Different local estrogen therapies for a tailored approach to GSM.

Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.

Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. METHODS: Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. CONCLUSION: The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

The role of staging and adjuvant chemotherapy in stage I malignant ovarian germ cell tumors (MOGTs): the MITO-9 study.

Background: Surgery followed by platinum-based chemotherapy is the standard of care for MOGCTs, except for stage IA dysgerminoma and stage IA grade 1 immature teratoma where surveillance only is recommended. The role of adjuvant chemotherapy and surgical staging is debated. Patients and methods: Data from 144 patients with stage I MOGTs were collected among MITO centers (Multicenter Italian Trials in Ovarian Cancer) and analyzed. Results: Fifty-five (38.2%) patients were affected by dysgerminomas, 49 (34%) by immature teratomas, 26 (18.1%) by yolk sac tumors and 14 (9.7%) by mixed tumors. Seventy-three (50.7%) patients receive surgery plus chemotherapy, while 71 (49.3%) patients underwent surgery alone. The latter group included 32 dysgerminomas (14 IA-13 Ix, 3 IB, and 2 IC), 34 immature teratomas (20 1A-13 IA grade 1, 6 Ix, 1 IB, and 7 IC), 4 mixed tumors and 1 yolk sac tumor. Forty-four patients did not received chemotherapy, even if it would have been indicated by recommended approach. 94 (65.3%) patients received peritoneal surgical staging. Twenty-three (15.9%) developed a recurrence. Incomplete surgical staging was associated with recurrence (P < 0.05; OR 2.37) at Cox regression analysis. Seven patients died. Four patients were affected by yolk sac tumors, two by mixed tumors and one by immature teratoma. Five patients died for disease, one for acute leukemia and one for suicide. Prognostic parameter analyses showed that yolk sac component is a predictor for survival (P < 0.05). Five-years OS rates were 96.8% and 88.7% in the surgically staged and the incomplete staged group, respectively, while 93.8% and 94.1% in the standard treatment and in the surveillance group, respectively. Conclusions: This study shows that surveillance seems not to affect survival; chemotherapy should be reserved for relapse resulting in high cure rate. Incomplete peritoneal surgical staging is associated with recurrence. Yolk sac histology worsens the prognosis.

Intralesional hemorrhage in Krukenberg tumor: a case report and review of the literature.

Acute abdomen due to female genital apparatus disease is very rare. Most are due to intralesional effusion of benign tumors. The authors present a 40-year-old woman with acute abdomen pain due to haemorrhagic ovarian metastasis of colorectal cancer, focusing on the role of imaging to get the management of the patient.

[Urinary hexafluoroisopropanol in the assessment of occupational exposure to sevoflurane: methodologic features and critical points]. / L'esafluoroisopropanolo urinario nella valutazione dell'esposizione professionale a sevofluorano: aspetti metodologici e punti critici.

The increasing use of sevoflurane as anaesthetic leads to the need for finding a biological index to evaluate the occupational exposure in surgical activity. Several studies indicate that Hexafluoroisopropanol (HFIP) is a specific sevoflurane metabolite quickly glucuronidated and excreted as HFIP-glucuronide in the urine (HFIPu). Therefore the HFIP removal kinetics in occupational exposure and the correlation between sevoflurane exposure and HFIPu are poorly understood. We studied no. 86 operating room workers of Novara Hospital to evaluate the correlation between the sevoflurane individual exposure (SE) and the HFIPu at the end of the shift expressed in microgram/L (A-HFIPu) and in microgram/g creat. (C-HFIPu). Therefore, in the same group of subjects we evaluated the HFIPu in the urine sampled at 8.00 a.m. before the work. The correlation coefficient was R2 = 0.782 (p < 0.0001) for SE/A-HFIPu and R2 = 0.862 (p < 0.0001) for SE/C-HFIPu; HFIPu normalized for urinary creatinine (C-HFIPu) is an index more suitable than the A-HFIPu. Furthermore we concluded for the usefulness of pre-shift HFIPu.

Iron overload and gene expression in HepG2 cells: analysis by differential display.

The aim of the present study was to evaluate the effect of iron overload on gene expression in HepG2 cells by differential display. Iron-treated cells showed a 50% decrease in apolipoprotein B100 (Apo B100) and a 2- and 3-fold increase in semaphorin cd100 and aldose reductase mRNA, respectively, with parallel variations in Apo B100 and aldose reductase proteins. These effects were time-dependent. Vitamin E prevented the increase in aldose reductase expression, but had no effect on Apo B100 and semaphorin cd100. Treatment with hydrogen peroxide and 4-hydroxy-2,3-nonenal increased only aldose reductase mRNA. These data suggest that iron can affect mRNA levels by lipid peroxidation-dependent and -independent pathways.