1-generation, the main occurrence being related to the neurogenic system (62% of the animals). Regular injections of nicotine before or after birth resulted in a reduction of malignancies by 17% and 22% (P = 0.08 and 0.0015), respectively. The difference in the incidence of neurogenic tumours proved to be highly significant (P less than 0.002) in rats of either sex, when nicotine was applied over 26 weeks following birth. There was a gender-specific imbalance in rats which received the carcinogen only, in favour of a lower tumour yield in females (P less than 0.04), which became less apparent when nicotine was given additionally. These findings suggest that nicotine is capable of modulating the expression of chemically induced tumours of the neurogenic system in a favourable way.

Animals↗

On the relevance of "second-line" cytotoxic chemotherapy in patients with metastatic breast cancer resistant to standard combinations.

85 clinical studies concerning second-line chemotherapy of metastatic breast cancer have been analyzed. With minor exceptions, the mean remission rates ranged between 0-10% (complete remission) and 20-40% (partial remission) for the most commonly used second-line chemotherapy modalities. The mean duration of response was 6 months, the average survival time 10 months. No significant differences in effectiveness and side effects were found when comparing the different second-line treatment programmes.

Antineoplastic Combined Chemotherapy Protocols↗

Influence of the application mode of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide on the localization of its carcinogenic expression in female NMRI-mice.

The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide FANFT) by gavage to female NMRI-mice resulted in a high incidence of neoplasms of the forestomach. From 117 effective animals which were pooled from 3 dosed groups, 30 squamous cell carcinomas and 26/117 papillomas of the forestomach were diagnosed. Only 5/117 neoplasms of the urinary bladder occurred. The average cumulative dose administered was 1180 mg/mouse, and the mean latent period for the induction of forestomach tumours was 574 days. The mode of application seems to be an important factor in the carcinogenicity of FANFT.

Adenocarcinoma↗

[Therapeutic effectiveness of various combination chemotherapy protocols in advanced epithelial ovarian cancer].

147 clinical studies concerning combination chemotherapy of advanced ovarian carcinoma have been analysed. The mean remission rates ranged between 30-40% (complete remission) and 20-40% (partial remission) for the most commonly used chemotherapy programmes. The mean duration of response was 12 months, whereas the average survival time was 20 months. In general, an advantage was found for cisplatinum-based combinations. Side effects observed were similar.

Antineoplastic Combined Chemotherapy Protocols↗

Pretreatment hemoglobin, platelet count, and prognosis in endometrial carcinoma.

We analyzed whether a low pretreatment hemoglobin level is a prognostic factor in endometrial cancer and whether it is associated with thrombocytosis. Two hundred and twelve patients with endometrial cancer treated with surgery were reviewed. Data were analyzed with Pearson's chi-squared test, Fisher's exact test in contingency tables, the Mann-Whitney U-test, the Student's t-test, and Kaplan-Meier estimates. Multivariate analysis was performed with the log-rank test and the Cox proportional hazard model. Thirty-nine patients (18%) had a pretreatment hemoglobin value of < 12.0 g/dL. These 39 patients had significantly higher rates of nonendometrioid histology, high-grade tumors, myometrial invasion of > 50%, adnexal involvement, lymph-vascular space involvement, and advanced FIGO stage than patients with hemoglobin > or = 12.0 g/dL. The rate of thrombocytosis was significantly higher in patients with a low hemoglobin level (36% vs. 8%, P < 0.01). The overall 5-year survival rate of patients with low pretreatment hemoglobin was 59% compared with 89% for those with hemoglobin > or = 12 g/dL (P < 0.01). In the multivariate analysis age, thrombocytosis, nonendometrioid histology, high-grade histology, and advanced FIGO stage were significantly associated with a poor prognosis whereas adnexal involvement, lymph-vascular space involvement, low hemoglobin and myometrial invasion were not. These data indicate that low pretreatment hemoglobin is a prognostic factor in patients with endometrial cancer and that it is associated with thrombocytosis. Low hemoglobin was strongly associated with other unfavorable prognostic factors so that it was significant in the univariate but not the multivariate analysis.

Endometrial Neoplasms↗

Long-term disease-free survival after breast cancer metastatic to the ovary.

The prognosis of patients with breast cancer symptomatically metastatic to the ovary is almost uniformly poor. In this case report, we present a 33-year-old para-4 with a symptomatic metastasis to the ovary. Previously, a modified radical mastectomy with adjuvant radiotherapy had been performed for invasive ductal carcinoma of the left breast. Laparotomy showed a 13-cm tumor of the left ovary; frozen section histology showed malignancy consistent with the previous breast cancer. The patient received adjuvant combination chemotherapy. About 5 years later, a carcinoma of the right breast was treated with conservative surgery and adjuvant radiation and chemotherapy. After a further 4 years, a recurrence at the left chest wall was treated with radiation. At the last follow-up, more than 13 years after the first breast cancer and 12 years after the ovarian metastasis, the patient was alive and well without evidence of disease. Bilateral oophorectomy is a therapeutic option in premenopausal patients with localized or advanced breast cancer. Our patient experienced long-term disease-free survival following an isolated metastasis to one ovary. This represents the first report of long-term survival of such a patient in the literature.

Adult↗

Can bowel endoscopy predict colorectal surgery in patients with an adnexal mass?

The objective of this retrospective study was to identify the ability of preoperative endoscopy of the lower gastrointestinal tract and other tests to predict large bowel resection in patients with an adnexal mass. We reviewed 573 patients with a suspected adnexal mass admitted for surgery between 1987 and 1997. Two hundred fifty four patients (44%) had preoperative sigmoidoscopy (n = 97) or colonoscopy (n = 157). We identified patients who underwent a colorectal operation as part of their surgery and correlated surgical findings with the results of preoperative endoscopy, preexisting clinical symptoms, preoperative pelvic exam and ultrasonography, and the CA125 level. The sensitivity and positive predictive value of bowel endoscopy for predicting large bowel surgery were 18% and 59%, respectively. Multivariate analysis showed preexisting bowel-related symptoms, a pelvic exam suggestive of malignancy, a CA125 value >1000 U/ml, and infiltration of the colorectal wall at bowel endoscopy to be independently associated with subsequent colorectal surgery. We conclude that preoperative bowel endoscopy cannot accurately predict colon resection in patients with a suspected adnexal mass. Preexisting bowel-related symptoms, a pelvic exam suggestive of malignancy and a CA125 value >1000 U/ml are associated with subsequent colorectal surgery.

Adnexal Diseases↗

Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study.

We have previously shown that interferon-gamma 1b (IFN-gamma) in combination with cyclophosphamide and cisplatin significantly prolongs progression-free survival in ovarian cancer. In this phase I/II study, we examined if administration of IFN-gamma is also safe in combination with the current standard treatment, paclitaxel and carboplatin. Thirty-four patients with newly diagnosed advanced epithelial ovarian cancer, FIGO stage III/IV, were treated for six to nine cycles with paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5) every 3 weeks. IFN-gamma was administered in an escalating dose from 6 days/cycle with 0.025 mg sc up to 9 days/cycle with 0.1 mg sc. As expected, administration of IFN-gamma was associated with flu-like symptoms. Grade 3/4 neutropenia was observed in 74% (25 out of 34) of patients. Other side effects, in particular peripheral neuropathies, were within the previously observed ranges for the paclitaxel plus carboplatin combination. Overall response rate (complete or partial response) in patients who received either six or nine doses (0.1 mg) of IFN-gamma/cycle (n = 28) was 71%. IFN-gamma is safe in combination with carboplatin and paclitaxel for first-line treatment of patients with advanced ovarian cancer. This combination should be further evaluated as an immunotherapeutic treatment option for ovarian cancer.

Adenocarcinoma, Mucinous↗

Significance of pretreatment serum hemoglobin and survival in epithelial ovarian cancer.

Tumor anemia is common in patients with malignant tumors and it was repeatedly demonstrated to be associated with impaired prognosis in patients with malignant tumors. We conducted a retrospective analysis based on 553 patients with histologically proven epithelial ovarian cancer. Blood hemoglobin levels were determined before surgery and patients with values <12 g/dl were considered anemic. Data analysis included univariate and multiple Cox models. Tumor anemia was present in 143 (25.9%) patients before surgery. Tumor anemia was present in 143 (25.9%) patients before surgery. In a multivariate Cox model, pretreatment hemoglobin values proved to be an independent prognostic factor for patients with stage I-II epithelial ovarian cancer (n=203), but failed to attain significance in patients with stage III-IV disease (n=350). Tumor anemia defined as pretreatment hemoglobin values <12 g/dl may indicate patients with stage I and II epithelial ovarian cancer, who are at increased risk of relapse.

Adenocarcinoma, Mucinous↗

Long-term survival of a patient with fallopian tube cancer presenting with a supraclavicular mass.

BACKGROUND: Five-year survival of patients with stage IV cancer of the fallopian tube is poor. Furthermore, patients with gynecological cancers presenting with a supraclavicular mass generally have an unfavorable prognosis. CASE REPORT: We describe a 70-year-old patient who presented with a left supraclavicular mass. The mass was removed and histology showed metastatic papillary adenocarcinoma strongly suggestive of papillary serous carcinoma. Abdominal hysterectomy and salpingo-oophorectomy showed a primary carcinoma of the fallopian tube. Postoperatively the patient received six cycles of carboplatin-based chemotherapy and is alive and well with no evidence of disease 5 years and 10 months after the primary diagnosis. CONCLUSION: Surgery and adjuvant carboplatin-based chemotherapy seem justified even in older patients with fallopian tube cancer and distant metastasis at the time of diagnosis.

Adenocarcinoma, Papillary↗

Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

BACKGROUND: To identify prognostic factors in stage III and IV endometrial cancer with special attention to pretreatment platelet count. MATERIALS AND METHODS: 59 patients with FIGO stage III or IV disease operated on between 1983 and 1993 were analyzed. Patients with preoperative thrombocytosis were compared with those without thrombocytosis. Prognostic factors were analyzed with a Cox proportional hazard model. RESULTS: With the exception of age, there were no significant differences between patients with or without thrombocytosis. At multivariate analysis, five-year disease-free survival was influenced significantly by FIGO stage (stage III vs stage IV; p = 0.009), thrombocytosis (p = 0.02) and cervical involvement (p = 0.024). Similarly, overall five-year survival was significantly influenced by stage (p < 0.001), cervical involvement (p = 0.005) and thrombocytosis (p = 0.01). Age, histology, grade, myometrial invasion, lymph-vascular space involvement or spread to adnexae were not significantly associated with survival. CONCLUSION: Thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

Adult↗

Prognostic parameters in carcinosarcomas of the uterus: a clinico-pathologic study.

BACKGROUND: Carcinosarcomas of the uterus are highly aggressive malignant neoplasms with early lymphatic and hematogenous spread. The most important prognostic factor in carcinosarcoma is the extent of the tumor at the time of diagnosis. The prognostic impact of other factors such as myometrial invasion, menopausal age, age, parity and adjuvant therapy is still being discussed controversially. MATERIALS AND METHODS: Nineteen patients with histologically proven carcinosarcoma were included in the analysis. The patients were staged according to a modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. For each patient, the histological material was reviewed by an experienced pathologist. Carcinosarcoma was defined histologically as any tumor of uterine origin composed of carcinomatous and sarcomatous components. RESULTS: The median follow-up time was 91 months (25% quartile, 47 months; 75% quartile, 145 months). The median overall survival of the 19 patients was 59 months, resulting in a 5-year overall survival rate of 43%. Three out of the nineteen (16%) patients demonstrated progressive disease while 6 out of 10 (32%) patients developed recurrent disease with a median disease free survival of 16 months (range 8-54). Eleven out of nineteen (58%) patients died of the disease. A univariate model revealed that early tumor stage (stage 1) (p<0.023), low myometrial invasion (p<0.017) and late onset of the menopause (p<0.050) were significantly associated with a lengthened overall survival in patients with carcinosarcoma. Age (p=0.34), parity (p=0.16) and adjuvant radiotherapy (p=0.45) did not influence overall survival of patients with carcinosarcoma. CONCLUSION: Early tumor stage, low myometrial invasion and late onset of the menopause are associated with a lengthened overall survival in patients with carcinosarcoma.

Adult↗