Papillomavirus umano e carcinomi del tratto aerodigestivo: il punto sulle evidenze nella babele dei dati scientifici

I carcinomi squamosi dell'orofaringe associati all'infezione da papillomavirus umano (HPV) costituiscono ormai una entità ben caratterizzata, che interessa prevalentemente maschi, giovani adulti o di mezza età, non fumatori. Essi hanno generalmente una prognosi più favorevole rispetto alla controparte non associate ad infezione, e per questo è stato proposto di dedicare a questo gruppo di pazienti un approccio terapeutico meno aggressivo. L'incidenza dei carcinomi dell'orofaringe associati a HPV è in rapido aumento nella maggior parte dei paesi occidentali, ma per quanto riguarda la popolazione italiana non sono disponibili dati epidemiologici in merito. Per quanto riguarda le altre regioni del distretto testa-collo, una più modesta porzione di lesioni displastiche di alto grado e di neoplasie appare essere correlata all'infezione da HPV, mentre il ruolo del virus nei tumori della laringe è stato parzialmente ridimensionato. HPV determina la trasformazione neoplastica delle cellule infettate tramite l'espressione dei suoi due oncogeni, E6 ed E7, che interagiscono con i meccanismi di apoptosi e regolazione del ciclo cellulare della cellula ospite. L'unica metodica in grado di documentare con certezza l'espressione degli oncogeni virali è attualmente l'amplificazione dell'RNA messaggero trascritto dai due oncogeni. Il consenso riguardo la strategia per l'identificazione dei pazienti affetti da carcinoma dell'orofaringe associato a HPV dal punto di vista clinico e diagnostico è tuttora limitato. Le metodiche diagnostiche più utilizzate, singolarmente o in combinazione, comprendono l'immunocolorazione con anticorpi diretti contro p16, l'ibridazione in situ per genotipi virali ad alto rischio e l'amplificazione del DNA virale mediate PCR. La possibilità di ottenere una diagnosi precoce grazie all'identificazione dell'infezione virale nelle cellule epiteliali esfoliate dal cavo orale o dall'orofaringe non ha finora fornito risultati soddisfacenti, tuttavia la persistenza del virus nel cavo orale in pazienti trattati per carcinoma dell'orofaringe ha dimostrato una significativa associazione con il rischio di recidiva del tumore. Non sono ancora disponibili sufficienti dati che documentino in maniera dettagliata la storia naturale dell'infezione a la sua progressione verso lo sviluppo di una neoplasia, e che definiscano con chiarezza le modalità di trasmissione e i fattori di rischio, comunque è chiaro che i comportamenti sessuali hanno un peso rilevante nel determinare il rischio di sviluppo di neoplasia dell'orofaringe HPV-correlata. La progressive diffusione nelle giovani generazioni del vaccino contro HPV, e soprattutto la sua estensione agli adolescenti di entrambi i generi è sicuramente destinata a modificare in maniera rilevante anche l'epidemiologica dei tumori HPV-correlati nel distretto testa-collo nel prossimo futuro

Case Report: All That Glisters Is Not* Cancer

Properly performed staging in non-small-cell lung cancer (NSCLC) is necessary to avoid wrong therapeutic decisions. Here we present a case which manifested as advanced NSCLC but ultimately was composed of two different and rare pathologies. The first is a TTF-1 positive axillary lymph node that could be defined either as an unusual isolated differentiated cancer of unknown primary or as an even rarer case of ectopic lung epithelium which underwent malignant transformation. The second is sarcoidosis, a sarcoid-like alteration, in remission after oral steroids. The main implication of a correct diagnosis regards patient outcome and the avoidance of toxic inappropriate systemic chemotherapy

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review

Background and purpose: Neuropathological studies can elucidate the mechanisms of nervous system damage associated with SARS-CoV-2 infection. Despite literature on this topic is rapidly expanding, correlations between neurological symptoms and brain pathology findings in COVID-19 patients remain largely unknown. Methods: We performed a systematic literature review on neuropathological studies in COVID-19, including 438 patients from 45 articles published by April 22, 2021. We retrieved quantitative data regarding demographic, clinical, and neuropathological findings. We carried out a Wilcoxon rank sum test or χ2 test to compare patients' subgroups based on different clinical and brain pathology features. Results: Neuropathological findings in COVID-19 patients were microgliosis (52.5%), astrogliosis (45.6%), inflammatory infiltrates (44.0%), hypoxic-ischemic lesions (40.8%), edema (25.3%), and hemorrhagic lesions (20.5%). SARS-CoV-2 RNA and proteins were identified in brain specimens of 41.9% and 28.3% of subjects, respectively. Detailed clinical information was available from 245 patients (55.9%), and among them, 96 subjects (39.2%) had presented with neurological symptoms in association with typical COVID-19 manifestations. We found that: (i) the detection rate of SARS-CoV-2 RNA and proteins in brain specimens did not differ between patients with versus those without neurological symptoms; (ii) brain edema, hypoxic-ischemic lesions, and inflammatory infiltrates were more frequent in subjects with neurological impairment; (iii) neurological symptoms were more common among older individuals. Conclusions: Our systematic revision of clinical correlates in COVID-19 highlights the pathogenic relevance of brain inflammatory reaction and hypoxic-ischemic damage rather than neuronal viral load. This analysis indicates that a more focused study design is needed, especially in the perspective of potential therapeutic trials

New frontiers and emerging applications of 3D printing in ENT surgery: A systematic review of the literature

3D printing systems have revolutionised prototyping in the industrial field by lowering production time from days to hours and costs from thousands to just a few dollars. Today, 3D printers are no more confined to prototyping, but are increasingly employed in medical disci- plines with fascinating results, even in many aspects of otorhinolaryngology. All publications on ENT surgery, sourced through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies fulfilled specific inclusion criteria and were included in our systematic review. Studies were classified according to the specific field of application (otologic, rhinologic, head and neck) and area of interest (surgical and preclinical education, customised surgical planning, tissue engineering and implantable prosthesis). Technological aspects, clinical implications and limits of 3D printing processes are discussed focusing on current benefits and future perspectives

Natural Language, Mixed-Initiative Personal Assistant Agents

The increasing popularity and use of personal voice assistant technologies, such as Siri and Google Now, is driving and expanding progress toward the long-term and lofty goal of using artificial intelligence to build human-computer dialog systems capable of understanding natural language. While dialog-based systems such as Siri support utterances communicated through natural language, they are limited in the flexibility they afford to the user in interacting with the system and, thus, support primarily action-requesting and information-seeking tasks. Mixed-initiative interaction, on the other hand, is a flexible interaction technique where the user and the system act as equal participants in an activity, and is often exhibited in human-human conversations. In this paper, we study user support for mixed-initiative interaction with dialog-based systems through natural language using a bag-of-words model and k-nearest-neighbor classifier. We study this problem in the context of a toolkit we developed for automated, mixed-initiative dialog system construction, involving a dialog authoring notation and management engine based on lambda calculus, for specifying and implementing task-based, mixed-initiative dialogs. We use ordering at Subway through natural language, human-computer dialogs as a case study. Our results demonstrate that the dialogs authored with our toolkit support the end user\u27s completion of a natural language, human-computer dialog in a mixed-initiative fashion. The use of natural language in the resulting mixed-initiative dialogs afford the user the ability to experience multiple self-directed paths through the dialog and makes the flexibility in communicating user utterances commensurate with that in dialog completion paths---an aspect missing from commercial assistants like Siri

Recent advancement on PD-L1 expression quantification : The radiologist perspective on CT-guided FNAC

PURPOSE: We aimed to evaluate the feasibility, accuracy, and safety of Programmed Death-1/ Programmed Death-Ligand 1 (PD-1/ PD-L1) expression quantification in cytology cell-block samples obtained through transthoracic CT-guided fine-needle aspiration cytology (FNAC) from the interventional radiologist's perspective.METHODS: We performed a consecutive unselected series of 361 CT-guided biopsies of pulmonary nodules and masses which came to our observation from June 2017 to October 2018. For each case, exhaustive clinical, morphologic, molecular and tomographic data were available. All the material obtained was fixed in formalin to obtain a cell-block for the pathologist, who performed immunohistochemical analysis to detect PD-L1 expression levels on each sample.RESULTS: Of all the analyzed samples, 93.6% (338/361) were defined to be diagnostic, including neoplastic (72%, 260/361) and non-neoplastic lesions (21.6%, 78/361); only 6.4% (23/361) of them resulted in nondiagnostic specimens. Non-small cell lung cancer (NSCLC) accounted for 73.8% of neoplastic lesions (192/260): most of them were adenocarcinoma (83%, 160/192), followed by squamous carcinoma (14%, 27/192) and poorly differentiated carcinoma (3%, 5/192). In 96% of NSCLC (184/192), the diagnosis was reached either in the absence of complications or with early minor complications. PD-L1 expression was evaluated in all 192 NSCLC cytology specimens: 180 immunostainings were found to be adequate for PD-L1 testing. In 76% of cases, PD-L1 expression level was lower than 50%.CONCLUSION: The findings of our study indicate that PD-L1 quantification using a cell-block approach on CT-guided FNAC is a feasible and safe technique and should be taken into account alongside with core biopsy approach, especially in case of advanced disease and/or fragile and older patients.PURPOSE We aimed to evaluate the feasibility, accuracy, and safety of Programmed Death-1/ Programmed Death-Ligand 1 (PD-1/ PD-L1) expression quantification in cytology cell-block samples obtained through transthoracic CT-guided fine-needle aspiration cytology (FNAC) from the interventional radiologist’s perspective. METHODS We performed a consecutive unselected series of 361 CT-guided biopsies of pulmonary nodules and masses which came to our observation from June 2017 to October 2018. For each case, exhaustive clinical, morphologic, molecular and tomographic data were available. All the material obtained was fixed in formalin to obtain a cell-block for the pathologist, who performed immunohistochemical analysis to detect PD-L1 expression levels on each sample. RESULTS Of all the analyzed samples, 93.6% (338/361) were defined to be diagnostic, including neoplastic (72%, 260/361) and non-neoplastic lesions (21.6%, 78/361); only 6.4% (23/361) of them resulted in nondiagnostic specimens. Non-small cell lung cancer (NSCLC) accounted for 73.8% of neoplastic lesions (192/260): most of them were adenocarcinoma (83%, 160/192), followed by squamous carcinoma (14%, 27/192) and poorly differentiated carcinoma (3%, 5/192). In 96% of NSCLC (184/192), the diagnosis was reached either in the absence of complications or with early minor complications. PD-L1 expression was evaluated in all 192 NSCLC cytology specimens: 180 immunostainings were found to be adequate for PD-L1 testing. In 76% of cases, PD-L1 expression level was lower than 50%. CONCLUSION The findings of our study indicate that PD-L1 quantification using a cell-block approach on CT-guided FNAC is a feasible and safe technique and should be taken into account alongside with core biopsy approach, especially in case of advanced disease and/or fragile and older patients

Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis

To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors