Rajjyoti Das, Gopi Satya Sai Reddy Gontu, Kishore Das, Anupam Das, Tashnin Rahman, Ashok Kumar Das, Kaberi Kakati
Publication date 11-07-2022
Kaviyarasi Renu, Vishnu Priya Veeraraghavan, Thirumal Raj A, Shankargouda Patil, Abilash Valsala Gopalakrishnan
Publication date 10-07-2022
Ciara Mulvihill, Kirsten Fitzgerald, Esther ORegan, Claire M. Healy, Timothy Ronan Leahy
Publication date 10-07-2022
Sandrine Vlavonou, Pierre-Antoine Laurent, Bertrand Gachot, Nadia Benmoussa
Publication date 12-07-2022
Venkatesh Kumaresan, Pitchiah Sivaperumal, A.S. Smiline Girija
Publication date 10-07-2022
Hai Huang, Lixia Li, Qinghua Cao, Haihua Jiang, Jun Li
Publication date 10-07-2022
Ciro Dantas Soares, Thalita Santana, Lucas Lacerda de Souza, Oslei Paes de Almeida, Alena Skálová, Albina Altemani, Alexandre de Oliveira Sales
Publication date 09-07-2022
Gargi S. Sarode, Nidhi Kumari, Sachin C. Sarode
Publication date 07-07-2022
Devaraj Ezhilarasan, Karthik Shree Harini, Thangavelu Lakshmi
Publication date 06-07-2022
Amith K.P, Shalini Thakur, Suresh Hanagvadi, K.S.N. Siva Bharani
Publication date 06-07-2022
Hemophilia is a hereditary disorder of coagulation that results in deficiency of factor VIII (Hemophilia A) or Factor IX (Hemophilia B) with characteristic X linked mode of inheritance, almost exclusively seen in males while females are asymptomatic carriers.
The common clinical manifestation in both is prolonged bleeding on trivial trauma, mainly into larger joints or muscles. Life threatening bleeding episodes can result spontaneously or from trauma to the head or internal organs. Replacement of deficient clotting protein, known as Anti Hemophilic Factor (AHF) is the main stay in the treatment of haemophilia. Any Surgical treatment of these patients is to be planned in Institution hospital where comprehensive care is available. The availability of AHF has enabled surgeons to take up surgeries in patients with haemophilia. We discuss PWH with congenital factor VIII deficiency presented with oral squamous cell carcinoma of left side lower jaw with main aim is to provide insight into surgical management and care protocol of these patients.
Patrick Tassone, Carla Caruso, Meghan White, Harim Tavares Dos Santos, Tabitha Galloway, Laura Dooley, Robert Zitsch, J. Lester Layfield, Olga Baker
Publication date 03-07-2022
The mechanisms of perineural invasion (PNI) in oral cavity squamous cell carcinoma are only partially understood, and no studies have specifically investigated the role of perineural fibroblasts in PNI. Here, we identified fibroblasts within the microenvironment of perineural invasion and assessed their expression of matrix metalloproteinase-2 (MMP-2). Tumor specimens from 12 patients with oral cavity squamous cell carcinoma and pathologically-confirmed perineural invasion were stained by immunohistochemistry (IHC) for vimentin (positive control) and MMP-2. Scoring was quantified and compared at nerves involved with PNI and nerves uninvolved with PNI. All 12 patients had perineural fibroblasts around involved and uninvolved nerves as marked by vimentin IHC staining. Perineural fibroblasts had detectable MMP-2 expression at areas of perineural invasion in all 12 patients, but no patients had MMP-2 expression by fibroblasts at nerves without PNI. MMP-2 is expressed by fibroblasts within the microenvironment of perineural invasion, and MMP-2 expression by fibroblasts is a possible mechanism of perineural invasion by oral cavity squamous cell carcinoma. MMP-2 may be an anti-cancer target among oral cavity squamous cell carcinoma patients with PNI.
Pubmed PDF WebKannan Balachander, Arumugam Paramasivam
Publication date 01-07-2022
Satya Ranjan Misra, Rupsa Das
Publication date 01-07-2022
Marcia Frias Pinto Marinho, Maria Clara Frias Lobo Marinho, Bruno Augusto Benevenuto de Andrade, Maria Augusta Visconti Rocha Pinto, Aline Corrêa Abrahão, Mário José Romañach, Michelle Agostini
Publication date 01-07-2022
Xi Yang, Xiujuan Yang, Tong Ji, Qin Zhou, Wei Liu
Publication date 30-06-2022
Shyamaladevi Babu, Madhan Krishnan, Vishnu Priya Veeraraghavan, Selvaraj Jayaraman
Publication date 29-06-2022
Siyi Li, Rongrong Li, Jing Xia, Zhen Zhang, Longwei Hu, Shijian Zhang, Jingjing Sun, Liya Wang, Lei Wang, Mengli Huang, Chen Hao, Beibei Wang, Jiang Li, Chenping Zhang
Publication date 28-06-2022
Luca Calabrese, Riccardo Nocini, Francesca Spirito, Luca Gazzini, Virginia Dallari, Ilaria Girolami, Lorenzo Lo Muzio
Publication date 28-06-2022
Joab Cabral Ramos, Luan César Silva, Isabel Schausltz Pereira Faustino, Ana Carolina Evangelista Colafemina, Mariana de Pauli Paglioni, Amanda Almeida Leite, Alan Roger Santos-Silva, Pablo Agustin Vargas, Marcio Ajudarte Lopes
Publication date 28-06-2022
Oral squamous cell carcinoma (OSCC) of the gingiva represents less than 6% of intraoral carcinomas. A 51-year-old male patient presented with a history of a symptomatic red spot with periods of remission and recurrence in the mandibular gingiva. On clinical examination red and white areas were observed in the gingiva, particularly around the left lower molars. Diagnosis of gingival lichen planus was suspected and topical corticosteroids was prescribed. A good clinical response was observed with reduction of symptom. The patient remained in regular follow-up and after 9 months, the lesion suddenly changed, became ulcerated and diagnosis of OSCC was established. The clinical manifestation of OSCC can eventually mimic other even more common lesions of the oral mucosa, highlighting the importance of considering OSCC as differential diagnosis of any unexplained and persistent lesion in the oral cavity.
Pubmed PDF WebKarthik Shree Harini, Devaraj Ezhilarasan, Thangavelu Lakshmi
Publication date 27-06-2022
Duraisamy Revathi, Ganapathy Dhanraj, V Ashok
Publication date 26-06-2022
Jessica L. Allen, River A. Hames, Natalie M. Mastroianni, Andrew E. Greenstein, Scott A. Weed
Publication date 09-07-2022
Locoregional and lymphovascular involvement of invasive head and neck squamous cell carcinoma (HNSCC) complicates curative treatment. Matrix metalloproteinase (MMP) 9 is a negative prognostic marker in HNSCC and targets multiple extracellular matrix (ECM) substrates, where it contributes to breaching basement membrane and stromal barriers enabling invasive spread. Andecaliximab (ADX) is a second-generation MMP9 inhibitor well tolerated in clinical trials of gastric and pancreatic adenocarcinoma. The impact of selective MMP9 targeting by ADX in HNSCC has not been evaluated. Established and patient-derived xenograft (PDX) cell lines were utilized in HNSCC invasion assays to determine the inhibitory ability of MMP9-mediated invasion by ADX. MMP9 expression was confirmed using immunohistochemistry (IHC) and immunoblotting. ECM degradation was evaluated with confocal microscopy. Cell invasion from tumor spheroids was monitored by phase microscopy. Histological evaluation was used to determine ADX efficacy in three-dimensional organotypic cultures containing cancer associated fibroblasts (CAFs). MMP9 was expressed in all established and PDX-derived cell lines. While the broad spectrum clinical MMP inhibitor marimastat (BB2516) blocked HNSCC invadopodia function and tumor spheroid invasion, ADX treatment failed to inhibit invadopodia-based matrix degradation, tumor cell or fibroblast-driven ECM invasion in collagen I-based matrices. ADX monotherapy was ineffective at blocking initial MMP-dependent events of HNSCC invasion, likely due to redundant functions of additional non-targeted MMPs produced by tumor cells and microenvironment. Combination of ADX with existing and emerging therapies targeting additional MMP activation pathways may warrant future investigation.
Pubmed PDF WebAntonio Ferrer-Sánchez, Jose Bagan, Joan Vila-Francés, Rafael Magdalena-Benedito, Leticia Bagan-Debon
Publication date 29-06-2022
To estimate the probability of malignancy of an oral leukoplakia lesion using Deep Learning, in terms of evolution to cancer and high-risk dysplasia. A total of 261 oral leukoplakia lesions with a mean of 5.5 years follow-up were analysed from standard digital photographs. A deep learning pipeline composed by a U-Net based segmentation of the lesion followed by a multi-task CNN classifier was used to predict the malignant transformation and the risk of dysplasia of the lesion. An explainability heatmap is constructed using LIME in order to interpret the decision of the model for each output. A Dice coefficient of 0.561 was achieved on the segmentation task. For the prediction of a malignant transformation, the model provided a sensitivity of 1 with a specificity of 0.692. For the prediction of high-risk dysplasia, the model achieved a specificity of 0.740 and a sensitivity of 0.928. The proposed model using deep learning can be a helpful tool for predicting the possible malignant evolution of oral leukoplakias. The generated heatmap provides a high confidence on the output of the model and enables its interpretability.
Pubmed PDF WebLara Alessandrini, Marco Ferrari, Stefano Taboni, Marta Sbaraglia, Leonardo Franz, Tommaso Saccardo, Bianca Maria Del Forno, Francesca Agugiaro, Anna Chiara Frigo, Angelo Paolo Dei Tos, Gino Marioni
Publication date 28-06-2022
The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo-angiogenesis and cancer progression.
The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens.
TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases.
TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox's model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p < 0.0001 for both) and surgical specimens (p < 0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p = 0.0032; HR = 6.112, 95%CI: 1.833-20.378) and CD105-assessed MVD (p = 0.0002; HR = 1.201, 95%CI: 1.090-1.322) as DFS predictor. In paired surgical specimens, both TSR (p = 0.0074; HR = 6.137, 95%CI: 1.626-23.172) and CD105-assessed MVD (p = 0.0005; HR = 1.172 95 %CI 1.071-1.282) retained their significance in multivariate analysis.
If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy.
Wei Deng, Guiyi Zhao, Zhengshi Li, Le Yang, Yudong Xiao, Sien Zhang, Kaixin Guo, Chunqing Xie, Yujie Liang, Guiqing Liao
Publication date 26-06-2022
To investigate the recovery process of swallowing function and ascertain swallowing pattern in patients undergoing total glossectomy (TG).
A cohort study was conducted in consecutive patients with tongue squamous cell carcinoma who received TG/hemiglossectomy (HG) from May 2017 to December 2019. Exposure factors included tongue resection range (HG and TG) and postoperative radiotherapy (PRT and non-PRT). The swallowing functions were evaluated by M.
D. Anderson dysphagia inventory (MDADI), water swallow test (WST), and tongue pressure (TP) at pretreatment, 1, 4, 7, 12, 18 and 24 months postoperatively. Videofluoroscopy swallowing study (VFSS) was applied to analyze swallowing pattern of TG patients.
A total of 67 patients were enrolled, of which 17 underwent TG and 50 underwent HG. Both MDADI and TP of the TG and PRT group were lower than those of the HG and non-PRT group. TG patients had no evident improvement in MDADI and TP after surgery. There was a higher risk of swallowing unsafety with abnormal WST outcome in TG (P < 0.001, OR = 106.52) than that in HG. VFSS analysis identified prolonged oral and pharyngeal transit time, disorganized swallowing sequence, abnormal hyoid bone movement, and frequent invalid swallows in patients with TG. A shortened OTT (<5066.50 ms) and a larger pharyngeal constriction ratio (PCR > 0.31) were associated with increased risks of penetration and aspiration.
Postoperative swallowing pattern is a characteristic of severely impaired safety and efficacy in patients with TG. Impaired OTT and PCR are variables that should be examined when determining the need for rehabilitation treatment.
Corbin D. Jacobs, Ian Barak, Sin-Ho Jung, Daniel J. Rocke, Russel R. Kahmke, Gita Suneja, Yvonne M. Mowery
Publication date 26-06-2022
To develop and validate a prediction model to estimate overall survival (OS) with and without postoperative radiotherapy (PORT) for resected major salivary gland (SG) cancers.
Adults in the National Cancer Database diagnosed with invasive non-metastatic major SG cancer between 2004 and 2015 were identified. Exclusion criteria included prior malignancy, pT1N0 or unknown stage, no or unknown surgery, and neoadjuvant therapy. Cox proportional hazards models evaluated the effect of covariates on OS. A multivariate regression model was utilized to predict 2-, 5-, and 10-year OS. Internal cross-validation was performed using 50-50 hold-out and Harrell's concordance index.
18,400 subjects met inclusion criteria, including 9,721 (53%) who received PORT. Distribution of SG involvement was 86% parotid, 13% submandibular, and 1% sublingual. Median follow-up for living subjects was 4.9 years. PORT was significantly associated with improved OS for the following subgroups by log-rank test: pT3 (p < 0.001), pT4 (p < 0.001), high grade (p < 0.001), node-positive (p < 0.001), and positive margin (p < 0.001).
The following variables were incorporated into a multivariate model: age, sex, Charlson-Deyo comorbidity score, involved SG, pathologic T-stage, grade, margin status, ratio of nodal positivity, and PORT. The resulting model based on data from 6,138 subjects demonstrated good accuracy in predicting OS, with Harrell's concordance index of 0.73 (log-rank p < 0.001).
This cross-validated prediction model estimates 2-, 5-, and 10-year differences in OS based on receipt of PORT for resected major SG cancers using readily available clinicopathologic features. Clinicians can utilize this tool to aid personalized adjuvant therapy decisions.
Matti Sievert, Nicolai Oetter, Konstantinos Mantsopoulos, Antoniu-Oreste Gostian, Sarina K. Mueller, Michael Koch, Matthias Balk, Vivian Thimsen, Florian Stelzle, Markus Eckstein, Heinrich Iro, Miguel Goncalves
Publication date 25-06-2022
Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo microscope-like images of the upper aerodigestive tract's mucosa in 1000-fold magnification. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignoma suspected mucosa requires strict evaluation criteria. This study aims to validate a score for oral cavity squamous cell carcinoma (OCSCC) diagnostic. We performed CLE and examined a total of twelve patients. All 95 sequences (778 s, 6224 images) originate from the area of the primary tumor 260 s, 2080 images) and unsuspicious mucosa of the oral cavity (518 s, 4144 images). Specimen were taken at corresponding locations and analyzed histologically in H&E staining as a reference standard. A total of eight examiners (four experienced and four inexperienced) evaluated the sequences based on a scoring system. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are inter-rater reliability and receiver operator characteristics. Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 88.7 %, 90.1 %, 87.4 %, 87.5 %, and 90.0 %, respectively, with inter-rater reliability and κ-value of 0.775, and an area under the curve of 0.935. The results confirm that this scoring system is applicable in the oral cavity mucosa to classify benign and malignant tissue.
Pubmed PDF WebLi-Mei Wang, Yuan-Yuan Tian, Xiao-ming Liu, Ye Cao, Lei Sui, Chi Mao, Hao Liu, Jia-Hui Ye, Yong-Sheng Zhou, Xin Peng, Hong-Qiang Ye, Ying-Bin Yan
Publication date 25-06-2022
The purpose of this retrospective study was to compare the differences in quality of life (QOL) outcomes between the conventional obturator prostheses (COP) and the pedicled submental artery island flap (SAIF) in the reconstruction of Brown IIb maxillary defects. The QOL of 116 eligible patients who had a lapse ≥ 12 months after the cancer-related maxilla ablation was evaluated by the University of Washington quality of life scale (UW-QOL), Performance Status Scale for Head and Neck (PSS-HN), and Obturator Functioning Scale (OFS). Patients in the SAIF group reported statistically and clinically significant higher overall QOL scores but lower chewing scores in the UW-QOL scale when compared with those in the COP group (P < 0.05). Clinically significantly higher scores were also observed in the recreation and anxiety domains in the UW-QOL scale for the SAIF group, but there was no statistical significances. The COP group reported more complaints about the nasal leakage when swallowing and the shape of the upper lip, and had a stronger willingness to avoid family or social events in the OFS (P < 0.05). For patients with Brown IIb defects, SAIF reconstruction can achieve reduced nasal leakage when swallowing, improved upper-lip contour, increased social activity, and superior overall QOL than COP. The inferior chewing function in the SAIF group indicated the need for dental rehabilitation with a conventional denture or osseointegrated implants.
Pubmed PDF WebGilberto Melo, Carolina Amália Barcellos Silva, Angela Hague, Eric Kenneth Parkinson, Elena Riet Correa Rivero
Publication date 12-07-2022
The purpose of this review was to summarise available literature concerning the anticancer effects of both putative and validated BH3-mimetics in head and neck squamous cell carcinomas. A literature search was performed and studies assessing malignant cell lines, xenograft models, and/or humans were considered eligible. A total of 501 studies were identified, of which 40 were included. One phase-II clinical trial assessing gossypol (combined with docetaxel) was found. The remaining 39 preclinical studies investigated cell lines and/or xenograft models involving the use of six validated BH3-mimetics (A-1210477, A-1331852, ABT-737, navitoclax, S63845, venetoclax) and six putative BH3-mimetics (ApoG2, gossypol, obatoclax, sabutoclax, TW-37, and YC137). In preclinical settings, most validated BH3-mimetics were capable of inducing apoptosis (in-vitro) and tumour growth inhibition (in-vivo). The majority of putative BH3-mimetics were also capable of inducing cell death, although important off-target effects, such as autophagy induction, were also described. Combinations with conventional anticancer drugs, ionising radiation, or multiple BH3-mimetics generally resulted in enhanced anticancer effects, such as increased sensitivity to apoptotic stimuli, especially considering some cell lines that showed resistance to either treatment alone. In conclusion, although clinical data are still insufficient to evaluate the anticancer effects of BH3-mimetics in head and neck squamous cell carcinomas, promising results in preclinical settings were observed concerning induction of cell death and inhibition of tumour growth. Therefore, further clinical trials are highly encouraged.
Pubmed PDF WebSarah C. Nyirjesy, Margaret Heller, Natalia von Windheim, Amelia Gingras, Stephen Y. Kang, Enver Ozer, Amit Agrawal, Matthew O. Old, Nolan B. Seim, Ricardo L. Carrau, James W. Rocco, Kyle K. VanKoevering
Publication date 10-07-2022
Microvascular free flap reconstruction has remained the standard of care in reconstruction of large tissue defects following ablative head and neck oncologic surgery, especially for bony structures. Computer aided design/computer assisted manufacturing (CAD/CAM) and 3-dimensionally (3D) printed models and devices offer novel solutions for reconstruction of bony defects. Conventional free hand techniques have been enhanced using 3D printed anatomic models for reference and pre-bending of titanium reconstructive plates, which has dramatically improved intraoperative and microvascular ischemia times. Improvements led to current state of the art uses which include full virtual planning (VP), 3D printed osteotomy guides, and patient specific reconstructive plates, with advanced options incorporating dental rehabilitation and titanium bone replacements into the primary surgical plan through use of these tools. Limitations such as high costs and delays in device manufacturing may be mitigated with in house software and workflows. Future innovations still in development include printing custom prosthetics, 'bioprinting' of tissue engineered scaffolds, integration of therapeutic implants, and other possibilities as this technology continues to rapidly advance. This review summarizes the literature and serves as a summary guide to the historic, current, advanced, and future possibilities of 3D printing within head and neck oncologic surgery and bony reconstruction. This review serves as a summary guide to the historic, current, advanced, and future roles of CAD/CAM and 3D printing within the field of head and neck oncologic surgery and bony reconstruction.
Pubmed PDF WebSaravanan Sekaran, Sivaperumal Pitchaiah, Dhanraj Ganapathy
Publication date 24-06-2022
Ilaria Pellegrini, Pasquale Quattrone, Gianpaolo Dagrada, Barbara Vischioni, Ester Orlandi, Elena Colombo, Lisa Licitra, Laura D. Locati
Publication date 23-06-2022
Dhanraj Ganapathy, Saravanan Sekaran, Sivaperumal Pitchaiah
Publication date 21-06-2022
Elisabetta Zanoletti, Giulia Tealdo, Leonardo Franz, Diego Cazzador, Piero Nicolai, Antonio Mazzoni
Publication date 21-06-2022
Kannan Balachander, Arumugam Paramasivam
Publication date 20-06-2022
Andrew W. Barrett, Brian S. Bisase
Publication date 20-06-2022
Dani Stanbouly, Elizabeth Philipone, Anthony B. Morlandt, Arshad Kaleem, Sung-Kiang Chuang, Neel Patel
Publication date 20-06-2022
The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes. This retrospective study was conducted using the FDA Adverse Event Reporting System (FAERS). The predictor variables were patient characteristics, country of treatment, and adverse events. The outcome variable was the rate of serious outcomes. Multivariate logistic regression was created to identify all significant risk factors of the outcome. P < 0.05 was considered statistically significant. The final sample consisted of 3,086 reports of adverse events from cetuximab therapy in head and neck cancer treatment, of which 2,746 reports were considered serious (89.0%) per the FAERS criteria. Mucosal inflammation was the most common adverse event. The strongest risk factor for a serious outcome was cetuximab therapy in countries outside the US (OR 105.2, P < 0.01). Polytherapy (OR 7.6, P < 0.01) was also a risk factor for serious outcome. Health-care providers should be aware of potential complications following cetuximab administration, particularly when administered in countries outside the US and in conjunction with other medications.
Pubmed PDF WebPitchiah Sivaperumal, Saravanan Sekaran, Kannan Kamala, Dhanraj Ganapathy
Publication date 19-06-2022
Karthik Shree Harini, Devaraj Ezhilarasan, Thangavelu Lakshmi
Publication date 08-06-2022
Bipin T. Varghese, Sindhu P. Nair, Deepak Janardhan
Publication date 08-06-2022
Malignant change of intralaryngeal ectopic thyroid tissues to papillary thyroid cancer is extremely rare. A case that was successfully managed with a conservation surgery of the larynx and an interval total thyroidectomy is presented. High index of suspicion and optimised surgery yields the best outcome as demonstrated in the description.
Pubmed PDF WebFrancesca De Felice
Publication date 07-06-2022
Maria Gabriella Donà, Francesca Rollo, Barbara Pichi, Silvia Moretto, Renato Covello, Raul Pellini, Maria Benevolo
Publication date 07-06-2022
K. Shree Harini, Devaraj Ezhilarasan
Publication date 07-06-2022
Hsueh-Ju Lu, Chih-Yu Peng, Hsien-Chun Tseng, Chung-Han Hsin, Chun-Yi Chuang, Chun-Chia Chen, Wei-Shiou Huang, Yu-Wei Chiu, Shun-Fa Yang
Publication date 22-06-2022
In approximately 50% of patients with oral cavity squamous cell carcinoma (OCSCC), the disease progresses after curative surgery. However, the role of salvage surgery (SS) is controversial, and life expectancy after SS is unknown. In this study, 262 patients with OCSCC with locoregional recurrence and second primary OCSCC were retrospectively enrolled and divided into a resectable (55.0%, 144/262) and unresectable (45.0%, 118/262) groups. After excluding neck recurrence only, SS had been performed 195 times in the resectable group. The corresponding preoperative clinicopathologic factors and postsurgery survival (PSS) of each SS were pooled for analysis. Median survival after disease progression was 64.2 and 10.4 months for the resectable and unresectable groups, respectively. In the resectable group, one-fifth (19.5%, 37/190) of the patients died within 1 year of SS (PSS < 1 year), and one-third (32.8%, 64/195) of the patients had undergone SS two or more times. The interval from the last surgery ≤ 12 months, depth of invasion of the last surgery > 1 cm, and clinical evidence of nodal disease at the preoperative evaluation were independent predictors of poor PSS. A scoring prediction model was established with 1 point for each factor. The results revealed 1-year postsurgery death rates of 10.3% in the low-risk group (score: 0-1) and 48.6% in the high-risk group (score: 2 or 3) (P < 0.001). In conclusion, an effective scoring model predicting life expectancy after SS for patients with OCSCC was established.
Pubmed PDF WebJingfeng Zong, Pengjie Ji, Cheng Lin, Ruiting Zhang, Yuebing Chen, Qiongjiao Lu, Xiane Peng, Jianji Pan, Shaojun Lin
Publication date 22-06-2022
To evaluate the prognostic value of plasma Epstein-Barr virus DNA level following the completion of two induction chemotherapy cycles (ICT; post This retrospective study included 534 patients with LA-NPC. Recursive partitioning analysis (RPA) was applied to derive a prognostic model for risk stratification. Kaplan-Meier survival analysis was used to determine the survival results, and survival rates were compared using the log-rank test. The Cox proportional hazard model was used for univariate and multivariate analyses. Multivariate analyses revealed that post Plasma EBV-DNA level after two ICT cycles is a powerful predictor of prognosis in patients with LA-NPC. RPA analysis revealed that stage N3 patients with detectable post
Pubmed PDF WebYuxin Wu, Can F. Koyuncu, Paula Toro, German Corredor, Qianyu Feng, Christina Buzzy, Matthew Old, Theodoros Teknos, Stephen Thaddeus Connelly, Richard C. Jordan, Krystle A. Lang Kuhs, Cheng Lu, James S. Lewis, Anant Madabhushi
Publication date 12-06-2022
Tissue slides from Oral cavity squamous cell carcinoma (OC-SCC), particularly the epithelial regions, hold morphologic features that are both diagnostic and prognostic. Yet, previously developed approaches for automated epithelium segmentation in OC-SCC have not been independently tested in a multi-center setting. In this study, we aimed to investigate the effectiveness and applicability of a convolutional neural network (CNN) model to perform epithelial segmentation using digitized H&E-stained diagnostic slides from OC-SCC patients in a multi-center setting. A CNN model was developed to segment the epithelial regions of digitized slides (n = 810), retrospectively collected from five different centers. Deep learning models were trained and validated using well-annotated tissue microarray (TMA) images (n = 212) at various magnifications. The best performing model was locked down and used for independent testing with a total of 478 whole-slide images (WSIs). Manually annotated epithelial regions were used as the reference standard for evaluation. We also compared the model generated results with IHC-stained epithelium (n = 120) as the reference. The locked-down CNN model trained on the TMA image training cohorts with 10x magnification achieved the best segmentation performance. The locked-down model performed consistently and yielded Pixel Accuracy, Recall Rate, Precision Rate, and Dice Coefficient that ranged from 95.8% to 96.6%, 79.1% to 93.8%, 85.7% to 89.3%, and 82.3% to 89.0%, respectively for the three independent testing WSI cohorts. The automated model achieved a consistently accurate performance for automated epithelial region segmentation compared to manual annotations. This model could be integrated into a computer-aided diagnosis or prognosis system.
Pubmed PDF WebNannan Han, Xing Li, Yupu Wang, Huasheng Li, Chunye Zhang, Xiaomei Zhao, Zun Zhang, Min Ruan, Chenping Zhang
Publication date 12-06-2022
This study aimed to investigate the potential role of nidogen 1 (NID1), a basement membrane component, in the growth and metastasis of salivary gland adenoid cystic carcinoma (SACC) and the underlying molecular mechanism. High-throughput next-generation sequencing was used to compare the gene expression profiles of SACC with and without lung metastasis. Luciferase gene reporter assays were used to measure the NID1 promoter activity. BALB/c nude mice were used to establish a lung metastasis model of SACC to evaluate the prometastatic activity of NID1. ChIP and dual-luciferase reporter assays were performed to confirm the HIF-1α-binding site in the NID1 promoter. NID1 expression in SACC was significantly increased and associated with lung metastasis (P = 0.011). The elevated NID1 expression was a predictor of poor outcomes in patients with SACC (P < 0.05). Overexpression of NID1 promoted cancer cell migration and invasion through PI3K/AKT pathway activation and subsequent epithelial-mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and vimentin. Furthermore, in vivo live monitoring of a mouse model of lung cancer demonstrated the pro-metastatic role of NID1 in SACC cell lung metastasis. Hypoxia-inducible factor 1α (HIF-1α) upregulation via transfection of an HIF-1α-overexpressing plasmid enhanced HIF-1α binding to the NID1 promoter and the subsequent transcriptional activity and expression of NID1. HIF-1α-activated NID1 overexpression promotes SACC cell metastasis via PI3K/AKT pathway activation and EMT. Thus, NID1 could be a novel biomarker and therapeutic target for preventing metastasis and treating patients with SACC in future.
Pubmed PDF WebHui-Dan Luo, Feng-Jun Xia, Jia-Hui Wu, Bin Yi
Publication date 10-06-2022
The efficacy of chemoradiotherapy regimen in the treatment of stage Ⅳ nasopharyngeal carcinoma (Ⅳ NPC) is not clear. This retrospective study aimed to reveal the benefit of chemoradiotherapy in Ⅳ-NPC and to develop a survival prognostic model for the disease prediction. The Surveillance, Epidemiology, and End Results (SEER) database at https://seer.cancer.gov was retrieved for stage Ⅳ NPC patients between 2004 and 2016. The patients were divided into two groups of radiotherapy and chemoradiotherapy according to the treatment method. Overall survival (OS) and cancer-specific survival (CSS) between the groups were compared using Kaplan-Meier analysis, log-rank test, and propensity matching score (PSM). Cox proportional hazards model, nomogram, and receiver operating characteristic (ROC) curve were employed to establish the prognostic model. A total of 729 patients with Ⅳ NPC were introduced, of whom 44 received radiotherapy and 685 received chemoradiotherapy. Results of statistical tests demonstrated that chemoradiotherapy was associated with improved OS and CSS, especially in the patients with ⅣA NPC (P < 0.05); further multivariate analysis with PSM confirmed that chemoradiotherapy benefited the patients' OS (HR: 0.24, 95% CI: 0.12-0.50; P < 0.001). Moreover, the efficacy of chemoradiotherapy was found significantly correlated to metastasis. Even though chemoradiotherapy had an obvious survival benefit in patients without metastasis, it only helped to improve the CSS in those with metastases. This study indicated that chemoradiotherapy could improve the survival of NPC patients at stage ⅣA and non-metastasis. The nomogram we established may provide reference for clinical treatment of NPC.
Pubmed PDF WebZejia Yang, Jipei Liao, Lisa Schumaker, Brandon Carter-Cooper, Rena G. Lapidus, Xiaoxuan Fan, Daria A. Gaykalova, Ranee Mehra, Kevin J. Cullen, Hancai Dan
Publication date 07-06-2022
To identify the most effective PI3K and EGFR inhibitors in HPV-positive head and neck squamous cell carcinoma (HNSCC) and investigate the efficacy of a combination of an ErbB family kinase inhibitor and a PI3K inhibitor to inhibit cell proliferation of HPV-positive HNSCC.
HPV-positive HNSCC cell lines were treated with the FDA approved ErbB kinase inhibitor, Afatinib or FDA-approved PI3K inhibitor, Copanlisib, alone or in combination, and phosphorylation and total protein levels of cells were assessed by Western blot analysis.
Cell proliferation and apoptosis were examined by MTS assay, flow cytometry, and Western blots, respectively.
Copanlisib more effectively inhibited cell proliferation in comparison to other PI3K inhibitors tested. HPV-positive HNSCC cells differentially responded to cisplatin, Afatinib, or Copanlisib. The combination of Afatinib and Copanlisib more effectively suppressed cell proliferation and induced apoptosis compared to either treatment alone. Mechanistically, the combination of Afatinib and Copanlisib completely blocked phosphorylation of EGFR, HER2, HER3, and Akt as well as significantly decreased the HPV E7 expression compared to either treatment alone.
Afatinib and Copanlisib more effectively suppress cell proliferation and survival of HPV-positive HNSCC in comparison to either treatment alone.