Serum M3/M21 in cervical cancer patients.

Cytokeratins are polypeptides which constitute a subclass of intermediate filaments in epithelial cells. The serum tumour marker M3/M21 is based on monoclonal antibodies against the epitopes M3 and M21 of cytokeratin 18. In the present study, we measured M3/M21 serum levels in 50 patients with FIGO stage IB-IIB cervical cancer and in 50 control subjects using a two-site radiometric immunoassay directed against soluble fragments of cytokeratin 18. Median serum levels of M3/M21 in patients with cervical cancer and in normal controls were 70.6 U/ml (range 0-397.7) and 6.5 U/ml (range 0-205.2), respectively (Mann-Whitney U-test, P = 0.0001). Median serum levels of M3/M21 prior to therapy and 4 weeks after therapy were 104.2 U/ml (range 24.6-397.7) and 39.3 U/ml (range 0-234.7), respectively (Mann-Whitney U-test, P = 0.004). We found a significant correlation between elevated M3/M21 serum levels and metastatic disease in pelvic lymph nodes (Mann-Whitney U-test, P = 0.002). 24 patients relapsed after complete remission. In these patients, elevated M3/M21 serum levels before the detection of relapse by computed tomography was observed in 13 cases. Considering these preliminary results, further studies with an increased number of patients are justified to clarify the prognostic value and the monitoring abilities of M3/M21 in cervical cancer patients.

Prognostic value of immunohistochemically detected CD44 isoforms CD44v5, CD44v6 and CD44v7-8 in human breast cancer.

We investigated the expression of CD44 isoforms containing variant exons v5, v6 and v7-8 in 115 human breast cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v5, CD44v6 and CD44v7-8 were detected in 56% (n = 64), 24% (n = 28) and 15% (n = 17), respectively. In 36 specimens of axillary lymph node metastasis, expression of CD44v5, CD44v6 and CD44v7-8 was found in 94% (n = 34), 92% (n = 33) and 89% (n = 32), respectively. Five year survival rates with or without CD44v5 and CD44v6 expression were 71% versus 86% (log-rank test, P = 0.02) and 62% versus 81% (log-rank test, P = 0.001), respectively. For disease-free survival, expression of CD44v5, CD44v6 and CD44v7-8 showed a prognostic impact (log-rank test, P = 0.004, P = 0.0001 and P = 0.0001, respectively). However, multivariate analysis revealed that all investigated CD44 isoforms failed to be independent predictors of the patient's outcome.

Menstrual phase and breast cancer surgery: influence on clinical outcome or pitfall of statistical analysis?

The influence of menstrual status at the time of surgery on the prognosis of women suffering from breast cancer is still discussed controversially. In our patient collective, including 149 patients, we obtained statistically significant results for six different time intervals, indicating that patients who underwent surgery between 11 and 22 days after the last menstrual period (LMP) have a poorer outcome. Focusing on the effect of statistical data evaluation strategy we designed a simulation study to evaluate the amount of type I error (error of a false positive test result) in a multiple testing situation involving a cyclical covariate. Accordingly, we corrected the minimum P-values for the occurring type I error rates. After that correction all six previously significant P-values failed to achieve statistical significance. The impact of different statistical data evaluation strategies in a multiple testing situation is discussed.

Levator ani muscle morphology and recurrent genuine stress incontinence.

OBJECTIVE: To assess the impact of levator ani muscle morphology on the outcome of patients with genuine stress incontinence undergoing reconstructive surgery of the pelvic floor. METHODS: A follow-up investigation was performed on 30 patients from a previous study, who had undergone hysterectomy with combined anteroposterior vaginal repair for pelvic floor relaxation and genuine stress incontinence. Biopsy specimens of the pubococcygeal muscle had been obtained during posterior colporrhaphy and subsequently evaluated for evidence of striated muscle tissue. Eleven patients had striated muscle tissue in the biopsy specimens (group A), whereas 19 subjects did not (group B). Before operation and at 41 months (range 37-44) after operation, the patients underwent urodynamics, perineal sonography, and perineometry. RESULTS: At follow-up, all patients in group A were continent, whereas ten of 19 patients (53%) in group B showed recurrent genuine stress incontinence (P < .01). Compared with group B (48.5 +/- 21.9%), group A patients (71.8 +/- 16.5%) had a significantly higher abdominal pressure transmission ratio at follow-up (P = .02). At postoperative perineal sonography, group A patients (107.7 +/- 14.0 degrees) showed a significantly smaller retrovesical angle during straining than did group B patients (134.6 +/- 25.9 degrees) (P < .01). CONCLUSION: The levator ani muscle morphology has prognostic importance for the outcome of patients with genuine stress incontinence undergoing anteroposterior vaginal repair.

Endometrial cancer in premenopausal women 45 years and younger.

OBJECTIVE: To evaluate the experience with endometrial carcinoma in women 45 years or younger at the Royal Hospital for Women, Sydney, Australia. METHODS: We evaluated the clinical history, morphology, treatment, and follow-up of 17 premenopausal women 45 years or younger who had been diagnosed with endometrial cancer. All histopathology was reviewed. RESULTS: Sixteen patients received their primary treatment at the Royal Hospital for Women, and one was referred with recurrent disease. Synchronous ovarian malignancies were found in five of 17 cases (29.4%), compared with 11 of 237 (4.6%) women older than 45 (P < .001). Three other patients had secondary ovarian involvement. Five (29%) patients had stage III or IV disease. Thirteen (76.5%) women were alive with no evidence of disease 12-78 months after primary surgery; two were lost to follow-up, but had no evidence of disease at 21 and 29 months, respectively. Two women died of recurrent disease. All but two patients with stage IV disease receiving primary treatment at the Royal Hospital for Women were offered hormone replacement therapy on discharge from the hospital. CONCLUSION: Ovarian and lymph node involvement were common in women 45 years and younger with endometrial cancer. Hormone replacement therapy did not appear to compromise survival.

Transurethral injection of silicone microimplants for intrinsic urethral sphincter deficiency.

OBJECTIVE: To assess the short-term efficacy of transurethral injection of silicone microimplants in women with intrinsic sphincter deficiency. METHODS: During January 1995 and December 1996, 32 women (mean age 64.3 years, range 39-85 years) with type III stress incontinence (intrinsic sphincter deficiency) underwent transurethral injection of silicone microimplants under general anesthesia. Twenty-eight had undergone previous continence surgery. Subjective and urodynamic assessments were made at 6 and 12 months after injection to evaluate success and short-term effects. RESULTS: Objective and subjective success rates were 75% and 59% at 6 and 12 months, respectively. Injections of silicone microimplants significantly increased maximum urethral closure pressure (maximum urethral pressure at rest: 34.40+/-16.46 cm H2O, 95% confidence interval [CI] 28.55, 40.25 versus 25.35+/-10.78 cm H2O, 95% CI 21.52, 29.18; P = .027). There were no complications after surgery up to 1 year. CONCLUSION: Transurethral silicone injections were effective in 60% of cases of intrinsic sphincter deficiency, although there was a time-dependent decrease.

Tension-free vaginal tape operation: results of the Austrian registry.

OBJECTIVE: To assess the use of and perioperative complications associated with the tension-free vaginal tape operation with a central registry. METHODS: Fifty-five gynecology units completed questionnaires on patients undergoing the tension-free vaginal tape operation. Information was collected on patient, surgical, and postoperative data. RESULTS: A total of 2795 patients were entered. Overall, 773 patients (28%) had undergone previous surgery for incontinence or prolapse; 1640 (59%) tension-free vaginal tapes were performed as isolated operations, and 1155 (41%) were done in combination with other procedures. The median operating time for tension-free vaginal tapes alone was 30 minutes (range 10-120). Of the isolated tension-free vaginal tapes, 727 (44%) were performed with local, 711 (43%) with regional, and 193 (12%) with general anesthesia. In patients undergoing tension-free vaginal tape only, postoperative bladder drainage was obtained with intermittent catheterization in 389 (24%) patients, an indwelling urethral catheter in 1032 (63%), and a suprapubic catheter in 143 (9%). The bladder perforation rate was 2.7% overall (n = 75) and higher in patients with than in those without previous surgery (4.4% compared with 2.0%, P =.01). There were four bladder perforations (3.3%) among the 120 patients with previous colposuspension. Most patients undergoing tension-free vaginal tape only were able to void the next day (range 0 to over 64). A total of 68 patients (2.4%) required reoperation for reasons related to the tape (39 to loosen, remove, or cut the tape, or to place a suprapubic catheter, 19 for hematoma, one for bowel injury). CONCLUSION: The tension-free vaginal tape has become a frequently performed operation in Austria. There are considerable variations in clinical practice. The risk of bladder perforation was increased in patients with previous surgery. Severe complications were rare.

Value of urethral pressure profilometry in the female incontinent patient: a prospective trial with an 8-channel urethral catheter.

OBJECTIVES: To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS: Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS: The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS: The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.

Immunohistochemical detection of mutant p53-suppressor gene product in patients with breast cancer: influence on metastasis-free survival.

Overexpression of p53-protein appears to be a common event in primary breast cancer. It has been proposed that the presence of elevated levels of this protein may be an independent prognostic factor and may be important for the ability of a tumor to metastasize. This study was performed to evaluate the influence of immunohistochemically detectable mutant p53-protein on metastasis-free survival of patients with breast cancer. Immunohistochemistry was performed on 117 paraffin-embedded biopsy specimens of consecutive patients with stage T1-T4 breast cancer, using a monoclonal antibody against p53 suppressor gene product. 29 (24.8%) specimens showed positive staining, whereas in 88 (75.2%) a negative staining reaction for p53 was found. Comparing time intervals to diagnosis of metastasis, using Kaplan-Meier curves, Log-Rank test revealed no significant differences in metastasis-free survival between p53 positive and negative patients (P = 0.32), whereas statistically significant differences were noted for tumor stage (P < 0.01), nodal status (P < 0.01), histological grading (P < 0.01) and estrogen receptor status (P = 0.03). Mutant p53-protein, as detected by immunohistochemistry in paraffin embedded tumor tissue, does not appear to influence metastasis-free survival in patients with breast cancer.

The serum tumor marker M3/M21 in the follow-up of breast cancer patients.

The aim of this study was to evaluate the new serum tumor marker M3/M21 in comparison to CA 15-3, CEA and MCA in the follow-up of breast cancer patients. We investigated 267 serum samples from 35 patients suffering from invasive breast cancer, International Union Against Cancer (UICC) stage pT1 to pT4. Cut-off values for M3/M21, CA 15-3, CEA, and MCA were 25 U/I, 30 U/I, 5 ng/ml and 11 U/I, respectively. Serum tumor marker results were correlated with the results of the clinical and radiological examinations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of serum CA 15-3, CEA and MCA were 47/85/61/76%, 24/90/55/70% and 39/84/55/73%, respectively. Serum M3/M21 showed a sensitivity of 45%, specificity of 81%, PPV of 73% and NPV of 69%. The combination of CA 15-3 and M3/M21 increased the sensitivity to 55%, with a specificity, PPV and NPV of 83%, 79% and 86%, respectively. CA 15-3 measurements showed a lead time effect in 5 patients, ranging from 3 to 7 (median 4.1) months. The combination of CA 15-3 and M3/M21 provided lead time effects in 7 cases, ranging from 2 to 8 (median 5.7) months. We conclude that the detection of breast cancer recurrence with CA 15-3 is improved by combination with M3/M21.

Expression of the adhesion molecule CD44v3 is a prognostic factor in vulvar carcinoma.

Our aim was to evaluate the prognostic value of CD44v3 overexpression in vulvar cancer patients. Twenty-five cases of squamous cell carcinoma of the vulva with International Federation of Gynecology and Obstetrics (FIGO) stages I to III were examined for overexpression of the CD44 isoform CD44v3. The correlation of CD44v3 overexpression with clinical stage, histologic grade and overall survival was investigated. Follow-up ranged from 36 to 120 months. Clinical stage and histologic grade did not correlate with CD44v3 overexpression. CD44v3 overexpression was associated with poorer overall survival (log rank: P < 0.03). Immunohistochemically detected CD44v3 overexpression is significantly correlated with a reduced overall survival rate for patients with vulvar carcinoma.

The influence of obesity on the disease-free survival in primary breast cancer.

Hyper-estrogenism is more common in obese than in non-obese women. Consequently obesity has been shown to increase the risk of hormone department tumors. Some investigators have claimed that obesity at the time of primary treatment may be an independent prognostic factor for breast cancer, but this issue is still controversial. Therefore, we conducted a retrospective analysis to assess the influence of obesity at the time of primary treatment on disease-free survival (DFS). Obesity was defined as an excess of more than 25% of ideal weight according to Broca's index ([Height (cm) -100])-10%). The Cox-model was used for multivariate analysis. Mean follow-up was 61 (range 6-126) months. 295 (62.3%) patients were classified as of normal weight and 178 (37.6%) as obese. Mean excess of ideal weight was 8.9 kilograms (kg) in premenopausal and 13.9 kg in postmenopausal patients (non-parametric t-test p < 0.00001). Patients with tumor size < 20mm, 20-50mm and > 50mm had a means excess of the real weight of 10.6kg, 12.5kg and 16.1kg, respectively (non-parametric t-test p < 0.0001). Percentual excess of real weight compared to ideal weight was 22.4 [+/-21.2] kg in patients without recurrence and 21.5 [+/-21.9] in patients with recurrent disease (nonparametric t-test p = 0.7256). Univariate analysis revealed no significant association between obesity and the DFS. Multivariate analysis identified axillary lymph node involvement as the only statistically significant prognostic factor for disease-free survival (RR 1.55; 95%-confidence interval 1.02-2.36; p:0.0368). Because of the high correlations and node-status, tumor size and histological grading, the other factors failed to be prognostically relevant in this analysis. Obesity was not found to influence DFS of patients with primary breast cancer and is therefore unlikely to constitute an independent prognostic factor. It may, however, contribute to delayed diagnosis, since a significant proportion of obese patients were diagnosed with local advanced disease.

Influence of delayed diagnosis on established prognostic factors in endometrial cancer.

To evaluate the influence of delayed diagnosis on prognostic factors in endometrial cancer, we conducted a retrospective chart analysis based on the data of 116 postmenopausal patients with FIGO stage I-IV endometrial carcinoma. The interval from the first episode of post-menopausal vaginal bleeding to definitive, histological diagnosis (bleeding interval) was compared with tumor stage and various histomorphologic features in endometrial cancer. The mean bleeding interval was 12.7 +/- 17.8 weeks in 74 patients with FIGO stage IA, IB endometrial carcinoma and 35.2 +/- 69.3 weeks in 42 patients with stage IC-IV disease (t-test, p: 0.011). FIGO stage IA, IB disease was diagnosed in 23/26 (88%) patients with a bleeding interval <4 weeks, and in 22/34 (64%) and 29/56 (51%) patients with bleeding intervals of 4-8 weeks and >8 weeks, respectively (Chi-square 10.358, p=0.006). The correlation with histologic grade, lymph-node status, vessel invasion and histologic subtypes did not reach statistical significance. Our data confirm the clinical impression that postmenopausal vaginal bleeding is an early symptom in patients with endometrial cancer, and that advanced disease in the majority of cases might come from delayed diagnosis in women with poor compliance.

Treatment with biologic response modifiers in patients with ovarian cancer.

The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN-gamma augmented natural killer activity in 2 of 3 patients.

Prophylactic cerclage in pregnancy. Effect in women with a history of conization.

OBJECTIVE: To evaluate the effect of prophylactic cerclage on the course of pregnancy in women with prior conization. STUDY DESIGN: In a retrospective, observational study, the outcome of pregnancies in 69 women with (n = 30) and without (n = 39) cerclage who previously underwent conization was evaluated regarding hospitalization due to threatened preterm labor and delivery before 37 weeks of gestation. RESULTS: The occurrence of preterm delivery was 23.3% in the cerclage group and 20.5% in the control group (P = .78). Women with prophylactic cerclage were hospitalized significantly more often due to threatened premature labor: with cerclage, 66.7%; without cerclage, 33.3% (P = .006). CONCLUSION: Prophylactic cerclage should be used more sparingly in women with a history of conization because it does not prevent premature delivery and tends to induce preterm uterine contractions.

[Is the Gaudenz Incontinence Questionnaire still relevant in diagnosis of urodynamic function?]. / Ist der Gaudenz-Inkontinenzfragebogen in der urodynamischen Funktionsdiagnostik noch aktuell?

The results of this study show that the Gaudenz incontinence questionnaire can still be used to help determine the history of the incontinent patient. However, the questionnaire cannot substitute--Gaudenz stressed this fact in his study--a complete urogynecologic workup. Especially delicate problems as urinary incontinence require reliable and objective diagnostics and therapy using the advantages of the available diagnostic potential.

[Urethrovesical morphology in continent women in spinal anesthesia]. / Urethrovesikale Morphologie bei kontinenten Frauen in Spinalanästhesie.

OBJECTIVE: To assess the influence of spinal anesthesia on bladder neck position and a clinical stress test in continent women. METHODS: In a prospective investigation, 14 women underwent urodynamic, sonographic and clinical assessment during spinal anesthesia. Results were compared to those obtained immediately preoperatively in the same patient. RESULTS: During spinal anesthesia, the bladder neck was found to be located significantly lower and more posterior, and in 4/7 parous patients (0/7 nullipara) the clinical stress test was positive. CONCLUSION: These data provide additional evidence for the importance of neuromuscular function in the etiology of pelvic floor dysfunction and genuine stress incontinence.