Giovanni Sisti

Labia Minora Reduction Techniques: A Comprehensive Literature Review

BACKGROUND Many studies of techniques to reduce the labia minora have been published in recent decades, including case reports and retrospective case series. However, to date, there has been no study of the overall complications or satisfaction rates associated with the broad spectrum of techniques. OBJECTIVES The authors performed a comprehensive literature review to determine outcomes and complications of labiaplasty techniques, including patient satisfaction. METHODS A search on PubMed/Medline was performed with the keywords labiaplasty, labioplasty, labial hypertrophy, and techniques plus labia minora reduction. The inclusion criterion was clinical studies in which techniques of labia minora reduction were described. Excluded from the study were publications not dealing with surgical procedures and review articles. RESULTS Thirty-eight studies, published from 1971 through 2014, were included; this represented 1981 treated patients. Eight labiaplasty techniques were identified from these studies: edge resection, wedge resection, deepithelialization, W-plasty, laser labiaplasty, custom flask, fenestration, and composite reduction. Satisfactory results, judged from clinical examination, were observed with all 8 techniques. Few postoperative complications occurred. In a small number of cases, complications required surgical revision or secondary resection. CONCLUSIONS All 8 labiaplasty techniques resulted in good outcomes, including high patient satisfaction and low morbidity.

Hepatotoxicity with low- and ultralow-dose flutamide: a surveillance study on 203 hyperandrogenic young females

OBJECTIVE To investigate the impact of low- and ultralow-dose regimens of flutamide on liver function of young hyperandrogenic females. DESIGN A 10-year surveillance study. SETTING University teaching hospital. PATIENT(S) Two hundred three hyperandrogenic young females (mean age: 20.9 ± 4.9 years). INTERVENTION(S) Inclusion criterion was receiving low- or ultralow-dose of flutamide as antiandrogenic treatment. Patients were categorized into Groups A and B, according to the administered dose (Group A = 62.5 mg/daily, Group B = 125 mg/daily). The two groups were further subdivided into subgroups (A1, A2, B1, B2) depending on the coadministration of estroprogestagen oral contraceptives (OCs) (A2, B2). MAIN OUTCOME MEASURE(S) Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were periodically evaluated and used as markers of hepatotoxicity. RESULT(S) Mild-to-severe increase of circulating AST/ALT was detected in 19 (9.4%; 95% CI = 5.9%-14.4%) patients during the first year of treatment (mild = 16 [7.9%, 95% CI = 4.7%-12.7%], moderate = 2 [0.9%, 95% CI = 0.1%-3.9%], severe = 1 [0.5%, 95% CI = 0.0%-3.1%]). No statistical differences were observed in relation to flutamide dose regimens and coadministration of OC. The median time to hypertransaminasemia was 12 weeks (range: 2-48) with no difference between Group A and Group B. A significant correlation was observed between hepatotoxicity and pretreatment BMI, ALT basal level, and AST basal level. CONCLUSION(S) Hepatotoxicity is a rare but possible event using low- and ultralow-dose regimens of flutamide. We need larger study populations in order to identify risk patterns for hepatotoxicity development.

Microorganisms in the Female Genital Tract during Pregnancy: Tolerance versus Pathogenesis

Microorganisms in the pregnant female genital tract are not always associated with pathology. The factors that influence the maternal response to microorganisms remain ill defined. We review the state of knowledge of microbe–host interactions in gestational tissues and highlight mechanisms that promote tolerance or pathogenesis. Tolerance to microorganisms is promoted during pregnancy by several mechanisms including upregulation of anti‐inflammatory mediators, induction of endotoxin tolerance, and possibly by regulation of autophagy. Conversely, an altered vaginal microbiota or a pre‐existing viral presence may result in induction of excessive inflammation and preterm labor. Although infections play a prevalent role in preterm birth, microbes are present in gestational tissues of women with healthy outcomes and may provide beneficial functions. The complex interactions between different microbial species and the maternal immune system during gestation remain incompletely elucidated.

Interaction between the inducible 70-kDa heat shock protein and autophagy: effects on fertility and pregnancy

A consequence of hsp70 (HSPA1A) induction is the inhibition of autophagy. Evidence of autophagy involvement in all aspects of the reproductive process is reviewed, and possible consequences of hsp70 induction at each developmental stage are postulated. It is proposed that aberrant external or internal stimuli that result in high levels of hsp70 production interfere with normal autophagy-related functions and lead to a decrease in the number of functional ova and spermatozoa, impaired pre- and post-implantation embryo development, and increased susceptibility to premature labor and delivery. The purpose of this review is to increase understanding of hsp70-autophagy interactions during reproduction. Interventions to modulate this interaction will lead to development of novel protocols to improve fertility and pregnancy outcome.

Hypermethylation of HOXA10 gene in mid‐luteal endometrium from women with ovarian endometriomas

A decrease in HOXA10 gene expression in eutopic mid‐secretory endometrium has been found in women with endometriosis‐associated infertility. Promoter hypermethylation of HOXA10 is thought to be the leading mechanism for epigenetic gene regulation in patients with endometriosis. In our series we documented significantly higher HOXA10 promoter methylation levels in women with ovarian endometriomas than in healthy controls during the mid‐luteal phase. Development of epigenetic‐based strategies for non‐surgical treatment of infertility related to ovarian endometriomas could be an attractive field of research in the coming years.

Induction of the 70 kDa heat shock protein stress response inhibits autophagy: possible consequences for pregnancy outcome

Abstract Aim: The induction of heat shock protein synthesis and activation of autophagy are intracellular processes stimulated under adverse conditions. We evaluated the relationship between intracellular concentrations of the inducible 70 kDa heat shock protein (hsp70) and autophagy induction in human peripheral blood mononuclear cells (PBMCs) following exposure to sera from pregnant and non-pregnant women. Methods: Autophagy was induced in PBMCs by incubation for 48 h with sera from 42 pregnant women at mid-gestation and 45 non-pregnant women. Intracellular concentrations of hsp70 and p62 were measured by ELISA. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration in the cytoplasm is inversely proportional to the extent of autophagy induction (high p62 = low autophagy). Results: The p62 concentration was highly correlated with the hsp70 level utilizing sera from both pregnant (Spearman r = 0.4731, p = 0.0015) and non-pregnant (Spearman r = 0.6214, p < 0.0001) women. Median p62 (7.4 ng/ml versus 2.7 ng/ml, p < 0.0001) and hsp70 (7.0 ng/ml versus 3.5 ng/ml, p = 0.0022) levels were higher when PBMCS were incubated with sera from pregnant women. Conclusion: The extent of autophagy in PBMCs is inversely proportional to the intracellular hsp70 concentration and sera from pregnant women induces hsp70 and inhibits autophagy to a greater extent than does sera from non-pregnant women. A stress response that induces hsp70 has the potential to interfere with autophagy-related events.

Arabin cervical pessary to prevent preterm birth in twin pregnancies with short cervix

A retrospective study was conducted to evaluate the effect of Arabin cervical pessary in twin pregnancies with cervical length (CL)  <25 mm between 21 and 31 weeks. Forty patients receiving pessary were matched with 40 controls without pessary. They were matched for gestational age (GA) at admission and CL. GA at delivery, delivery before 36, 34 and 32 weeks, latency between detection of short cervix and delivery, and duration of hospital admission were compared between groups. Women with the pessary delivered at higher GA compared to controls (35 vs. 33 weeks, p = 0.02). Cervical pessary significantly reduced the incidence of delivery  <36 and  < 34 weeks (p < 0.05), but not before 32 weeks. Interval between detection of short cervix and delivery was longer in the pessary group and duration of hospital admission was shorter (p = 0.03) compared to women without pessary.

Epidemiology and outcomes of squamous ovarian carcinoma; a population-based study.

OBJECTIVE Squamous ovarian carcinoma (SOC) is a rare tumor. Scarcity of information about the epidemiology and prognosis of SOC hinders attempts at optimal patient management. This retrospective study of a large cohort details the clinicopathological and demographic characteristics and prognosis of women with SOC. METHODS A cohort of patients drawn from the National Cancer Institutes Surveillance Epidemiology and End Results (SEER) database who were diagnosed with SOC between 1988 and 2012 were analyzed. Observed and disease-specific survival was estimated by Kaplan-Meier plots in women who underwent surgery as part of their cancer-related treatment. A Cox hazard regression analysis was performed to determine independent predictors of cancer-specific survival in patients with SOC. RESULTS We identified 341 patients with SOC with a median age at diagnosis of 55 years. Stage I, II, III and IV tumors were noted in 34%, 15%, 20.5% and 24.9% of patients, respectively. Five-year cancer-specific survival was 86% for stage I, 54.3% for stage II, 36.3% for stage III and 2.8% for stage IV disease patients. Observed and cancer-specific survival was better for patients that underwent lymphadenectomy (p=0.031). Postoperative radiotherapy was not associated with improved survival. In a multivariate analysis, independent predictors of improved cancer-specific survival were younger age, lower disease stage and lymphadenectomy. CONCLUSIONS SOC is typically a unilateral malignancy with a tendency toward loco-regional spread. Stage I patients have a relatively high survival rate; however, the prognosis is poor for women with abdominal or distant spread. Lymphadenectomy, but not postoperative radiotherapy, is associated with improved survival.

Prevalence of lymph node metastasis and prognostic significance of lymphadenectomy in apparent early-stage malignant ovarian sex cord-stromal tumors

OBJECTIVE The aim of this retrospective population-based study was to investigate the prevalence of lymph node metastasis in patients with apparent early stage malignant sex cord-stromal tumors (SCSTs) and the effect of regional lymph node sampling/lymphadenectomy (LND) on their survival. METHODS A cohort of patients diagnosed with malignant SCSTs between 1988 and 2012 was drawn from the National Cancer Institutes Surveillance, Epidemiology, and End Results database. Overall and Cancer Specific Survival, stratified by performance of LND, were calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank and Breslow tests. A multivariate Cox proportional analysis was performed to determine the effect of LND on overall mortality. RESULTS A total of 1156 patients with SCST met the inclusion criteria; 1000 (86.5%) and 156 (13.5%) patients had apparent stage I and II disease, respectively. LND was performed in 572 (49.5%) patients. Lymph node metastases were pathologically confirmed in 19 patients (3.3%). Five-year cancer specific survival (CSS) was similar, 92.7% and 94.7%, for patients who did or did not undergo LND, respectively. According to multivariate analysis overall mortality did not differ between the two groups after controlling for age, histology and apparent stage. CONCLUSIONS Regional lymphatic mode metastasis in patients with apparent early stage SCSTs is uncommon and lymphadenectomy did not confer a survival benefit in this cohort.

Autophagy induction by sera from women undergoing an in vitro fertilization cycle varies with subsequent outcome

Autophagy maintains intracellular homeostasis during placental development and embryogenesis. We evaluated if differences in the autophagy-inducing capacity of sera from women undergoing an in vitro fertilization (IVF) cycle predicted subsequent pregnancy outcome. In this retrospective study, sera collected from 94 women at the time of intrauterine embryo implantation were incubated with peripheral blood mononuclear cells (PBMCs) from healthy donors. The PBMCs were lysed and autophagy induction measured by determination of the p62 concentration. A reduced capacity for autophagy induction was associated with defective implantation while an elevated level of autophagy was associated with ectopic pregnancy.