Colony formation in vitro as a prognostic indicator for primary breast cancer.

Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.

Preliminary analysis of combined treatment with prednimustine and 4'epidoxorubicin in advanced breast cancer.

In an effort to define a well-tolerated therapeutic regimen for advanced breast cancer, we have studied a combination of 4'epidoxorubicin, 50 mg/m2 IV on day 1, and prednimustine, 100 mg/m2 PO on days 3 to 7 given every 3 weeks. Twenty-nine patients have been entered, and 22 are presently evaluable for response. Median age of the evaluable patients is 62 (range, 36 to 77), and median performance status (SAKK) is 2. Five patients had received chemotherapy, 16 hormonal therapy, five radiation therapy, and five no prior therapy for advanced disease. Most patients were in a high-risk group, with dominant visceral metastatic sites in 19 out of 22 cases. We have observed eight partial responses, nine no changes, and five progressions. Median response duration is 6 months. It is too early to discuss median overall survival. Toxicity is evaluable in 27 patients who received at least one course with a full dose of chemotherapy. Hematologic toxicity has been low, with only four patients having leukocyte nadirs below 2000/mm3 and three patients with thrombocyte nadirs below 100,000/mm3. Major alopecia (requiring a wig) was observed in eight patients. Emesis (controlled by minor antiemetics) was reported in six cases. This well-tolerated regimen is active in advanced high-risk elderly breast cancer patients, but dosage might be too low for younger patients and nonpretreated patients.

Drug kinetics in pregnancy.

Any drug given to a pregnant woman must be considered as possibly harmful in the fetus, since all drugs administered to the mother cross the placental membrane, although at different rates. Important physiological changes occur in pregnancy, which may influence the kinetics of drugs. Differences in gastrointestinal function are likely to alter drug absorption rates in the stomach or gut. Ventilatory alterations modify pulmonary drug absorption or elimination. Important changes in haemodynamics and alterations in body water compartments influence drug distribution and elimination. Renal drug elimination is generally enhanced, whereas hepatic drug elimination may be modified in different ways. Computerised pharmacokinetic models representing the compartmental aspects of the fetal-maternal unit and fetal-maternal drug interrelationships may be used to predict kinetic consequences of fetal drug exposure. Such information may be a useful guide for the clinical use of drugs during pregnancy, particularly for treatment of fetal disease.

Clinical significance of urethral instability.

Variations of urethral pressure were registered with microtransducers in 427 gynecologic patients with lower urinary tract symptoms during urethrocystometry. Urethral instability (variation of urethral pressure greater than 15 cm of water) was found in 16.4% of patients. The comparison of the urinary symptoms and the urodynamic data between patients with urethral instability (without previous surgery for incontinence, N = 57), and patients with stable urethra (variation of urethral pressure less than 5 cm of water, N = 269) showed that urethral instability was related to frequency, nycturia, urgency, and a history of urethral syndrome. In 27% of patients, the urethral instability was associated with a bladder instability. The comparison between patients with urethral instability and stable bladder (N = 51) and patients with bladder instability and stable urethra (N = 41) revealed that bladder instability seems to be more important than urethral instability as a factor associated with nycturia, urgency, and urge incontinence.

Cancer of the cervix stage Ib and IIa: survival related to treatment and histopathological risk factors.

Forty-five patients with carcinoma of the cervix stage Ib or IIa underwent primary radical surgery. The patho-histological examination of the surgical specimens showed, that pelvic lymph node metastases, tumour volume, depth of tumour invasion, lymphatic or vascular permeation and parametrial involvement were significant bad prognostic factors. The histological types of squamous cell carcinomas and local lymphoplasmocytic stromal reaction to the tumour had no statistical prognostic significance. A simple and objective method of assessing tumour volume is described. A 5-year actuarial survival rate for patients with metastatic pelvic lymph nodes (33% of the patients in this study) treated by surgery and additional postoperative external whole pelvis radiotherapy was 55%. This is significantly lower than the 86% 5-year actuarial survival rate of patients without pelvic lymph node metastases treated by surgery alone (P less than 0.05). The postoperative radiotherapy of carcinoma of the cervix with bad prognostic factors including pelvic lymph node metastases seems to improve local tumour control and perhaps survival in a subgroup of node negative tumours presenting other histopathological risk factors.

Preoperative cervical dilatation for first trimester induced abortion: comparison of two prostaglandin analogues.

The present study compares two methods of local application of prostaglandins prior to surgical abortion in the first trimester. Fifty patients were treated with a vaginal tablet of Gemeprost (E1 analogue); 50 others by the intra-cervical application of PGF2 alpha gel. Gemeprost was found to be superior to the PGF2 alpha gel. Several hypotheses are formulated to explain this observation. The side effects of the two methods are compared and discussed.

Combination of chemotherapy with methotrexate, bleomycin, and cis-platinum, and radiation therapy for locally advanced carcinoma of the cervix.

Sixteen non-pretreated patients with locally advanced cervical cancer (FIGO Stage IIIb) were treated with two 3-week cycles of platinum, bleomycin, and methotrexate (PBM), which were followed by radiation therapy. Response to both modalities was seen in 11 patients (69%), and three patients (19%) had a progression-free survival of more than 2 years. Radiation therapy was proven to be feasible after two cycles of PBM combination chemotherapy.

SPECT study of the fluid distribution in the intra-abdominal space during intraperitoneal treatment of ovarian cancer.

Only limited progress has been achieved in the treatment of ovarian cancer, the most common fatal gynaecological malignancy. Peritoneal dialysis with drugs known to be effective in ovarian cancer and large intraperitoneal fluid volumes (Belly Bath) have been used. The two critical determinants for a successful intraperitoneal chemotherapy programme are: (1) complete accessibility of the drug to all tumour-bearing areas; and (2) drug penetration into the residual tumour masses. We show that the scintigraphic technique in tomographic mode after administration of MAA-99Tcm-containing dialysate is a valuable adjunct for evaluation of patients undergoing intraperitoneal chemotherapy.

[Intra-epithelial neoplasia of the vulva and smoking]. / Néoplasies intra-épithéliales de la vulve et tabagisme.

VIN III etiology is multifactorial with a predominant role held by human papillomavirus infections, especially infections with HPV type 16. Other cofactors are also involved. We reviewed our patients presenting with VIN III, focusing our attention on smoking. Out of 37 patients 29 (78%) were smokers and among those who presented with a relapse after treatment (11 patients) all were smokers. We discuss mechanisms by which tobacco could act as a cofactor in VIN III.

Squamous-cell carcinoma antigen (SCC-A) values related to clinical outcome of pre-invasive and invasive cervical carcinoma.

The serum concentration of squamous-cell carcinoma antigen (SCC-A), a subfraction of tumour antigen, was determined by RIA from healthy donors (control group) and from patients with malignant cervical disease. Ninety-six percent (173/180) of the healthy patients had squamous-cell carcinoma antigen serum levels below 2 ng/ml. Ten of 70 (14.3%) patients with CIN III, 53.8% (34/62) of patients with invasive squamous-cell carcinoma stage I, 85.8% (30/35) with stage II and 96.5% (27/28) with stage III/IV had squamous-cell carcinoma antigen serum levels above 2 ng/ml. We observed that 22.5% (11/49) of patients with a tumour volume below 10 ml and 92.6% of patients with a tumour volume greater than 10 ml had squamous-cell carcinoma antigen levels above 2 ng/ml (p less than 0.005). SCC-A was correlated with recurrence or progressive disease in 90.0% of cases. Other risk factors such as depth of invasion, microscopic parametrial involvement, lymphatic and/or vascular space permeation and histological grade were not correlated with squamous-cell carcinoma antigen. Furthermore, this marker increased 4.3 +/- 2.7 months before clinical evidence of recurrence or progressive disease. We conclude that serial serum levels of squamous-cell carcinoma antigen provide a means for early detection of recurrence or progressive disease. This tumour marker might also be useful for monitoring the treatment effects and has some prognostic value.

Microfluorometric grading of mammary tumors. A pilot study.

Material obtained from 24 women with benign and malignant breast lesions was subjected to comparative morphologic and cytophotometric DNA analysis. All the cases of benign tumors, as well as benign tissue samples obtained from tumor-containing breasts, exhibited DNA values corresponding to the diploid control value. The tumors classified as carcinoma in situ or highly differentiated invasive cancers (grade I) showed a distribution of the DNA values significantly different from the diploid control values. The tumors classified s grade II and III showed a shift to the "triploid" area or were totally aneuploid. The results of the present pilot study suggest that quantitative cytophotometric DNA analysis can be used for grading the malignancy of breast tumors in combination with conventional histologic examination. Additional studies of larger groups of women may yield further information on the microfluorometric grading of malignancy. Such studies may also contribute to the further development and use of automated methods of cytologic diagnosis.

Metabolic response to lower abdominal surgery: analgesia by epidural blockade compared with intravenous opiate infusion.

To determine whether the type of peri-operative analgesic regimen affects the metabolic response during and after surgery, we studied 19 women undergoing abdominal hysterectomy under propofol anaesthesia. Patients were randomized to receive either continuous intravenous opioid or a bupivacaine-opioid mixture through a lumbar epidural catheter. Total body oxygen consumption and carbon dioxide excretion, blood glucose and haemodynamic variables were determined up to 24 h after surgery. No differences in any metabolic or haemodynamic variables were noted during surgery. In the post-operative period, the increase in oxygen consumption up to pre-operative values, the urinary nitrogen excretion and the changes in acute phase proteins were similar in both treatment groups. In contrast, the respiratory quotient was significantly higher in the lumbar epidural group than in the intravenous opioid group, 0.87 (SD 0.04) vs 0.77 (SD 0.06) (P < 0.05) and the hyperglycaemic response was more delayed in the epidural group. These data suggest that prolonged sympathetic blockade associated with epidural analgesia might contribute to better preservation of glucose homeostasis in the perioperative period.

Modifications of the urethral rest and stress profiles after different types of surgery for urinary stress incontinence.

Full urodynamic assessment, including urethral profiles at rest and under stress, using microtransducers, was made before and at least 6 months after surgery for urinary stress incontinence in 86 patients. Cure was assessed objectively. Procedures compared were Burch colposuspension, Pereyra urethrovesical suspension and anterior colporrhaphy. The Burch colposuspension increased the pressure transmission ratio more efficiently than the vaginal operations and the cure rate was 91%. Only 50% of Pereyra operations were successful and success was related to an increase in the functional urethral length and in the pressure transmission ratio. The success rate for anterior colporrhaphy was 57% and was associated with a significant decrease in the maximal urethral closure pressure and the continence area. The prognostic value of the urethral profiles at rest and under stress and the therapeutic implications are discussed.