Search

Introduction Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients. Methods At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19. Results The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention. Conclusion We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.

The increasing demand for further aesthetic outcome improvement in implant-based breast reconstruction after nipple-sparing mastectomy (NSM) leads to major novelties, including endoscopic and robotic NSM with the aim to limit scar visibility. In this paper, we report our experience with a novel and simplified surgical approach—single-axillary-incision non-endoscopic NSM and node surgery followed by an endoscopic DTI breast reconstruction—by focusing on reconstructive indications, technical refinements and aesthetic outcomes. Between June 2016 and October 2019, 14 women underwent this novel technique using definitive anatomical silicone gel filled, totaling 20 breasts. Reconstructive evaluation methods were clinically and photography-based assessment. Breast-Q has been used to quantify patient satisfaction. Feasibility and safety data are also provided. The average follow-up time was 11 months (range 3–42 months). No local–regional recurrence occurred during follow-up. Median operation time was 340 min; mean hospital stay was 4.1 days. The average mastectomy specimen weight was on average 139 g (ranging from 98 to 182 g). The average implant volume for the reconstructed side was 306 cc (ranging from 165 to 550 cc). Patients’ satisfaction was high to very high. Authors’ experience suggests that non-endoscopic transaxillary NSM, node surgery and endoscopic direct-to-implant breast reconstruction is a valid, oncological safe, aesthetically sound scarless option in breast cancer patients with small to moderate breast size. It should represent the incision of choice in patient with previous breast surgery with scars that may compromise flap/NAC vascularity using traditional NSM incisions. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed. Objectives: To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches. Methods: We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones. Results: EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability. Conclusions: We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.

SUMMARY INTRODUCTION Surgical therapy for vulvar cancer involves wide defects that often require flap-based reconstruction. The goal of the reconstruction is fast wound healing with low donor site morbidity. MATERIALS AND METHODS This is a retrospective observational cohort study in which we reviewed all patients who underwent surgery for vulvar cancer followed by reconstruction using the Superficial Circumflex Iliac Artery Perforator (SCIP) flap between 2015 and 2020. The primary outcome measure of this investigation was the incidence of wound complications. Secondary outcomes were the surgical indications in terms of establishing the anatomical subunits involved in the resection that made us choose this flap for reconstruction. This study adheres to the STROBE guidelines. RESULTS Thirty-two patients were included; in two cases, the flap was performed bilaterally for a total of 34 SCIP flaps. The mean age of patients was 70.6±8.6years, and the mean BMI was 26.8±4.7. The SCIP flap was always feasible. The mean flap size was 128.8±74.3cm2. Three patients showed wound complication. In every patient, the defect involved the vulva, perineum and inguinal area; in 18 patients, the mons pubis was also involved. The mean follow-up was 30 months. During the follow-up, six patients died, and four showed local or nodal cancer relapse. CONCLUSION Our results suggest that the SCIP flap advantages for the reconstruction of vulvoperineal defects secondary to vulvar cancer surgery are low complication rate, minimal donor site morbidity, quick dissection, proximity of donor and recipient sites, possibility to harvest large skin islands of variable thickness and chimeric flaps.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic cancer with poor outcomes in locally advanced disease. This study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of exclusive (chemo)radiotherapy (eRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer radical raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Seven Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 90 patients (patient populations shown in table 1), with a median age of 76 years (range 32-92). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (26%); instead, the rate of severe skin fibrosis was 4.4%. After a median follow-up of 10 months (range 1-199), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 42.2%, 40%, and 36.7%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. Clinical outcomes are still confirmed to be poor. The results suggest the clinical evaluation of the impact of treatment standardisation, in terms of doses and volumes, in a further perspective study.

Introduction/Background* Investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology A series of 101 patients surgically treated at our Center from 2016 to 2020 were retrospectively enrolled: 53 node negative (Group A) and 48 node positive (Group B). A total of 146 samples, 101 primary tumor (T) and 45 nodal metastasis (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF and CD31. The reactions were evaluated on qualitative and semi-quantitative scale. Generalized Linear Model (GLM) and Cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Result(s)* Mismatch repair proteins (MMR), ER, PR and HER2/neu were excluded from data analysis because of homogeneous expression in all samples. Group A: the p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs 6.2%, p = 0.04). Group B: PD-L1-positive and high EGFR expression were found respectively in 77.1% and 97.9% patients, (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups tumoral immune infiltration (CD3 expression), was mainly moderate/intense (80% vs. 95%). VEGF showed strong/moderate-diffuse expression in 13.9% of T samples. CD31 was used to study tumoral micro vessel density (MVD) with no difference between Group A and Group B. p53 and PD-L1 showed a significant association with nodal metastasis. Odds ratio (OR) for p53 mutation was 4.26 (CI 95% = 1.14 – 15.87, p = 0.03); OR for PD-L1 positivity was 2.68 (CI 95% = 1.0 – 7.19, p The cluster analysis identified 3 and 4 sub-groups of molecular profiles respectively in Group A and B, with no different prognosis. Moreover, the molecular profile of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusion* These results support a potential role of immune checkpoint inhibitors and anti-EGFR drugs in a subset of patients with VSCC, especially with worse prognosis (metastatic, HPV-independent). It is mandatory to repeat the panel in the metastatic site to identify changes of marker expression.

Introduction/Background* Sentinel node biopsy (SNB) is the standard of care for vulvar cancer patients clinically N0 (cN0) at preoperative assessment, with unifocal primary tumor, Methodology According to the Grosnapet study design, lymph node status was assessed by pre-operative PET/CT scan and cN0 patients were enrolled on the base of the following criteria: a) Tumor > 4 cm, b) Multifocal tumors, c) previous complete excision; d) contralateral nodal involvement, e) previous RTCT treatment or f) vulvar recurrence. Vulvar surgery was performed according to current recommendations, as appropriate. Sentinel lymph node was detected by radiotracer and blue dye to reach the maximum detection rate. Radical lymphadenectomy was always provided after SNB, according to the standard of care. Both PET/CT scan and SNB were compared to final pathology report. Patients were followed up quarterly, undergoing clinical visit, groin ultrasound and PET/CT scan. Result(s)* During the study period, 72 patients were considered eligible for a total of 111 groins included. Median patient’s age was 73yrs. Histopathology revealed 16 (14.4%) groins with metastatic sentinel nodes (SLNs). Only one case had further involved non SLNs. Overall, 18/274 (6.5%) SLN excised were positive at histology. Median metastasis diameter was 4.8 (1.5-12). One false negative SN was identified (NPV 99%). PET/CT showed an NPV of 92%. After a median follow-up of 38 months (range 1-97 months), 19 recurrences and 6 deaths were registered. The 3-year disease-free survival (DFS) was 72.6%. Conclusion* This is the largest series that strongly support the use of SNB in cN0 patients currently excluded. A careful preoperative study could safely select eligible patients. Further validation is advisable.

Introduction/Background* There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from those infiltrated by cancer or lymphoma. Methodology The Vulvar International Tumor Analysis (VITA) collaborative group was established involving gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The steering committee for the study held special meeting to discuss the problems of standardization and to formulate terms and procedures to derive morphologic end-points by B-mode imaging and end-point of vascularity and blood flow by color Doppler imaging. The recommendations of the steering committee were distributed to each participating center and subsequently refined. The following consensus is going to be tested in international multicentric interobserver and diagnostic accuracy studies. Result(s)* We present a consensus of international multidisciplinary VITA group on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature is not limited to inguinal lymph nodes as part of vulvar cancer staging; it can be used for the assessment of peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes. Conclusion* VITA terms and definitions were developed as a basis for international standardization of lymph node assessment by ultrasound and lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes.

Introduction:Ovarian cancer is the leading cause of death among gynecological malignancies. Its usual clinical manifestation is at advanced stages, with nutritional impairment, weight loss, and a consequent decline in skeletal muscle mass and strength (defined as sarcopenia). The relationship between sarcopenia and decreased survival was demonstrated not only in ovarian cancer but also in other cancer types, such as hepatocellular, pancreatic, lung, colon, cervical, metastatic breast, and renal cancer. The aim of this study is to review the current evidence regarding the relationship between sarcopenia and the surgical and oncological outcomes in ovarian cancer patients.Methods:The systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) statement. The terms “SARCOPENIA” AND “OVARIAN CANCER” were systematically used to search PubMed and Scopus databases. Original reports in English language were identified, with the purpose to include all relevant papers regarding the role of sarcopenia and indicators of skeletal muscle quality assessment in gynecological ovarian cancer.Results:A total of 9 studies were considered eligible for the present review. The strength of recommendation was moderate and the level of evidence was low in all selected articles. No prospective studies were conducted and most of the papers were case-control series comparing ovarian cancer sarcopenic population vs. non sarcopenic population.Conclusion:Sarcopenia appears to have an important role in oncological outcomes of ovarian cancer patients. However, sarcopenia occurrence during disease history and mechanisms underlying the possible impairment in prognosis should be better investigated. Prospective trials are awaited in order to obtain a better insight in this topic.

Objective To evaluate the feasibility of fusion of ultrasound imaging and three-dimensional (3D) single-photon-emission computed tomography/computed tomography (SPECT/CT) in detecting sentinel lymph nodes in women with vulvar cancer. Methods This was a prospective pilot single-center study. Patients with vulvar cancer who were candidates for sentinel lymph-node biopsy were enrolled between December 2018 and February 2019. Fusion imaging virtual navigation using 3D SPECT/CT and ultrasound was performed to investigate the tumor-draining lymph node. All clinical, imaging, surgical and histological information was collected prospectively and entered into a dedicated Excel file. Feasibility and success of fusion imaging virtual navigation and time needed to perform the three steps of fusion imaging were evaluated. Results Ten lymph-node sites were evaluated in five consecutive women with a histological diagnosis of vulvar cancer. Fusion imaging virtual navigation was feasible and completed successfully for all (10/10) draining sites. Median overall time to perform fusion imaging was 32 (range, 25-40) min and the time decreased from the first to the last examination. Conclusions The present study demonstrated that fusion imaging virtual navigation using 3D SPECT/CT and ultrasound is feasible and able to detect sentinel lymph nodes in women with vulvar carcinoma. Fusion imaging using ultrasound for detection of sentinel lymph nodes opens up multiple diagnostic and therapeutic opportunities in gynecological oncology. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Background The superficial circumflex iliac perforator (SCIP) flap has many ideal features, such as fast dissection, possibility to harvest thin, pliable, wide skin island, and concealed donor site scar. In spite of these features, its use was limited because of the wide anatomical variation of the pedicle, which is relatively shorter and has a smaller caliber than other more popular perforator flaps. Several names were given to the branches and perforators in the literature, thus adding confusion to the understanding of its anatomy. Methods We performed a surgical and a radioanatomical study of the SCIP pedicles analyzing high-resolution contrast-enhanced computed tomography (CT) scan of 95 groins, with particular attention to the deep branch (DB) of the superficial circumflex iliac artery (SCIA). Twenty-three of these patients were also studied by detecting the surgical anatomy during SCIP flap harvest. We employed a system of coordinates based on the line between pubic tubercle (PT) and anterior superior iliac spine (ASIS) to describe the position of the perforator of the DB. Results We found a 100% correlation between surgical and radiological findings. The length of the DB from the origin to the point in which its perforator pierced the sartorius fascia ranged from 1.6 to 6.5 cm, mean = 3.62 ± 0.92 cm. The distance between the origin of the DB and the inguinal ligament ranged from 1.1 to 7.5 cm, mean = 2.8 ± 1 cm. The perforator of the DB could be found in 91% of the cases within a box of 4 cm × 3 cm drawn caudally to the line joining the PT with the ASIS. This vessel can show a vertical or horizontal course in the subcutaneous layer. Conclusion Our findings confirm other previous studies and add new information about the position and the course of the perforator of the DB of the SCIA. Important features of the SCIP pedicles can be investigated by the color Doppler ultrasound and CT scan.

To investigate the expression of biological markers in primary vulvar Paget’s disease (VPD). Forty-one patients referred to a single major Center for Gynecologic Oncology from January 2008 to June 2018 were enrolled retrospectively: 30 non-invasive-VPD and 11 invasive-VPD. A total number of 60 samples, from all the 41 vulvar sites (VS), 8 metastatic lymph node sites (MLS) and 11 successive recurrent disease in vulvar site (RVS), were tested for an immunohistochemical panel, including the following markers: PD-L1, CD3, MSH2, MSH6, MLH1, PMS2, HER2/neu, EGFR, p16, p53, Ki67, ER, PR, AR, VEGF and CD31. We found a positive PD-L1 in 10% of non-invasive-VPD and 27% of invasive-VPD (18% VS; 38% MLS). ER and AR were expressed respectively in more than 70% and 75% of all specimens. HER2/neu amplification was found in 21% of non-invasive-VPD and 45% of invasive-VPD (40% VS; 38% MLS). A machine learning cluster analysis identified three groups among non- invasive-VPD: cluster-1 with higher median ER expression (40%); cluster-3 with more frequent HER2/neu overexpression (46%). Among invasive-VPD, two clusters were found: the second with more frequent HER2/neu overexpression (67% vs. 0%) and nodal metastases (100% vs. 25%). Repeating the IHC panel on the correspondent MLS and RVS, it significantly changed, respectively, in 50% and 27%. This study reveals the expression of PDL-1 and ER and confirms the expression of HER2/AR in VPD; new bases are provided to design multicenter clinical trials on personalized target therapies.

Objective To evaluate the feasibility and clinical application of fusion imaging with virtual navigation, combining 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) with real-time ultrasound imaging, in assessing superficial lymph nodes in breast-cancer and gynecological-cancer patients. Methods This was a pilot study of breast- and gynecological-cancer patients with abnormal uptake of 18 F-FDG by axillary or groin lymph nodes on PET/CT scan, examined at our institution between January 2017 and May 2019. Fusion imaging was performed, uploading preacquired PET/CT DICOM images onto the ultrasound machine and synchronizing them with real-time ultrasound scanning performed at the lymph-node site. In the first phase, we assessed the feasibility and reliability of fusion imaging in a series of 10 patients with suspicious lymph nodes on both PET/CT and ultrasound, and with full correspondence between both techniques in terms of size, shape and morphology of the lymph nodes (Group A). In the second phase, we included 20 patients with non-corresponding findings between PET/CT and ultrasound: 10 patients with lymph nodes that were suspicious or pathological on PET/CT scan but not suspicious on ultrasound assessment (Group B), and 10 patients with suspicious or pathological lymph nodes on both PET/CT and ultrasound but with no correspondence between the two techniques in terms of number of affected lymph nodes (Group C). Results In the 30 selected patients, fusion imaging was assessed at 30 lymph-node sites (22 inguinal and eight axillary nodes). In the first phase (Group A), the fusion technique was shown to be feasible in all 10 lymph-node sites evaluated. In the second phase, fusion imaging was completed successfully in nine of 10 cases in Group B and in all 10 cases in Group C. In all groups, fusion imaging was able to identify the target lymph node, guiding the examiner to perform a core-needle aspiration biopsy or to inject radiotracer for selective surgical nodal excision, according to the radio-guided occult lesion localization technique. Conclusion Fusion imaging with virtual navigation, combining PET/CT and real-time ultrasound imaging, is technically feasible and able to detect target lymph nodes even when PET/CT and ultrasound findings are inconsistent. Fusion imaging can also be used to guide the performance of core-needle aspiration biopsy, avoiding further surgical diagnostic procedures, or the injection of radiotracer for selective surgical nodal excision, enabling more sparing, selective surgery. This innovative technique could open up multiple diagnostic and therapeutic opportunities in breast and gynecological oncology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Introduction Sentinel node biopsy (SNB) is the standard of care in women with breast cancer (BC) and clinically non suspicious axillary lymph nodes (LNs), due to its high negative predictive value (NPV) in the assessment of nodal status. SNB has significantly reduced complications related to the axillary lymph node dissection, such as lymphedema and upper limb dysfunction. Evidence acquisition The gold standard technique for SNB is the blue dye (BD) and technetium labelled nanocolloid (Tc-99m) double technique. However, nuclear medicine is not available in all Institutions and several new tracers and devices have been proposed, such as indocyanine green (ICG) and superparamagnetic iron oxides (SPIO). All these techniques show an accuracy and detection rate not inferior to that of the standard technique, with different specific pros and cons. The choice of how to perform a SNB primarily depends on the surgeon's confidence with the procedure, the availability of nuclear medicine and the economic resources of the Institutions. In this setting, new tracers, hybrid tracers and imaging techniques are being evaluated in order to improve the detection rate of sentinel lymph nodes (SNs) and minimize the number of unnecessary axillary surgeries through an accurate preoperative assessment of nodal status and to guide new minimally invasive diagnostic procedures of SNs. In particular, the contrast-enhanced ultrasound (CEUS) is an active field of research but cannot be recommended for clinical use at this time. Evidence synthesis The ICG fluorescence technique was superior in terms of DR, as well as having the lowest FNR. The DR descending order was SPIO, Tc, dual modality (Tc/BD), CEUS and BD. Conclusions This paper is a narrative review of the most common SNB techniques in BC with a focus on recent innovations.

Axillary lymph node metastases of occult breast cancer (CUPAx) is an unusual condition that represents both a diagnostic and therapeutic challenge. The first steps in the diagnostic work-up of patients with CUPAx are the histological analysis of the lymph node metastasis and the execution of basic breast diagnostic imaging (mammography and ultrasound). In the case of occult breast cancer, breast Magnetic Resonance (MR) must be performed. Breast MR identifies a suspicious lesion in many patients and second-look ultrasound detects a corresponding ultrasound alteration in about half of cases, allowing the performance of a US-guided biopsy. In the case of an MR-only lesion, MR-guided biopsy is mandatory. We present a case of CUPAx in which contrast-enhanced spectral mammography (CESM) is used to help the detection of occult breast cancer and to guide stereotactic vacuum breast biopsy (VABB). CESM is a new breast imaging technique that is proving to have good performance in breast cancer detection and that is showing potential in the identification of occult breast cancer in a CUPAx setting. The use of an innovative and personalized breast imaging approach in breast cancer patients improves diagnostic possibilities and promises to become the focus in decision strategies.

Simple Summary Locally advanced vulvar cancer (LAVC) requires a multidisciplinary management. The aim of this paper is to conduct a review of all relevant studies regarding the role of radiotherapy in LAVC. Based on the available evidence, radiotherapy, with or without concurrent chemotherapy, has a relevant role in neoadjuvant, adjuvant or exclusive treatments. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, in view of a better treatment personalization. Abstract Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients’ age and comorbidities, in view of a better treatment personalization.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Aim The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging. Patients and methods PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated. Results Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively. Conclusions Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one.

Introduction The aim of this study is to revise the experience of two reference centers for vulvar cancer treatment during the last 2 years, evaluating the ECT procedure in terms of clinical outcome and side effects profile. Methods Data were retrospectively collected from November 2017 to November 2019 in two Italian oncologic Institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli. ECT was offered in a palliative setting to patients with a primary or recurrent vulvar cancer diagnosis unsuitable for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anaesthesia. Intravenous Bleomycin was administered. Follow-up examinations were performed at 1, 3 and 6 months. Results 15 patients were included in the study. No intra-procedure complications occurred. 1 patient had pneumonia during post-operative stay. 1-month overall response rate (2 CR and 10 PR) was 80%. At 3-month follow-up, 3 patients (20%) showed PD, 3 patients (20%) died from the ongoing disease, 1 patients (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. 8 out of 13 patients (61.5%) were alive at 6-month follow-up, whereas 6 out of 12 patients (50%) were alive at 1-year follow-up. Conclusion ECT has proven to be a feasible, easy to perform, reproducible and repeatable procedure. For these reasons, it may have a role in the management of VC, especially as palliative treatment when other therapies are no longer applicable.

Purpose This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.

ObjectiveUltrasound examination represents the most important diagnostic method to preoperatively assess gynecological diseases. However, the ultrasound characteristics of vaginal pathologies are poorly investigated. The aim of this study was to describe the clinical and ultrasound characteristics of vaginal lesions detected at ultrasound.MethodsThis was a single center, prospective, observational study including patients with vaginal masses examined from January 2017 to May 2019. Morphologic sonographic characteristics of the lesions were described as unilocular, multilocular, unilocular-solid, multilocular-solid, and solid. For the analysis, patients were grouped into a 'malignant group', including patients with confirmed malignancy at final histology, and a 'benign group', including patients with a confirmed benign pathology at final histology and patients without a histological diagnosis but with a lesion that manifested no changes during follow-up.Results44 patients were enrolled. 22 (50%) of 44 lesions were benign: 12 (54.5%) of these underwent ultrasound follow-up and did not show any changes at the 12 month follow-up whereas 10 (45.5%) lesions had surgical excision which confirmed the benign nature. The remaining 22 (50%) of 44 lesions underwent surgery because of suspicion of malignancy: histology confirmed a malignancy in 20 (90.9%) of 22 cases. Benign lesions were described as follow: 11/24 (45.8%) unilocular, 3/24 (12.5%) multilocular with two locules, and 10/24 (41.7%) solid lesions. Malignant lesions were solid in 19/20 (95%) cases and multilocular-solid in 1/20 (5%). Most benign lesions had a color score of 1–2 (20/24, 83.4%) while malignant lesions had a color score of 3–4 (18/20, 90%).ConclusionA typical ultrasound image of a benign lesion was a unilocular cyst or hypoechoic solid mass with no or minimal vascularization on color Doppler examination. Malignant vaginal lesions were hypoechoic solid tumors with irregular margins and moderate/rich vascularization or multilocular-solid. Ultrasound should be used to supplement the clinician in the management of vaginal lesions.

The diagnosis of breast cancer (BC) during pregnancy is uncommon. It has varied among different studies from 1:10,000 to 1:3000 of all pregnancies, with a median age of 33 years. Pregnancy-associated BC represents a challenge in terms of clinical management to guarantee both maternal and fetal security in choosing the right treatment. This situation is complex and requires a multidisciplinary approach, including the surgeon, anesthesiologist, oncologist, radiotherapist, psychologist, and maternal-fetal medicine specialist. In the present review, we examined the management of pregnancy-associated BC, focusing on pathophysiologic background, risk factors, diagnosis, staging procedures, anesthesia, surgical management, and systemic treatment.

Introduction. Elderly patients are underrepresented from a majority of clinical trials and the choice of the best treatment becomes a challenge. The optimal treatment should be personalized and based on a multidisciplinary approach that includes radiation oncologists, surgeons, geriatricians, medical oncologists, social workers, and support services. The global evaluation of the patients and the creation of nomograms may facilitate the definition of long-term treatment benefits minimizing the use of unnecessary therapy. Material and Method. A systematic research using PubMed, Scopus, and Cochrane library was performed to identify full articles analyzing the efficacy of APBI in elderly patients with breast cancer. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results. Seven papers fulfilled the eligibility criteria. The number of evaluated patients was 405 and the median age was 77.7 years. The disease-free survival (DFS) range was 96.1%–100%, the grade 3-4 toxicity range was 0%–6.6%, the cancer-specific survival (CSS) range was 97.9%–100%, and the overall survival (OS) range was 87%–100%. All studies reported excellent/good cosmetic results in a range of 74% to 99%. Conclusion. Accelerated partial breast irradiation (APBI) results in a safe and effective substitute for the adjuvant external beam radiotherapy in selected elderly early-stage breast cancer patients. Based on the relatively low toxicity, APBI should be advised in selected patients with life expectancies larger than 5–10 years.

ObjectiveSince vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer.MethodsData were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer.ResultsA total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3–42) and median operative time was 13 (range 7–20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up.ConclusionsElectrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

Introduction Nipple-sparing mastectomy (NSM) has known an exponential diffusion worldwide for prophilaxis and therapeutic mastectomies in selected candidates, being oncologically safe and improving reconstructive outcomes and patients' satisfaction. The two most common used skin incisions are the radial and inframammary fold ones, which represent an imperfect aesthetic solution. The aim of this work was to give insights on our surgical technique, which allows to perform the NSM, node surgery, and endoscopic direct-to-implant reconstruction using a cosmetic axillary incision. Materials and methods Between June 2016 and January 2019, 7 consecutive patients underwent NSM, lymph node surgery and endoscopic direct-to-implant reconstruction using a small cosmetic axillary incision for breast cancer treatment in a single Institution. An operative rigid endoscope with working channel (Richard Wolf) was used to dissect the entire submuscular-subfascial pocket. The mean age of the patients was 42.8 years old (range: 36-49 years). The evaluation methods were clinical and photography-based assessments, as well as the BREAST-Q which was used to quantify patient satisfaction. Results The average follow-up time was 9 months (range 3-22 months). Tumor-free margins were obtained in all cases. No tumor recurrence or metastasis occurred during follow-up. No major complications were experienced. There were no cases of malposition, wrinkling, or rippling. All patients were satisfied with their esthetic results, especially the absence of visible scars. Conclusions From our preliminary experience, NSM combined with endoscopic immediate reconstruction via axillary incision for breast cancer treatment seems to be a promising new procedure in cup A and B breasts alternative to the conventional techniques, as it allowed to have safe and pleasant aesthetic and oncologic outcomes.

IntroductionMultidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board.MethodsCoupling surgical and oncological international guidelines with “case-by-case” discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale.ResultsThe analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18–87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6–72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxicities occurred.DiscussionThe outcomes of this series support the benefit of a multidisciplinary personalized approach in the management of vulvar cancer.

Nowadays, the overall attention is focused on de-escalating treatments for breast cancer (BC) including surgery, radiotherapy and chemotherapy. The introduction of sentinel lymph node biopsy (SLNB) has led to less invasive surgical approaches for accurately staging the axilla, with axillary lymph node dissection (ALND) progressively confined to a limited group of patients. One of the goal of surgery in de-escalating approaches is to reduce surgical morbidity by restricting or avoiding axillary surgery with no effect on survival. In this context the importance of imaging study for preoperative identification of axillary metastasis, in order to reduce axillary surgery, is gradually improving while the role of intraoperative assessment of sentinel nodes is progressively becoming limited to restricted groups of patients. According to the results of the ACOSOG Z0011 and following the most important guidelines, ALND can be safely omitted in selected patients treated with breast conserving surgery (BCS) with one or two positive SLNB while the adoption of SLNB positive alone in patients undergoing mastectomy is not yet defined. The increased employment of neoadjuvant chemotherapy (NAC) and the use of SLNB in patients after NAC plays an important role in de-escalation of axillary surgery in this group of patients. However current studies on this topic are still controversial, mainly about clinically positive lymph nodes (cN+) pre NAC patients or how to manage positive SLNB in post NAC patients. Some authors have collected predictive factors of positive non sentinel lymph nodes (NSLNs) in nomograms, considered an useful tool to avoid unnecessary further surgery. Elderly women represent specific group of patients where the axillary approach needs to be properly resized. The management of axilla in BC is in continuous evolution and ongoing studies could make even SLNB useless in the next future.

Ductal carcinoma in situ (DCIS) represents a disease that includes different risk categories and does not necessarily turn into invasive cancer. The 20% of all newly diagnosed breast cancers consist in DCIS, with an incidence increased due to the widespread diffusion of screening programs. Once upon a time, mastectomy was considered the gold standard in treatment of DCIS, but over the years, breast-conserving surgery (BCS) has been included as the treatment of choice for patients with small lesions. Several randomized trials demonstrated that adjuvant treatment as radiation and ET reduce the risk of local recurrence, including invasive recurrences. Therefore, in patients with DCIS susceptible to conservative surgery, the key decision for management is represented by the addition of radiotherapy (RT) or ET. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring therapies to the individual, with the goal of optimizing the balance of risks and benefits. From the observation of the first data showing how such treatments are not clearly associated with an improvement in disease specific mortality, the upcoming hypothesis is to consider omitting some of such treatments or to plan close surveillance for low risk lesions. Prospective studies on women treated with BCS alone have identified low risk lesions. Actually, the main challenge is how to recognize cases that will not progress to invasive lesions. Despite all the studies carried out and the many available data, there are no unique and universally accepted treatment criteria, so some issues of controversy are still open.

Pathogenic mutations in two autosomal dominant genes, BRCA1 and BRCA2 , with high penetrance are supposed to be the cause for an approximated 5–7% risk of all breast cancer (BC) and ovarian cancer (OC). Compared to sporadic BC, BRCA mutated ( BRCAmut ) BC differs for lifetime risk of onset and sensitivity to systemic therapies. A hereditary BC syndrome should be taken into account when there are numerous relatives with BC early-onset (typically before menopause). Moreover, BRCAmut carriers showed a lifetime possibility of manifesting OC. When a BC diagnosis is made in young patients or in suspicious personal relatives’ anamnesis, be aware of being carriers of a BRCA mutation may influence the decision making-process about surgical procedure and prevention strategies. In this review, we examined surgical treatment choice for BRCAmut BC, risk of ipsilateral breast recurrence (IBR) and contralateral breast cancer (CBC). We examined the role of breast-conserving therapy (BCT), risk-reducing mastectomy (RRM) and preventive risk-reducing salpingo-oophorectomy (RRSO) with a special consideration about advantage in terms of mortality reduction for both conservative and prophylactic measures. We also reviewed the sensitivity of mutated BC to platinum-based antineoplastic drugs and poly (ADP-ribose) polymerase inhibitors (PARPi) by emphasizing the results of clinical trials recently published.

Background: Worldwide, breast cancer (BC) is the most common malignancy in the female population. In recent years, its diagnosis in young women has increased, together with a growing desire to become pregnant later in life. Although there is evidence about the detrimental effect of chemotherapy (CT) on the menses cycle, a practical tool to measure ovarian reserve is still missing. Recently, anti-Mullerian hormone (AMH) has been considered a good surrogate for ovarian reserve. The main objective of this paper is to evaluate the effect of CT on AMH value. Methods: A systematic review and meta-analysis were conducted on the PubMed and Scopus electronic databases on articles retrieved from inception until February 2021. Trials evaluating ovarian reserves before and after CT in BC were included. We excluded case reports, case-series with fewer than ten patients, reviews (narrative or systematic), communications and perspectives. Studies in languages other than English or with polycystic ovarian syndrome (PCOS) patients were also excluded. AMH reduction was the main endpoint. Egger’s and Begg’s tests were used to assess the risk of publication bias. Results: Eighteen trials were included from the 833 examined. A statistically significant decline in serum AMH concentration was found after CT, persisting even after years, with an overall reduction of −1.97 (95% CI: −3.12, −0.82). No significant differences in ovarian reserve loss were found in the BRCA1/2 mutation carriers compared to wild-type patients. Conclusions: Although this study has some limitations, including publication bias, failure to stratify the results by some important factors and low to medium quality of the studies included, this metanalysis demonstrates that the level of AMH markedly falls after CT in BC patients, corresponding to a reduction in ovarian reserve. These findings should be routinely discussed during oncofertility counseling and used to guide fertility preservation choices in young women before starting treatment.

To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1-10 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no gross residual disease (NGR) at interval debulking surgery (IDS).Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1-10 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed.207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p 0.0001 respectively). After a median follow up of 56.4 months (range 59.2-65.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022).IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications.

Introduction Ovarian cancer is the seventh most common cancer among women in the developed world, and most women with ovarian cancer are diagnosed at an advanced stage of disease, when large intraperitoneal dissemination has already occurred. An accurate preoperative assessment of the tumor dissemination is pivotal for adequate counseling among risks and benefits of an aggressive surgical procedure, often required to achieve a complete cytoreduction. When performed by an experienced sonographer, ultrasound has an invaluable role in the primary diagnosis of gynecological cancer, in the assessment of tumor extent in the pelvis and abdominal cavity; however, there is a paucity of data on its use in the evaluation of the extent of disease of such patients. Evidence acquisition The search retrieved 208 articles in the best matching results list. Selection by abstract and full-text, yielded 15 publications that contained information on the role of ultrasound examination in the assessment of diffused peritoneal malignancies. Evidence synthesis Sonographic appearance of metastatic nodules in peritoneum and omentum were firstly analyzed in preliminar descriptive studies, together with a systematic method to scan the abdomen and pelvis in in the staging of diffused gynecological malignancies. To date, three prospective studies mainly focused on the specific role of ultrasound (without comparison with other imaging modalities) in the evaluation of intra-abdominal tumor extension in ovarian cancer patients. In these studies, authors were in agreement to conclude that ultrasound has a very reliable role in the staging of ovarian cancer. In particular, ultrasound examination showed a high sensitivity (range 81.4-91%) and specificity (range 88-96%) in the diagnosis of peritoneal carcinomatosis, as well as in omental involvement (sense 67-94%, specificity 90%). In a recent prospective study ultrasound shows similar accuracy of CT scan in the staging of ovarian cancer patients (71% vs. 75%) when compared with surgical results. Conclusions Even if ultrasound is a largely diffuse and practice imaging technique, there is a paucity of data in literature on its use in the evaluation of the extent of disease in ovarian cancer patiens. Nevertheless, this review has demonstrated that ultrasound has a high accuracy in staging advanced ovarian cancer patients. In certain settings, ultrasound has already replaced CT scan in the pre-operative evaluation of pelvic and abdominal disease. Finally, ultrasound allows to perform a biopsy in patients with peritoneal carcinomatosis obtaining an adequate specimen for histologic diagnosis.

Objective To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer. Methods This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status. Results Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) length of the dominant LN (cut-off, 8.4 mm; sensitivity, 63.9%; specificity, 90.6%); C/medulla (M) thickness ratio of the dominant LN (cut-off, 1.2 mm; sensitivity, 70.4%; specificity, 91.5%), the combination of S length and C/M thickness ratio (sensitivity, 88.9%; specificity, 82.4%); and the FOA analysis (sensitivity, 85.9%; specificity, 84.2%). Conclusions Preoperative ultrasound assessment, with or without the addition of cytology, has a high accuracy in assessing inguinal LN status in patients with vulvar cancer. In particular, the combination of two ultrasound parameters (S length and C/M thickness ratio) provided the greatest accuracy in discriminating between negative and positive LNs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

This study investigated whether radiomic features derived from preoperative PET images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included if they had a unifocal primary cancer at least 2.6 cm in diameter, received a preoperative 18F-FDG PET/CT scan followed by surgery, and had at least 6 mo of follow-up data. 18F-FDG PET images were analyzed by semiautomatically drawing a volume of interest on the primary tumor in each PET image, followed by extraction of 83 radiomic features. Unique radiomic features were identified by principal-component analysis (PCA), after which they were compared with histopathology using nonpairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan–Meier method. Results: Forty women were included. PCA revealed 4 unique radiomic features, which were not associated with histopathologic characteristics such as grade, depth of invasion, lymph-vascular space invasion, and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran’s I, a feature that identifies global spatial autocorrelation, correlated with OS (P = 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran’s I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran’s I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings.

Purpose This review was to focus on breast brachytherapy cosmetic assessment methods state of the art and to define the advantages and disadvantages related to. Methods and Materials We conducted a literature review of the major experience on breast brachytherapy cosmetic assessment methods in several databases (PubMed, Scopus, and Google Scholar databases). To identify the relevant works, a task force screened citations at title and abstract level to identify potentially relevant paper. An expert board reviewed and approved the text. The assessment systems were classified into three main groups: ( 1 ) the Oncological Toxicity Scales, ( 2 ) the Independent Patients Perspective Measures, ( 3 ) the Patient-Related Outcome Measures. Each cosmetic assessment method was evaluated following six parameters: ( 1 ) anatomical site, ( 2 ) advantages, ( 3 ) disadvantages, ( 4 ) subjective/objective, ( 5 ) quantitative/qualitative, ( 6 ) computers or pictures needs. Results Eleven assessment methods were selected. Three methods were classified as Oncological Toxicity Scale, six in the Independent Patients Perspective Measures classification, and two as Patient-Related Outcome Measures. Six methods are subjective, while eight are objective. Four systems are classified as quantitative, four as qualitative while three both. Five systems need informatics support. Moreover, each method was discussed individually reporting the main characteristics and peculiarities. Conclusions Cosmesis is one major end point for the patient who has a malignancy of low lethal potential. In modern personalized medicine, there is a need for standardized cosmetic outcome assessments to analyze and compare the results of treatments. No gold standard methods currently exist. The result of this review is to summarize the various cosmesis methods, defining the strengths and weaknesses of each one and giving a line in research and clinical practice.

BACKGROUND Lymph node metastases represent the most important negative prognostic predictor in vulvar carcinoma. Therefore, an accurate preoperative assessment of suspicious lymph nodes would be fundamental for a personalized therapy. The aim of this article was to assess the reliability of ultrasound-guided fine-needle aspiration cytology (FNAC) in the preoperative assessment of nodal metastatic disease in 43 patients with vulvar cancer. METHODS In total, 43 FNAC specimens of clinicoradiologically suspicious lymph nodes with corresponding nodal resection specimens were collected from 2016 to 2018 at Catholic University Hospital in Rome. Cytohistologic correlation was performed. Patients were treated with wide local excision of the vulvar mass followed by bilateral inguinofemoral lymphadenectomy and radiotherapy if the tumor involved a lymph node or the vulvar margins. RESULTS Cytologic examination agreed with histology in 37 of 43 cases (86.04%). The authors observed a positive FNAC result in 14 of 20 histologically confirmed metastatic lymph nodes, 6 false-negative cases, and no false-positive results. The sensitivity and specificity of cytological examination were 76.92% and 100%, respectively. All patients with FNAC-positive results showed metastatic disease in other surgically resected inguinofemoral nodes. Eleven of 29 patients (37.9%) with FNAC-negative results also showed metastatic disease in subsequent lymphadenectomy specimens, but the extent of metastases was always

Objective Ablative surgery for vulvar cancer can involve the resection of perineum, vagina, urethra, groins, mons pubis, and abdominal wall creating complex defects. In our opinion, ALT flap is an ideal flap for reconstruction, because of low incidence of complications, long pedicle outside the radiotherapy field, capability of carrying fascia and muscle, possibility of sensate reconstruction, and low donor site morbidity. The purpose of this report is to describe our experience with ALT flap for reconstruction after vulvar cancer extirpative surgery, discussing our indications for complex defects and focusing on its versatility. Patients and Methods We performed a retrospective review of 15 cases of complex postoncologic gynecological wounds, reconstructed with 16 pedicled ALT flap, after vulvar cancer ablative surgery between 2014 and 2016. Age of the patients ranged from 44 to 77, with mean age of 62.6. Postoperative outcomes were evaluated. Results The flap size ranged from 12 × 8 cm to 22 × 15 cm., in two cases we harvested vastus lateralis to fill the dead space after pelvic exenteration. In nine flaps, we could include only 1 perforator, in 7 we could use two, 5 were septocutaneous and 18 myocutaneous with a pedicle length ranging from9cm.to15cm.We had no flap necrosis.3 flaps showed dehiscence of a part of the wound that healed by dressings. In one case of obese patient the donor site showed partial wound edge necrosis, and required secondary grafting. During follow-up that ranged from 1 month to 2 years, cancer relapsed locally in 5 patients. Global performance and specific pain improved after surgery. Conclusion ALT flap should be included in the first line options for reconstructions of complex defects resulting from vulvar cancer surgery because of its reliability and versatility. © 2016 Wiley Periodicals, Inc. Microsurgery, 2016.

Background. Extra-mammary Paget’s disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). Methods. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. Results. A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression’s rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. Conclusions. This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD.

Objective The study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative 18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients. Methods From July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology. Results Forty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%. Conclusions Our data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB.

OBJECTIVE Groin dissection is the procedure with the highest risk of lower limb lymphedema.As lymph stasis causes irreversible alterations to the limb over time,therapies should be administered in early stages,or better yet, lymphatic drainage impairment should be prevented.We developed a new preventive approach to lymphedema after groin dissection, and we report our preliminary experience. PATIENTS AND METHODS We enrolled 5 patients undergoing bilateral groin dissection for vulvar cancer. Preoperative study of lower limbs lymphatic function was obtained by lymphoscintigraphy, with lymphatic transport index, indocyanine green (ICG) lymphography, and volume measurement with lower extremity lymphedema (LEL) index calculation. At the end of lymphadenectomy, one groin was closed in the standard way. On the other side, a lymphatic flap pedicled on the distal perforator of the deep branch of the superficial circumflex iliac vessels, was transposed into the groin region. Lymphatic function examination of the limbs was repeated 6 months after surgery. RESULTS Before surgery no patient showed lymphatic drainage impairment at lymphoscintigraphy or lymphography, LEL index was in every limb lower than 250 (mean: 217.3 ± 13.83). After surgery the limbs treated with the flap showed no pathological swelling, LEL-index

This study aimed to assess the value of dual-timepoint 18F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18F-FDG LN uptake relative to background. Semiquantitative analysis included SUVmax and the corresponding retention index of SUVmax, measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18F-FDG PET/CT for an SUVmax cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUVmax cutoff of greater than 0. Conclusion: Standard 18F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation.

Objective To create a comprehensive algorithmic approach to reconstruction after vulvar cancer ablative surgery, which includes both traditional and perforator flaps, evaluating anatomical subunits and shape of the defect. Methods We retrospectively reviewed 80 cases of reconstruction after vulvar cancer ablative surgery, performed between June 2006 and January 2016, transferring 101 flaps. We registered the possibility to achieve the complete wound closure, even in presence of very complex defects, and the postoperative complications. On the basis of these experience, analyzing the choices made and considering the complications, we developed an algorithm to help with the selection of the flap in vulvoperineal reconstruction after oncologic ablative surgery for vulvar cancer. Results We employed eight types of different flaps, including 54 traditional fasciocutaneous V-Y flaps, 23 rectus abdominis myocutaneous flaps, 11 anterolateral thigh flaps, three V-Y gracilis myocutaneous flaps, three free style perforators V-Y flaps from the inner thigh, two Limberg flaps, two lotus flaps, two deep inferior epigastric artery perforator flap, and one superficial circumflex iliac artery perforator flap. The structures most frequently involved in resection were vulva, perineum, mons pubis, groins, vagina, urethra and, more rarely, rectum, bladder, and lower abdominal wall. Conclusion The algorithm we implemented can be a useful tool to help flap selection. The key points in the decision-making process are: anatomical subunits to be covered, overall shape and symmetry of the defect and some patient features such as skin laxity or previous radiotherapy. Perforator flaps, when feasible, must be considered standard in vulvoperineal reconstruction, although in some cases traditional flaps remain the best choice.

Background: In advanced ovarian cancer, maximal efforts have to be attemptedto achieve optimal cytoreduction, as this represents the keystone in the therapeutic management. This large, prospective study aims at investigating the role of computed tomography (CT) scan in predicting the feasibility of optimal cytoreduction in ovarian cancer. Methods: A total of 195 consecutive patients with clinical/radiographic suspicion of advanced ovarian/peritoneal cancer were enrolled at the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso, Italy. Preoperative CT scans were performed with a high-speed scanner (CT Hi Speed Nx/i Pro; 2-slice; GE Medical System). All patients underwent standard laparotomy, and maximal surgical effort was attempted. The following CT parameters were used: peritoneal thickening, peritoneal implants >2 cm, bowel mesentery involvement, omental cake, pelvic sidewall involvement and/or hydroureter, suprarenal aortic lymph nodes >1 cm, infrarenal aortic lymph nodes >2 cm, superficial liver metastases >2 cm and/or intraparenchimal liver metastases any size, large volume ascites (>500 ml). Clinical data included were age, Ca125 serum levels, and ECOG-PS. Radiographic and clinical features exhibiting a specificity >75%, a positive and negative predictive value >50%, an accuracy >60% in predicting surgical outcome were assigned a point value of 2. With this scoring system, a predictive index (PI) was calculated for each patient. Results: The PI scores ranged from 0 to 6, and from 0 to 8, in Model 1 (including only radiographic parameters) and in Model 2 (including radiographic and clinical data). The AUC was 0.78+0.035 in Model 1, and 0.81+0.031 in Model 2. Therefore, the addition of ECOG-PS data led to the improvement of the diagnostic performances (z=2.41, P-value

Endometriosis is a common gynecologic disease, which generally follows a benign course. Notwithstanding, several clinical and histologic studies as well as molecular data show that endometriosis could be a precursor of sporadic endometrioid and clear cell carcinomas at extrauterine loci. Several reports have implicated alterations of the hMLH1 and p16ink4a(p16) genes, in particular hypermethylation of the promoter region, and of the PTEN gene, principally genetic mutations, in endometrial and ovarian cancers and have indicated that these alterations are already present in precancer conditions. In this report, we analyzed the methylation status of hMLH1 and p16 and the protein expression of PTEN and hMLH1 in 46 cases of endometriosis stages III and IV to better define the possible involvement of these genes in the malignant transformation of endometriosis. We found abnormal methylation of hMLH1 in 4 of the 46 cases (8.6%). In addition, these cases had no detectable hMLH1 protein expression. Regarding patients with hMLH1 alterations, 2 were classified as stage IV and 2 showed coexistent endometriosis and carcinoma. Only 1 case of endometriosis (2.17%), classified as atypical, showed abnormal methylation of p16. Reduced PTEN protein expression was detected in 7 of 46 cases (15.21%): 5 were clinically classified as stage IV, and the other 2 presented both cancer and hypermethylated hMLH1. Our preliminary study suggests that reduced expression of both hMLH1 and PTEN may be involved in the malignant evolution of endometriosis and should be used as markers of neoplastic transformation in aggressive endometriosis with elevated tumor markers. © 2002 Wiley-Liss, Inc.

Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients. A total of 82 courses are evaluable, with a median number of three cycles administered per patient (range 2–8). GEM was administered on days 1 and 8 by 30-min intravenous infusion immediately after CAE given by 60-min intravenous infusion on day 1; cycles were repeated every 21 days. The starting doses were CAE 20 mg/m2 and GEM 600 mg/m2. Following dose levels were 20/800; 20/1,000; 30/800; 30/1,000; 35/800, and 35/1,000 for CAE and GEM, respectively. The MTD was reached at dose level 5, with febrile neutropenia and thrombocytopenia as dose-limiting toxicities. After the MTD, granulocyte-colony stimulating factor was administered in 15% of cycles. Non-hematological toxicity was mild and manageable. All patients are so far evaluable for response. Among them, 5 partial responses (21.7%; 95% confidence interval, CI: 4.9–38.5), 5 disease stabilizations (21.7%, 95% CI: 4.9–38.5) and 13 progressions (56.6%, 95% CI: 36.4–76.8) have been registered. These results warrant further research in a phase II study.

BACKGROUND:: The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. METHODS:: A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. RESULTS:: The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to O12,013, O13,232, and O15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8-6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient=O12.6). CONCLUSIONS:: This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.