Lymphomas of the Vulva: A Review of the MITO Rare Cancer Group.

Since they are very rare tumors, lymphomas of the vulva are often not properly recognized. Patients with vulvar lymphoma are generally elderly and the classical manifestation of the disease is a vulvar mass. No significant age differences have been found between primary and secondary lymphoma. To make a correct diagnosis, it is therefore necessary to use not only histological examination but also the genetic and molecular profile in order to establish optimal therapeutic management. Literature analysis confirm the good prognosis of this disease.

Aggressive Angiomyxoma of the Lower Female Genital Tract: A Review of the MITO Rare Tumors Group.

Aggressive angiomyxoma (AAM) is a rare, locally aggressive, myxoid mesenchymal neoplasm primarily found in the pelvic and perineal regions of young adult females. It is a slow growing and locally infiltrating tumor. Preoperative diagnosis is difficult due to the rarity of these tumors and absence of characteristic signs and symptoms. The primary management is tumor excision. Incomplete excision is common because of the infiltrating nature of the neoplasm and absence of a definite capsule. Other non- surgical modalities have been employed, such as radiotherapy, embolization, GnRH analogues or other anti-estrogenic agents. Local relapses occur in 30-40% of the cases, and often appear many years (sometimes decades) after the first excision. Occasional distant metastasis has also been reported. A limited number of cases have been reported in the literature, mostly in the form of small case series or isolated case reports. Therefore, the aim of this paper by a team of experts from the MITO rare tumors group is to review clinical findings, pathologic characteristics and outcome of patients affected by this rare condition in order to be able to offer up-to-date guidance on the management of these cases.

Aggressive Angiomyxoma of the Lower Female Genital Tract in Pregnancy: A Review of the MITO Rare Tumors Group.

Deep (aggressive) angiomyxoma of the lower genital tract is a rare malignancy affecting women of reproductive age. Being a hormone-sensitive tumor, its growth is particularly benefitted during pregnancy. Surgical excision with complete resection is indicated, even if a wait-and-see approach can be considered until delivery, to avoid destructive surgeries. The mode of delivery is to be evaluated based on the location and size of the neoplasm; vaginal delivery is not contraindicated, as long as the tumor does not obstruct the birth canal. Positive surgical margins are the most important prognostic factor for recurrence. Adjuvant therapy with gonadotropin-releasing hormone analogues may be proposed after pregnancy, in the case of non-radical surgery. Despite the high local relapse rate, the outcomes for mother and child are favorable. Since recurrences can occur after many years, the patient should be included in long-term follow-up.

Muscle-Sparing Skin-Reducing Breast Reconstruction with Pre-Pectoral Implants in Breast Cancer Patients: Long-Term Assessment of Patients' Satisfaction and Quality of Life.

INTRODUCTION: Breast cancer is the most frequently diagnosed tumor in women; globally, it accounts 23% of all cancer deaths. Breast reconstruction after oncologic surgery has become crucial to enhance patients' quality of life and alleviate the psychological distress related to the disease. The aim of this study was to assess quality of life and esthetic satisfaction of breast cancer patients undergoing muscle-sparing skin-reducing breast reconstruction (MS-SR) with pre-pectoral implants. METHODS: Sixty-three patients who met definite oncological and reconstructive criteria were enrolled in the study. Specific questionnaires (EORTC QLQ-C30, QLQ-BR23) were administered preoperatively, 1, and 12 months after MS-SR breast reconstruction to evaluate patients' QoL. Satisfaction with procedure and related Quality of Life were assessed through BREAST-Q questionnaire preoperatively and 12 months after surgery. RESULTS: Sixty-three breast cancer patients underwent MS-SR. Seventy-eight procedures were carried out; in 15 patients a bilateral reconstruction was performed. One month after surgery, both EORTC QLQ-C30 and QLQ-BR23 average scores demonstrated a slight drop since preoperative values, but a significant improvement in QoL was documented 12 months after BR (p < 0.05). BREAST-Q test showed significant psychophysical and esthetic satisfaction 12 months postoperatively. CONCLUSIONS: Muscle-sparing skin-reducing breast reconstruction is an established and reliable technique. EORTC QLQ-C30, QLQ-BR23 and BREAST-Q scores showed an improvement of patients' QoL and esthetic satisfaction. Reduction of pain and other surgery-related symptoms are cornerstones of patient well-being. Both physicians and patients should build a thorough awareness of the silver lining of muscle-sparing skin-reducing breast reconstruction based on the high safety profile and highly satisfactory patient-reported results.

Inflammatory Biomarkers as Promising Predictors of Prognosis in Cervical Cancer Patients.

INTRODUCTION: Increasing evidence demonstrates a crucial role of inflammation in inducing and promoting several cancers. Pro-inflammatory upregulation of cytokines such as IL-6 has been implicated in cervical cancer development and progression through several mechanisms, for example, by inducing platelet production, activation, and aggregation. The aim of the study was to evaluate the effective prognostic impact of inflammatory biomarkers such as platelet count, platelet to lymphocyte ratio (PLR), and IL-6 in cervical cancer patients. MATERIALS AND METHODS: Between 2016 and 2019, 108 out of 159 patients with cervical cancer have been enrolled. Cutoff level of pretreatment platelet count and PLR was identified by using the ROC curve. IL-6 tumoral and peritumoral expression was analyzed and stratified as low and high (low expression: 0 and +1; marked expression: +2 and +3). RESULTS: Median follow-up duration was 30 months (range 16-44). Patients with higher platelet counts showed worse DFS and OS (DFS p < 0.001; OS p < 0.001). Cumulative rates of DFS and OS in patients with lower PLR were higher than in patients with higher values of PLR (DFS p = 0.032; OS p < 0.001). Survival analysis showed a better prognosis in patients with lower IL-6 expression (DFS p < 0.001; OS p < 0.001). CONCLUSION: Nowadays, causal relationship between inflammation, innate immunity, and cancer is more widely accepted. However, many of the molecular and cellular mechanisms mediating this relationship remain unresolved. Ongoing inflammatory response was associated with poor outcomes in cervical cancer patients. A higher pretreatment platelet count and PLR value associated with higher IL-6 tumoral expression could be used to predict poor prognosis in cervical cancer patients.

Modified intestinal isolation bag as promising tool in promoting bowel resumption after ovarian cancer cytoreductive surgery: a randomized clinical trial.

PURPOSE: Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery. METHODS: A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups. RESULTS: Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3 days from surgery and they were susceptible to be discharged within 5 days, compared, respectively, to 34.3% of Group 2 (n = 15). Advantages were more evident in patients whose surgery took over 220 min (OR 0.02, CI 95% 0.001-0.57; p < 0.001) despite the type of surgical effort made. CONCLUSION: Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

Quality of Life and Early Functional Evaluation in Direct-to-Implant Breast Reconstruction After Mastectomy: A Comparative Study Between Prepectoral Versus Dual-Plane Reconstruction.

BACKGROUND: In conservative mastectomies, in which the native skin envelope is preserved, positioning an implant in the submuscular plane commonly leads to functional consequences like upper limb movement impairment and animation phenomena. In recent years, however, a new conservative prepectoral breast reconstruction technique has been proposed, with demonstrated surgical safety and aesthetic effectiveness. The aim of our study was to explore and compare the functional and aesthetic outcomes of the prepectoral/acellular dermal matrix (ADM)-wrapped implant procedure versus subpectoral/ADM-assisted reconstruction. PATIENTS AND METHODS: A retrospective nonrandomized comparative study of 94 patients (121 breasts) undergoing direct-to-implant breast reconstruction after skin-/nipple-sparing and skin reduction was conducted from February 2013 to October 2017. Fifty-five patients (group A) received subpectoral ADM-assisted reconstruction with dual-plane implant positioning, and 39 patients (group B) received prepectoral partially or totally ADM-wrapped implant reconstruction. Patients were allocated to either group A or B depending on the mastectomy flap thickness and vitality, as assessed clinically during the operation. Details of rehabilitation program, postoperative pain at 72 hours, postoperative analgesic therapies, demographic data, and complications were recorded. Upper limb function was assessed before and 1 month after surgery by a physiatrist according to a precise protocol. Patients were asked to fill in the BREAST-Q reconstruction questionnaire after surgery to evaluate outcomes. RESULTS: Differences in upper limb function between groups, namely flexion (P = .03), abduction (P = .003), internal rotation (P = .02), and external rotation (P = .05), were statistically significant. Although most patients required postoperative rehabilitation, the individual rehabilitation intervention frequency was greater in the subpectoral group (91% in group A vs 74% in group B). There was also a significant difference in postoperative pain (within 72 hours), with less pain perceived in the prepectoral group (P = .01). Furthermore, prepectoral patients reported slightly better postoperative quality of life than subpectoral patients, particularly in the domains of sexual well-being (P = .005) and satisfaction with breast (P = .002). CONCLUSION: In our case series, prepectoral implant positioning with partial or total ADM coverage led to less impairment of upper limb function in terms of flexion, abduction, and internal and external rotation, and also reduce the need for rehabilitation. Furthermore, as a result of the less invasive procedure, prepectoral patients had less immediate postoperative pain and were more satisfied with breast appearance.

Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients.

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis. Consistently different biopotential values were detected in cancerous tissue versus non-cancerous tissue across all cases (p < 0.001). High tumour biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour load, and negatively correlated with stroma. Within our EOC cohort and specifically the high-grade serous subtype, low biopotential levels associated with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively). Changes in biopotential levels significantly correlated with common apoptosis related pathways. Lactate and glucose levels measured in paired tissues showed significantly higher lactate/glucose ratio in tissues with low biopotential (p < 0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite monitoring as a biomarker modality profiling EOC to predict surgical and clinical outcomes.

Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection.

BACKGROUND: Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis. METHODS: A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016. Women were randomized in two groups, standard treatment (metronidazole 500 mg twice a day for 7 days or fluconazole 150 mg orally once a day for 2 consecutive days) plus short-term (3 months) vaginal Lactobacillus implementation (group 1, short probiotics treatment protocol group, n = 60) versus the same standard treatment plus long-lasting (6 months) vaginal Lactobacillus rhamnosus BMX 54 administration (group 2, treatment group, n = 57). RESULTS: After a median follow up of 14 months (range 9-30 months) the chance to solve HPV-related cytological anomalies was twice higher in probiotic long-term users (group 2) versus short probiotics implementation group (group 1) (79.4% vs 37.5%, p = 0.041). Moreover, a total HPV-clearance was shown in 11.6% of short schedule probiotics implementation patients compared to a percentage of 31.2% in vaginal Lactobacilli long term users (p = 0.044), assessed as negative HPV-DNA test documented at the end of the study period. CONCLUSIONS: The consistent percentage of clearance of PAP-smear abnormalities and HPV-clearance obtained in long-term treatment group has been interestingly high and encouraging. Obviously, larger and randomized studies are warranted to confirm these encouraging results, but we believe that eubiosis re-establishment is the key to tackle effectively even HPV-infection. TRIAL REGISTRATION: Retrospectively registered on PRS NCT03372395 (12/12/2017).

Vulvo-vaginal reconstruction after radical excision for treatment of vulvar cancer: Evaluation of feasibility and morbidity of different surgical techniques.

BACKGROUND: Vulvar cancer is a rare disease accounting for approximately 5% of female genital tract tumors worldwide. Currently surgery represents the mainstay alone or sometimes, in combination with chemo-radiotherapy, for locally advanced tumors and recurrent disease. However, significant physical and sexual impairment mostly due to anatomical distortion of external genitalia are a consequence of radical surgical treatment. Postoperative reconstruction after demolitive surgeries improves aesthetic and functional results, guarantees an adequate coverage of large tumors and assures safe surgical margin. The present study aimed to analyze feasibility and complication rates of fascio-cutaneous flap after excision for vulvovaginal malignancies. METHODS: PubMed (MEDLINE), Web of Science, and CINAHL were searched for records of validated vulvovaginal reconstructive techniques after demolitive surgery for vulvar cancer. All cohorts were rated for quality using a scoring method taking into account the design of the study, the sample size and quality of report of surgical data and complications. RESULTS: A total of 24 studies met all eligibility criteria for this systematic review. All the studies were realized between 1996 and 2015. The overall sample size was 443 patients. Two major group of flap according to type of movement were identified: Advancement Flap (V-Y Gluteal Fold Flap; Medial Thigh Flap) and Transpositional Flap (Lotus Petal Flap; Gluteal Thigh Flap; Gluteal Fold Flap and Anterolateral Thigh Flap). The overall complications rates reported for advancement (26.7% among 165 patients on 11 series) and transposition flaps (22.3% among 278 patients on 13 series) were comparable. CONCLUSIONS: A tailored procedure, based on patients' characteristics, size and location of the defect is still the goal of a successful reconstructive surgery. Proper planning of the surgical procedures, knowledge of the different surgical options and technical skills are required in order to obtain reliable and satisfying results.

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.

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.

Skin-Reduction Breast Reconstructions with Prepectoral Implant.

UNLABELLED: 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.

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.

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.

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.

Vulvar malignancy in neurofibromatosis syndrome.

Type 1 neurofibromatosis (NF1) is a dominantly inherited neurologic disorder that affects primarily the skin, bones, and peripheral nervous system. It may be associated with a variety of clinical manifestations including cafe-au-lait spots, skinfold freckling, Lisch nodules, and visceral neurofibromas. Individuals affected by NF1 harbor an increased risk for both benign and malignant tumors. Malignant transformation is usually observed in the form of neurosarcoma. Rarely, NF1 affects the genital tract, and isolated vulvar localization is extremely rare. Here is reported a rare case of a solitary neurosarcoma of the vulva in a 43-year-old woman affected by NF1 syndrome treated with surgical excision. The purpose of this case is to underline the possibility of association between NF1 and genital tract sarcoma and to suggest an accurate evaluation of rapid growth vulvar mass in this setting.