[Emergencies in gynecology--what must I not forget?]. / Notfälle in der Gynäkologie--was darf ich nicht vergessen?

Emergency consultations happen frequently in gynaecology and may be due to abdominal pain, itching, utero-vaginal bleeding, rape, emergency contraception, insertion of foreign bodies, prolapse and urinary tract infection. Considering pregnancy in patients with child bearing potential is essential. Vaginal bleeding may be due to atrophy, infection, carcinoma or pregnancy. In the latter it is crucial to differentiate between ectopic, pathologic or physiologic pregnancy. In postmenopausal women further investigations by the gynaecologist are mandatory to exclude malignancy. Patients who have been raped need psychological, forensic and gynaecological support. Sexually transmitted disease including HIV must be considered and prophylactic drugs should be administered. If unprotected intercourse has occurred the "morning after pill" can be considered within 72 hours after intercourse or an IUD up to five days. Prolapse occurs rarely as an acute problem but may induce urinary retention. Urinary tract infection is a common complaint and should be treated with antibiotics.

Ovarian cancer. an institutional review of patterns of care, health insurance and prognosis.

The purpose of this study was to investigate the prognostic importance of the health insurance status in 145 consecutive patients with ovarian cancer diagnosed between 1984 and 1996. All patients had basic (Type III) insurance to cover outpatient treatment and hospital expenses for a per diem flat fee; some patients had one of two types of supplemental private insurance (Type I and Type II) to cover the treatment by physicians of their choice and fee-for-service hospital treatment. The prognostic impact of health insurance was evaluated by multivariate statistical methods. The median follow-up was 81.9 months (range: 21-181); the 5-year probability of survival was 72% (standard error of the mean (SEM) 9.8%) for stage I, 53% (SEM 16.2%) for stage II, 17% (SEM 5. 9%) for stage III and 11% (SEM 5.5%) for stage IV cancer. Age, stage, histological grade and debulking surgery were independent predictors of survival in multivariate proportional hazards regression analysis. Patients with private insurance were younger and received more chemotherapy than patients with basic insurance. In multivariate analysis, insurance was an independent predictor of survival: patients with Type II insurance had a hazard ratio of 2.31 (95% confidence interval (CI): 1.05-5.04), and patients with Type III insurance had a hazard ratio of 3.30 (95% CI 1.52-7.17) compared with the reference group of Type I insured patients. Health insurance status was an independent predictor of survival in ovarian cancer. Research is needed to devise strategies to improve the medical care of patients with basic insurance.

EGFR dependent expression of STAT3 (but not STAT1) in breast cancer.

STAT proteins constitute a family of transcription factors whose activation by cytokine and non-cytokine receptors leads to tyrosine phosphorylation, dimerization and translocation from the cytoplasm to the nucleus. In the nucleus they activate the transcription of specific genes by binding to consensus DNA elements. STATs 1 and 3 can be activated by both cytokine and non-cytokine receptors, and bind as homodimers or heterodimers to viral simian sarcoma virus (sis)-inducible elements such as that found in the c-fos promoter. Activation of c-Src and EGF receptor tyrosine kinases is associated with progression of breast cancer. Both these events lead to activation of STAT proteins, Src kinases activate STAT3 dependent transcription in mammary epithelial cells and EGF receptor activation can lead to activation of STATs 1 and 3. STAT3 activation has been demonstrated to have a role in oncogenesis and increasingly, activated STAT proteins are found to be activated in human cancer. In this study we describe detailed immunohistochemical analysis of nuclear and cytoplasmic STATs 1 and 3 expression in primary breast carcinomas and correlate this with EGFR, HER2, p53, ER, PR, p21/waf1, Bcl-XL and Ki-67 expression. We also compared expression between normal and tumor tissue. We report here a highly significant correlation between nuclear STAT3 expression and breast cancers compared to normal tissue. We also report a very strong correlation between nuclear STAT3 and EGFR expression in breast cancers. These data clearly demonstrate a strong association between STAT3 activation and breast tumorigenesis and strengthen the assertion that STAT3 activation may play an important role in the tumorigenic conversion of breast tissue mediated by tyrosine kinase signaling pathways.

Whole-abdomen radiation in patients with advanced ovarian carcinoma after surgery, chemotherapy, and second-look laparotomy.

Forty-three patients with ovarian carcinoma were treated with whole-abdomen radiation (moving strip +/- pelvic radiation), 15 patients had not received prior chemotherapy, and 28 patients were irradiated following chemotherapy and second-look laparotomy. Ten of these had been treated with a variety of chemotherapy regimens (L-PAM, CHAD, Hexa-CAF). Eighteen patients were treated in an ongoing prospective trial with combination chemotherapy consisting of melphalan, cis-platinum, and hexamethylmelamine++ (HexaPAMP). Thrombocytopenia was the limiting toxicity. A temporary pause in the radiation schedule allowing platelets to recover made it possible to complete treatment in 80% of the patients. The acute toxic effects, which included the expected side effects of radiation therapy on intestine, liver and lung, were not more frequent or more severe in the patients who had received prior chemotherapy than in those who had radiation therapy alone. Thirty-four of 43 patients (stage I, seven patients; stage II, seven patients; stage III, 27 patients; stage IV, two patients) are alive and without evidence of disease 26 + months (range 7 to 64 months) after entering the postsurgical treatment program.

Pathologic data of prognostic significance for remission induction in advanced ovarian carcinoma.

Sixty-eight patients with "advanced ovarian carcinoma" were entered into an ongoing phase-II trial for remission induction with cis-platinum (DDP) 80 mg/m2 i.v. on day 1 followed by forced saline diuresis, melphalan (L-PAM) 12 mg/m2 i.v. on day 2 and hexamethylmelamine (HMM) 130 mg/m2 p.o. X 14 days from days 8-21 in six monthly cycles following operative resection and/or staging. Fifty-one patients were evaluable for response, ten had not completed six courses and could not be assessed, two patients died early (one probably of toxicity), and five patients refused treatment and follow-up. Thirty-Two patients had serous, endometrioid or undifferentiated carcinomas of the ovary. Of these, 11 (35%) achieved a pathologically proven complete remission (CR), five (16%) were NED after second-look (residual disease in ovary or removed omentum with all other biopsies and cytology washings negative), eight (32%) achieved a partial remission (PR), and three (12%) had progressive disease. None of the seven patients with clear-cell carcinoma and none of the three patients with Mullerian tumor of the ovary responded. Six of nine patients with tumors of uncertain origin or proven metastasis to ovary did not respond to treatment. These preliminary results indicate that advanced ovarian carcinomas form a heterogeneous group of recognizable neoplastic diseases with striking variation in response to treatment.

A mathematical model for the estimation of human embryonic and fetal age.

Precise determination of donor age in human embryonic and fetal tissue is crucial for cell transplantation due to the existence of distinct time windows within which successful grafting is possible. This study demonstrates that between 4-12 wk postconception embryonic and fetal age can be estimated based on various morphometric parameters measured on a routine basis in suction abortion material. The greatest length, the neck-rump length, the foot length, and the proximal and distal arm and leg length were correlated with the anamnestic and ultrasonographically estimated age. Multivariate regression analyses showed a linear correlation between age and the logarithmic value of the various morphometric parameters. The best correlation was found for a mathematical model combining the limb parameters (r = 0.904; p < 0.001; n = 37). A prospective follow-up study (n = 40) was carried out to test the validity of the mathematical model. A high correlation was found between the calculated age and the estimated age based on anamnestic data (r = 0.749, p < 0.001). Outliers due to errors in the anamnestic data were readily identified by comparing anamnestic with calculated age. This method allows determination of embryonic and fetal age within and beyond the age group of the Carnegie classification and may, therefore, be useful for the needs of experimental and clinical cell transplantation.

Clear cell adenocarcinoma of the cervix associated with a rare genitourinary malformation.

BACKGROUND: Cervical adenocarcinoma and genitourinary malformations are relatively common disorders, yet their coexistence is rare. CASE: A 49-year-old woman developed clear cell adenocarcinoma in the atretic hemicervix of a communicating uterus type 7 and had ipsilateral renal agenesis. Compared with the unaffected right hemicervix, only the tumor-involved glands of the atretic left hemicervix contained ciliated tuboendometrial cells. Four and a half years after radical hysterectomy and pelvic radiation, she showed no evidence of recurrence. CONCLUSION: In contrast to current opinion, communicating uteri type 7 are associated with ipsilateral renal agenesis. Our histologic findings support the hypothesis that tuboendometrial cells are the cells of origin for cervical clear-cell adenocarcinoma.

Computed tomography prior to second-look operation in advanced ovarian cancer.

Twenty-six patients treated with chemotherapy for ovarian cancer underwent a second-look laparotomy after clinical response (or in the absence of evidence of progressive disease). Abdominopelvic computed tomography (CT) was performed before this operation. Five patients (19%) who had been demonstrated as being free of disease by computed tomography were found to have a tumor larger than 1 cm. Computed tomography sensitivity was good in detection of lymph node metastases (83%), average for pelvic residual tumor (63%) and the omentum (50%), and low for other peritoneal locations (11%). Before second-look operation, the computed tomography scan provides useful surgical information about residual disease in retroperitoneal lymph nodes. However, negative computed tomography findings do not exclude residual tumor or confirm complete remission and therefore cannot replace the second-look laparotomy at this time.

Tubal sterilization by means of endoluminal coagulation: an in vivo study in rabbits.

This study was conducted to investigate the effectiveness and safety of endoluminal tubal coagulation in obliterating the tubal lumen in rabbits. Forty female rabbits were subjected to laparotomy and hysterotomy. Endoluminal tubal coagulation was induced over a length of 3 cm in the proximal, extramural fallopian tube by using a heated stainless steel cannula or a cylindrical diffusing tip emitting argon laser radiation for one to 5 minutes. Tubal patency was evaluated by observing patterns of injected methylene blue and/or breeding success rates. Postoperative recovery was uneventful in all animals. A negative methylene blue test indicated occlusion in 51 of 52 tubes (tubal occlusion rate 98.1%), and a contraception rate of 100% in all 17 uteri in which the tube had been treated. The described endoluminal tubal coagulation method proved suitable for safe and effective sterilization in rabbits and has potential as a new transcervical tubal sterilization method for humans.

Intrauterine occlusion body (IUB). Preliminary report.

The IUB or SOF-T is a further development of the IUD with additional functions and properties. In 368 IUB insertions over a period of 48 months, there was no intrauterine pregnancy. There was a low removal rate due to bleeding, pain, infection or partial expulsion in 277 insertions performed at two university centers over an average period of 8-1/2 cycles. In 80 cases tubal occlusion was directly or indirectly proven by different methods. The improved ultrasound localisation of the IUB is possibly responsible for its effectiveness and the soft ends are probably the main reason for its improved tolerance compared to other IUDs.

Umbilical endometriosis.

We report two women who presented with a recurrent, mildly painful, bluish nodule in the umbilicus. Both patients complained of local tenderness and occasional bleeding that increased during menstruation. Neither patient had had previous pelvic surgery. Excision of the lesions revealed a primary umbilical endometriosis; in one case, a simultaneous laparoscopy showed a pelvic endometriosis. We review the current literature and discuss the possible etiopathogenesis and when a laparoscopy is indicated to diagnose a concomitant pelvic endometriosis. Umbilical endometriosis is a very rare disease but should be considered in the differential diagnosis of umbilical lesions.

Lymphadenectomy in high risk endometrial carcinoma stage I and II: no more morbidity and no need for external pelvic radiation.

The objectives of this retrospective study were to analyze the morbidity of surgical staging and to evaluate the omission of external radiotherapy in high-risk patients with stage I and II endometrial carcinoma when the lymph nodes were negative. From 1988 to 1996, 63 of 117 patients underwent a pelvic and periaortic lymphadenectomy. The decision to perform lymphadenectomy was influenced by patient general health. Patients with lymphadenectomy had a better physical status (P < 0.0001). Lymphadenectomy increased mean operative time (P < 0.0001) and blood loss (P < 0.01), but there was no increase in postoperative complications. At a median follow-up of 54 months, there was one cuff recurrence in 56 patients. Nineteen high-risk patients without external pelvic radiation had the same disease-free survival rate as 37 low-risk patients (P = 0.1). In the group without lymphadenectomy, the disease-free survival for 18 high-risk patients and 32 low-risk patients was similar (P = 0.21). Surgical staging in properly selected patients does not increase postoperative complications and brachytherapy without external radiotherapy is associated with excellent disease-free survival when the lymph nodes are negative.

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.

Effects of 5-aminolaevulinic acid on human ovarian cancer cells and human vascular endothelial cells in vitro.

Results are reported on the cellular effects and the sensitivity of cultured tumor epithelial cells (TEC) derived from human ovarian cystadenocarcinoma and human umbilical vein-derived endothelial cells (HUVEC) to exogenous 5-aminolaevulinic acid (ALA) and ALA-induced photodynamic therapy (PDT). Cellular alterations and PDT efficiency were evaluated using colorimetric thiazolyl blue (MTT) assay, trypan blue exclusion assay, electron microscopy, and gel electrophoresis. ALA-induced protoporphyrin IX (PpIX) accumulation in TEC was associated with a concentration and time-dependent significant decrease in mitochondrial activity, increase in cell membrane permeability, and dark toxicity. Maximum PpIX loaded TEC demonstrated a high sensitivity to PDT. Neither cellular alterations nor PDT effects were observed in HUVEC under identical experimental conditions. These results indicate a potential clinical value for the use of ALA-mediated PDT to treat minimal residual disease in mucinous ovarian carcinoma. In addition, the ALA-induced PpIX cytotoxicity may be exported to a new chemotherapeutic regimen via a conventionally viewed photochemotherapeutic agent.

Combined bilateral tubal and multiple intrauterine pregnancy after ovulation induction.

Over the last 20 years, the frequency of multiple pregnancy has increased mainly because of the introduction of exogenous pituitary gonadotropins in the treatment of sterility. The incidence of ectopic pregnancies also increased during the same period of time. This paper describes the first reported case of a simultaneous bilateral tubal and multiple intra-uterine pregnancy after ovulation induction with human gonadotropins.

Urethral isolation of Chlamydia trachomatis in women with urinary incontinence.

The overall prevalence of Chlamydia trachomatis (CT) infection in 168 patients with urinary incontinence was 7.7%. However, in patients with urethral instability CT was found significantly more often than in those with stable urethra (P less than 0.001). Clinical and urodynamic improvement followed the treatment with doxycycline in 8 out of 9 patients with urethral instability. According to our results urethral infection with CT may play an important role in the etiology of urge incontinence and urethral instability.

[Laser therapy in gynecology]. / Lasertherapie in der Gynäkologie.

Laser therapy is being implemented with increasing frequency in medicine. Carbon dioxide laser is the system most commonly used in gynaecology and the main indications are disease of the uterine cervix, vagina, vulva or perineum. When used in conjunction with the microscope or laparoscope during reconstructive operations on the adnexa, laser speeds up the surgical procedure and brings out the inherent advantages of this technique, namely, precise separation or destruction of tissue, absence of postoperative oedema, uncomplicated wound healing, minimal mechanical trauma, decreased postoperative pain and good haemostasis. With good maintenance and practice laser systems all work well. The only disadvantage is their high cost.

[Evaluation of tumor extension in invasive cancer of the uterine cervix. Diagnostic evaluation of cervix cancer]. / Bilan d'extension tumorale lors de cancer invasif du col utérin. Bilan diagnostique et cancer du col.

Cancer of the uterine cervix accounts for approximately 30% of deaths from malignancies in gynecology and this rate has remained unchanged for more than 40 years. The most important prognostic factor is the extent of the disease at the beginning of treatment. There is, however, a discrepancy of some 50% between clinical and postoperative staging. The aim of this study was to evaluate different diagnostic investigations leading to the preoperative classification (FIGO) of 261 patients with cervical cancer. Data of presurgical clinical and radiological examinations were compared with postoperative histopathological findings. Rectovaginal palpation and computerized tomography (CAT) both showed a positive predictive value of 60%. The performance of CAT and lymphography in the diagnosis of lymph node metastasis was poor with positive predictive values of 36.3 and 20%, respectively. In the absence of parametrial infiltration on palpation, cystoscopy and rectoscopy are superfluous since they are always normal. Urography, because of the possibility to show the topographic anatomy of the urinary tract, was justified in all cases. The value of surgical staging and more recent techniques such as sonography and magnetic resonance is discussed.

[Guideline for the diagnosis of postmenopausal bleeding. PMPB Working Group of the SGGG]. / Leitlinie zur Abklärung von postmenopausalen Blutungen. Arbeitsgruppe PMPB der SGGG.

2.1. History and clinical-gynecological investigation including a Pap smear are the first step in the clarification. The history should make sure if there is in fact bleeding from the genital and not from the urological or the intestinal region. Drug intake should be recorded, and risk factors for the development of endometrial carcinoma should be considered. This will not affect further investigation. The clinical-gynecological investigation should prove the source of postmenopausal bleeding according to the anatomical site--uterine, infra-, or suprauterine. The causes of infrauterine bleeding may easily be diagnosed by means of inspection of the external genitalia and further by using a speculum. The causes of uterine bleeding are of major importance. Cytology and colposcopy, supported by bimanual investigation, exclude cervical carcinoma as a cause of bleeding. Atypical endometrial cells on the cytological smear arouse suspicion of endometrial carcinoma. 2.2. Transvaginal sonography (TVS) is the next step if the above-mentioned investigations are negative. Both adnexa should always be investigated and the findings sonographically documented, so that solid cystic masses in the adnexal area can be better identified as suprauterine causes of postmenopausal bleeding. Then the uterus should be investigated. Further procedures are decided from the results of measurement of the longitudinal section of the endometrium at the level of maximum endometrial thickness. If the endometrial thickness is _<4 mm, an observant attitude can be assumed. After 3 months the patient should be controlled against using TVS. If bleeding recurs or the endometrial thickness is >4 mm on TVS, the procedure given in subparagraph 2.3 should be followed. In case the endometrial thickness is >4mm or not measurable, a histomorphological investigation according to subparagraph 2.3 should be performed. In such cases, saline infusion sonohysterography(SIS) is useful as a simple method to supplement TVS. It can aid in the decision making as to which further, more invasive measures should be taken (endometrial biopsy/hysteroscopic resection). Computerized tomography or magnetic resonance imaging are, as a rule, not indicated in patients with postmenopausal bleeding. 2.3. A definite diagnosis is possible only on the basis of a histological investigation. If TVS or SS show evidence of a polypoid state, removal under hysteroscopic control is the diagnostic method of choice. In cases of symmetrical or asymmetrical thickening of the endometrium on SIS, a less invasive biopsy may be sufficient. If the biopsy specimen does not yield representative diagnostic material, one should proceed as described above. A fractionated curettage should as a rule not be performed solely, but in combination with hysteroscopy.

[Breast carcinoma--when is mastectomy still appropriate?]. / Mammakarzinom--wann noch Ablatio mammae?

Conservative therapy is now an established treatment for early-stage breast cancer when the extent of breast resection is sufficient and when adequate radiotherapy can be given. Ten-year local recurrence rates ranging from 3% to 20%, approximately 0.8% per year have been reported. At the Department of Gynecology of the University of Berne we changed our approach to the local treatment and the frequency of breast conserving surgery rose in one year to 61% for tumors 2 cm or less (T1) and 31% for T2. Our aim is now to limit axillary dissection to patients with nodal involvement. We have therefore started to identify those patients by removing the sentinel node.