Lentigo Maligna and Lentigo Maligna Melanoma of the External Ear: Clinical and Dermoscopic Features of 19 Patients.

External ear lentigo maligna/lentigo melanoma (LM/LMM) represents approximately 1%-4% of all primary cutaneous melanomas. Over the past 20 years, dermoscopy has proven highly effective in early detection of LM/LMM, with recent studies identifying perifollicular linear projections (PLP) as a specific diagnostic criterion for early LM. However, in clinical practice, LM and LMM turn out to be very difficult to distinguish based on dermoscopic findings. Therefore, our retrospective monocentric study aimed to investigate dermoscopic characteristics, as well as the epidemiological and clinical data of 19 patients diagnosed with the external ear (EE) LM/LMM at the Oncologic Dermatology Unit in Bologna. Dermoscopic images were obtained using the FotoFinder Medicam 800HD, and specific criteria validated by the International Dermoscopy Society (IDS) for atypical pigmented facial lesions were assessed. Fisher's exact test was primarily used for statistical comparisons. As results, most of the patients were male (74%) with an average age (± SD) at diagnosis of 69.8 (± 15.1) years old. LMM appeared more commonly observed in elderly patients as compared to LM (mean 71.6 vs. 66.7, p = 0.514), presenting as pigmented macule (89.5%) of the ear lobule (23.9%). A statistically significant difference (p = 0.01) of tumour' diameter between LMM and LM was reported with the first resulting more than twice the size of the latter. Concerning dermoscopic findings, asymmetric pigmented follicles, obliteration of the follicular openings and grey circles were more frequently observed in LMM compared to LM (63.2% vs. 31.6%; 63.2% vs. 26.3%; 47.4% vs. 15.8%, respectively).

Non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths worldwide. The management of NSCLC has improved considerably, especially in the past 10 years. The systematic screening of populations at risk with low-dose CT, the implementation of novel surgical and radiotherapeutic techniques and a deeper biological understanding of NSCLC that has led to innovative systemic treatment options have improved the prognosis of patients with NSCLC. In non-metastatic NSCLC, the combination of various perioperative strategies and adjuvant immunotherapy in locally advanced disease seem to enhance cure rates. In metastatic NSCLC, the implementation of novel drugs might prolong disease control together with preserving quality of life. The further development of predictive clinical and genetic markers will be essential for the next steps in individualized treatment concepts.

From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma.

BACKGROUND: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. METHODS: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. RESULTS: Associations were found between systemic inflammation markers-NLR, MLR, and PLR-and tumor microenvironment factors, such as TILs and CD8+ cell prevalence-elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. DISCUSSION: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. CONCLUSIONS: Future integration into cancer classification could improve risk stratification and treatment guidance.

Basosquamous carcinoma: Comprehensive epidemiological, clinical, dermoscopic, and confocal features from a single center institution.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and aggressive nonmelanoma skin cancer (NMSC) that exhibits features of both BCC and squamous cell carcinoma (SCC). The gold standard for diagnosis is histopathological examination. BSC is often challenging to diagnose and manage due to its mixed histological features and potential for aggressive behavior AIM: To identify specific features aiding clinicians in differentiating BSCs using non-invasive diagnostic techniques. METHODS: We conducted a retrospective descriptive, monocentric study of the epidemiological clinical, dermoscopic, and reflectance confocal microscopy (RCM) features of histopathologically proven BSCs diagnosed between 2010 and 2023. A total of 192 cases were selected. RESULTS: The study population consisted of 17 men (60.9%). Total 95.8% of patients at the time of diagnosis were ≥50 years. BSC occurred in the head and neck area in 124 cases (63.1%) of which 65 (33.9%) were in the H-zone. For 47.4% of patients, BSC presented as a macule with undefined clinical margins (43.3%). Dermoscopic images were available for 98 cases: the most common parameter was the presence of whitish structureless areas (59 [60.2%]), keratin masses (58 [59.2%]), superficial scales, and ulceration or blood crusts (49 [50%] both). Vessels pattern analysis revealed hairpin vessels (exclusively) and linear irregular vessels as the most frequent (55 [56.1%] both). RCM examination was performed in 21 cases which revealed specific SCC features such as solar elastosis (19 [90.5%]), atypical honeycomb pattern (17 [89%]), proliferation of atypical keratinocytes (16 [80%]) combined with BCC' ones as bright tumor islands (12 [57.8%]), and cleft-like dark spaces (11 [53.4%]). DISCUSSION: Our study reflects the largest cohort of BSCs from a single institution. We described an incidence rate of 4.7%, higher than reported in the Literature, with the involvement of patients ≥50years in almost 96% of cases and an overall male predominance. At clinical examination, BSC was described as a hyperkeratotic macule with undefined clinical margins with one or more dermoscopic SCC' features, whereas the presence of typical BCC aspects was observed in less than 10% of cases, differently from what was previously reported. At RCM analysis, BSCs presented with an atypical honeycomb pattern with proliferation of atypical keratinocytes, hyperkeratosis, and in nearly 55% of patients, bright tumor islands with cleft-like dark spaces. CONCLUSION: The distinctive dermoscopic patterns, along with the RCM features aid in the differentiation of BSCs from other NMSCs.

Reflectance confocal microscopy as noninvasive tool for monitoring tirbanibulin efficacy in actinic keratosis.

Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage.

Impact of the Surface Microenvironment on the Redox Properties of a Co-Based Molecular Cathode for Selective Aqueous Electrochemical CO2-to-CO Reduction.

Electrode-confined molecular catalysts are promising systems to enable the efficient conversion of CO2 to useful products. Here, we describe the development of an original molecular cathode for CO2 reduction to CO based on the noncovalent integration of a tetraazamacrocyclic Co complex to a carbon nanotube-based matrix. Aqueous electrochemical characterization of the modified electrode allowed for clear observation of a change of redox behavior of the Co center as surface concentration was tuned, highlighting the impact of the catalyst microenvironment on its redox properties. The molecular cathode enabled efficient CO2-to-CO conversion in fully aqueous conditions, giving rise to a turnover number (TONCO) of up to 20 × 103 after 2 h of constant electrolysis at a mild overpotential (η = 450 mV) and with a faradaic efficiency for CO of about 95%. Post operando measurements using electrochemical techniques, inductively coupled plasma, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy characterization of the films demonstrated that the catalysis remained of molecular nature, making this Co-based electrode a new promising alternative for molecular electrocatalytic conversion of CO2-to-CO in fully aqueous media.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Multimodal Spectroscopic Analysis of the Fe-S Clusters of the as-Isolated Escherichia coli SufBC2D Complex.

Iron-sulfur (Fe-S) clusters are essential inorganic cofactors dedicated to a wide range of biological functions, including electron transfer and catalysis. Specialized multiprotein machineries present in all types of organisms support their biosynthesis. These machineries encompass a scaffold protein, on which Fe-S clusters are assembled before being transferred to cellular targets. Here, we describe the first characterization of the native Fe-S cluster of the anaerobically purified SufBC2D scaffold from Escherichia coli by XAS and Mössbauer, UV-visible absorption, and EPR spectroscopies. Interestingly, we propose that SufBC2D harbors two iron-sulfur-containing species, a [2Fe-2S] cluster and an as-yet unidentified species. Mutagenesis and biochemistry were used to propose amino acid ligands for the [2Fe-2S] cluster, supporting the hypothesis that both SufB and SufD are involved in the Fe-S cluster ligation. The [2Fe-2S] cluster can be transferred to ferredoxin in agreement with the SufBC2D scaffold function. These results are discussed in the context of Fe-S cluster biogenesis.

Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC.

INTRODUCTION: Controversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC. METHODS: A search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and R2 with 95% confidence interval were calculated by the bootstrapping approach. RESULTS: Seven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the R2 of pCR and MPR with 2-year EFS were 0.82 (0.66-0.94) and 0.81 (0.63-0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07-0.19) and 0.11 (0.05-0.22), respectively. For the 2-year OS, the R2 of pCR and MPR were 0.55 (0.09-0.98) and 0.52 (0.10-0.96), respectively. At the trial level, the R2 for the association of OR for response and HR for EFS was 0.58 (0.00-0.97) and 0.61 (0.00-0.97), respectively. CONCLUSIONS: Our analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.

Results of an exploratory survey within ESTS membership in 2022 on current trend of robotic-assisted thoracic surgery and its training perspectives.

OBJECTIVES: Robotic-assisted thoracic surgery (RATS) is increasingly used in our specialty. We surveyed European Society of Thoracic Surgeons membership with the objective to determine current status of robotic thoracic surgery practice including training perspectives. METHODS: A survey of 17 questions was rolled out with 1 surgeon per unit responses considered as acceptable. RESULTS: A total of 174 responses were obtained; 56% (97) were board-certified thoracic surgeons; 28% (49) were unit heads. Most responses came from Italy (20); 22% (38) had no robot in their institutions, 31% (54) had limited access and only 17% (30) had full access including proctoring. Da Vinci Xi was the commonest system in 56% (96) centres, 25% (41) of them had dual console in all systems, whereas RATS simulator was available only in half (51.18% or 87). Video-assisted thoracic surgery (VATS) was the most commonly adopted surgical approach in 81% of centres (139), followed by thoracotomy in 67% (115) and RATS in 36% (62); 39% spent their training time on robotic simulator for training, 51% on robotic wet/dry lab, which being no significantly different to 46-59% who had training on VATS platform. There was indeed huge overlap between simulator models or varieties usage; 52% (90) reported of robotic surgery not a part of training curriculum with no plans to introduce it in future. Overall, 51.5% (89) responded of VATS experience being helpful in robotic training in view of familiarity with minimally invasive surgery anatomical views and dissection; 71% (124) reported that future thoracic surgeons should be proficient in both VATS and RATS. Half of the respondents found no difference in earlier chest drain removal with either approach (90), 35% (60) reported no difference in postoperative pain and 49% (84) found no difference in hospital stay; 52% (90) observed better lymph node harvest by RATS. CONCLUSIONS: Survey concluded on a positive response with at least 71% (123) surgeons recommending to adopt robotics in future.

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

miR-122 and miR-21 are Stable Components of miRNA Signatures of Early Lung Cancer after Validation in Three Independent Cohorts.

Several panels of circulating miRNAs have been reported as potential biomarkers of early lung cancer, yet the overlap of components between different panels is limited, and the universality of proposed biomarkers has been minimal across proposed panels. To assess the stability of the diagnostic potential of plasma miRNA signature of early lung cancer among different cohorts, a panel of 24 miRNAs tested in the frame of one lung cancer screening study (MOLTEST-2013, Poland) was validated with material collected in the frame of two other screening studies (MOLTEST-BIS, Poland; and SMAC, Italy) using the same standardized analytical platform (the miRCURY LNA miRNA PCR assay). On analysis of selected miRNAs, two associated with lung cancer development, miR-122 and miR-21, repetitively differentiated healthy participants from individuals with lung cancer. Additionally, miR-144 differentiated controls from cases specifically in subcohorts with adenocarcinoma. Other tested miRNAs did not overlap in the three cohorts. Classification models based on neither a single miRNA nor multicomponent miRNA panels (24-mer and 7-mer) showed classification performance sufficient for a standalone diagnostic biomarker (AUC, 75%, 71%, and 53% in MOLTEST-2013, SMAC, and MOLTEST-BIS, respectively, in the 7-mer model). The performance of classification in the MOLTEST-BIS cohort with the lowest contribution of adenocarcinomas was increased when only this cancer type was considered (AUC, 60% in 7-mer model).

Basic Elements of Artificial Intelligence Tools in the Diagnosis of Cutaneous Melanoma.

Cutaneous melanoma (CM) incidence has dramatically increased in the last years. Early diagnosis is of paramount importance in terms of prognosis. Artificial Intelligence (AI) tools are being proposed for clinicians and pathologists as an adjunct support in the diagnostic process. We described herein an overview of the most important parameters that a potential AI tool should take into consideration in histopathology to evaluate a skin lesion. First of all, recognition of a melanocytic or non-melanocytic nature. Furthermore, melanocytic lesions should be stratified according to at least four parameters: silhouette and asymmetry; identification and spatial distribution of the cells; mitosis count; presence of ulceration. According to the number of parameters the AI tools might stratify the risk of CM and prioritize the pathologist's work.