[Advances in the use of bevacizumab for the treatment of respiratory papilloma].

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

Global, regional, and national cancer burdens of respiratory and digestive tracts in 1990-2044: A cross-sectional and age-period-cohort forecast study.

BACKGROUND: Understanding the current status and future trends of cancer burdens by systems provides important information for specialists, policymakers, and specific risk populations. METHODS: The aim of this study was to compare the current and future cancer burdens of the gastrointestinal (GI) and respiratory tracts in terms of their magnitude and distribution. Data from a total of eight cancers of the digestive and respiratory tracts in the Global Burden of Disease (GBD) database were collected. The age-standardized incidence/death rates (ASIR/ASDRs), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) were analyzed. Future trends were predicted with Bayesian age-period-cohort (BAPC) and NORDPRED models. RESULTS: In 2019, there was a significant increase in DALY for both digestive and respiratory tract cancers compared to 1990. Meanwhile, ASIR increased slightly and ASDR decreased notably. In 2019, the global cancer burdens of respiratory and digestive tracts were 38568363.53 and 66912328.72 in DALY, 34.28 and 55.32 in ASIR, and 656.82 and 808.22 in ASDR per 100,000 population with changes of +54.63% and +43.93%, +2.92% and +5.65%, and -17.39% and -26.83% compared to those in 1990, respectively. Significant cross-regional differences in the cancer burdens were observed among the regions. Compared to four representative chronic diseases, the burden of cancers showed less remission and greater global inequalities. The burdens of both digestive and respiratory tract cancers were higher in males than in females in terms of the ASIR, ASDR, and DALY. The incidence and mortality rates of respiratory tract cancers were up to 3-4 times higher in males than in females, whereas the difference between male and female rates of digestive tract cancers was relatively smaller. The main risk factor associated with all kinds of digestive and respiratory tract cancers is tobacco, leading to 18.5 in ASDR and 3.38×107 in DALY for respiratory tract cancers; 8.29 in ASDR and 1.60×107 in DALY for digestive tract cancers, in 2019. Additionally, alcohol use contributes to most digestive and respiratory tract cancers (1.23/1.03 in ASDR and 1.60×106/2.57×106 in DALY for respiratory tract cancers; 4.19/3.82 in ASDR and 4.49×106/8.06×106 in DALY for digestive tract cancers), except for stomach cancer and tracheal, bronchus, and lung cancer. The cancer burdens of respiratory and digestive tracts are likely to decrease substantially between 2020 and 2044. For most metrics, except for the ASIR and male-to-female ratios of ASDR and ASDALY in digestive tract cancers, the worldwide variances of burden metrics have been decreasing in the past decades and will possibly maintain stable trends in the future. CONCLUSIONS: The epidemiology of respiratory and GI tract cancers has common features and individual characteristics that are reflected in geography, age characteristics, and risk factors. Current epidemiological status, future trends, and the globalization of these disease burdens are important factors for making scientific planning of resources to minimize the cancer burden metrics and their cross-regional inequalities.

Air pollution and mortality for cancer of the respiratory system in Italy: an explainable artificial intelligence approach.

Respiratory system cancer, encompassing lung, trachea and bronchus cancer, constitute a substantial and evolving public health challenge. Since pollution plays a prominent cause in the development of this disease, identifying which substances are most harmful is fundamental for implementing policies aimed at reducing exposure to these substances. We propose an approach based on explainable artificial intelligence (XAI) based on remote sensing data to identify the factors that most influence the prediction of the standard mortality ratio (SMR) for respiratory system cancer in the Italian provinces using environment and socio-economic data. First of all, we identified 10 clusters of provinces through the study of the SMR variogram. Then, a Random Forest regressor is used for learning a compact representation of data. Finally, we used XAI to identify which features were most important in predicting SMR values. Our machine learning analysis shows that NO, income and O3 are the first three relevant features for the mortality of this type of cancer, and provides a guideline on intervention priorities in reducing risk factors.

Surgical treatment of 186 sinonasal inverted papillomas and analysis of the immunohistochemical and molecular features associated with recurrences.

INTRODUCTION: Inverted papillomas (IP) are benign epithelial tumors with a tendency to be locally invasive and with disposition to recur. The aim of our study is to present the results of IP treatment, considering pathological, immunohistochemical and molecular features of recurrence. MATERIAL AND METHODS: From 1978 to 2020, 186 sinonasal IPs surgeries corresponding to 152 patients were treated in our center. We performed a pathology evaluation of all the recurrent cases reviewing the histological diagnosis, the presence of mixed component other than IP, the koilocytic changes, the p16 over expression and HPV-DNA detection. RESULTS: Overall recurrence rate was 19 % (35/186). The 35 IP recurrences correspond to 22 patients, 9 of whom presented a single recurrence (single recurrence group) while 13 of them presented more than one recurrence (multi-recurrent group). Immunohistochemical analysis showed a higher percentage of p16 overexpression (54 % vs 33 % p = 0.415) and HPV-DNA presence (23 % vs 0 % p = 0.240) in the multi-recurrent group compared with single recurrence group. In addition, the revision showed more IP with exophytic papilloma focus (38 vs 22 % p = 0.648) and a higher proportion of IP with koilocytotic changes (61 % vs 22 % p = 0.099) in the multirecurrent group. There is no significant difference between groups in our results. CONCLUSION: The analysis of our patients may differentiate between two groups with recurrent papillomas. A single recurrence group where the cause of recurrence is probably an anatomical problem related to an incomplete resection, and a second pattern, the multi-recurrence group, where HPV infection may be the main cause of recurrence.

Multiparametric MRI-based radiomics nomogram for predicting malignant transformation of sinonasal inverted papilloma.

AIM: To investigate the feasibility of a radiomics nomogram model for predicting malignant transformation in sinonasal inverted papilloma (IP) based on radiomic signature and clinical risk factors. MATERIALS AND METHODS: This single institutional retrospective review included a total of 143 patients with IP and 75 patients with IP with malignant transformation to squamous cell carcinoma (IP-SCC). All patients underwent surgical pathology and had preoperative magnetic resonance imaging (MRI) and computed tomography (CT) sinus studies between June 2014 and February 2022. Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1WI), T2-weighted images (T2WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) were performed to select the features extracted from the sequences mentioned above. Independent clinical risk factors were identified by multivariate logistic regression analysis. Radiomics nomogram was constructed by incorporating independent clinical risk factors and radiomics signature. Based on discrimination and calibration, the diagnostic performance of the nomogram was evaluated. RESULTS: Twelve radiomics features were selected to develop the radiomics model with an area under the curve (AUC) of 0.987 and 0.989, respectively. Epistaxis (p=0.011), T2 equal signal (p=0.003), extranasal invasion (p<0.001), and loss of convoluted cerebriform pattern (p=0.002) were identified as independent clinical predictors. The radiomics nomogram model showed excellent calibration and discrimination (AUC: 0.993, 95% confidence interval [CI]: 0.985-1.00 and 0.990, 95% CI: 0.974-1.00) in the training and validation sets, respectively. CONCLUSION: The nomogram that the combined radiomics signature and clinical risk factors showed a satisfactory ability to predict IP-SCC.

Outcome prediction for critical care patients with respiratory neoplasms using a multilayer perceptron neural network.

OBJECTIVE: The variation in mortality rates of intensive care unit oncological patients may imply that clinical characteristics and prognoses are very different between specific subsets of patients with cancer. The specific characteristics of patients with cancer have not been included as risk factors in the established severity-of-illness scoring systems and comorbidity scores, showing limitations in predicting mortality risk. This study aimed to devise a predictive tool for in-hospital mortality for adult patients with a respiratory neoplasm admitted to the intensive care unit, using an artificial neural network. METHODS: A total of 1,221 stays in the intensive care unit from the Beth Israel Deaconess Medical Center were studied. The primary endpoint was the all-cause in-hospital mortality prediction. An artificial neural network was developed and compared with six severity-of-illness scores and one comorbidity score. Model building was based on important predictors of lung cancer mortality, such as several laboratory parameters, demographic parameters, organ-supporting treatments, and other clinical information. Discrimination and calibration were assessed. RESULTS: The AUROC for the multilayer perceptron was 0.885, while it was <0.74 for the conventional systems. The AUPRC for the multilayer perceptron was 0.731, whereas it was ≤0.482 for the conventional systems. The superiority of multilayer perceptron was statistically significant for all pairwise AUROC and AUPRC comparisons. The Brier Score was better for the multilayer perceptron (0.109) than for OASIS (0.148), SAPS III (0.163), and SAPS II (0.154). CONCLUSION: Discrimination was excellent for multilayer perceptron, which may be a valuable tool for assessing critically ill patients with lung cancer.

Non-destructive diagnostic testing of cardiac myxoma by serum confocal Raman microspectroscopy combined with multivariate analysis.

The symptoms of cardiac myxoma (CM) mainly occur when the tumor is growing, and the diagnosis is determined by clinical presentation. Unfortunately, there is no evidence that specific blood tests are useful in CM diagnosis. Raman spectroscopy (RS) has emerged as a promising auxiliary diagnostic tool because of its ability to simultaneously detect multiple molecular features without labelling. The objective of this study was to identify spectral markers for CM, one of the most common benign cardiac tumors with insidious onset and rapid progression. In this study, a preliminary analysis was conducted based on serum Raman spectra to obtain the spectral differences between CM patients (CM group) and healthy control subjects (normal group). Principal component analysis-linear discriminant analysis (PCA-LDA) was constructed to highlight the differences in the distribution of biochemical components among the groups according to the obtained spectral information. Principal component analysis was combined with a support vector machine model (PCA-SVM) based on three different kernel functions (linear, polynomial, and Gaussian radial basis function (RBF)) to resolve spectral variations between all study groups. The results showed that CM patients had lower serum levels of phenylalanine and carotenoid than those in the normal group, and increased levels of fatty acids. The resulting Raman data was used in a multivariate analysis to determine the Raman range that could be used for CM diagnosis. Also, the chemical interpretation of the spectral results obtained is further presented in the discussion section based on the multivariate curve resolution-alternating least squares (MCR-ALS) method. These results suggest that RS can be used as an adjunct and promising tool for CM diagnosis, and that vibrations in the fingerprint region can be used as spectral markers for the disease under study.

Occupational exposures in the rubber tire industry and risk of cancer: a systematic review.

OBJECTIVE: This study aimed at investigate the association between cancer and the rubber tire industry using indicators used to estimate exposure, such as duration or historical time period of exposure. METHODS: A systematic review using MEDLINE was carried out. The Preferred Reporting Items for Systematic Reviews (PRISMA) statement guided the systematic review. The Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) was used to analyze biases in the selected studies. RESULTS: A total of 240 articles were initially selected. Of these, 17 were included in this systematic review of 15 different cohorts and one case-control study. Five cohorts were composed of rubber industry employees including some who worked in the rubber tire industry, whereas the other 10 cohorts were composed exclusively of rubber tire industry employees. An increased risk of lung/respiratory cancer is possible in the oldest time periods without duration of exposure showing any association according to the analysis. The work areas of mixing and milling as well as compounding seem to be more specifically associated with this risk, which could be expected because of the exposure to fumes containing carcinogenic agents. CONCLUSIONS: Having worked in the rubber tire industry in the past, especially in milling, mixing as well as compounding may be associated with an increased risk of lung/respiratory cancer.

Papilomatosis laringea recurrente con compromiso pulmonar: reporte de caso / Recurrent laryngeal papillomatosis with pulmonary involvement: case report

La papilomatosis respiratoria recurrente es una enfermedad neoplásica causada por el virus del papiloma humano y caracterizada por el crecimiento de lesiones proliferativas exofíticas que afectan la mucosa de las vías respiratorias. En su epidemiología se presenta una distribución bimodal, con una forma juvenil en menores de 20 años, más agresiva, con múltiples lesiones papilomatosas y alta frecuencia de recurrencia, en comparación con la forma adulta. El compromiso pulmonar es poco frecuente y su manejo es un desafío. Se presenta el caso de un varón de 13 años con antecedente de papilomatosis laríngea desde los dos años. El paciente mostró dificultad respiratoria y múltiples nódulos estenosantes en laringe y tráquea, y varios quistes pulmonares visualizados en la tomografía de tórax. Se le realizó exéresis de las lesiones papilomatosas y traqueostomía. Recibió dosis única de bevacizumab 400 mg intravenoso y terapias respiratorias con evolución favorable, sin recurrencias en el seguimiento.

Recurrent respiratory papillomatosis is a neoplastic disease caused by the human papillomavirus and characterized by the growth of exophytic proliferative lesions affecting the mucosa of the respiratory tract. This condition has a bimodal age distribution; the juvenile form affects those under 20 years of age, is more aggressive and presents multiple papillomatous lesions and high frequency of recurrence, compared to the adult form. Pulmonary involvement is rare and challenging to treat. We present the case of a 13-year-old male with a history of laryngeal papillomatosis since the age of two years. The patient showed respiratory distress and multiple stenosing nodules in the larynx and trachea, as well as several pulmonary cysts identified on chest CT. The patient underwent excision of the papillomatous lesions and tracheostomy. Then, the patient received a single dose of intravenous bevacizumab 400 mg and respiratory therapies with favorable evolution, without recurrences during follow-up.

The Clinical Characteristics in Children with Sinonasal Inverted Papilloma: A Case Report and Review of the Literature.

Sinonasal inverted papilloma (SNIP) is one of the most common benign epithelial tumors but rarely occurs in children. The case of a 9-year-old Chinese boy, who presented with a left maxillofacial hump, nasal obstruction, and left nasal cavity and maxillary sinus masses under nasal endoscopy, is reported. The lesion was first diagnosed as a sinonasal tumor. However, to our surprise, the mass was determined to be an inverted papilloma after a detailed histological examination. We retrospectively reported the clinical data of this case and reviewed the relevant literatures on SNIP. This report aims to provide new insights into the clinical characteristics in children with SNIP and improve the understanding of this disease.

Frequent Recurrence of Sinonasal Inverted Papilloma With Carcinoma In Situ in a Multifocal Attachment Pattern: A Case Report and Review of the Literature.

Sinonasal inverted papilloma (SIP) is a benign tumor originating from the nasal cavity and paranasal sinuses. Sinonasal inverted papilloma is characterized by local infiltration, high recurrence, and malignant transformation, and its associated dysplasia ranges from mild, moderate, severe, carcinoma in situ (CIS) to invasive squamous cell carcinoma. Sinonasal inverted papilloma with carcinoma in situ (IPwCIS) is the highest degree of dysplasia, which is a stage of malignant transformation of IP. Surgical excision and proper adjuvant therapy can help reduce recurrence rates and suppress further deterioration. In this study, we present a patient with IPwCIS who developed 3 recurrences with a multifocal attachment pattern in less than 18 months. We report the clinical manifestations, development, and treatment process in detail. We also performed a literature review to analyze the characteristics of the disease. Despite comprehensive treatment methods, tumor recurrence and further deterioration of IPwCIS persist.

Evaluation of Inflammatory Blood Markers in Sinonasal Inverted Papilloma.

OBJECTIVE: Sinonasal inverted papillomas are benign neoplasms of the nasal cavity and paranasal sinuses. They have characteristic features such as a high risk of recurrence and possible malignant transformation. This study was conducted to investigate the relationship between sinonasal inverted papilloma and inflammatory blood markers. PATIENTS AND METHODS: Sixty-five patients who were diagnosed histologically as having sinonasal inverted papilloma and 65 age- and sex-matched healthy controls were included in the study. Inflammatory blood markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) of the patient and control groups were compared. RESULTS: There were no statistically significant differences between the patients and controls for white blood cell, platelet, hemoglobin, neutrophil, and lymphocyte counts (P > .05). No statistically significant difference was found between the patients and controls for NLR, PLR, RDW, MPV, and PDW (P > .05). In the logistic regression analysis model, which was created to investigate the effects of inflammatory blood markers in determining the patient group, the increase in the NLR and decrease in the PLR were found to be statistically significant factors (P = .008, P = .039). CONCLUSION: This is the first study in the literature to investigate the relationship between sinonasal inverted papilloma and inflammatory blood markers, and the results suggest that NLR and PLR may be used to distinguish patients with sinonasal inverted papilloma from controls.

A Giant Cardiac Hemangioma Encroaching on the Right Coronary Artery.

The cardiac hemangioma is a relatively rare cardiac tumor. It can occur in different locations in the heart. We describe a patient with a giant cardiac hemangioma encroaching on the right coronary artery who underwent a successful surgical resection. Complete resection of the tumor was achieved without damaging the function of the right coronary artery. Nonetheless, meticulous follow-up is required as recurrence is possible.

Nasal Septal Angiofibroma.

Juvenile nasopharyngeal angiofibroma is a benign vascular tumor seen predominantly in adolescent males in the second decade of life. Extranasopharyngeal angiofibroma includes vascular fibrous masses that occur outside the nasopharynx. The diagnosis of an angiofibroma is based on the clinical presentation and imaging, with biopsies being avoided to avoid excessive bleeding. Computed tomography scan is considered sufficient for the diagnosis of extranasopharyngeal angiofibroma as it clearly delineates and identifies the tumor.

Not Always a Thymoma - About a Mediastinal Cavernous Hemangioma.

A mediastinal cavernous hemangioma is difficult to distinguish from other types of mediastinal tumours. They are usually asymptomatic and incidentally discovered in an imaging study but can present with compressive symptoms or by infiltration of adjacent structures. A 64-year-old woman with a prior history of triple negative invasive carcinoma of the breast, under surveillance was referred after a Chest CT-scan showed a soft tissue 40x20 mm mediastinal mass, suggestive of a thymoma, and as such no tissue biopsy was obtained. A right-side uniportal VATS was performed, the anterior mediastinum dissected and the mass was exposed, and several anomalous veins were identified. Histopathology showed 36x31x15 mm mass, compatible with a cavernous hemangioma of the anterior mediastinum. This case, whilst not questioning the NCCN statement suggesting not doing a tissue biopsy, points to the fact that rare differential diagnosis, like a Cavernous Hemangioma do exist, and a careful and sound judgement is needed at all times.

Left Atrial Myxoma Infected With Fusobacterium Nucleatum.

Cardiac myxomas are the most common primary cardiac tumours in adults. Clinical presentation is variable, with few cases of infected myxomas reported in the literature. We describe a rare case of a 63-year-old patient who presented with splenic abscesses and a left atrial mass suggestive of emboligen myxoma. The patient underwent a successful emergency sur- gical excision of the atrial mass followed by splenectomy. Blood cultures were positive for Fusobacterium nucleatum, whereas the histopathological examination of the excised mass confirmed the presence of a myxoma with a marked inflammatory infiltrate. All these findings allowed us to confirm the diagnosis of definite infected myxoma. Some aspects related to the aetiology, diagnosis and management of this entity are discussed.

Association between human papillomavirus infection and malignant transformation of sinonasal inverted papilloma: A systematic review and meta-analysis.

PURPOSE: Although sinonasal inverted papilloma malignant transformation has not been entirely understood, some studies have suggested that human papillomavirus acts as a potential oncogenic agent in the progression of sinonasal inverted papilloma to squamous cell carcinoma. The purpose of this study was to assess the association between human papillomavirus infection and sinonasal inverted papilloma transformation, taking also into account human papillomavirus types and their distribution in different geographic areas. MATERIALS AND METHODS: The literature from the last 25 years was examined. The systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: A total of 163 malignant sinonasal inverted papilloma and 961 non-malignant sinonasal inverted papilloma were included in the overall analysis. From this sample it was possible to recognize a statistically significant increase in risk of malignancy of sinonasal inverted papilloma for human papillomavirus infection (OR = 2.43, 95 % CI: 1.45-4.08, I2 = 14.0 %). A positive association for patients with high-risk human papillomavirus types was noted (OR = 10.20, 95 % CI: 3.66-28.42, I2 = 15.9 %). In all the 3 geographical areas analyzed the presence of high-risk human papillomavirus significantly increased the probability of malignant transformation. CONCLUSIONS: High-risk human papillomavirus infection plays a key role in the malignant transformation of sinonasal inverted papilloma and its research during histological examination can be of paramount importance. More prospective studies are needed to help further tease out this association.

Urothelial carcinoma with tonsillar metastasis in a dog.

Given its unusual lymphatic drainage system, the tonsil is a rare site of metastasis, with few reports in the human and veterinary literature. Prognosis in cases of tonsillar metastasis is reportedly poor. We describe here a unique case of urinary bladder urothelial carcinoma (UC) with metastasis to the tonsil in an 11-y-old, spayed female, mixed-breed dog. At presentation, the patient had a history of a growing neck mass and increasing lethargy, hyporexia, weight loss, drooling, and diarrhea for 2 wk. A carcinoma was diagnosed by cytology. Given the poor prognosis, the patient was euthanized. Postmortem examination revealed masses in the inguinal region, cranioventral neck region including tonsil, and urinary bladder. Histologically, the masses were composed of large polyhedral cells arranged in dense sheets and nests with occasional large, clear, intracytoplasmic vacuoles. Neoplastic cells were multifocally positive for uroplakin III and cytokeratin 8/18 by immunohistochemistry. UC with metastasis to tonsil and lymph nodes was diagnosed.