Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

The value of dynamic magnetic resonance imaging in interdisciplinary treatment of pelvic floor dysfunction.

PURPOSE: The purpose of this study was to determine the value of dynamic pelvic floor MRI relative to standard clinical examinations in treatment decisions made by an interdisciplinary team of specialists in a center for pelvic floor dysfunction. METHODS: 60 women were referred for dynamic pelvic floor MRI by an interdisciplinary team of specialists of a pelvic floor center. All patients were clinically examined by an urologist, gynecologist, a proctological, and colorectal surgeon. The specialists assessed individually and in consensus, whether (1) MRI provides important additional information not evident by physical examination and in consensus whether (2) MRI influenced the treatment strategy and/or (3) changed management or the surgical procedure. RESULTS: MRI was rated essential to the treatment decision in 22/50 cases, leading to a treatment change in 13 cases. In 12 cases, an enterocele was diagnosed by MRI but was not detected on physical exam. In 4 cases an enterocele and in 2 cases a rectocele were suspected clinically but not confirmed by MRI. In 4 cases, MRI proved critical in assessment of rectocele size. Vaginal intussusception detected on MRI was likewise missed by gynecologic exam in 1 case. CONCLUSION: MRI allows diagnosis of clinically occult enteroceles, by comprehensively evaluating the interaction between the pelvic floor and viscera. In nearly half of cases, MRI changed management or the surgical approach relative to the clinical evaluation of an interdisciplinary team. Thus, dynamic pelvic floor MRI represents an essential component of the evaluation for pelvic floor disorders.

[Results of fertility preserving operations in malignant ovarian tumors]. / Ergebnisse fertilitätserhaltender Operationen bei malignen Ovarialtumoren.

Indication for fertility preserving surgery results from the patient's age, the histologic tumor type and the stage of the ovarian malignancy. Approximately 80-85 % of these lesions are ovarian cancers. 10-15 % tumors with low malignant potential (LMP) and approx. 5 % germ cell tumors. Of the ovarian cancers approx. 15 % of LMP tumors 50 %, and of germ cell tumors more than 90 % occur in patients below 40 years of age, in which fertility preserving surgery might be considered. An adequate operative staging permits a conservative procedure for ovarian cancers stage Ia. Due to the good prognosis of LMP-tumors (10 year survival, all stages, approx. 90 %) and the low rate of recurrences after conservative surgery of 6.8 % (10/147), a fertility preserving operation is feasible in select cases also in more advanced stages than Ia. In cases of germ cell tumors, which in the majority of cases are unilateral, even if the tumor extends beyond the ovaries, an adnexectomy will suffice. A successful chemotherapy, e.g. with bleomycin, etoposid, and cisplatin leads to remission rates of > 90 %. The reduced number of patients treated according to the above criteria in 90 % had a normal menstrual cycle after surgery and chemotherapy. Besides numerous case reports on successful pregnancies, there are also reports in literature on results in larger patients groups. Thus it has been reported that of 99 patients with an ovarian cancer stage I. 56 underwent conservative surgery. Child-bearing desire, present in 17 of these women, could be fulfilled in all cases (Colombo et al. 1995). Bianci and coworkers also described successful pregnancies (14/48) after conservative treatment of tumors of LMP. Numerous case reports have been published showing that after fertility preserving surgery of germ cell tumors pregnancies may also be successful. Since especially in ovarian cancers recurrences may occur at a later time, a hysterectomy with removal of the contralateral adnexa is suggested after complete family planning or when the patient enters the menopause. The possibilities offered by in vitro-fertilization have theoretically enlarged the spectrum of fertility preserving surgery. Thus, individual authors propose the conservation of the uterus after bilateral ovarectomy-keeping the option of a pregnancy by oocyte donation open for the patient. As further alternative conservation of a restovary after removal of the uterus and one adnexa is discussed. In these cases the patient's oocytes are preserved for feasible in vitro-fertilization in a "substitute" mother. Results of such fertility preserving procedures have not yet been published.

Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma.

Both nuclear DNA content and S-phase fraction (SPF) can be helpful in predicting prognosis in certain malignancies. We investigated in a retrospective study the prognostic significance of nuclear DNA content and SPF as measured by flow cytometry of tumor specimens from 162 women with nonpretreated surgically staged FIGO stage I endometrial cancer using clearly defined inclusion criteria. A total of 139 (86%) cases were found to be diploid, whereas 23 (14%) were aneuploid. Ploidy showed a correlation with histologic grade, estrogen as well as progesterone receptor levels, and depth of myometrial infiltration. Univariate analysis of follow-up data showed an increased relative risk (RR) for recurrence-free survival (RFS) for grade 3 tumors (RR = 2.11, ns), for age (RR = 1.04, P = 0.023) as a continuous variable, and for SPF in diploid tumors (RR = 3.10, P = 0.035). In addition, univariate analysis of overall survival revealed similar results with a slightly increased relative risk for ploidy (RR = 1.52, ns). Multivariate analysis of RFS showed age as the only independent prognostic factor. Multivariate analysis of RFS for diploid tumors showed no independently significant factor; however, age as a continuous variable with a relative risk of 1.04 and SPF with a relative risk of 2.94 were of borderline significance. Our results suggest that abnormalities of the nuclear DNA content and SPF in this homogeneous group of patients are associated with clinical and morphological prognosticators; however, ploidy is no independent prognostic factor for RFS. For diploid tumors, SPF might be a possible independent prognostic factor.

Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.

PURPOSE: We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.

Estrogen and progesterone receptors in endometrial cancer and their prognostic relevance.

Three hundred and nine malignant endometrial tumors were biochemically analyzed with respect to estrogen (ER) and progesterone (PR) receptors. Fifty-seven percent of endometrial carcinomas were ER and PR positive (greater than or equal to 50 fmole/mg of cytosol protein); 24% were negative for both receptors. Five sarcomas and 16 of 21 mixed müllerian tumors were receptor negative. Receptor status correlated with clinical stage and grade of histological differentiation, but not with myometrial invasion. Anamnestic data on patients showed no differences between those with receptor-negative and receptor-positive tumors. Five-year survival rate (stage I) and median survival time (stages II-IV, recurrences) for patients with ER+/PR+ and ER-/PR+ endometrial cancer were significantly better than for ER-/PR- and ER+/PR- patients. A multivariate analysis demonstrated progesterone receptor as a significant prognostic factor next to clinical stage. Estrogen receptor had no significant prognostic relevance. A retrospective analysis of gestagen treatment and progesterone receptor status confirms the importance of PR, possibly independent of hormonal treatment.

[Pregnancy and labor in idiopathic thrombocytopenic purpura (Werlhof disease)]. / Schwangerschaft und Geburt bei idiopathischer thrombozytopenischer Purpura (M. Werlhof).

The managing of the pregnant patient with immune thrombocytopenic purpura (ITP) is complicated by the unavailability of the foetal platelet count and the risk of bleeding. We report on our experiences of 17 pregnancies in 15 patients, who delivered in the Department of Gynaecology of Freiburg University from 1969 to 1989 (frequency: 0.5 per 1,000). ITP was established prior to pregnancy in 9 of 15 patients, and developed in 6 cases during pregnancy. The a patients received steroid therapy ante partum. However, maternal platelet count did not relate to infant platelet count. Eleven infants were born vaginally, six by caesarean section. One of the 17 live births died immediately post partum at the 28th week of gestation. Six infants were temporarily thrombocytopenic at delivery without further morbidity. Based on our experience and the literature, an individual management of delivery for parturient patients with ITP is recommended.

DNA analysis, chemoresistance testing and hormone receptor levels as prognostic factors in advanced ovarian carcinoma.

Fifty patients with advanced (stage III or IV) ovarian carcinoma were followed-up until the date of their death or their fifth year of survival. Prognostic factors, including those currently in use, as well as ploidy and proliferation, chemoresistance testing and hormone receptor levels of the tumours were analysed for predictive value and independence from each other. In the univariate analysis, only stage, residual tumour, second-look status, chemoresistance, ploidy and proliferation were significantly correlated with survival. After being tested in a multivariate Cox regression model, however, only the results of chemoresistance testing at initiation of therapy, and second-look status at a later point, retained prognostic significance. Within the group of patients with a positive second-look, i.e., with the worst prognosis, the chemoresistance test was still able to discriminate between two subgroups with significantly different survival.

Prognosis of the adenocarcinoma of the cervix uteri: a comparative study.

The different prognoses for patients with adenocarcinomas and squamous cell carcinomas of the cervix uteri were proved by matched-pair analysis. One hundred forty-four patients with adenocarcinoma treated in 1964-1985 were compared in a ratio of 1:2 with 268 patients with squamous cell carcinoma comparable in age, stage, and treatment modality. In both groups 45% of patients were in stage I, 38% in stage II, 15% in stage III, and 2% in stage IV. Five- and 10-year survivals of patients with adenocarcinoma were significantly lower than for those with squamous cell carcinoma (53% resp. 42% vs 68% vs 58%, P = 0.006). In an analyses of patients' prognosis according to clinical stage there was no significant difference between both groups in stages III and IV treated exclusively by radiotherapy. No significant differences were found in stage I and II patients treated by radical surgery. However, the most significant difference in prognosis was seen in stage I and II patients treated by radiotherapy. Five-year survival was 58.6% in stage I adenocarcinomas compared with 85.0% in squamous cell carcinomas. It can be concluded from these results that a discussion of the problem of FIGO staging is more necessary than a discussion of the different radiosensitivities of these two histological types. Surgical treatment must have the same priority as radical surgery or staging laparotomy for exact histologic staging in adenocarcinomas of the cervix uteri.

Flow-cytometric prognostic factors for the survival of patients with ovarian carcinoma: a 5-year follow-up study.

Fresh surgical specimens of 37 patients with previously untreated ovarian carcinomas were investigated by means of flow cytometry. The aim of the study was to look for cellular prognostic factors, in addition to the well-known clinical prognostic factors, of survival time for these patients. All patients underwent chemotherapy after surgery, and all patients had a minimum of 5 years of follow-up. Patients with diploid or near-diploid tumors (DNA index less than or equal to 1.25) survived significantly longer than those with aneuploid tumors (DNA index greater than 1.25, P = 0.02). Patients whose tumors showed a high proportion of SG2M phase cells (greater than 17%) or a low proportion of G0/G1 phase cells had shorter survival times than those with tumors with a low proportion of SG2M phase tumor cells (less than or equal to 17%, P = 0.01) or a high proportion of G0/G1 phase tumor cells. There is no significant relationship between cytometric data and stage. Different surgical procedures, cytostatic treatment, histological tumor type, and differentiation had no significant effects on the survival time of patients in this study. Thus, the data from this study demonstrate strong cytometric prognostic factors of the survival of patients with ovarian carcinomas.