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.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding ( p < .005), easy bruising ( p = .028), fissures ( p = .008), petechiae/splinter hemorrhages ( p < .001), and bleeding/blistering or open sores ( p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum ( p = .013) and the perianal region ( p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population ( p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population ( p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group.

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review.

BACKGROUND: PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. METHODS: We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. RESULTS: This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). CONCLUSION: This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Impact of COVID-19 on surgical activities and personnel: lessons for the future.

BACKGROUND: COVID-19 pandemic has impacted professional, economic and social activities. In the surgical field, it has brought changes to operating activities, the organization of workforces, the protection measures for patients and personnel against possible intraoperative transmissions as well as training young surgeons. This study intends to assess the extent of this impact in our institution. METHODS: The patients operated on in nine Operating Units (OUs) in the period February 1 - March 31, 2020, with follow-ups on April 30, 2020, were evaluated both retrospectively and prospectively. Organizational, clinical and impact parameters on staff were evaluated. RESULTS: Of the 833 consecutive admitted patients, 742 were operated on, 705 of whom were recruited for the study. Compared to the same period in 2019 there was a decrease in the number of operations (742 compared to 1187), similar use of intensive care unit (ICU), a diagnostic activity only for symptomatic patients, heterogeneity in organizational behaviors, an impact on staff who highlighted concerns about getting sick or passing the infection on to others (87.64%) or their family members (75.14%). CONCLUSIONS: The present study made it possible to detect the need to make significant changes in the clinical, organizational and teaching fields, for which some operational proposals are suggested.

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. METHODS: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. RESULTS: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). CONCLUSION: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

KID Syndrome and Hidradenitis Suppurativa: A Rare Association Responding to Surgical Treatment.

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis characterized by keratitis, neurosensorial auditory impairment and ichthyosiform skin involvement. Frequent complications of the syndrome are chronic, opportunistic cutaneous infections, and the development of skin cancers. Several cases of association between KID syndrome and other conditions, including hidradenitis suppurativa (HS), are described in the literature. This correlation could be explained by the hyperproliferative state of the epidermis, which occurs in KID syndrome and may favor follicular plugging. OBJECTIVES: The aim of this study was to describe a very rare case of association between KID syndrome and HS and its complex therapeutic management. RESULTS: The failure of the drugs commonly used in HS and the excellent results of surgery, although difficult to achieve, were experienced. CONCLUSION: Despite the technical difficulties related to surgery, namely, cutaneous superinfections, frequent dehisce of the suture, and closure by secondary intention, the authors strongly recommend the surgical approach in these patients.

Prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers: what is going on in a region of northern Italy?

BACKGROUND: BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40-45 for BRCA2 mutation carriers. STUDY QUESTION: Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. STUDY DESIGN: Multicentre data collection by invitation to report current RRSO practices. RESULTS: A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p =  0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42-68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. CONCLUSIONS: The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.

Data on correction of pelvic organ prolapse by laparoscopic lateral suspension with mesh: A clinical series.

This DIB article provides additional data on laparoscopic lateral suspension with mesh for correcting pelvic organ prolapse. Data come from a multicentric sample of Italian women (https://doi.org/10.1016/j.ejogrb.2019.07.025). Data are collected retrospectively. Descriptive and raw data on surgery and descriptive and raw data on symptoms of pelvic organ prolapse pre-surgery and post-surgery are provided. Kaplan-Meier curves and scores of 7-items King's Health Questionnaire for quality of life assessment are also reported.

Molecular biomarkers predicting early development of endometrial carcinoma: A pilot study.

OBJECTIVE: Endometrial carcinoma represents the most common gynaecological cancer and the sixth most frequent cancer among women worldwide. The 5-year survival of patients with stage I endometrial carcinoma is 75%-88% versus 50% for stage III or 15% for stage IV disease. Therefore, early detection could improve survival rates. Specifically, in the most prevalent, type 1 endometrial cancer develops from hyperplastic endometrium. The aim of the study was to evaluate the utility of cancer gene mutations from endometrial biopsies towards predicting synchronous or metachronous development of malignant lesions. The aim of the study was to evaluate whether endometrial biopsies could already carry mutations in cancer genes useful for predicting or anticipating subsequent cancer development. METHODS: Patients with a previous endometrial biopsy negative for cancer, followed by a subsequent biopsy positive for cancer, were included in the study. A fifty cancer genes targeted next-generation sequencing panel were used to investigate mutations in matched non-cancerous and malignant samples. RESULTS: All biopsies from cancer tissues harboured mutations in one or more of the following genes: APC, CTNNB1, FBXW7, HNF1A, KRAS, MTOR, NRAS, PIK3CA, PTEN, RB1 and TP53. Additionally, 50% of the biopsies from matched non-cancerous tissues exhibited mutations in PTEN, KRAS or PIK3CA genes. CONCLUSIONS: These results suggest that detecting pathogenic mutations in oncogenes or tumour suppressor genes in an otherwise benign condition is associated with a risk of developing a malignant disease. Given the identification of mutations several months or years before the appearance of a malignancy, our finding suggests that a closer monitoring of patients who present such molecular alterations in non-cancerous uterine mass is warranted.

Correction of pelvic organ prolapse by laparoscopic lateral suspension with mesh: A clinical series.

OBJECTIVE: Illustrating the outcomes of laparoscopic lateral suspension by mesh for pelvic organ prolapse repair. STUDY DESIGN: A retrospective observational study was conducted collecting medical records of 48 patients treated between May 2016 and April 2018 in two different centers in Italy. Pre- and post-operative clinical evaluations as well as patients' satisfaction scores were considered. Patients were followed for two years. Statistical analysis was determined using the chi-square test in intention-to-treat and per-protocol analyses, while Kaplan-Meier curves were built for assessing the prolapse recurrence and the symptoms recurrence. The Steel-Dwass test for pairwise comparisons was used to compare median scores from the King's General Health Perception Questionnaire answers. RESULTS: Regarding the anatomical result, the outcome was either optimal or satisfactory (PoP-Q ≤1) at 12 months in 92% of patients for anterior compartment, in 100% for apical compartment, and in 75% for posterior compartment (intention-to-treat). Kaplan-Meier curves depicted a repair of prolapse in 70% of cases, with better outcomes for the anterior and the apical compartment. Patient self-perception of health was over 80% at each follow-up evaluation. CONCLUSION: Laparoscopic lateral suspension is a reasonable technique for treatment of pelvic organ prolapse. Further studies are needed to prove such a technique versus alternative surgeries.

Isthmocele: From Risk Factors to Management.

OBJECTIVE: The aim of the present study was to perform a comprehensive review of the literature to provide a complete and clear picture of isthmocele-a hypoechoic area within the myometrium at the site of the uterine scar of a previous cesarean section-by exploring in depth every aspect of this condition. METHODS: A comprehensive review of the literature was performed to identify the most relevant studies about this topic. RESULTS: Every aspect of isthmocele has been studied and described: pathophysiology, clinical symptoms, classification, and diagnosis. Its treatment, both medical and surgical, has also been reported according to the actual literature data. CONCLUSION: Cesarean section is the most common surgical procedure performed worldwide, and one of the consequences of this technique is isthmocele. A single and systematic classification of isthmocele is needed to improve its diagnosis and management. Further studies should be performed to better understand its pathogenesis.

OBJETIVO: O objetivo do presente estudo foi realizar uma revisão abrangente da literatura a fim de fornecer um quadro completo e claro da istmocele­uma área hipoecoica dentro do miométrio no local da cicatriz uterina de uma cesariana anterior­aprofundando todos os aspectos desta condição MéTODOS: Uma revisão abrangente da literatura foi realizada para identificar os estudos mais relevantes sobre este tema. RESULTADOS: Todos os aspectos da istmocele foram estudados e descritos: fisiopatologia, sintomas clínicos, classificação e diagnóstico. Os tratamentos médico e cirúrgico também foram relatados de acordo com os dados reais da literatura. CONCLUSãO: A cesárea é o procedimento cirúrgico mais comum realizado em todo o mundo, e uma das consequências desta técnica é a istmocele. Uma classificação única e sistemática da istmocele é necessária para melhorar seu diagnóstico e manejo. Novos estudos devem ser realizados para melhor entender sua patogênese.

Outcome of endometrial cancer after lymphadenectomy: a single center retrospective analysis with long-lasting follow-up.

BACKGROUND: Role of lymphadenectomy in endometrial cancer is unclear. Our objective is to assess the role of lymphadenectomy in endometrial cancer. METHODS: The study reviewed retrospectively 829 cases of endometrial cancer from a single non-oncological center from 1981 to 2014. Multivariable Cox regression analyses were performed. Independent variables were: 2009 FIGO stage, histological type of endometrial cancer (non-endometrioid, endometrioid, grading 1, 2 and 3), radicality on parametria, lymphatic dissection (any kind) (yes/no), any kind of chemotherapy, any kind of radiotherapy, brachytherapy, patients' age. Dependent variable was death for endometrial cancer and first relapse. Time variable was the semester of follow-up. P value for significance was set <0.05. RESULTS: Many data about the extension of node dissection were missing. Pelvic node dissection or sampling seem the more common procedure performed. At the 10-semester of follow-up, at the 20-semester of follow-up and at the 30 semester of follow up, lymphadenectomy does not improve overall survival at a p value of less than 0.05. Lymphadenectomy reduces the risk of relapse at the 10 semester and 20-semester of follow-up. CONCLUSIONS: Lymphadenectomy plays a role in preventing relapses but it is not proved that non-aggressive lymphadenectomy in endometrial cancer improves overall survival at p level of 0.05. Therefore, it cannot be excluded that a very small improvement in long lasting survival in few cases of endometrial cancer could be due to node dissections.

Clinical governance network for clinical audit to improve quality in epithelial ovarian cancer management.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several hospitals throughout the region provide primary treatment for these patients and it is well know that treatment quality is correlated to the hospital that delivers. The aim of this study was to investigate the management and treatment of EOC in a Region of the North Italy (Emilia-Romagna, Italy). METHODS: A multidisciplinary group made up of 11 physicians and 3 biostatisticians was formed in 2009 to perform clinical audits in order to identify quality indicators and to develop Region-wide workup in accordance with the principles of evidence-based medicine (EBM). The rationale was that, by setting up an oncogynecology network so as to achieve the best clinical practice, critical points would decrease or even be eliminated. Analysis of cases was based on the review of the medical records. RESULTS: 614 EOC patients treated between 2007 and 2008 were identified. We found only 2 high-volume hospitals (≥ 21 patients/year), 3 medium-volume hospitals (11-20 operated patients/year), and 7 low-volume hospitals (≤ 10 operated patients /year). Only 222 patients (76.3%) had a histological diagnosis, FIGO surgical staging was reported only in 206 patients (70.9%) but not all standard surgical procedures were always performed, residual disease were not reported in all patients. No standard number of neoadjuvant chemotherapy cycles was observed. CONCLUSIONS: The differences in terms of treatments provided led the multidisciplinary group to identify reference centers, to promote centralization, to ensure uniform and adequate treatment to patients treated in regional centers and to promote a new audit involving all regional hospitals to a complete review of the all the EOC patients.

Pseudo-Meigs' syndrome caused by a uterine leiomyosarcoma: a new clinical condition.

INTRODUCTION: Pseudo-Meigs' syndrome is a rare condition characterized by female genital cancer, ascites, hydrothorax and tumors other than benign ovarian tumors. CASE REPORT: A 30-year-old woman arrived at our clinic with pelvic pain and dyspnea. She underwent an exploratory laparotomy for a large pelvic mass complicated by ascites and hydrothorax. Cytological examination of the effusions was negative for malignant cells. Histological analysis of the tumor mass revealed a uterine epithelioid leiomyosarcoma. After surgery, we observed resolution of the effusions. CONCLUSION: Uterine leiomyosarcoma and pseudo-Meigs' syndrome are two rare entities. To our knowledge, there are no similar reports in the literature, and therefore we present this new clinical condition due to its high scientific evidence.

Papilloma and polyoma DNA tumor virus sequences in female genital tumors.

Human papillomaviruses (HPVs) and BKV, JCV, and SV40 polyomaviruses (PYVs) are oncogenic viruses associated with different human tumors. Our aim was to determine if PYV and HPV sequences could be detected in human genital tumors. HPV types 6b, 11, 16, and 18 and PYV were investigated in 22 genital tumor samples and the corresponding adjacent normal tissues, by PCR and filter hybridization. HPV and PYV sequences were also searched in six sperm fluid and four peripheral blood cell (PBC) samples. HPV-16 sequences were revealed in 7 of 14 cervical tumors and 1 of 1 vaginal adenocarcinoma, whereas 1 of 14 cervical carcinoma tested positive for HPV-18. Interestingly, each normal cervical tissue surrounding the neoplasm obtained from the same patient was positive for HPV type-16 and -18 with the same prevalence detected in tumors. BKV sequences were found in 9 of 14 cervical tumors, 1 of 7 vulvar tumors, and 1 of 1 adenocarcinoma, but also in normal tissues from cervix (13 of 14), vulva (6 of 7), sperm fluid (5 of 6) and PBC (3 of 4) samples. SV40 sequences were detected in 1 of 14 normal cervical tissue, 2 of 6 sperm fluids and 1 of 4 PBCs. None of the samples were JCV positive. To our knowledge, this is the first investigation reporting on the simultaneous association of both HPV and PYV with human genital tumors. These results suggest that PYV, together with HPV, may be involved as a cofactor in the onset/progression of human genital tumors, and raise the possibility that PYV act synergistically with HPV to enhance their pathogenicity in vivo. In addition, HPV and PYV may complement each other in infecting human genital tissues.