Lavinia Domenici

Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature

High-risk human papillomaviruses (HPVs) are involved in the etiopathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. After taking HPV into account, smoking habit appears to be the most significant environmental risk factor, and the risk of this malignancy increases significantly with intensity and duration of smoking. Women with human immunodeficiency virus (HIV) infection experience a higher incidence of CIN and invasive cervical cancer. Among HIV+ women, the highly active antiretroviral therapy increases the regression rate of CIN, but the majority of these lesions do not regress to normal. As far as oral contraceptives (OCs), a systematic review of 28 studies found that, compared with never pill users, the relative risk (RR) of cervical cancer increased with increasing duration of OC use. The results were similar for squamous cell carcinoma and adenocarcinoma, and the RRs decreased after pill discontinuation. However, by weighing risks and benefits, the World Health Organization does not recommend any change in OC practice. There is no correlation between hormone replacement therapy and cervical cancer. Experimental data have shown that estradiol and progesterone can modulate the host immune response to HPV16. Prophylactic vaccination in conjunction with cervical screening is the best prevention strategy for cervical cancer.

Targeted drug delivery via folate receptors in recurrent ovarian cancer: A review

Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate–chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate–chemotherapy conjugates.

Skin-Reduction Breast Reconstructions with Prepectoral Implant.

Summary: Skin-reduction mastectomy with prepectoral implant reconstruction is a novel technique for immediate breast reconstruction, with subcutaneous implant placement in patients eligible for skin-reducing mastectomy. Implants were placed above the pectoralis muscles in a compound pocket made by a dermal flap and acellular dermal matrix. The procedure was performed on 33 breasts in 27 selected patients. In three cases, there was skin ischemia; in one case, it healed spontaneously; and in two patients, a surgical necrosectomy and primary closure were needed. No implant loss occurred. This new technique proved to be a useful alternative, with good cosmetic results, in selected patients requiring mastectomy. These preliminary results need to be confirmed by long-term and comparative studies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Laparoscopic Adnexectomy of Suspect Ovarian Masses: Surgical Technique Used To Avert Spillage

Herein is described and evaluated a safe laparoscopic adnexectomy technique for retroperitoneal dissection of suspect ovarian masses including the underlying peritoneum fixed to the ovary. Adopting this technique in cases of suspect adnexal masses enables the reduction of spilling and ensures an intact specimen. Twenty-two consecutive patients with suspect adnexal masses 10 cm or smaller underwent laparoscopic adnexectomy. Patients with bilateral suspect ovarian masses that required bilateral adnexectomy were enrolled only if they were no longer of childbearing age. Laparoscopy was feasible in all patients. No tumor spillage occurred. In 5 patients (23.6%), minilaparotomy was required to extract the specimen. Mean (SD) operating time was 80 (35-160) minutes, and estimated blood loss was 50 (10-100) mL. No major intraoperative complications occurred. Median (range) postoperative stay was 1 (1-3) day. Definitive pathologic analysis revealed benign pathologic conditions in 18 patients (81.8%), an ovarian tumor with low malignant potential in 3 patients (13.7%), and ovarian cancer in 1 patient (4.5%) in whom findings at frozen-section analysis were inconclusive. Median (range) follow-up of malignant ovarian tumors and of tumors with low malignant potential was 27 (21-29) months. No recurrence or port-site metastasis developed during follow-up. The data are encouraging for adoption of this technique to avert spillage during laparoscopic management of suspect adnexal masses, especially those firmly adherent to the peritoneum. However, the procedure must be validated in a larger series of patients to standardize the technique.

Prognostic role of inguinal lymphadenectomy in vulvar squamous carcinoma: Younger and older patients should be equally treated. A prospective study and literature review

OBJECTIVE This study analyzed the prognostic significance of nodal involvement in vulvar squamous carcinoma and its correlation with other prognostic factors, focusing the research on comparison between <75 and ≥75years old patients. METHODS We prospectively enrolled patients with >1-mm-deep stromal invasion, Ib-III stage vulvar cancer. Patients underwent unilateral or bilateral inguinal lymphadenectomy, according to tumor localization. RESULTS In total, 131 patients met inclusion criteria; 93 (71%) underwent bilateral and 38 (29%) unilateral lymphadenectomy with 36 (27%) of them presenting nodal disease. At Kaplan-Meier analysis factors associated to prognosis were nodal status (in very elderly patients also) and number of resected nodes both in bilateral and unilateral lymphadenectomy groups. In univariate analysis, covariates associated with survival included age, in terms of overall survival (OS) but not with disease free-survival (DFS) and disease-specific survival (DSS), grading, nodal status, the presence of bilateral nodal metastases, the number of resected nodes in both unilateral, in terms of OS and DSS but not of DFS and bilateral lymphadenectomy and the number of metastatic nodes. In multivariate analysis covariates associated with survival were age, the number of positive nodes and the number of resected nodes in bilateral lymphadenectomy. CONCLUSIONS Results confirm the prognostic role of nodal status in very elderly patients also. Although DSS in older patients resulted worse, lymphadenectomy is not associated with more complications, suggesting its importance in older patients too. Furthermore, the resection of less than 15 lymph nodes in bilateral lymphadenectomy seems to have a negative impact on survival.

Sexual Health and Quality of Life Assessment among Ovarian Cancer Patients during Chemotherapy

Background: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. Objective: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). Patients and Methods: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. Results: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). Conclusion: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.

Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other “imitators of preeclampsia.” Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life.

Laparotomic myomectomy in the 16th week of pregnancy: a case report.

Myomectomy is rarely performed during an ongoing pregnancy because of fear of miscarriage and the risk of an uncontrolled haemorrhage necessitating a hysterectomy. In cases where myomectomy is undertaken, most are performed at the time of cesarean section or with a laparoscopic approach. We report a case of a successful laparotomic myomectomy in the 16th week of pregnancy. A 35-year-old primigravida was admitted to our department with acute abdominal pain and hydronephrosis (serum creatinine 1.6 mg/dL). Imaging revealed a large implant myoma compressing the bladder, ureters, rectus, and gestational chamber and causing hydronephrosis. Laparotomic myomectomy was successfully performed and pregnancy continued uneventfully until the 38th week when a cesarean section was performed. Surgical management of myomas during pregnancy is worth evaluating in well-selected and highly symptomatic cases.

Surgery for Recurrent Uterine Cancer: Surgical Outcomes and Implications for Survival—A Case Series

Objective The purpose of this study was to describe the patterns of relapse in uterine cancer (UC) and the role of surgery in the recurrent setting. Methods We describe surgical and clinical outcomes of all patients who underwent surgery for recurrent UC in a gynecological oncology tertiary referral center between May 1, 2013, and April 30, 2016. Progression-free survival and overall survival were estimated using Kaplan-Meier methods with the surgery at relapse being the starting point. Results We evaluated 15 patients with a median age of 66 years. The predominant histology was the endometrioid variant (n = 11; 73.3%). The median interval between the end of previous treatment and relapse surgery was 24 months (range, 8–164). Locoregional pelvic recurrences were the most common type of recurrence (n = 13; 86.7%) with the para-aortic lymph node space being the most commonly affected extrapelvic site (13%). Patients predominantly presented with a multifocal pattern of relapse (n = 10; 66.7%) requiring multivisceral resections such as bowel (n = 7; 46.6%) and/or bladder/ureteric resections (n = 8; 53.3%) to achieve complete tumor clearance. All patients were operated tumor free with a 30-day major morbidity and mortality rate of 6.7% and 0%, respectively. Five patients (33.3%) received postoperative chemotherapy or radiotherapy. Five patients (33.3%) relapsed, and 3 died within a mean follow-up of 12.4 months (95% confidence interval [CI], 6.5–18.2). Two of those patients had a sarcoma. Mean progression-free survival and overall survival for the entire cohort postrelapse surgery was 21.7 months (95%CI, 13.9–29.5) and 26.0 months (95%CI, 18.4–33.7), respectively. Survival was significantly worse in patients with nonendometrioid histology (P < 0.0001). Conclusions Surgery for UC relapse seems feasible with acceptable morbidity and high complete resection rates despite the multifocal patterns of relapse in a selected group of patients in a reference center for gynecological cancers. Larger scale studies are warranted to establish the value of surgery at relapse for UC.

Is removing 9 lymph nodes a correct cutoff to define optimal lymphadenectomy?: The open question of lymph node count.

To the Editor: W e read with great interest the paper published by van Beekhuizen et al1 titled ‘‘Lymph node count at inguinofemoral lymphadenectomy and groin recurrences in vulvar cancer.’’ This retrospective study showed that overall risk of groin recurrence after inguinofemoral lymphadenectomy (without nodal metastases), in patients with squamous cell carcinoma, is low (1.6% per groin). However, it significantly increases in patients with poorly differentiated tumors and lymph node count less than 9 at lymphadenectomy. Analyzing results reported by the authors, among 134 patients eligible for the analysis, in only 4 women groin recurrences occurred, with 1 developing contralateral metastasis, so that exclusively 3 of them were evaluated. In total, it is a very small sample, although significance was found, either at Kaplan-Meier analysis or at Cox proportional hazards model (both at univariate and multivariate analysis), even if confidence intervals were not reported. Moreover, van Beekhuizen et al did not report time to recurrence in this analysis. We think that this parameter could represent interesting data, considering that groin recurrence in those patients in whom the lymphadenectomy consisted in the removal of less than 9 lymph nodes might be associated to undetected nodal metastasis. Finally, most of the studies about lymphadenectomy differentiated the median number of resected nodes for bilateral and unilateral removal, reporting higher medians, overall in patients who underwent bilateral lymphadenectomy. Because these studies showed that a significant prognostic role was related to higher number of resected nodes at bilateral lymphadenectomy but with major medians of removed lymph nodes,2Y4 we think that in the study by van Beekhuizen et al, this value could have been altered by the analysis of survivals of both patients who underwent unilateral and bilateral lymphadenectomy. We strongly believe that inguinofemoral nodes count is a very important prognostic factor, both in bilateral and unilateral lymphadenectomy and in patients with either positive and negative nodes, so that further studies are needed to better establish parameters necessary to define optimal level of lymphadenectomy.