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BackgroundCosts related to the care of melanoma patients have been rising over the past few years due to increased disease incidence as well as the introduction of innovative treatments. The aim of this study is to analyse CMM cost items based on stage at diagnosis, together with other diagnostic and prognostic characteristics of the melanoma.MethodsAnalyses were performed on 2,647 incident cases of invasive CMM that were registered in 2015 and 2017 in the Veneto Cancer Registry (RTV). Direct melanoma-related costs per patient were calculated for each year ranging from 2 years before diagnosis to 4 years after, and were stratified by cost items such as outpatient services, inpatient drug prescriptions, hospital admissions, hospice admissions, and emergency room treatment. Average yearly costs per patient were compared according to available clinical-pathological characteristics. Lastly, log-linear multivariable analysis was performed to investigate potential cost drivers among these clinical-pathological characteristics.FindingsOverall, the average direct costs related to melanoma are highest in the first year after diagnosis (€2,903) and then decrease over time. Hospitalization costs are 8 to 16 times higher in the first year than in subsequent years, while the costs of outpatient services and inpatient drugs decrease gradually over time. When stratified by stage it is observed that the higher expenditure associated with more advanced stages of CMM is mainly due to inpatient drug use.ConclusionThe results of the present study show that grouping patients according to tumour characteristics can improve our understanding of the different cost items associated with cutaneous malignant melanoma. CMM patients experience higher costs in the first year after diagnosis due to higher hospitalization and outpatient services. Policy makers should consider overall and stage-specific annual costs when allocating resources for the management of CMM patients.

Abstract Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965, a massive environmental contamination by PFAS has occurred in northeastern Italy. This study compared histopathology and prognosis between melanoma patients exposed (n = 194) and unexposed (n = 488) to PFAS. All patients were diagnosed and/or treated for melanoma at the Veneto Oncological Institute and the University Hospital of Padua (Italy) in 1998–2014. Patients were categorized in exposed or unexposed groups according to their home address and the geographical classification of municipalities affected by PFAS contamination as provided by Veneto Government in 2018. Presence of mitoses was found in 70.5% of exposed patients and 58.7% of unexposed patients (p = 0.005). Median follow-up was 90 months (IQR 59–136). 5-year overall survival was 83.7% in exposed patients and 88.0% in unexposed patients (p = 0.20); 5-year disease-specific survival was 88.0% in exposed patients and 90.9% in unexposed patients (p = 0.50); 5-year disease-free survival was 83.8% in exposed patients and 87.3% in unexposed patients (p = 0.20). Adjusting for imbalanced characteristics at baseline (presence of mitoses), survival was not statistically different between exposed and unexposed patients (overall survival: HR 1.10, 95% CI 0.77 to 1.58, p = 0.57; disease-specific survival: HR 0.99, 95% CI 0.62 to 1.59, p = 0.99; disease-free survival: HR 1.10, 95% CI 0.74 to 1.64, p = 0.62). Although the magnitude of PFAS exposure was not quantifiable, our findings suggested that exposure to PFAS was associated with higher level of mitosis in melanoma patients, but this did not translate into a survival difference. Further studies are required to investigate this relationship and all effects of PFAS on prognosis.

BackgroundSoft tissue sarcomas (STS) are rare malignancies which prognosis varies significantly by primary site, histological subtype, and tumor stage. Their low incidence, and the complexity of their clinico-pathological characteristics demand standardized, cancer-tailored diagnostics and therapies managed at high-volume, multidisciplinary care centers. This study evaluates the quality of STS management in north-east Italy (Veneto Region) through a list of ad hoc defined clinical indicators.MethodsThis population-based study concerns all incident cases of STS in 2018 (214 cases) recorded in the adult population censored by the Veneto’s regional Cancer Registry. Based on the international literature, a multidisciplinary working group of experts identified a set of indicators for monitoring the quality of diagnostic, therapeutic, and end-of-life clinical interventions. The quality of care was assessed by comparing the reference thresholds with the indicators’ values achieved in clinical practice.ResultsDiagnostic procedures showed poor adherence to the thresholds, with a low percentage of histological diagnoses validated by a second opinion. The indicators relating to the surgical treatment of superficial, small, low-grade STS, or of medium, high-grade STS of the head–neck, trunk, or limbs were consistent with the thresholds, while for intermediate, high-grade (large-sized, deep) and retroperitoneal STS they fell significantly below the thresholds.ConclusionA critical evaluation of the clinical indicators allowed to uncover the procedures needing corrective action. Monitoring clinical care indicators improves cancer care, confirms the importance of managing rare cancers at highly specialized, high-volume centers, and promotes the ethical sustainability of the healthcare system.

Clear Cell Sarcoma (CCS) of soft tissue is a rare and highly malignant neoplasm primarily affecting young adults, often presenting in the deep soft tissues of the extremities. Despite morphological and immunophenotypic similarities to melanoma, CCS arises from connective tissues and is characterized by a distinct genetic hallmark: the EWSR1-ATF1 fusion resulting from t(12;22)(q13;q12) translocation. This genetic signature is absent in melanoma, making molecular diagnosis essential for accurate differentiation. Additionally, recent evidence highlights the utility of PRAME as an immunohistochemical marker to distinguish CCS from melanoma and other neoplasms. Clinically, CCS commonly involves tendons and aponeuroses, with metastatic potential leading to poor prognoses despite optimal local disease management. Histologically, CCS features lobular growth, spindle-to-epithelioid cells with clear cytoplasm, and low mitotic activity, often necessitating a multimodal diagnostic approach incorporating histopathology, immunohistochemistry, and molecular testing. Therapeutically, wide surgical excision remains the cornerstone for localized disease, with sentinel lymph node biopsy aiding in staging. Adjuvant radiotherapy is considered in select cases, while chemotherapy has limited efficacy in metastatic settings. Emerging treatments, including targeted therapies focusing on EWSR1-ATF1-driven pathways and immune checkpoint inhibitors, offer hope for improved outcomes. This review synthesizes current knowledge on CCS, emphasizing diagnostic challenges, the role of PRAME, and advancements in therapeutic strategies to enhance patient care. [ABSTRACT FROM AUTHOR]

Simple Summary: Nevoid melanoma is a rare melanoma subtype that closely resembles a common nevus clinically and histologically. For this reason, diagnosis is easily missed. Both dermatologists and pathologists should be aware of this entity since its recognition might avoid severe consequences for the patient and medicolegal issues. Only a few papers on clinical and dermoscopic characteristics of nevoid melanoma are available. This study analyzes the clinical and pathological characteristics of nevoid melanoma in a population of patients affected by this rare subtype. It compares the prognosis and survival of these patients to data from classical melanoma featured in the literature. Additionally, by analyzing available dermoscopic images of nevoid melanoma, we aim to identify dermoscopic features that might help clinicians to suspect nevoid melanoma, reducing misdiagnosis. Background: Diagnosis of nevoid melanoma (NeM) is often difficult because NeM closely resembles a common nevus clinically and histologically. Methods: A retrospective study was conducted on 110 patients diagnosed with and/or treated for primary nevoid melanoma at the Veneto Institute of Oncology and at the University Hospital of Padua from August 1999. Results: Mean Breslow thickness was of 1.4 mm. Sentinel lymph node biopsy was conducted in nearly half of the patients, and positivity was detected in 16.7% of them. Twenty-four clinical and 23 dermoscopic pictures were collected. Papular and macular lesions prevailed over nodular and plaque-type lesions. Different hues of brown, pink, and red color were most represented. Twenty nevus-like NeMs and four multicomponent-pattern NeMs were observed. The Most frequent dermoscopic patterns for nevus-like NeM were atypical pigmented reticulum, irregular globules and dots, and hyperpigmented blotches. Atypical vessels, asymmetric peripheric striae, blue-white veil, and areas of regression were less frequent and prevailed in multicomponent pattern NeM. A structureless pattern was also featured. Many patients in the series had multiple melanomas. However, none of them had numerous multiple nevoid melanomas. Conclusions: NeM should not be regarded as a separate biological entity from classical melanoma, and the same histological and clinical prognostic factors apply to NeM. Clinically and dermoscopically, it often resembles benign nevi, although some clues such as evolution and some dermoscopic patterns could suggest malignancy. Clinical suspicion might prove crucial to further pathological analysis and recognition. [ABSTRACT FROM AUTHOR]

Abstract Background The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. Methods A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. Results The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P

BackgroundLong-term survivors of cutaneous malignant melanoma (CMM) risk subsequent malignancies due to both host-related and environmental risk factors. This retrospective population-based study differentially assesses the risk of synchronous and metachronous cancers in a cohort of CMM survivors stratified by sex.MethodsThe cohort study (1999–2018) included 9,726 CMM survivors (M = 4,873, F = 4,853) recorded by the cancer registry of all 5,000,000 residents in the Italian Veneto Region. By excluding subsequent CMM and non-CMM skin cancers, the incidence of synchronous and metachronous malignancies was calculated according to sex and tumor site, standardizing for age and calendar year. The Standardized Incidence Ratio (SIR) was calculated as the ratio between the number of subsequent cancers among CMM survivors and the expected number of malignancies among the regional population.ResultsIrrespective of the site, the SIR for synchronous cancers increased in both sexes (SIR = 1.90 in males and 1.73 in females). Both sexes also demonstrated an excess risk for synchronous kidney/urinary tract malignancies (SIR = 6.99 in males and 12.11 in females), and women had an increased risk of synchronous breast cancer (SIR = 1.69). CMM male survivors featured a higher risk of metachronous thyroid (SIR = 3.51, 95% CI [1.87, 6.01]), and prostate (SIR = 1.35, 95% CI [1.12, 1.61]) malignancies. Among females, metachronous cancers featured higher SIR values than expected: kidney/urinary tract (SIR = 2.27, 95% CI [1.29, 3.68]), non-Hodgkin’s lymphoma (SIR = 2.06, 95% CI [1.24, 3.21]), and breast (SIR = 1.46, 95% CI [1.22, 1.74]). Females had an overall increased risk of metachronous cancers in the first 5 years after CMM diagnosis (SIR = 1.54 at 6–11 months and 1.37 at 1–5 years).ConclusionAmong CMM survivors, the risk of metachronous non-skin cancers is higher than in the general population and differs significantly by sex. These results encourage sex-tailored interventions for metachronous secondary cancer prevention.

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease’s categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0–49 than for the rest of the region’s population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0–49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies.

Introduction: Methods for production of fresh, health food are needed in view of long-term, deep-space manned missions. To this end, crops tailored for better performance under non-terrestrial conditions may be obtained by the exploitation of biochemical patterns related to specialized metabolites known to confer protection against environmental challenges and to be beneficial to human health.Methods: In this work, for the first time, MicroTom plants have been engineered specifically for agrospace applications to express PhAN4, a MYB-like transcription factor able to regulate the biosynthesis of anthocyanins that influence tomato genes possibly involved in agrospace-relevant functions. Results:PhAN4 engineering underpinned the genetic background of the dwarf tomato MicroTom while maintaining yield and photosynthetic capacity. PhAN4 expression resulted in the accumulation of anthocyanins and polyphenols, a differential carotenoid profile, increased antioxidant scavenging capacities of fruits compared to the original genotype. Improved ability to counteract ROS generation and to preserve plant protein folding after ex-vivo gamma irradiation was observed.Discussion: These results highlights that the manipulation of specific metabolic pathways is a promising approach to design novel candidate varieties for agrospace applications.

PurposeSoft tissue sarcomas represent approximately 1% of all malignancies, and diagnostic radiology plays a significant role in the overall management of this rare group of tumors. Recently, quantitative imaging and, in particular, radiomics demonstrated to provide significant novel information, for instance, in terms of prognosis and grading. The aim of this study was to evaluate the prognostic role of radiomic variables extracted from apparent diffusion coefficient (ADC) maps collected at diagnosis in patients with soft tissue sarcomas in terms of overall survival and metastatic spread as well as to assess the relationship between radiomics and the tumor grade.MethodsPatients with histologically proven soft tissue sarcomas treated in our tertiary center from 2016 to 2019 who underwent an Magnetic Resonance (MR) scan at diagnosis including diffusion-weighted imaging were included in this retrospective institution review board–approved study. Each primary lesion was segmented using the b50 images; the volumetric region of interest was then applied on the ADC map. A total of 33 radiomic features were extracted, and highly correlating features were selected by factor analysis. In the case of feature/s showing statistically significant results, the diagnostic accuracy was computed. The Spearman correlation coefficient was used to evaluate the relationship between the tumor grade and radiomic features selected by factor analysis. All analyses were performed applying p0.05, each). A moderate statistically significant correlation emerged only between Imc1 and the tumor grade (r=0.457, p=0.005).ConclusionsIn conclusion, the radiomic feature Imc1 acts as a predictor of metastatic spread in patients with soft tissue sarcomas and correlates with the tumor grade.

Background: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high‐income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. Objective: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost‐of‐illness and the diagnostic‐therapeutic performance indicators by patient age category. Methods: This population‐based cohort study included 2435 incident CMM (age range 15–65 years; age 15–39 = 394; age 40–65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's‐V tested the strength of association between pairs of variables. The Kaplan–Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper–Pearson exact method. Results: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low‐stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). Conclusions: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients. [ABSTRACT FROM AUTHOR]

Abstract Background Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry. Methods Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated. Results Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure. Conclusions Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management.

IntroductionPromoting standardization and quality assurance (QA) in oncology on the strength of real-world data is essential to ensure better patient outcomes. Wide excision after primary tumor biopsy is a fundamental step in the therapeutic pathway for cutaneous malignant melanoma (CMM). The aim of this population-based cohort study is to assess adherence to wide local excision in a cohort of patients diagnosed with CMM and the impact of this recommended procedure on overall and disease-specific survival.Materials and MethodsThis retrospective cohort study concerns CMM patients diagnosed in the Veneto region (north-east Italy) in 2017, included in the high-resolution Veneto Cancer Registry, and followed up through linkage with the regional mortality registry up until February 29th, 2020. Using population-level real-world data, linking patient-level cancer registry data with administrative records of clinical procedures may shed light on the real-world treatment of CMM patients in accordance with current guidelines. After excluding TNM stage IV patients, a Cox regression analysis was performed to test whether the completion of a wide local excision was associated with a difference in melanoma-specific and overall survival, after adjusting for other covariates.ResultsNo wide excision after the initial biopsy was performed in 9.7% of cases in our cohort of 1,305 patients. After adjusting for other clinical prognostic characteristics, Cox regression revealed that failure to perform a wide local excision raised the hazard ratio of death in terms of overall survival (HR = 4.80, 95% CI: 2.05–11.22, p < 0.001) and melanoma-specific survival (HR = 2.84, 95% CI: 1.04–7.76, p = 0.042).ConclusionBy combining clinical and administrative data, this study on real-world clinical practice showed that almost one in ten CMM patients did not undergo wide local excision surgery. Monitoring how diagnostic-therapeutic protocols are actually implemented in the real world may contribute significantly to promoting quality improvements in the management of oncological patients.

Gene expression manipulation of specific metabolic pathways can be used to obtain bioaccumulation of valuable molecules and desired quality traits in plants. A single-gene approach to impact different traits would be greatly desirable in agrospace applications, where several aspects of plant physiology can be affected, influencing growth. In this work, MicroTom hairy root cultures expressing a MYB-like transcription factor that regulates the biosynthesis of anthocyanins in Petunia hybrida (PhAN4), were considered as a testbed for bio-fortified tomato whole plants aimed at agrospace applications. Ectopic expression of PhAN4 promoted biosynthesis of anthocyanins, allowing to profile 5 major derivatives of delphinidin and petunidin together with pelargonidin and malvidin-based anthocyanins, unusual in tomato. Consistent with PhAN4 features, transcriptomic profiling indicated upregulation of genes correlated to anthocyanin biosynthesis. Interestingly, a transcriptome reprogramming oriented to positive regulation of cell response to biotic, abiotic, and redox stimuli was evidenced. PhAN4 hairy root cultures showed the significant capability to counteract reactive oxygen species (ROS) accumulation and protein misfolding upon high-dose gamma irradiation, which is among the most potent pro-oxidant stress that can be encountered in space. These results may have significance in the engineering of whole tomato plants that can benefit space agriculture.

BackgroundMerkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC.MethodsA retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens.Results143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor.ConclusionsAutoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.

Forequarter amputation is a very demolitive surgical procedure that affects the quality of life and it is performed when the tumour involves the proximal end of homerus and the shoulder. We describe here the case of a female patient with a recurrent dedifferentiated liposarcoma of the upper limb already treated with tumour asportation, isolated limb perfusion and upper limb amputation through the shoulder, who returned to our attention for a recurrence of the sarcoma in the stump. We then performed a forequarter amputation in a previous amputated limb. Since the patient underwent numerous surgical procedures, our last surgical approach was a quite challenging one. To our knowledge, it is the first described case of an interscapular-thoracic disarticulation after a previous amputation to the shoulder.

The treatment of cutaneous and subcutaneous localizations from breast cancer (BC) is still a therapeutic challenge. Electrochemotherapy (ECT) is one of the available options, and it is characterized by the association between the administration of a chemotherapic agent (Bleomycin) with the temporary raise of permeability of the cellular membrane induced by the local administration of electrical impulses (electroporation). ECT represents an effective therapy for loco-regional control of this disease. This study aimed to investigate the predictive factors of response in cutaneous and subcutaneous localizations from breast cancer treated with ECT. We decided to evaluate the response to this treatment in 55 patients who underwent ECT between January 2013 and March 2020 at our Institute. We performed a monocentric retrospective cohort study. ECT was administered following the ESOPE (European Standard Operative Procedure of Electrochemotherapy) guidelines, a set of criteria updated in 2018 by a panel of European experts on ECT who defined the indications for selecting the patients who can benefit from the ECT treatment and the ones for technically performing the procedure. The responses were evaluated with the RECIST criteria (Response Evaluation Criteria in Solid Tumor). We found after 12 weeks of treatment a complete response (CR) in 64% of our patients. From the analysis divided for subgroups of covariates is emerged that lower BMI, reduced body surface, and absence of previous radiation treatment could be predictive for a better complete response. This study suggests that the efficacy of the ECT treatment is related to the concurrent systemic therapies while administering ECT. The association between ECT and immunotherapy has offered better results than the association between ECT and chemotherapy (p-value = 0.0463). So, ECT is a valuable tool in the treatment of cutaneous and subcutaneous metastases from breast cancer and its efficacy in local control of these lesions improves when it is well planned in a therapeutic scenario.

A 54-year-old lady was referred to our institute because of a massive thoracic neoplasm arising from the thoracic wall which infiltrated and dislocated the left breast. Twenty years before, the patient had undergone a quadrantectomy with axillary dissection for an infiltrating ductal carcinoma of the left breast, followed by adjuvant radiotherapy and chemotherapy. A true-cut biopsy of the mass showed a low differentiated malignant neoplasm with spindle-shaped cells. The patient underwent a total-body CT scan which showed a 16 × 15 × 10 cm largely necrotic mass with irregular and undefined margins, with little homolateral round-shaped cervical and mesenteric lymph nodes but no distant metastases. After a multidisciplinary discussion, we proposed surgery as the first therapeutic option. The planned treatment was a wide excision of the mass with the underlying ribs (II-VI) followed by the reconstruction of the thoracic wall using titanium bars covered by the acellular porcine dermis, latissimus dorsi flap, and finally, skin grafts from the thighs.

IntroductionAmong white people, the incidence of cutaneous malignant melanoma (CMM) has been increasing steadily for several decades. Meanwhile, there has also been a significant improvement in 5-year survival among patients with melanoma. This population-based cohort study investigates the five-year melanoma-specific survival (MSS) for all melanoma cases recorded in 2015 in the Veneto Tumor Registry (North-Est Italian Region), taking both demographic and clinical-pathological variables into consideration.MethodsThe cumulative melanoma-specific survival probabilities were calculated with the Kaplan-Meier method, applying different sociodemographic and clinical-pathological variables. Cox’s proportional hazards model was fitted to the data to assess the association between independent variables and MSS, and also overall survival (OS), calculating the hazard ratios (HR) relative to a reference condition, and adjusting for sex, age, site of tumor, histotype, melanoma ulceration, mitotic count, tumor-infiltrating lymphocytes (TIL), and stage at diagnosis.ResultsCompared with stage I melanoma, the risk of death was increased for stage II (HR 3.31, 95% CI: 0.94-11.76, p=0.064), almost ten times higher for stage III (HR 10.51, 95% CI: 3.16-35.02, p

Malignant melanoma (MM) is the most lethal skin cancer. AXL is a tyrosine kinase receptor involved in several oncogenic processes and might play a role in blocking necroptosis (a regulated cell death mechanism) in MM through the downregulation of the necroptotic-related driver RIPK3. The aim of this study was to evaluate the clinical impact of the expression of AXL and RIPK3 in 108 primary cutaneous MMs. Association between AXL and RIPK3 immunoreactivity and clinical–pathological variables, sentinel lymph node status, and tumor-infiltrating lymphocytes (TILs) was assessed. Immunoreaction in tumor cells was detected in 30 cases (28%; range, 5%–80%) and in 17 cases (16%; range, 5%–50%) for AXL and RIPK3, respectively. Metastases in the sentinel lymph nodes were detected in 14 out of 61 patients, and these were associated with AXL-positive immunoreactivity in the primary tumor (p < 0.0001). No association between AXL and TILs was found. RIPK3 immunoreactivity was not associated with any variables. A final logistic regression analysis showed Breslow and AXL-positive immunoreactivity as the stronger predictor for positive sentinel node status [area under the receiver operating characteristic curve (AUC) of 0.96]. AXL could be a potential new biomarker for MM risk assessment, and it deserves to be further investigated in larger studies.

Simple Summary: In-transit metastases (ITM) are a challenging aspect of advanced melanoma, traditionally treated with surgery. However, recent advances in systemic therapies, such as immune checkpoint inhibitors and targeted treatments, have significantly improved patient outcomes. These modern therapies are now often preferred over surgery alone. This article reviews the benefits of combining systemic and locoregional treatments, highlighting their potential to enhance survival and quality of life for patients with ITM. By integrating these approaches, we aim to provide a comprehensive strategy for optimizing melanoma treatment outcomes. In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens. [ABSTRACT FROM AUTHOR]

Background. Basal cell carcinomas (BCCs) are common human malignancies with a rising incidence in recent years. While BCCs have a low mortality rate, they are often associated with significant local skin damage characterized by erythema, skin ulceration, and persistent pigmentation. Surgery, radiotherapy, and systemic chemotherapy have traditionally been the principal treatments for these skin injuries. However, electrochemotherapy has recently been proposed as a novel local treatment with promising results for various skin cancers, including BCC, while avoiding the side effects of conventional therapies. ECT involves a local electrical stimulus that enhances cell membrane permeability, thereby enabling the targeted intracellular accumulation of the chemotherapeutic agent. Case Report: We report a case of a 68-year-old man with an ulcerated BCC, following his progress up to 14 months post-ECT treatment, with positive outcomes. Discussion and Conclusions: We achieved a complete clinical response and noted an improvement in the patient's quality of life. This technique is fast, repeatable, requires minimal hospitalization, and reduces healthcare costs and adverse effects compared to major surgery. Therefore, it can be considered an alternative or complementary approach to traditional surgery for treating BCC of the head and neck. [ABSTRACT FROM AUTHOR]

The “Veneto Cancer Registry” records melanoma as the most common cancer diagnosed in males and the third common cancer in females under 50 years of age in the Veneto Region (Italy). While melanoma is rare in children, it has greater incidence in adolescents and young adults (AYA), but literature offers only few studies specifically focused on AYA melanoma. The aim of this study was to describe the characteristics, surgical treatment, and prognosis of a cohort of AYA melanoma in order to contribute to the investigation of this malignancy and provide better patient care. This retrospective cohort study included 2,752 Caucasian patients (702 AYA and 2,050 non-AYA patients) from the Veneto Region who were over 15 years of age at diagnosis, and who received diagnosis and/or treatment from our institutions between 1998 and 2014. Patients were divided in adolescents and youth (15-25 years), young adults (26-39 years) and adults (more than 39 years) for the analysis. We found statistically significant differences in gender, primary site, Breslow thickness, ulceration, pathologic TNM classification (pTNM) stage and tumor subtype among the age groups. Disease-specific survival and disease-free survival were also different among the age groups. Our findings suggest that the biological behavior of melanoma in young people is different to that in adults, but not such as to represent a distinct pathological entity. Additional and larger prospective studies should be performed to better evaluate potential biological and cancer-specific differences between AYAs and the adult melanoma population.

BackgroundCutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR).MethodsMelanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors.ResultsThe median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62).ConclusionsThe nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

BackgroundMelanoma of unknown primary (MUP), accounts for up to 3% of all melanomas and consists of a histologically confirmed melanoma metastasis to either lymph nodes, (sub)cutaneous tissue, or visceral sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma. This study aimed to investigate the characteristics, treatment strategies, and prognostic factors of MUP patients, in order to shed some light on the clinical behavior of this malignancy.MethodsAll the consecutive patients with a diagnosis of MUP referring to our institutions between 1985 and 2018 were considered in this retrospective cohort study. The records of 173 patients with a suspected diagnosis of MUP were retrospectively evaluated for inclusion in the study. Patient selection was performed according to the Das Gupta criteria, and a total of 127 MUP patients were finally included in the study, representing 2.7% of the patients diagnosed with melanoma skin cancer at our institutions during the same study period. A second cohort of all consecutive 417 MKP patients with AJCC stages IIIB–IV, referring tions in the period considered (1985–2018), was included in the study to compare survival between MUP and MKP patients. All the diagnoses were based on histopathologic, cytologic and immunohistochemical examination of the metastases. All tumors were re-staged according to the 2018 American Joint Committee on Cancer (AJCC) 8th Edition.ResultsMedian follow-up was 32 months (IQR: 15–84). 3-year progression-free survival (PFS) was 54%, while 3-year overall survival (OS) was 62%. Worse OS and PFS were associated with older age (P = 0.0001 for OS; P = 0.008 for PFS), stage IV (P < 0.0001 for OS; P = 0.0001 for PFS) and higher Charlson Comorbidity Index (P < 0.0001 for OS and P = 0.01 for PFS). Patients with lymph node disease showed longer PFS (P = 0.001) and OS (P = 0.0008) than those with (sub)cutis disease. Complete lymph node dissection (CLND) was the most common surgical treatment; a worse OS in these patients was associated with the number of positive lymph nodes (P = 0.01), without significant association with the number of retrieved lymph nodes (P = 0.79). Survival rates were lower in patients undergoing chemotherapy (CT) and target therapy (TT), and higher in those receiving immunotherapy (IT). 417 patients with AJCC stages IIIB–IV of Melanoma Known Primary (MKP) were included for the survival comparison with MUP. 3-year PFS rates were 54 and 58% in MUP and MKP, respectively (P = 0.30); 3-year OS rates were 62 and 70% in MUP and MKP, respectively (P = 0.40).ConclusionsThe most common clinical scenario of our series was a male patient around 59 years with lymph node disease. We report that CLND associated with IT was the best treatment in terms of survival outcome. In the current era of IT and TT for melanoma, new studies have to clarify the impact of novel drugs on MUP.

Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature.Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival.Results: The median age at diagnosis was 68 years (58–78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172).Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.

O artigo tem por objetivo analisar a influência da sociedade patriarcal na legislação penal brasileira. O presente artigo é dividido em três partes. Na primeira, explico o conceito do feminismo. Na segunda, um breve histórico de como a legislação tratou e trata as mulheres, o que pode significar muito de nossa sociedade patriarcal. Por último, na terceira parte, conclamo todos os homens (e mulheres antifeministas) a tomarem parte do feminismo e tornar um mundo melhor, sem depender de qualquer forma de Estado paternalista, simplesmente, fazendo, cada um, a sua parte.

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics.Methods: This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database.Results: 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival.Conclusion: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.

Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine neoplasm of the skin. Due to its rarity, the management of MCC is not standardized across centers. In this article, we present the experience of the Veneto region in the North-East of Italy, where a committee of skin cancer experts has proposed a clinical pathway for the diagnosis and treatment of MCC. Putting together the evidence available in the international literature, we outlined the best approach to the management of patients affected with this malignancy step- by- step for each possible clinical situation. Crucial in this pathway is the role of the multidisciplinary team to deal with the lack of robust information on each aspect of the management of this disease.

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth’s surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the “coast-plain-hill gradient” could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.

The strengthening effect of a mild temperature treatment on the antimicrobial efficacy of essential oils has been widely reported, often leading to an underestimation or a misinterpretation of the product’s microbial status. In the present study, both a traditional culture-based method and Flow Cytometry (FCM) were applied to monitor the individual or combined effect of Origanum vulgare essential oil (OEO) and mild heat treatment on the culturability and viability of Escherichia coli in a conventional culture medium and in a fruit juice challenge test. The results obtained in the culture medium showed bacterial inactivation with an increasing treatment temperature (55 °C, 60 °C, 65 °C), highlighting an overestimation of the dead population using the culture-based method; in fact, when the FCM method was applied, the prevalence of injured bacterial cells in a viable but non-culturable (VBNC) state was observed. When commercial fruit juice with a pH of 3.8 and buffered at pH 7.0 was inoculated with E. coli ATCC 25922, a bactericidal action of OEO and a higher efficiency of the mild heat at 65 °C for 5′ combined with OEO were found. Overall, the combination of mild heat and OEO treatment represents a promising antimicrobial alternative to improve the safety of fruit juice.

Abstract Background Dysfunction of the circadian clock and polymorphisms of some circadian genes have been linked to cancer development and progression. We investigated the relationship between circadian genes germline variation and susceptibility or prognosis of patients with soft tissue sarcoma. Patients and methods We considered the 14 single nucleotide polymorphisms (SNPs) of 6 core circadian genes that have a minor allele frequency > 5% and that are known to be associated with cancer risk or prognosis. Genotyping was performed by q-PCR. Peripheral blood and clinic-pathological data were available for 162 patients with liposarcoma or leiomyosarcoma and 610 healthy donors. Associations between the selected clock genes polymorphisms and sarcoma susceptibility or prognosis were tested assuming 3 models of inheritance: additive, recessive and dominant. Subgroup analysis based on sarcoma histotype was performed under the additive genetic model. Multivariate logistic regression and multivariate Cox proportional hazard regression analyses were utilized to assess the association between SNPs with patient susceptibility and survival, respectively. Pathway variation analysis was conducted employing the Adaptive Rank Truncated Product method. Results Six out of the 14 analyzed SNPs were statistically significantly associated with susceptibility or prognosis of soft tissue sarcoma (P