Flavia Sorbi

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.

Methylation of the HOXA10 homeobox gene promoter is associated with endometrial cancer: A pilot study

Methylation in the promoter region represents an epigenetic mechanism that silences expression of various homeobox genes in cancers. We compare the methylation profile of HOXA10 promoter gene in 19 histologically proven endometrioid cancers and 27 normal endometrial tissues. Endometrial cancer tissue displays significantly higher methylation status in HOXA10 gene promoter than normal tissue, suggesting a possible role of epigenetic changes in HOXA10 gene regulation in tumorigenesis. Further studies in human tissue and cell lines are necessary to validate these preliminary results and to investigate HOXA10 expression according to methylation status in endometrial cancer.

Rate of second primary tumors following diagnosed choriocarcinoma: A SEER analysis (1973–2010)

OBJECTIVE Approximately 1 in 6 of new cancers has been reported to represent a second primary tumor (SPT). Choriocarcinomas (CCs) are of interest in regard to the rate of SPTs because of the potential exposure to carcinogenic therapy and reports of the benefits of its high human gonadotropin (hCG) levels on cancer incidence. METHODS We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with gestational CC who subsequently developed a SPT. This is a retrospective study, following a cohort of patients during the period 1973-2010. RESULTS We found 818 patients with primary gestational CC. Nineteen patients had a SPT after the CC. Occurrence of several types of cancer resulted significantly higher when compared to the incidence rate in the general population. In particular the highest incidence rate ratios (IRRs) were registered for acute myeloid leukemia (AML) (6.3) and thyroid cancer (2.6). The expected rate of lung, breast, colorectal and uterine corpus cancers instead resulted lower than the rate in the general population. Regarding the IRR in the population under 50 years of age, the higher IRRs were related to AML (20) and non-Hodgkin lymphoma (NHL) (5). CONCLUSION The association of thyroid cancer and CC has not been described previously. Increases in hematological cancer following CC lend further support to the established data. The decrease in breast and colon cancers in all age groups supports past data and decreases in uterine and lung cancers are new observations meriting further study.

Endometrial carcinoma in high-risk populations: is it time to consider a screening policy?

Endometrial carcinoma (EC) is the leading female genital tract malignancy in industrialized countries. It will become an important public health problem in the coming years in the USA and Europe, where its incidence is increasing, and next‐generation interventions should include periodical screening in high‐risk women. In this review, we discuss the importance to gynaecologists of detecting women at high risk and offering an adequate screening programme. Screening for EC is particularly challenging and there is currently no proven programme for the surveillance of women estimated to be at an increased risk of developing this form of cancer. The data in the literature, including this and previous issues of Cytopathology, and personal experience suggest that endometrial liquid‐based cytology (LBC) might play an essential role in a screening policy for EC. LBC may enable practitioners to reduce age‐adjusted mortality for women at high risk for EC.

Ability of cervical length to predict spontaneous preterm delivery in twin pregnancies using the receiver-operating characteristic curve analysis and an a priori cut-off value

Abstract In this retrospective study based on cervical length (CL) measurements between 20 and 24 + 6 weeks, we examined the ability of CL to predict spontaneous preterm birth (SPTB) in 222 twin pregnancies using the receiver-operating curve (ROC) analysis and an a priori cut-off. CL predicted SPTB before 34 weeks. Using the ROC the selected cut-off was 37.5 mm. Positive predictive value (PPV) and negative predictive value (NPV) regarding SPTB before 34 weeks for 37.5 mm were 15.7% and 5.3% respectively. Using the 5th percentile, PPV and NPV regarding SPTB before 34 weeks for 24 mm were 41.7% and 91.4%, respectively. The 5th centile of CL measurements should be employed in clinical practice. CL measurement is an adequate screening tool for SPTB since it has a high NPV. Studies on CL measurement and SPTB should explain which methodology they adopted to obtain a cut-off value and the rationale of their choice.

LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

Introduction A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. Background LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. Discussion We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. Conclusion LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

Role of medical therapy in the management of uterine adenomyosis

Adenomyosis is a benign uterine condition affecting women at various ages with different symptoms. The management of these patients is still controversial. Few clinical studies focusing on medical or surgical treatment for adenomyosis have been performed. No drug is currently labelled for adenomyosis and there are no specific guidelines to follow for the best management. Anyhow, medical treatments are effective in improving symptoms (pain, abnormal uterine bleeding and infertility). The rationale for using medical treatment is based on the pathogenetic mechanisms of adenomyosis: sex steroid hormones aberrations, impaired apoptosis, and increased inflammation. Several nonhormonal (i.e., nonsteroidal anti-inflammatory drugs) and hormonal treatments (i.e., progestins, oral contraceptives, gonadotropin-releasing hormone analogues) are currently used off-label to control pain symptoms and abnormal uterine bleeding in adenomyosis. Gonadotropin-releasing hormone analogues are indicated before fertility treatments to improve the chances of pregnancy in infertile women with adenomyosis. An antiproliferative and anti-inflammatory effect of progestins, such as dienogest, danazol and norethindrone acetate, suggests their use in medical management of adenomyosis mainly to control pain symptoms. On the other hand, the intrauterine device releasing levonorgestrel resulted is extremely effective in resolving abnormal uterine bleeding and reducing uterine volume in a long-term management plan. Based on new findings on pathogenetic mechanisms, new drugs are under development for the treatment of adenomyosis, such as selective progesterone receptor modulators, aromatase inhibitors, valproic acid, and anti-platelets therapy.

Epidemiology and Risk Factors of Uterine Fibroids

Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, physical activity, stress, and smoking). Some of the epidemiological data were conflicting; consequently, further studies are needed to better understand the factors that influence fibroid prevalence.

Laparoscopic Splenectomy as Quaternary Cytoreduction for Isolated Parenchymal Splenic Recurrence of Epitelial Tubo-Ovarian Cancer: Report of a Case and Literature Review.

Isolated parenchymal splenic lesions are very rare and may occur as recurrences in the form of epithelial tubo-ovarian cancer (ETOC). We report a case of solitary parenchymal splenic recurrence of ETOC, which developed 50 months after the initial treatment. A 66-year-old woman underwent laparotomic primary cytoreduction in 2008. After platinum-based chemotherapy, she developed recurrences; thus, she underwent secondary and tertiary cytoreduction in 2011 and 2012 respectively. In April 2013, CT scan documented a solitary parenchymal splenic lesion and it was confirmed by FDG PET/CT. She underwent quaternary cytoreduction by laparoscopic splenectomy. Histopathological evaluation revealed metastatic parenchymal disease consistent with recurrent ETOC. She was alive and disease-free for ten months since splenectomy. In literature there are 35 cases of isolated spleen parenchymal metastasis of ETOC and our report is the first case of laparoscopic splenectomy in the setting of quaternary cytoreduction. Laparoscopic splenectomy as quaternary cytoreduction is safe and feasible and could be congruent to the well-established experiences already reported for the primary, secondary or even tertiary cytoreduction where the absence of residual disease has been translated in a significant survival benefit.

Two successful pregnancies in Herlyn–Werner–Wunderlich syndrome

and here we describe what appears to be only the 12th such case of a pregnant woman who suff ered this. Immediately aft er being diagnosed with agranulocytosis, the patient was given emergency treatment involving the cessation of ritodrine therapy, intramuscular injections of G-CSF and antibiotics to prevent infection. Both the patient and her twin fetuses showed good prognosis. A review of the literature supports the effi cacy of this treatment approach. Previous cases and ours suggest that ritodrine should be used carefully for avoiding premature labour, and that white blood cell counts and temperature should be monitored regularly in pregnant women receiving this drug.