Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

OBJECTIVES: Nodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition. Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. METHODS: Clinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. RESULTS: Fifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case. Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT. Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. CONCLUSIONS: In this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Hormone Replacement Therapy in Post-Menopause Hormone-Dependent Gynecological Cancer Patients: A Narrative Review.

BACKGROUND: Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause. METHODS: A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]). RESULTS: HRT can be prescribed to patients with early-stage, grade I-II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery. Caution should be exercised in administering HRT after serous borderline tumors and endometrioid OC, and HRT is not recommended in low-grade serous OC. HRT is not contraindicated in AC survivors. After surgery for EC, HRT can be prescribed in women with early-stage low-grade EC. There is not enough data to give indications to patients with advanced EC. CONCLUSIONS: HRT can be discussed with patients, evaluating the risks and benefits of hormone-dependent gynecological cancer. Counseling should be performed by gynecologic oncologists experienced in the management of these patients.

Development and clinical application of a tool to identify frailty in elderly patients with gynecological cancers.

OBJECTIVE: Frailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have received unanimous consent or been specifically designed for women with gynecological malignancies.This study's aim was to develop a clinical application of a screening tool to identify frail patients >70 years old diagnosed with either ovarian or endometrial cancers. METHODS: A 20 item questionnaire was developed and administered to the cohort before surgery or neoadjuvant chemotherapy. A cut-off for frailty definition was determined by analyzing the correlation of questionnaire scores with the completion of treatments. The association between frailty and treatment related complications was assessed using a Chi-squared test for categorical variables and a t-test for continuous variables. RESULTS: Our study included 100 patients, 50% diagnosed with endometrial cancer and 50% with ovarian cancer. A questionnaire score of 4 was the best cut-off for frailty definition (sensitivity 77%, specificity 100%). Surgical grade III and grade IV complications were observed only in frail patients (p=0.01) and hospitalization was significantly longer in frail women affected by ovarian cancer (p=0.01). Frail patients were more exposed to chemotherapy administration delay (p=0.0005), treatment discontinuation (p=0.001) and hematological toxicities, especially anemia ≥grade 2 (p=0.009) and thrombocytopenia any grade (p=0.0001). CONCLUSION: With a cut-off score of 4, our tool can identify frail patients with significantly higher incidence of grade III-IV postoperative complications, length of stay, medical treatment discontinuation rates and hematological toxicities.

No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

Fractional CO2 vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors.

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO2 vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO2 laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO2 vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.

A novel HPLC method for the concurrent analysis and quantitation of seven water-soluble vitamins in biological fluids (plasma and urine): a validation study and application.

An HPLC method was developed and validated for the concurrent detection and quantitation of seven water-soluble vitamins (C, B(1), B(2), B(5), B(6), B(9), B(12)) in biological matrices (plasma and urine). Separation was achieved at 30°C on a reversed-phase C18-A column using combined isocratic and linear gradient elution with a mobile phase consisting of 0.01% TFA aqueous and 100% methanol. Total run time was 35 minutes. Detection was performed with diode array set at 280 nm. Each vitamin was quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples (24 plasma and urine samples from abstinent alcohol-dependent males). Interday and intraday precision were <4% and <7%, respectively, for all vitamins. Recovery percentages ranged from 93% to 100%.