Adult ovarian granulosa cell tumors: analysis of outcomes and risk factors for recurrence.

OBJECTIVE: Adult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall survival. METHODS: Patients with primary adult granulosa cell tumors treated in three international referral centers between July 1999 and December 2018 were included. The following data were anonymously exported from the prospective database: age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, surgical procedures, progression-free survival, and overall survival. Descriptive statistical analysis regarding tumor and treatment characteristics was performed. Survival analyses included Kaplan-Meier functions and Cox proportional hazard ratios (HR). RESULTS: A total of 168 patients with primary adult granulosa cell tumors were included. Median age was 50 years (range 13-82). With regard to stage distribution, 54.2% (n=91) of patients were FIGO stage IA, 1.2% (n=2) were stage IB, 26.8% (n=45) were stage IC, and 17.9% (n=30) were FIGO stage II-IV. 66.7% (n=112) of patients underwent surgical restaging, of whom 17.9% (n=20) were moved to a higher stage. In addition, 36 (21.4%) patients underwent fertility-sparing surgery. After a median follow-up of 61 months (range 0-209), 10.7% of patients (n=18) had recurrent disease and 4.8% (n=8) died of disease. Five-year progression-free survival was 86.1% and estimated overall survival was 95.7%. Five-year progression-free survival was worse for patients with advanced stages (FIGO stage IA/B vs IC: HR 5.09 (95% CI 1.53 to 16.9); FIGO stage IA/B vs II-IV: HR 5.62 (95% CI 1.58 to 19.9)). Nineteen patients receiving adjuvant chemotherapy had lower estimated 5-year progression-free survival compared with patients not receiving chemotherapy (49.7% vs 91.1%, p<0.001; HR 9.15 (95% CI 3.62 to 23.1)). CONCLUSION: The prognosis of patients with primary adult granulosa cell tumors is mainly determined by FIGO stage. The outcome of patients with FIGO stage IC is comparable to those with advanced stages. Fertility-sparing surgery seems to be a safe procedure in stage IA. Our data do not support the use of adjuvant chemotherapy in early and advanced stages of adult granulosa cell tumors.

The Obstetrician Gynecologist's role in the screening of infants at risk of severe plagiocephaly: Prevalence and risk factors.

This study was conducted to determine the prevalence, maternal and/or neonatal risk factors for severe plagiocephaly in order to early detect and refer infants at risk. A prospective observational study was conducted, involving 4337 infants who visited the Perinatology Center at San Pietro Fatebenefratelli Hospital in Rome, evaluated following the Plagiocephaly Severity Scale of Atlanta. ©The plagiocephaly prevalence resulted 1.89%, considering moderate to severe forms. Maternal risk factors include primiparity, older age, gestational diabetes, and uterine fibromatosis. Neonatal risk factors are early term gestational age, low weight, twin pregnancy, and prolonged labor with an emergency cesarean section. Screening for severe plagiocephaly should begin antenatally. Although the low prevalence, identifying infants at risk can prevent potential permanent sequelae. We suggest a multidisciplinary approach for the management of plagiocephaly, involving the figure of the Obstetrician Gynecologist, who can highlight the risk factors ranging from obstetric and birth conditions.

Dataset on patients with Recurrent Borderline Ovarian Tumors and Table with Review of Literature on Fertility and Oncologic Outcomes of patients with Borderline Ovarian Tumors.

The data presented here is related to the research article entitled "FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS" by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above.

Low-grade Serous Tumors: Are We Making Progress?

PURPOSE OF REVIEW: This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. RECENT FINDINGS: Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice.

Adult primary cervical rhabdomyosarcomas: A Multicentric cross-national case series.

OBJECTIVES: Adult primary cervical rhabdomyosarcoma is a very rare disease and data regarding treatment are sparce. The goal of this study was to report on our experience with the management of this rare entity, along with an evaluation of the literature. METHODS: We conducted a review of the medical records at four centers from January 1990 to December 2017. We reviewed clinical characteristics including age at diagnosis, BMI, medical history and tumor stage, as well as treatment in the primary and recurrent settings and follow-up data. We reclassified tumors according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group. RESULTS: A total of 15 patients were included in the analysis. Median age at diagnosis was 35 years (range 17-55). Median tumor size at presentation was 5 cm (range 3-10). Eleven patients had the embryonal variant, including five showing the botryoid subtype. Four patients had a pleomorphic rhabdomyosarcoma. Eleven patients had disease classified as IRS Clinical Group I, while the remaining four fell into groups II or III. Fertility-sparing treatment was offered to five patients. Primary treatment types were: surgery alone in eight patients, surgery followed by adjuvant chemotherapy in six patients, and neoadjuvant chemotherapy in two patients. The main risk factors for relapse were: IRS clinical group greater than I, tumor size greater than 5 cm, lymph nodal involvement, and non-embryonal histology. At a median follow-up of 35 months (range 3-282), we observed a 5-year overall survival rate of 78.2% and a progression-free survival of 58.2%. No patient in the IRS I group died of the disease. Three out of four patients in the IRS II-III group died of the disease (survival range 5-16 months following treatment). CONCLUSION: Our data show that cervical rhabdomyosarcomas account for at least two prognostic groups, demonstrating the existence of low-risk and high-risk patterns. The best predictor of prognosis appearsd to be the IRS clinical group classification system. IRS Group I tumors had an overall good prognosis and rarely recurred; when they did recur they were mainly local, following conservative treatment.

Current practice and physicians' opinion about preoperative hair removal as a part of ERAS pathway implementation in gynecology and gynecology-oncology: a NOGGO-AGO survey of 148 gynecological departments in Germany.

PURPOSE: To gather standardized information about current practices and doctors' opinions on preoperative hair removal (PHR) from the surgical site and to evaluate the extent of PHR as one of the elements of enhanced recovery after surgery (ERAS) pathways that is established in the clinical routine in gynecology and gynecology-oncology departments in Germany. METHODS: We performed a nationwide survey among 638 primary, secondary and tertiary health care gynecological departments in Germany. Data were obtained by sending a multiple-choice questionnaire about preoperative management of hair removal. The authors also evaluated the awareness of doctors regarding PHR as well as the method and time frames of PHR. The results were compared to the existing standard of procedure (SOP) and guidelines. RESULTS: 148 units (23.2%) took part in the survey; participants in the survey were mostly chief physicians in 47.3% of the cases. Half (50.7%) of all the responses came from certified gynecological cancer centers. A SOP regarding PHR was reported as present in 113 clinics (76.4%). 83.8% of all units are performing PHR for midline laparotomy, 52.7% in laparoscopic operations, and 45.3% in vaginal operations. 48% used a clipper, while 43.2% utilized a single-use razor. 56.1% shaved instantly before the operation, whereas 35.8% did it the day before and earlier. 40.3% of chief physicians believe that PHR causes more surgical site infections (SSI) compared to only 11.5% of junior doctors. CONCLUSION: PHR in gynecological departments in Germany is performed very heterogeneously and SOPs are often not based on guidelines and ERAS principles. Around one-third of the German gynecological clinics keep strictly to the guidelines. The awareness on PHR and SSI among junior doctors is very low.

Conservative treatment for well-differentiated endometrial cancer: when and why it should be considered in young women.

The aim of this review was to update current knowledge on the conservative treatment of endometrial cancer (EC) based on a literature review. A web-based search in the MEDLINE database was carried out on EC management and treatment. All relevant information has been collected and analysed. Case series were mainly found in the literature search. Conservative treatments were offered to young patients with stage I low-grade endometrioid carcinomas of the endometrium. Different options included high/low dose progestin treatments, hysteroscopic resection of the disease, a levonorgestrel intrauterine device or a combination of various strategies. The overall complete response rate was near 76.5% with a recurrence rate of up to 33.8%. Pregnancy outcomes reached rates of 64.8% for live births. The current clinical outcomes show that conservative treatment aimed at preserving fertility is feasible for stage I endometrial well-differentiated adenocarcinomas in motivated patients under close monitoring.

Low-grade Serous Ovarian Carcinoma.

In the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer. Therefore the current treatment of LGSOC is based on smaller trials, retrospective series, and subgroup analysis of large clinical trials on ovarian cancer. Surgery plays a major role in the treatment of patients with LGSOC. In the systemic treatment of LGSOC, hormonal treatment and targeted therapies seem to play an important role.

Complete remission of cerebral endometriosis with dienogest: a case report.

The most recent evidences suggest the use of progesterone mimicking drugs for the treatment of endometriosis. Particularly, dienogest has been largely tested. However, the standard treatment of extra-pelvic endometriosis is debated. Particularly, cerebral localization of endometriosis is a very rare clinical condition. The surgical approach for such a particular disorder would consist in difficult procedures, thus leading to prefer the medical treatment. We hereby report the clinical case of a cerebral localization of endometriosis treated with dienogest who experienced a complete remission of the disease.

Catamenial pneumothorax caused by thoracic endometriosis.

BACKGROUND: Thoracic endometriosis syndrome is a rare form of extrapelvic endometriosis characterized by the presence of functioning endometrial tissue in pleura, lung parenchyma, and airways, associated with a high rate of infertility. CASE REPORT: We have reported a case of successful management and treatment of thoracic endometriosis syndrome that occurred in a 37-year-old female patient. She underwent thoracoscopic resection of the lesion. During follow-up, we revealed the recurrence of a previously surgically treated thoracic endometriosis. She was initially treated with a gonadotropin-releasing hormone agonist; subsequently this was replaced by a prophylactic treatment with Dienogest. CONCLUSION: The diagnosis of thoracic endometriosis is challenging. The first line of treatment is medical, whereas the surgical treatment is performed secondly. Moreover, surgical treatment can lead to a significant rate of recurrence, often reduced by a coadjutant medical treatment.

Fibroblastic Malignant Peripheral Nerve Sheath Tumour of the Uterine Cervix: Report of a Case and Literature Review With Emphasis on Possible Differential Diagnosis.

Cervical sarcomas are rare neoplasms, accounting for <1% of all cervical malignancies and characterized by an aggressive course despite radical excision. We report the clinical and microscopic features of a spindle cell sarcoma arising as a polypoid endocervical mass in a 45-yr-old woman. The neoplasm was characterized by a monotonous, mildly atypical proliferation of spindle cells, displaying a fibrosarcoma-like parallel pattern of highly dense fascicles, growing under the cervical epithelium. Mitotic activity was conspicuous, with up to 40 mitoses per 10 HPF. On immunohistochemistry, tumor cells were patchy S-100 protein positive. Additional immunohistochemical markers performed to rule out smooth muscle, melanocytic, epithelial, and sarcomatous differentiation were negative. A possible monophasic synovial sarcoma was also excluded by negative fluorescence in situ hybridization t(X;18) analysis. Interestingly, the neoplasm showed a focal CD34 positivity, as reported in normal fibrocytic cells of the endocervical stroma. Giving the morphologic and immunohistochemical features, the neoplasm was eventually defined as malignant peripheral nerve sheath tumor. Histologic examination following radical surgery revealed the neoplasm was confined to the uterine cervix (FIGO stage IB1) and at 12 mo of follow-up, the patient is still free of disease. Malignant peripheral nerve sheath tumors are highly aggressive sarcomas that can rarely involve the uterine cervix. They have to be differentiated from melanoma, leiomyosarcoma, endometrial stromal sarcoma, synovial sarcoma, and other spindle cell neoplasms.

Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

BACKGROUND/AIM: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. PATIENTS AND METHODS: A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. RESULTS: A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. CONCLUSION: Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed.

Conization in Early Stage Cervical Cancer: Pattern of Recurrence in a 10-Year Single-Institution Experience.

OBJECTIVE: The main objective of this study was to analyze the pattern of recurrence after conization and pelvic lymphadenectomy in early-stage cervical cancer (CC). METHODS: We retrospectively identified 60 patients with early-stage CC who referred to the European Institute of Oncology (IEO; Milan, Italy) for fertility-sparing surgery. All of them underwent conization and pelvic lymphadenectomy (one received neoadjuvant chemotherapy followed by simple trachelectomy because of the size of the tumor). RESULTS: In total, 54 patients were considered for final analysis; only 23 patients were entirely treated at IEO. Relapse occurred in 7 (13%) of 54 patients, and in 6 cases (86%) it was local. One patient experienced a pelvic lymph node recurrence (in a woman who conceived 4 months after conservative surgery). However, this was an atypical case for site and timing of recurrence with the consistent doubt that the nodal involvement was already present before conization. Thus, analyzing only IEO population, the recurrence rate was lower (9%), becoming 4% excluding the atypical case with nodal involvement. CONCLUSIONS: In our series, the relapse was mainly local (on the cervix). However, the pattern of recurrence and recurrence rates after conization and pelvic lymphadenectomy for early-stage CC are still unclear. Further studies, comparing conization with radical trachelectomy, are necessary to confirm that the adoption of this procedure in clinical practice is safe. Our data highlight that the management of such as a particular condition in dedicated and highly specialized centers is mandatory.

Clinical factors and malignancy in endometrial polyps. Analysis of 1027 cases.

STUDY OBJECTIVE: To assess the prevalence of polyps carrying a malignancy and match association between clinical factors and oncologic progression. STUDY DESIGN: A retrospective study (Canadian Task Force classification II-3) at a university hospital in Rome, Italy. We retrospectively analyzed data from 1027 women consecutively treated for endometrial polyps at our center in the period 2002-2011. The association of malignancy with hormonal status, tamoxifen, hypertension, symptoms, diabetes mellitus, obesity, and hormonal replacement therapy in pre- and post-menopausal women was assessed. RESULTS: Mean age was 45.8±10.8 years. Benign polyps accounted for 95.8% of the total, pre-malignant for 2.67%, malignant for 1.54%. Our data showed that post-menopausal and older women (>60y) with endometrial polyps have a higher risk of developing a related endometrial cancer (OR: 3.05, 95% CI [1.54, 6.19], p<0.001 and OR: 2.8, 95% CI [1.38, 5.56], p≤0.003. Also we observed that women with AUB in the post-menopausal period displayed a risk of malignancy (OR: 31.1, 95% CI [10.3,111], p value <0.001). CONCLUSION: Special attention should be drawn to symptomatic post-menopausal patients that appear to be at higher risk of malignancy. Symptomatic pre-menopausal women and asymptomatic post-menopausal women with polyps may be a group with intermediate-risk. These patients should undergo an individualized management plan, balancing both risks and benefits of surgical intervention after discussion with the patient.

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

BACKGROUND: The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. OBJECTIVE: The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. STUDY DESIGN: Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. RESULTS: The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. CONCLUSION: HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up.

Multiple intraepithelial neoplasias of the lower female genital tract: the reliability of HPV mRNA test.

OBJECTIVE: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms. MATERIALS AND METHODS: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment. RESULTS: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02). CONCLUSIONS: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

Vaginal intraepithelial neoplasia: a therapeutical dilemma.

Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics.

Laparoscopic injury of the obturator nerve during fertility-sparing procedure for cervical cancer.

BACKGROUND: Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. CASE PRESENTATION: A 28-year-old woman with stage IB cervical cancer underwent fertility-sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. CONCLUSION: Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively.

Life-threatening bleeding after pelvic lymphadenectomy for cervical cancer: endovascular management of ruptured false aneurysm of the external iliac artery.

Late rupture of external iliac artery pseudo-aneurysm is an uncommon complication in patients who undergo extensive gynecologic radical surgeries. A 28-year-old woman with stage IB cervical cancer underwent pelvic lymphadenectomy and extrafascial trachelectomy. Two months after surgery, massive bleeding from ruptured pseudo-aneurysm of the external iliac artery occurred. Endovascular management with covered stent placement was feasible and safe to stop bleeding.