Hans Rudolf Tinneberg

Management of stage I cervical sarcoma botryoides in childhood and adolescence

Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood. The botryoid variant arises in infancy from the vagina or urinary bladder and extremely rarely from the uterine cervix. Treatment regimes range from local excision of the tumour to radical hysterectomy with adjuvant multidrug therapy and/or radiotherapy. In cases of minimal cervical invasion, the less invasive local excision in combination with adjuvant chemotherapy has resulted in excellent survival rates with complete functional preservation of the bladder, rectum, vagina, and ovaries. We present here a 30-year literature review and a case report of a cervical sarcoma botryoides in a 5-year-old girl. Conclusion:based on the literature review and our own observation, we recommend minor surgical approaches in combination with chemotherapy as the treatment of choice for early stage I cervical rhabdomyosarcoma.

Modulatory Effect of Acetylcholine on Gonadotropin-Stimulated Human Granulosa Cell Steroid Secretion

The aim of this study was to explore the direct action of acetylcholine on gonadotropin-stimulated progesterone (P) and estradiol (E2) secretion of human granulosa cells (GCs) cultured in serum-free medium. Human GCs were isolated from preovulatory follicular fluid aspirated from 22 women undergoing in vitro fertilization at the University Women’s Hospital of Tübingen. The production of progesterone and E2 was measured in the presence and absence of acetylcholine, carbachol, atropine, luteinizing hormone (LH) or follicle-stimulating hormone (FSH) using radioimmunoassay. Statistical analysis of the data was performed by ANOVA and Newman-Keuls test. Administration of acetylcholine or carbachol (10–5M) resulted in a significant increase in P and E2 secretion. This response was specifically blocked by the muscarinic receptor antagonist atropine. Similarly, carbachol resulted in a significant increase in P and E2 output, though the response to it was somewhat reduced when compared to that evoked by acetylcholine. Acetylcholine did not show any additive effect on LH-stimulated P secretion, while it augmented the stimulatory effect of FSH on P release. In contrast, carbachol markedly diminished the stimulatory effect of LH on P secretion, while it caused no change in FSH-induced P output. When administered together, acetylcholine did not modify the stimulatory effect of FSH on E2 secretion, however, it markedly elevated LH-induced E2 output. Similar to this, carbachol significantly increased LH-induced E2 release, however it decreased FSH-stimulated E2 secretion. We suggest that acetylcholine has a direct modulatory effect on gonadotropin-stimulated steroid production of GCs, an effect that is mediated via muscarinic receptors. This effect may have a physiological role in the regulation of GC function during the menstrual cycle.

Intravenous immunoglobulin (IVIG): modes of action in the clinical management of recurrent pregnancy loss (RPL) and selected autoimmune disorders

Abstract Recurrent pregnancy loss has been associated with autoimmune responses to membrane phospholipids and alloimmune reactions against paternally derived molecules on the trophoblast. The problem is psychologically and economically stressful as it undermines the capacity of some couples to reproduce and participate effectively in the day-to-day economic activities. This article reviews the adoption of intravenous immunoglobulin as a form of therapy for the clinical management of recurrent pregnancy loss and of selected autoimmune disorders. Side effects, contraindications and safety of use are discussed.

Recommendations by the gynecologic endoscopy working group of the german society of obstetrics and gynecology for the advancement of training and education in minimal-access surgery

Endoscopic minimal-access operative techniques have gained increasing significance in gynecology so that the most gynecological operations in health centers and clinics are now performed via an endoscopic approach: Endoscopy has proven beneficial for patients by reducing morbidity rates, reducing postoperative pain symptoms and shortening hospital stay. The German healthcare system is undergoing a process of change with increasing integration of ambulatory and inpatient care and a fundamental reform of the DRG-based hospital financing system. Economic restructuring of the healthcare system through personnel and time cutbacks in conjunction with increasing sub-specialization has clearly had a negative impact on the quality of medical training received by the next generation of young doctors. In particular, for specialist surgical areas the average training clinic has insufficient time or capacity to adequately teach surgical techniques, including minimal-access surgery. Unfortunately, this undesirable development lowers the standard of the surgical techniques required to become a specialist. The German Gynecologic Endoscopy Working Group (AGE) wish to redress this situation by offering young doctors the opportunity to participate in a structured training plan and a step-by-step guide to endoscopic minimal-access surgery. AGE will name endoscopic training centers throughout Germany—according to the pre-defined criteria—which will offer courses and the opportunity to attend lectures. Doctors may receive a certified graded qualification from the AGE to determine their knowledge and experience of endoscopy. This concept was first presented at the second “Forum operative gynecology” conference in November 2005 in Berlin. It was discussed and optimized by the AGE council and accepted at the AGE general meeting on 19 May 2005 by the executive committee, advisory board and members of the general meeting. With this concept, we wish to make a contribution to improving the training of young gynecologists and, in the long term, to lower the amount of avoidable surgical complications in gynecological endoscopy. The concept is sub-divided into a personal qualification (MIS I–III) and an institutional qualification as approved certified training centers.

Relationship between the Monoamine, Progesterone and Estradiol Content in Follicular Fluid of Preovulatory Graafian Follicles after Superovulation Treatment

We measured the progesterone, estradiol (E2), serotonin (5-HT), noradrenaline (NA) and dopamine (DA) contents of follicular fluid (FF) samples obtained from 35 patients undergoing in vitro fertilization and embryo transfer. Progesterone and E2 were determined by radioimmunoassay, and monoamines were measured by a spectrofluorimetric method. Significantly higher progesterone and NA levels were found (p < 0.01) in FF from cycles in which the oocyte cleaved and resulted in pregnancy compared to FF containing uncleaved oocytes. NA and DA contents were significantly higher in FF from cycles resulting in pregnancy than in FF containing cleaved oocytes not resulting in pregnancy (p < 0.01). There were significantly lower NA and 5-HT levels in FF containing uncleaved oocytes compared to the latter group (p < 0.05). Significant positive correlations were found between progesterone and 5-HT (r = 0.67) and between NA and DA (r = 0.93) in the pregnant group; between progesterone and E2 (r = 0.84) in FF containing uncleaved oocytes; between progesterone and E2 (r = 0.71) and between NA and DA (r = 0.62) in FF from cycles in which the oocyte cleaved but did not result in pregnancy. The results suggest that the follicular hormonal changes associated with oocyte maturation may be locally modulated by monoamines.

Serotonin may alter the pattern of gonadotropin-induced progesterone release of human granulosa cells in superfusion system

Serotonin plays a hormonal function in several nonneuronal peripheral tissues, such as the ovaries. Our aim was to investigate whether there is a modulatory action of serotonin on gonadotropin-induced steroid secretion of human granulosa cells. In granulosa cell culture, serotonin was administered alone or in combination with luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Also, granulosa cells were transferred into a dynamic superfusion apparatus and challenged by FSH and LH alone or along with serotonin. Estradiol and progesterone concentrations of samples were measured by radioimmunoassay. As expected, administration of FSH, LH, and serotonin alone resulted in a significant estradiol and progesterone release in cell culture, as well as a significant increase in progesterone release in dynamic superfusion system. In cell culture, co-administration of serotonin with gonadotropins had no additive effect on gonadotropin-induced secretion of progesterone, while it further augmented that of estradiol. In superfusion system, when gonadotropins were added along with serotonin, the increase in progesterone release was markedly less, while peaks of hormone response were remarkably prolonged compared to challenges by LH and FSH alone. The observed effects of serotonin on gonadotropin-induced steroid release of granulosa cells may reveal further details about the regulation of granulosa cell function.

Sentinel lymph nodes in gynaecological malignancies: Frontline between TNM and clinical staging systems?

Numerous investigations have recently proved the importance of sentinel lymph node detection in various malignant tumours. It is widely accepted that this procedure is to be recommended only in patients with early stage tumours. The lymph node status and prognosis are closely related. Appropriate staging is essential in the management of malignant tumours and should be individualised. In many cases, the nodal status does not correlate with the clinical stage of the disease. In this survey, we consider some of the most common gynaecological malignancies and the type of staging most appropriate to them. Differences between these staging systems, and controversies concerning them, are related to the concept of sentinel lymph node investigation. The authors believe that sentinel node sampling is in fact a beneficial method in both early and advanced stage disease for determination of the tumour status and individualisation of surgical interventions.

Primary Signet Ring Cell Mucinous Ovarian Carcinoma: A Case Report and Literature Review

A 24-year-old female patient presented with an extremely rare primary signet cell carcinoma of the right ovary 1 year after surgery for a mucinous borderline tumour of the left ovary. Relaparotomy was carried out with right adnexectomy, appendectomy and partial omentectomy. Surgery was followed by 6 courses of paclitaxel/carboplatinum chemotherapy. After an initial response, the patient again developed increasing ascites. The patient was transferred to our hospital and a re-relaparotomy was carried out, completing the operation. After 3 courses of pegylated doxorubicin/trabectedin, the clinical course showed a positive response and a decline of the tumour marker CEA in peripheral blood. After 5 months, ascites developed in the retroperitoneum so that the chemotherapy had to be changed. In spite of a positive response with the new chemotherapy, the patient died of a very rare pulmonary complication after 1 month within 2 days.

Scavenger Capacity of Follicular Fluid, Decidua and Culture Medium with Regard to Assisted Reproduction: An in vitro Study Using Electron Paramagnetic Resonance Spectroscopy

The natural scavenger capacity of follicular fluid of women pre-treated for in vitro fertilization (IVF) embryo transfer, Ham’s F10 nutrient mixture used for oocyte culture and endometrium samples were studied in a hydroxyl free radical generating system, using electron paramagnetic resonance (EPR) spectroscopy. The EPR signals appearing after the addition of samples to the reaction mixture show a diversely decreasing production of phenyl-tertier-butylnitrone spin adducts. Presumably, the follicular fluid and endometrium samples contain active factors which function as radical scavengers. The findings suggest that appropriate augmentative antioxidative therapy might be advised for IVF patients.

Organic Hydroperoxide-Induced Chemiluminescence of Follicular Fluid and Blood Serum Samples Obtained from Women Pretreated for in vitro Fertilization

The organic hydroperoxide-induced chemiluminescence of follicular fluid obtained from in vitro fertilized patients and its differently separated fractions were evaluated. Peroxidative stress causes a different photo-emission in the samples which alludes to some factors playing a role in the maintenance of the pro-oxidant/antioxidant balance. Interactions between the protein compounds of the samples and the organic hydroperoxide associate with formation of excited species contributing to the distinctive light emission processes. The technique offers a special re-interpretation of the scavenger state relating to the components of follicular fluid.