Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

[Stage-adapted treatment of cervical carcinoma]. / Therapieentscheidung beim Zervixkarzinom: Was müssen Sie berücksichtigen? Uberleben - Beschwerdefreiheit - Kinderwunsch.

The treatment of cervical carcinoma is stage-dependent. For FIGO stages I-IIA, radical hysterectomy with pelvic lymphonodectomy is usually performed in Germany. The indication for adjuvant radiochemotherapy is made depending upon the risk of recurrence. Total mesometrial resection (TMMR) is a new therapeutic procedure with few side effects that may replace the conventional Wertheim method in the near future. Trachelectomy is an option for preserving childbearing-ability and with correct diagnosis, results similar to that of the classic technique can be achieved. At present, minimally invasive procedures should still be performed at specialized medical centres. For advanced stages, primary combined radiotherapy plus adjuvant radiochemotherapy or primary combined radiochemotherapy are used in addition to surgery.

[Value of pelvic MRI in the preoperative diagnosis of endometriosis]. / Wertigkeit der Magnetresonanztomographie (MRT) des Beckens in der präoperativen Diagnostik der Endometriose.

PURPOSE: To determine the value of magnetic resonance imaging (MRI) of the pelvis in the preoperative diagnosis of endometriosis. MATERIALS AND METHODS: Over a period of 8 months, preoperative MRI of the pelvis were obtained in 13 patients with suspected endometriosis (mean patient age 34.6 years; range 25 - 47 years). RESULTS: In 9 of 13 patients (69 %), the diagnosis of endometriosis was made by MRI and confirmed by laparoscopy in 8 cases. In 2 of 13 patients, endometriotic lesions were detectable by laparoscopy only. In the remaining 2 patients, no endometriosis was visible on MRI or by laparoscopy. MRI was able to visualize a total of 19 endometriotic lesions, with 14 (74 %) confirmed by histopathologic examination following laparoscopy. Five of these 19 lesions (26 %) visible on MRI were not seen by laparoscopy. Using laparoscopy and subsequent histopathologic examination, 27 endometriotic lesions were diagnosed, with 13 (48 %) not seen on the preoperative MRI. CONCLUSION: MRI and laparoscopy are complementary diagnostic tools that will best document the full extent of endometriosis when combined. MRI can visualize additional lesions inaccessible to laparoscopy. Thus, MRI of the pelvis should used preoperatively for surgical treatment planning.

Presynaptic 5-HT autoreceptors modulate N-methyl-D-aspartate-evoked 5-hydroxytryptamine release in the guinea-pig brain cortex.

Guinea-pig cerebral cortical slices preincubated with [3H]5-hydroxytryptamine ([3H]5-HT) were superfused with Mg(2+)-free Krebs' solution. N-Methyl-D-aspartate (NMDA) stimulated tritium overflow in a concentration-dependent manner. The NMDA-evoked overflow was abolished by omission of CA2+ or presence of 1.2 mM Mg2+, but only partly inhibited by tetrodotoxin. The competitive and noncompetitive NMDA receptor antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) and dizocilpine, respectively, also blocked the stimulatory effect of NMDA. Furthermore, the NMDA-evoked tritium overflow was inhibited by 5-carboxamidotryptamine in a manner susceptible to blockade by methiothepin, which given alone facilitated overflow. This facilitatory effect was increased in the presence of 6-nitroquipazine, a selective 5-HT reuptake inhibitor. It is concluded that the release of 5-HT in the guinea-pig cerebral cortex is stimulated via NMDA receptors, which are in part located on the serotoninergic axon terminals, and that the NMDA-evoked 5-HT release is modulated via inhibitory 5-HT autoreceptors.

Evidence for presynaptic location of inhibitory 5-HT1D beta-like autoreceptors in the guinea-pig brain cortex.

The effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on tritium overflow evoked by high K+ were determined in superfused synaptosomes and slices, preincubated with [3H]5-HT, from guinea-pig brain cortex. In addition, we estimated the potencies of 5-HT receptor ligands in inhibiting specific [3H]5-HT binding (in the presence of 8-hydroxy-2(di-n-propylamino)tetralin and mesulergine to prevent binding to 5-HT1A and 5-HT2C sites) to guinea-pig cortical synaptosomes and membranes. 5-HT receptor agonists inhibited the K(+)-evoked tritium overflow from synaptosomes and slices. In synaptosomes the rank order of potencies was 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl] -1H-indole-3-yl] ethylamine (L-694,247) > 5-carboxamidotryptamine (5-CT) > oxymetazoline (in the presence of idazoxan) > or = 5-HT > sumatriptan > or = 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969). The potencies of the agonists in inhibiting tritium overflow from slices correlated with those in synaptosomes, suggesting that the same site of action is involved in both preparations. In synaptosomes the nonselective antagonist at cloned human 5-HT1D alpha and 5-HT1D beta receptors, methiothepin, shifted the concentration-response curve for 5-CT to the right (apparent pA2: 7.87). In contrast, ketanserin at a concentration which should block the 5-HT1D alpha, but not the 5-HT1D beta, receptor did not alter the inhibitory effect of 5-CT on tritium overflow. In cortical synaptosomes and membranes, [3H]5-HT bound to a single site with high affinity. In competition experiments, 5-HT receptor agonists and antagonists inhibited specific [3H]5-HT binding. In synaptosomes the rank order was L-694,247 > methiothepin > 5-CT > 5-methoxytryptamine > 5-HT > or = sumatriptan > or = oxymetazoline > RU 24969 > ketanserin > ritanserin. A very similar rank order was obtained in cerebral cortical membranes. The potencies of the 5-HT receptor agonists in inhibiting tritium overflow from synaptosomes and slices correlated with their potencies in inhibiting [3H]5-HT binding to synaptosomes and membranes. In conclusion, the 5-HT receptors mediating inhibition of 5-HT release in the guinea-pig cortex are located on the serotoninergic axon terminals and, hence, represent presynaptic inhibitory autoreceptors. The [3H]5-HT binding sites in cerebral cortical synaptosomes and membranes exhibit the pharmacological properties of 5-HT1D receptors. The correlation between the functional responses and the binding data confirms the 5-HT1D character of the presynaptic 5-HT autoreceptors. According to the results of the interaction experiment of ketanserin and methiothepin with 5-CT on 5-HT release, the presynaptic 5-HT autoreceptors can be subclassified as 5-HT1D beta-like.

Stimulation of serotonin release in the rat brain cortex by activation of ionotropic glutamate receptors and its modulation via alpha 2-heteroreceptors.

Rat brain cortex slices were used to study (1) the release of 5-hydroxytryptamine (5-HT) induced by activation of N-methyl-D-aspartate (NMDA) or non-NMDA receptors and (2) the alpha 2-adrenoceptor-mediated modulation of NMDA-evoked 5-HT release. Cortical slices were preincubated with [3H]5-HT in the presence of the selective noradrenaline uptake inhibitor, maprotiline (to avoid false labelling of noradrenergic axon terminals), and the superfused with solution containing the 5-HT reuptake inhibitor, 6-nitroquipazine. In slices superfused with Mg(2+)-free medium, NMDA and L-glutamate, in a concentration-dependent manner, elicited an overflow of tritium. The NMDA-evoked tritium overflow was abolished by omission of Ca2+ ions, almost completely suppressed by 1.2 mM Mg2+ and only partly (by about 60%) inhibited by tetrodotoxin. Dizocilpine (formerly MK-801), an antagonist at the phencyclidine site within the NMDA-gated channel, also decreased the NMDA-evoked overflow. The competitive NMDA receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) caused a parallel shift of the NMDA concentration-response curve to the right. The NMDA-induced tritium overflow was not affected by addition of exogenous glycine but was inhibited by 5,7-dichlorokynurenic acid, an antagonist at the glycine site of the NMDA receptor. Spermidine slightly increased the NMDA-induced tritium overflow whereas arcaine, an antagonist at the polyamine site of the NMDA-receptor, caused a decrease. Ifenprodil and eliprodil, which exhibit different affinities for NMDA receptors composed of different subunits were highly potent (in the nanomolar range) in inhibiting the NMDA-evoked tritium overflow. Noradrenaline reduced, whereas the alpha 2-adrenoceptor antagonist idazoxan facilitated, the NMDA-evoked overflow. Idazoxan shifted the concentration-response curve of noradrenaline to the right. In slices superfused with solution containing 1.2 mM Mg2+, kainic acid or (RS)-alpha-amino-3-hydroxy-5-methyl-4 -isoxazole propionic acid (AMPA) also caused a concentration-dependent overflow of tritium, which again was not completely (by about 75 and 50%, respectively) inhibited by tetrodotoxin. The kainate-evoked tritium overflow was inhibited by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not affected by CGP 37849 or arcaine. The AMPA-evoked tritium overflow was also decreased by CNQX. It is concluded that activation of NMDA or non-NMDA receptors elicits a release of 5-HT in the rat brain cortex. The receptors are at least partly located on the serotoninergic nerve terminals. The results with ifenprodil and eliprodil are compatible with the view that the NMDA receptor involved contains the NR2B subunit. The NMDA-evoked 5-HT release is modulated by presynaptic alpha 2-adrenoceptors.