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Biomedical subjects

R Keiling

Publications and source records attributed to R Keiling.

At least 19 recordsLinked to original sources

Cervical and vaginal cancer associated with pessary use.

From 1967 to 1990, 96 previously untreated patients with cervicovaginal cancer associated with a history of vaginal pessary use to control uterovaginal prolapse were referred to eight radiation therapy departments in France. Sixty-eight patients had cervical cancer, and 28 had vaginal cancer. The mean interval between pessary insertion and cancer diagnosis was 18 years, with a range of 1 to 41 years. Most patients received radiation therapy and brachytherapy. Few (5%) had Grade 3 treatment side effects. The overall 5-year relative survival rate was 54%; nonsurvival was related to locoregional recurrence. Because almost all tumors occurred at the site of pessary insertion, foreign body chronic inflammation in association with viral infection may be the cause of the tumors.

Aged

Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer.

A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.

Adult

[Locoregional recurrence of breast cancer. Long-term course of 49 cases treated by excision and omentoplasty].

Extensive local recurrence of breast cancer may require wide parietal resection, demanding the use of other tissues to compensate for the loss of substance. We preferably resort to omentoplasty when the defect is larger than 300 cm2. A group of 49 patients with recurrence of the tumor in the breasts (treated with omentoplasty) has been studied, with special emphasis on long-term results. In our series, 86% of the patients were followed up for more than 4 years, with an actuarial survival rate of 46% after 7 years. It thus appears that this procedure can be advocated for slow-developing cancers, the local recurrence of which is extensive and usually isolate for various reasons (most often a deficient initial local treatment).

Aged

Two partial remissions induced by an LHRH analogue in two postmenopausal women with metastatic breast cancer.

We report two cases of metastatic breast cancer occurring in two postmenopausal women. Treatment with a luteinizing hormone-releasing hormone (LHRH) analogue, D-TRP6-LHRH, induced partial remission. The blood levels of the follicle stimulating hormone (FSH) and luteinizing hormone (LH) fell sharply under treatment, but the levels of estradiol, estriol, and estrone did not change significantly. We also described the putative mechanisms of action of the LHRH analog.

Aged

Radiotherapy alone in carcinoma of the intact uterine cervix according to G. H. Fletcher guidelines: a French cooperative study of 1383 cases.

A French Cooperative study of 1383 cases with invasive carcinoma of the intact uterine cervix treated with radiation therapy alone, using the guidelines provided by G. H. Fletcher led to the following conclusions: The techniques of treatment were easily reproducible in 9 French centers, working in a prospective cooperative study; Results similar to those of the original study were achieved in Stages I and IIA (MDAH substaging) with a locoregional failure rate of 7%; In Stage IIB, the locoregional failure rate of 16% is also comparable in both studies; Locoregional failures in Stage III are slightly lower than those reported in Houston, probably reflecting differences in patient's prognostic factors in France and Texas; The 5-year survival rate obtained in advanced Stages (UICC FIGO staging) are among the highest in the literature (76% in Stage IIb, 62% in Stage IIIa and 50% in Stage IIIb); The rate of severe complications remains acceptable and decreased throughout the study thanks to a better use of computer dosimetry.

Female

Variations in the percentages of lymphocyte subtypes during the menstrual cycle in women.

In view of the well-known circadian variations in lymphocytes and their subtypes, we decided to study the possible variations in the proportions of these cells during the menstrual cycle in women. In order to do this, lymphocyte populations were determined during 3 successive cycles on D1, D13, D14, D15 and D25 in 6 women with 28-day cycles who were not on oral contraceptives. In each of these women, we then compared the percentages of lymphocyte subtypes during the different periods of the cycle; this amounted to over 400 comparisons. A statistically significant variation, at the 1% level was found in only one case, when comparing the percentages of T4 lymphocytes on D1 and D13. In the light of this experience, we can therefore assume that there are no statistically significant variations in the proportions of lymphocyte subtypes during the menstrual cycle in women, which does not exclude the possibility of variations in their total numbers.

Adult

A quantified approach to the analysis and prevention of urinary complications in radiotherapeutic treatment of cancer of the cervix.

This paper is the report of a dosimetric study of 79 urinary complications after radical radiation treatment (1975-1979) of 624 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit-Delclos applicator). Dosimetric-computerized studies were expressed as the maximum bladder dose on the trigone, as proposed by the I.C.R.U. Bladder doses were actually studied as a function of intracavitary irradiation and intracavitary + external irradiation. The results show a significant difference in patients with and without complications based on the dose reaching the bladder. The relative contribution of external therapy and intracavitary irradiation and their value can serve as one of the primary indicators for predicting complications. These values should be determined before placement of intracavitary sources. We found that the dose to the critical organs cannot be defined as a single number. These results argue in favor of adapting individual patient therapy based on rectal and bladder dosimetry and may be adjustable to all treatment modalities.

Brachytherapy

[Determination of sub-populations of circulating T lymphocytes in alcoholic cirrhosis using monoclonal antibodies OKT3, 4, 5, Leu 2 and Leu 15. Effect of hepatitis B virus infection].

Peripheral T lymphocyte subpopulations were quantified in 24 alcoholic cirrhotic patients, 11 of them having anti-HBs and/or anti-HBc antibodies, and were compared with 35 healthy control subjects, 10 of them having anti-HBs and/or anti-HBc antibodies. The monoclonal antibodies utilized (OKT3, OKT4, OKT8 in simple staining, Leu 2 and Leu 15 in double staining) are considered as markers of mature (CD3), helper (CD4), cytotoxic/suppressor (CD8, Leu 2), suppressor (Leu [2+ 15+), and cytotoxic (Leu 2+ 15-) T cells. In cirrhotics, when compared to controls, the number of CD3 cells was reduced (p less than 0.01); the proportion of CD4 cells was within normal range, and that of CD8 cells diminished (p less than 0.001), contrasting with an increased proportion of Leu 2+ cells (p less than 0.01), related to an increased proportion of Leu 2+ 15+ cells. Leu 2+ 15- lymphocytes were within normal range. In control subjects, a decreased proportion of Leu 2+ 15+ cells was found (p less than 0.05) when Ac HBs and/or Ac HBc were present. In cirrhotics having at least one serologic marker of hepatitis B virus infection, when compared with negative ones, increased proportions of Leu 2+ (p less than 0.05) and Leu 2+ 15+ (p less than 0.05) cells were found. These results show that data concerning T lymphocyte subpopulations are conflicting when various types of antibodies are used. However, they suggest abnormalities of immune regulation, possibly a defect of T suppressor cell function. Hepatitis B virus infection probably modifies immune regulation in alcoholic cirrhosis, and perhaps in normal subjects.

Antibodies, Monoclonal

[Resection-reconstruction of the femur shaft by a massive allograft fixed by an interlocking nail].

Case report of a central midshaft osteosarcoma of the femur, treated conservatively under Rosen procedure. Bone resection was followed by reconstruction with a deep frozen (-196 degrees) conserved massive homograft, fixed by an interlocked Kuntscher's nail. The purpose of this paper is to expose the advantages of this type of fixation, V.S. conventional nails, or plates. X-Ray showed a bridging bone spindle between host and graft cortical bone, induced by initial stability of the nail, and a rapid fusion after secondary dynamisation of the nail, by removing one screw. We obtained an early functional recovery and a complete and rapid autonomy necessary to allow social and school reinsertion, whatever should the medium or long term presumed survival be.

Adolescent

[French FAC vs FEC study in advanced breast cancer].

239 patients were evaluable: 116 in the FAC arm, 123 in the FEC arm. There is no significant difference in the therapeutic responses between 2 regimens: 52 +/- 9% vs 49 +/- 9%. Duration of responses (273 vs 303 d) and overall survival were also similar. FEC appears less myelotoxic, less toxic also in terms nausea, vomiting and grade 3 alopecia than the adriamycin combination. 9 patients required treatment cessation due to grade 2 cardiac dysfunction with 3 CHF, against no case in the epirubicin regimen.

Antineoplastic Combined Chemotherapy Protocols

Phase II clinical evaluation of doxifluridine.

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.

Adult

Mitoxantrone combined to vincristine, cyclophosphamide and fluorouracil in advanced breast cancer.

In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose. After the EORTC Clinical Screening Group phase II trial we have conducted an "expected difference method" comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m2), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study. The reasons for similarity of action will be presented and discussed.

Adult

Results of radiotherapy alone in 581 patients with Stage II carcinoma of the uterine cervix.

From January 1976 to December 1978, 581 previously untreated patients with Stage II carcinoma of the uterine cervix were treated by radiotherapy alone in nine departments of radiotherapy in France. This retrospective analysis was undertaken in an attempt to evaluate the therapeutic results and prognostically significant factors. The initial clinical staging and the therapeutic guidelines were as outlined at the U.T. M. D. Anderson Hospital in Houston; all our patients were treated by standardized protocols combining external beam irradiation and intracavitary irradiation with cesium sources. The overall locoregional control rate was 83.2%, with total disease control of 74.5%. Uncorrected actuarial survival rates are 76% at 3 years and 68% at 5 years. The incidence of severe posttherapeutic complications is 7.2%. Clinical substaging, patient's age at the time of the diagnosis, lymphangiogram findings, and tolerance to external irradiation were all found to have prognostic significance. According to those findings, the possibilities of improving the results are discussed.

Actuarial Analysis

Pulmonary function assessment during bleomycin therapy.

20 male patients were treated for various tumors, most of them by combination therapy program including Cis-diammino-dichloroplatinum, Methotrexate and Bleomycin, the mean total dose for this last drug being 225 mg in 3 months (75 mg-300 mg). Spirometric tests, carbon monoxide diffusing capacity (DLCO) and its components Dm (membrane diffusing capacity) and Vc (capillary blood volume) were performed before each course and at the end of the chemotherapy, to assess their value in detecting Bleomycin pulmonary toxicity. There was no statistically significant change in any ventilatory nor diffusional test among these 20 patients, carefully selected for the absence of cardiopulmonary history. There was a slight decrease of DLCO for 3 patients having received 300 mg of Bleomycin. The lack of cardiopulmonary history, the mean total dose under the toxic threshold, and perhaps the insufficient delay between the end of the treatment and the last control test, may explain this absence of variability of functional tests.

Adult