Günter Köhler

LIPID METABOLISM DURING TREATMENT OF ENDOMETRIOSIS WITH THE PROGESTIN DIENOGEST

The effects of a new progestational compound, dienogest (17α‐cyano‐methyl‐17β‐hydroxy‐estra‐4,9‐dien‐3‐one) on lipid metabolism have been studied in 84 otherwise healthy women with laparoscopically proven endometriosis. The women, aged 17 to 45, years were treated with 2 mg dienogest in tablet form daily for 24 weeks. The progestin was highly effective on endometriotic lesions and symptoms, showing an objective endoscopic and a subjective symptomatic improvement in 80% and 83% respectively. Triglycerides, total cholesterol, HDL‐cholesterol, LDL‐cholesterol and the LDL‐cholesterol/HDL‐cholesterol ratio were determined before and after 1, 3 and 6 months use of the progestin. There was a maximum decrease of —5.8% in HDL‐cholesterol and of —6.5% in triglycerides after 6 months of therapy vis‐à‐vis the pretreatment values. The maximum increase in LDL‐cholesterol of +5.0% was recorded by the end of the first month of dienogest ingestion. The LDL‐cholesterol/HDL‐cholesterol ratio rose from 1.6 to 1.8 during the course of therapy. There were no significant changes. The data suggest that 2 mg dienogest has little influence on lipid metabolism and provides also in this respect a suitable approach to the hormonal therapy of endometriosis.

Polypropylene mesh implantation in combination with vacuum-assisted closure in the management of metastatic or locally recurrent vulvar cancer: case report and review of literature.

Background: Mesh reconstruction, especially in combination with vacuum-assisted closure, might improve healing and reduce the surgical morbidity of extensive inguinofemoral lymphadenectomy or extensive local resection in progressive cancer of the vulva. Cases: Radical vulvectomy combined with inguinofemoral lymphadenectomy was performed in 2 patients (P1, P2). The inguinofemoral wound bed was stabilized by polypropylene mesh implantation and sealed with vacuum closure system. In 1 patient with local recurrence of vulvar cancer (P3), local excision and stabilization of the wound were performed by mesh implantation. Conclusions: Mesh implantation fulfills 2 purposes: (1) it protects exposed vessels and the wound can be vacuum sealed; and (2) it stabilizes the surgical bed, permitting the required radical excision locally and inside the vascular compartment.

Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-eastern German Society of Gynecological Oncology

Objective The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer. Methods Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m2 (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally. Results Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%. Conclusions Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.

Selective Pretreatment Diagnostic Imaging for Detecting Remote Metastases in Patients with Endometrial Cancer

Objectives: Various diagnostic tests are available to rule out metastases. However, not all of these tests provide significant information. Based on data collected at our institution, we have analyzed the significance of various imaging methods. Patients and Methods: In 337 patients with fully staged endometrial carcinoma, the results of chest X-rays, bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography of the liver, kidneys and abdomen were analyzed. Results: In the 7 patients who showed metastases, the liver was the most frequently affected organ. Hepatic CT is associated with a likelihood ratio (LR) of 9.0, hence representing a valuable technique. In cases with a pretest probability of 1.19% (independent of the disease stage), CT results in a post-test probability of 9.78%, putting into question the usefulness of the method for confirming metastases. With all other analyzed diagnostic modalities, even less information is gained. Conclusion: The routine use of the above diagnostic methods, indiscriminate of the disease stage, is not justified. LRs provide an estimate of the information gained by a diagnostic procedure.

Neoadjuvant Chemotherapy and Brachytherapy – a New Perspective in the Therapy of Advanced Cervical Carcinoma

A prospective study with a neoadjuvant radiochemotherapy (NRCHT) regime was designed in order to achieve operability or to increase efficacy of subsequent external irradiation in locally advanced cervical carcinoma. The therapy consisted of 3 courses carboplatin 300 mg/m2 on day 1 plus ifosfamide 2 g/m2 on days 1–3 repeated every 4 weeks in combination with 5 intracavitary brachytherapy courses with altogether 40 Gy/A. In case of operability patients underwent radical hysterectomy with lymphadenectomy. In all other cases followed a full course of external-beam irradiation consisting of 50.5 Gy in the ICRU50 reference point. 44 patients (x = 53.6 years) with stage IIB (3) and IIIB (41) cancers were enrolled. After NRCHT clinical CR and PR were achieved in 7 (15.9%) and 31 (70.4%) patients, respectively (total 86.3%). Surgery was possible in 15 (34.1%) patients. Histological CR was observed in 10 (66.7%) of them. Two (4.6%) patients experienced a NC and 3 (6.8%) a PD. One (2.3%) woman with PD died due to myelosuppression. All patients with CR and PR received 3 further chemotherapy courses after surgery or irradiation. The 5-year overall survival according to Kaplan and Meier was 63% in all patients but 80% and 54% in the operated and in the irradiated group, respectively. The preliminary data indicate that therapeutic results of advanced cervical cancer may be improved by NRCHT. Schlüsselwörter Zervixkarzinom . Neoadjuvante Chemotherapie . Brachytherapie

Uterine Sarcomas and Atypical Smooth-Muscle Tumors: Clinic, Diagnostics and Appropriate Surgical Therapy

In Europe, the incidence of leiomyosarcomas (LMS), low-grade endometrial stromal sarcomas (LG-ESS), high-grade endometrial stromal sarcomas (HG-ESS), undifferentiated uterine sarcomas (UUS), adenosarcomas (AS), and atypical smooth muscle tumors (synonym: STUMP – smooth muscle tumor of uncertain malignant potential) is around 1.2 cases/100,000 women (LMSs and LG-ESSs: around 0.9/100,000). Median age at the time of initial diagnosis of an LMS, an HG-ESS, a UUS, and an AS is 53, 58, 63 and 56 years, respectively, and is thus beyond menopause, with the exception of STUMPs and LG-ESSs (46 and 44 years). STUMPs are pathogenetically similar to LMSs, can recur after organ-sparing surgery in particular, and can also metastasize as LMS. Two of the following criteria must be fulfilled for an LMS to be classified as such: tumor cell necroses, ≥10 mitoses/10 HPF, and significant diffuse or multifocal moderate-to-severe atypia. One factor is sufficient for a STUMP to be diagnosed as such. However, it is unavoidable that a lesion be classified as an LMS when multiple TCNs have been positively and securely identified. LG-ESSs consist of uniform tumor cells that are reminiscent of proliferative endometrial stroma. The cellular atypia are typically low-grade, tumor cell necroses are rather the exception, and the number of mitoses is usually low. They express estrogen and progesterone receptors almost without exception. HG-ESSs consist both of a cytological low-grade component and of more predominant high-grade sections with higher grades of atypia, ample tumor cell necroses, and usually a clearly elevated mitotic index. UUSs are characterized by high-grade atypia, numerous mitoses and tumor cell necroses, with no specific type of differentiation. ASs are comprised of a benign adenous epithelial component and a sarcomatous component. The latter, in turn, can be LG-ESS, HG-ESS, UUS, LMS or another high-grade sarcoma. LG-ESSs and ASs with an LG-ESS-component have a relatively good prognosis, while the prognosis is extremely poor for the other types. Prognosis is primarily dependent on size and spread of the tumor as well as on the surgical techniques applied. Damaging the tumor (morcellation, enucleation, clamping, cutting) results in a shorter progression free interval and poorer overall survival. According to current data, for LG-ESSs and ASs with an LG-ESS component, tumor injury (only) results in a shorter progression-free interval and has no impact on survival. Apparently, causing damage to the uterus is already enough to impact negatively on prognosis. The therapeutic method of choice for uterine sarcomas is thus total hysterectomy without injuring the uterus. All surgical procedures that imply damaging the uterus or the tumor are to be deemed inappropriate. This includes all forms and variants of supracervical hysterectomy. The fundamental problem lies in the fact that, due to the diagnostic difficulties (and the fact that diagnostics are often insufficient or inadequate), 51 resp. 68 % of LMSs and LG-ESSs are operated under the indication or assumption of an LM. Oophorectomy is not necessary when a sarcoma that is confined to the uterus (!) is subjected to adequate and appropriate (!) surgery. There is no indication for systematic lymphadenectomy, parametric resection, or omentectomy. Adjuvant measures are not yet established. Where there is a postoperative incidental diagnosis following uterus-preserving surgery, hysterectomy should be subsequently performed with due haste. Should such surgery not take place, for various reasons, it is currently recommended that patients undergo follow-up laparoscopy and R0-resection of potential tumor residuals or early recurrences within three to six months. Aftercare is organized in accordance with the gynecologic oncological criteria. In order to prevent inadequate surgical procedures being performed on the basis of an indicated diagnosis of leiomyoma, an easy-to-use diagnostics flowchart is provided, the flow of which is based on patient age as well as results and findings from clinical and sonographic examinations. According to current data, performing an enucleation, a supracervical hysterectomy, or any form of morcellation without prior knowledge of sonographic presentation must be regarded as erroneous.