The prognostic value of DNA ploidy and S-phase estimate in primary breast cancer: a prospective study.

In this prospective study, the independent prognostic value of DNA ploidy in combination with the major clinico-pathological characteristics (histological grade, nodal status, tumor size, estrogen and progesterone receptor status, number of tumors, multicentricity, lympho-vascular infiltration) was evaluated in a series of 399 breast-cancer patients. The mean follow-up time was 4.5 years. The DNA content was measured using image cytometry on fresh tumor samples. The overall survival of tetraploid and slowly proliferating diploid cases was significantly different compared with that of aneuploid and rapidly proliferating diploid cases (p = 0.0002). Thus, DNA ploidy combined with S-phase estimate (DNA histogram type) appeared to be good prognostic factors. In a multivariate survival analysis, DNA histogram type was not an independent prognostic factor unless the histological grade was excluded. This effect of DNA histogram type on survival was also observed among patients with grade-I or -II tumors and patients with small tumors. In conclusion, DNA histogram type was a valuable prognostic factor in univariate analysis, and provided independent complementary information for patients considered at low or intermediate risk by classical pathological findings.

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.

[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.

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

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.

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.

Surgery as part of a combined modality approach for inflammatory breast carcinoma.

From November 1977 to February 1984 21 patients with inflammatory breast carcinoma (IBC) were treated in a prospective, nonrandomized study with initial chemotherapy, consisting of a combination of chlorambucil, methotrexate, 5-fluorouracil, and doxorubicin. Modified radical mastectomy was performed after three courses of chemotherapy followed by another six courses of the same chemotherapy. Locoregional radiotherapy concluded the treatment program. All patients responded clinically to the initial chemotherapy. Modified radical mastectomy provided a direct histologic control of the effectiveness of the treatment and, in case of tumor persistence, allowed cytoreduction. No scarring problems were observed and postoperative chemotherapy could be administered without any delay. Radiotherapy was decisive for locoregional tumor control which was obtained in all patients who were treated strictly according to the protocol. Dermal lymphatic involvement represented in this series of clinical inflammatory breast carcinoma no pejorative feature and positive hormone receptors failed to be of predictive value for response to treatment. Considerably variable tumor persistence after initial chemotherapy and the results relative to local tumor control advocate surgery as part of a combined modality approach for inflammatory breast carcinoma.

Serum CA 125 in epithelial ovarian cancer. A longitudinal study.

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.

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.

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.

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.

Urodynamic and clinical assessment of the Lyodura sling operation for urinary stress incontinence.

A Lyodura sling operation for urinary stress incontinence was performed on 36 patients. The success rate was 89%, when success was defined as absence of objective urine loss at coughing or straining, with full bladder in the upright position and during a Urilos test, at least 6 months after surgery. Full urodynamic assessment, including urethral rest and stress profiles, were performed before, and 6 months after, surgery. Success of the operation depended mainly on enhancement of urethral pressure transmission. Functional length of the urethra and maximal urethral pressure did not influence the success rate. The procedure is especially suitable in patients with some degree of uterine or vaginal prolapse.

Longitudinal study of CEA and CA125 in ovarian cancer.

Carcinoembrionic antigen (CEA) and cancer antigen 125 (Ca125) levels were measured at regular intervals over a 24-month period in 19 patients with proven ovarian cancers. In 91.5% of the cases with recurrent or progressive disease, Ca125 levels were increased whereas only 34% of these patients had increased CEA levels. Furthermore, reduction of the tumoral mass was associated with a decrease of Ca125 levels in all patients. It is proposed that determination of Ca125 levels in ovarian cancer might provide a valuable prognostic tool for the assessment of the evolution of the disease.