Aerodigestive Tract Malignancies Research Articles

Pattern of Upper Aerodigestive Tract Malignancies, a Histo-pathological Experience at MMCH.

Background: Cancer of Upper aerodigestive tract is common. It was felt that at Muhammad Medical CollegeHospital (MMCH) Mirpurkhas, we are getting quite a few biopsies and specimen of the disease. Hence we decided to look at biopsies received and diagnosed as Cancer of Upper aerodigestive tract.Aims: To determine the histo-pathological variants and their grades that are predominant in areas around MMCHMethods: We looked at the records of 320 biopsies of Upper aerodigestive tract sent with a clinical diagnosis ofCarcinoma over the last 5 years.Results: 242/320 (75.7%) were found to be neoplastic whereas 78/320 (24.3%) were non neoplastic.Conclusions: Cancer of Upper aerodigestive tract is common is common in areas around MMCH.Keywords: Cancer, upper aerodigestive tract, oral cavity, esophagus, pharynx, and larynx.

Impact of Treatment Related Side Effects in Quality of Life of Patients with Head and Neck Cancer

Cancer is the leading cause of death in all parts of the world. Head and neck cancer (HNC) comprises a unique group of aero-digestive tract malignancies that include the seventh most common cancer in the world. As patients receiving chemotherapy would usually experience many side effects and these can affect their quality of life captiously. So that this study can be used in amelioration of the Quality of life of patients with head and neck cancer. By understanding the quality of life status, therapy could be optimized accordingly or take precautionary measures to avoid that specific effect. A Cross-sectional study was carried out among 25 samples in the Department of Oncology, ESI PGIMSR, Rajajinagar of Bengaluru. The data was collected by using EORTC QLQ C 30 and HNC 35 questionnaires and responses were recorded. All information was processed and analyzed by using Microsoft Excel. The majority of the subjects included in the study were males (23, 92%) followed by females (8, 8%) The highest number of subjects included in the study belonged to the 50-59 years age group (9, 36%) followed by 60-69 age group (8, 32%). Out of 25 study subjects, 15 patients had social habits of smoking (37%) Alcohol consumption (15,39%), tobacco chewing (5,13%) and No habits (4,11%). The Quality-of-Life score obtained from the 25 study subjects who were undergoing any treatment was found to have a neutral to good quality of life (not excellent). The average raw score and the respective linear score were found to be 4.16,52.66 for global health status, the Functional scale was found to have 1.76,74.8 and the Symptom scale was found to be 1.88,29.29. The correlation was done in SPSS software and found a negative value which interpreted as the increasing Side Effects is leading to the decline in quality of life.

Exploring The Potential of Human Papilloma Virus: An Overview

Human papillomavirus (HPV) infection is the most frequent viral sexually transmitted infection in the world. HPV is currently the most prevalent infection responsible for female cancers, with more than 90% of cervical cancers - the fourth deadliest malignancy in women- having been diagnosed. Additionally, genital and upper aerodigestive tract malignancies, as well as cutaneous and anogenital warts, are also linked to HPV infection. Cervical screening programs that are organized have the potential to be more effective than opportunistic screening programs. Nonetheless, screening programs have consistently been linked to lower cervical cancer incidence and mortality. Over the last 40 years, developed countries have achieved such a reduction in cervical cancer incidence and mortality. This is largely because of organized cytological screening and immunization programs. In women with no indication of previous or current HPV infection, HPV vaccinations are very efficient at preventing infection and illnesses caused by vaccine-specific genotypes. Despite the effective implementation of the HPV vaccination program in many nations around the world, challenges with HPV prevention and treatment of linked diseases will persist in developing and poor countries. This review provides an insight into various aspects of HPV infection.

Upper Aero-Digestive Tract Malignancies in Botswana: Clinicopathological Features and Human Papillomavirus Genotypes in an Hiv-Endemic Setting

Upper Aero-Digestive Tract Malignancies in Botswana: Clinicopathological Features and Human Papillomavirus Genotypes in an Hiv-Endemic Setting

PO-1225 Dysphagia and treatment prolongation due to CRT for upper aerodigestive tract malignancies

PO-1225 Dysphagia and treatment prolongation due to CRT for upper aerodigestive tract malignancies

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

P31 Trans-oral surgery alone in the management of upper aerodigestive tract malignancy – A case series

P31 Trans-oral surgery alone in the management of upper aerodigestive tract malignancy – A case series

319. SIGNIFICATIONS OF EXPRESSION OF TOLL-LIKE RECEPTORS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA CELLS

Abstract Well known risk factors of Esophageal squamous cell carcinoma (ESCC) are habit of alcoholic drinking, smoking and poor diet. Moreover, recent reports showed that poor oral health is associated with upper aerodigestive tract malignancies including ESCC. We previously reported that among 232 ESCC patients who had preoperative assessment of oral function by dentist, about 70% of patients were diagnosed with periodontitis and about half of those patients were needed dental extraction. Toll-like receptors (TLRs), a family of pattern recognition receptors, are able to recognize pathogen-associated molecular patterns (PAMPs) associated with a wide range of viruses, bacteria, fungi and parasites and thus play key roles in innate immune responses. Among these TLRs, TLR4 recognizes LPS, which construct the cell wall of gram-negative bacteria. Based on these findings, it is supposed that continuous exposure of LPS from gram-negative periodontal bacteria induces chronic inflammation caused by inflammatory cytokines from TLR4 signals, then carcinogenesis and progression of ESCC occurs. Among these TLRs, TLR4 recognizes LPS, which construct the cell wall of gram-negative bacteria. We reported that ESCC patients who had higher TLR4 expression status in resected main tumor specimen showed significantly poor overall survival compared to lower patients after esophagectomy. (Sato Y, et al. Esophagus 2020) On the other hand, TLR3 recognizes dsRNA released form cell invading viruses. We previously reported that ESCC patients who had higher TLR3 expression status in resected main tumor specimen showed significantly better overall survival compared to lower patients after esophagectomy. (Sato Y, et al. Am J Surg. 2018). Though TLR3 and TLR4 are in the same TLR family, those functional mechanism and relationships to prognosis in ESCC are totally different. Because TLR4 signaling is stimulatory on proliferative ability of ESCC, it is supposed that improvement of oral health inhibits carcinogenesis and progression of ESCC. On the other hand, because TLR3 signaling is suppressive, TLR3 agonist should be a possible candidate of therapeutic agent.

The Role of Modified Killian's Method in the Evaluation of Hypopharyngeal and Supraglottic Cancers.

Priyanka Schilling AmarObjectives Hypopharyngeal cancer is one of the upper aerodigestive tract malignancies with the poorest prognosis. The aim of this study was to assess the role of modified Killian's (MK) method in routine, outpatient-based flexible laryngoscopy to improve visualization and assess the extent of supraglottic and hypopharyngeal cancers. Materials and Methods An observational study was conducted in a tertiary hospital in India where fifty consecutive patients who presented to the outpatient clinic with suspected hypopharyngeal and supraglottic malignancy underwent a conventional laryngoscopy as well as MK method. The site and extent of the tumor on endoscopy were recorded and the videos were graded independently by two investigators on Murono's scale from 1 to 5. A subset of these patients who underwent direct laryngoscopy under general anesthesia was also scored with the above scale. The scores were compared to check the accuracy of flexible laryngoscopy with the MK method in staging cancer. Statistical Analysis Descriptive statistics were given using mean (standard deviation [SD]) for continuous variables and frequency (percentage) for categorical variables. The difference between the mean scores was analyzed using the paired-t test. The agreement between the scales and the observer, that is, the inter- and intraobserver agreement, was presented with concordance rate and Kappa weighted analysis. Results In this study, the mean scores of the Murono's scale grading of the conventional method, MK method, and direct laryngoscopy were 1.42 (SD: 0.64), 2.94 (SD: 0.95), and 4.30 (SD: 1.49), respectively, which showed significant improvement in scores with MK method. In addition, the subset analysis demonstrated a significant agreement between direct laryngoscopy and MK method. Conclusion The MK method is a good diagnostic test and a valuable adjunct to diagnostic flexible laryngoscopy in the evaluation and staging of hypopharyngeal and supraglottic cancers.

Investigating factors associated to dysphagia and need for percutaneous endoscopic gastrostomy in patients with head and neck cancer receiving radiation therapy.

Purpose: In this study we sought to investigate factors associated to dysphagia and subsequent need for percutaneous gastrostomy (PEG) usage, in patients with head and neck cancer receiving radiation therapy.Methods: The records of 123 patients with non-metastatic, stage I-IV head and neck cancer who were submitted to radiation therapy were retrospectively reviewed. Logistic regression models were used to investigate for associations between the outcomes of interest (grade ≥2 dysphagia and need for [PEG] usage) and potential predictive factors.Results: Mean dose to pharyngeal constrictor muscles (OR=1.08, p=.002), concurrent chemotherapy (OR=3.78, p=0.015) and upper aerodigestive tract malignancies (OR=3.27, p=0.044) were associated with dysphagia grade≥2. A threshold of constrictors mean dose for dysphagia manifestation was also identified at 43 Gy (OR=4.51, p=0.002). Need for PEG use was correlated with definitive treatment (OR=7.03, p=.022), nasopharyngeal (OR=12.62, p=0.003), upper aerodigestive tract (OR=9.12, p=0.007) or occult primary malignancies (OR=10.78, p=0.016).Conclusion: Patients suffering from upper aerodigestive tract malignancies, those with calculated constrictors mean dose >43 Gy, or planned to receive concurrent chemotherapy-radiotherapy should be closely monitored during treatment for dysphagia manifestation. Prophylactic PEG could be considered for patients receiving definitive therapy of the nasopharynx, upper aerodigestive tract or occult primary malignancies.

Narrow band imaging in early diagnosis of laryngopharyngeal malignant and premalignant lesions

Objectives: (1) To assess the diagnostic accuracy of narrow-band imaging (NBI) in the assessment of benign, premalignant, and malignant vocal fold lesions. (2) To evaluate the diagnostic value of NBI in detection of recurrence in upper aero-digestive tract malignancy.Methods: This was a prospective, observational study done between December 2018- November 2019 in the Department of Otolaryngology. One hundred six patients of suspected benign, premalignant, malignant lesions of larynx and hypopharynx along with recurrence cases of upper aerodigestive tract malignancy who have completed chemoradiation therapy. All patients were subjected to white light endoscopy (WLE), NBI, and biopsy for histopathological diagnosis. In WLE, laryngeal lesions were classified into three types: malignant, suspected malignant, and benign. NBI images were classified into 5 types based on the intrapapillary capillary loop (IPCL) patterns: Type I-IV were considered benign and Type V lesion was considered malignant. At the end, WLE and NBI findings were correlated with histopathological reports.Results: The diagnostic accuracy of NBI in diagnosing benign, premalignant, and malignant lesions is significantly better than WLE. The sensitivity of NBI in detecting malignant lesions is significantly greater than WLE. NBI has proved to be of great value in identifying lesions that could be missed by WLE alone, as combined sensitivity of NBI and WLE is significantly higher than WLE alone.Conclusion: NBI is an excellent technique for early detection of laryngopharyngeal malignancies with significantly higher sensitivity than WLE alone.

Hoarseness in an older adult: Ortner syndrome.

A detailed examination in an older adult presenting with chronic hoarseness is mandatory to exclude an upper aerodigestive tract malignancy. We describe a 71-year-old chronic smoker with essential hypertension who presented with hoarseness and vocal fatigue for 5 months. Laryngoscopic examination showed left vocal fold paralysis with phonation gap. No growth was seen at all laryngeal and hypopharyngeal subsites. The rest of the head and neck, chest, upper limbs and neurovascular examination were unremarkable. A plain chest radiograph demonstrated a cause for the left recurrent laryngeal nerve palsy. The diagnosis, complications and definitive management of the underlying cause and resultant voice problem will be discussed.

Comorbid Dysphagia and Malnutrition in Elderly Hospitalized Patients.

Elderly individuals account for one-third of all hospitalizations. The goal of this study was to evaluate the prevalence of dysphagia in elderly patients admitted to a tertiary care center. It also sought to investigate how dysphagia is identified, how it covaries with malnutrition and other conditions, and how it impacts hospital stay. Case Series. A retrospective chart review was performed. All patients >65 years admitted to a tertiary care center in January and February 2016 were included. Patients with primary psychiatric diagnoses and patients with upper aerodigestive tract malignancy or surgery were excluded. A total of 655 patients were identified. Mean age was 76.6 years. Twenty-four percent (155 patients) had dysphagia while 43% (282 patients) had malnutrition. Thirteen percent (84 patients) had both dysphagia and malnutrition. Fifty percent of patients who had malnutrition were seen by speech language pathology (SLP). One hundred percent of malnourished patients that saw SLP were identified as having dysphagia. Three hundred and eighty-two patients (58%) were seen by the dietician but not by SLP. Multiple logistic regression indicated that the presence of dysphagia was positively associated with age, presence of malnutrition, admission to either cardiology or neurology service as compared to medicine service, and history of stroke. One-quarter of elderly patients admitted to our tertiary care center had dysphagia. Dysphagia, especially when linked with malnutrition, has poorer outcomes and increased healthcare costs. Our data suggests a possible disconnect between malnutrition diagnosis and dysphagia identification. This is an important area of intervention that has the potential to improve the treatment and outcomes of these patients. 4 Laryngoscope, 131:2441-2447, 2021.

Diagnostic Yield and Therapeutic Impact of Face and Neck Imaging in Patients Referred with Otalgia without Clinically Overt Disease.

Otalgia may be secondary to serious pathology, such as upper aerodigestive tract malignancies, and CT or MR imaging of the skull base, face, and neck is often performed to detect clinically occult lesions. The diagnostic yield, management impact, and therapeutic impact of imaging in this clinical scenario, however, have yet to be elucidated. CT and MR imaging in patients who presented with otalgia without clinically overt disease was retrospectively analyzed from a single center over a 9-year period. The cohort was subdivided into groups, depending on the presence of additional symptoms and a history of head and neck cancer. Relevant diagnostic outcome findings were categorized, and the diagnostic yield and impact of imaging on management and therapy were calculated for each group. In our study cohort of 235 patients, the diagnostic yield of imaging for otalgia, with or without other symptoms, in patients who lacked a history of head and neck cancer was negligible for upper aerodigestive tract malignancy (1%), abnormalities related to otalgia (2%), and other moderate or major findings (2%). Although equivocal or unimportant findings occasionally resulted in additional investigations, the therapeutic impact was also very low (2%). The diagnostic yield for upper aerodigestive tract malignancy (34%) and therapeutic impact increased (34%) when there was a history of head and neck cancer. The diagnostic yield and therapeutic impact of imaging for otalgia without clinically overt disease are very low, unless there is a history of head and neck cancer.

Speech Therapy in the Treatment of Globus Pharyngeus: Development of a Mobile Application to Improve Patient Access

Introduction: Globus pharyngeus is a well-known disorder accounting for 3-4% of ENT referrals. Various treatment strategies have been proposed for this condition, including speech and language therapy. The aim of this article is to highlight the evidence-based approach to the development of a mobile application to improve patient access to speech therapy as a treatment for globus pharyngeus.Patients and Methods: A literature search was performed to identify articles exploring the use of speech therapy as a management option for this disorder. A survey of speech and language therapists (SLT) in the UK to determine patient access to this treatment and their views on the development of a mobile application is also described.Results: Four studies were identified, including one randomised controlled study. All articles demonstrate a significant improvement in symptoms following the use of speech therapy. SLTs from 27 departments responded to the survey. The globus pharyngeus patient workload was variable and in excess of 1000 patients per year in some departments. Most respondents supported the development of a mobile application for speech therapy for use by globus pharyngeus patients.Conclusion: Speech therapy is an effective treatment for globus pharyngeus patients. Speech therapy is not available in all NHS Trusts in England and some SLT departments have a high workload. Alternative methods for the delivery of this effective treatment should be considered including the use of mobile applications. It is important to rule out the possibility of upper aerodigestive tract malignancy before referring a patient for speech therapy.

P-228 SGNLVA-005: Open-label, phase 2 study of ladiratuzumab vedotin (LV) for aerodigestive tract malignancies

LIV-1 is a transmembrane protein with putative zinc transporter and metalloproteinase activity. It has been linked to the epithelial-to-mesenchymal transition that leads to malignant progression and metastasis. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death.

Sgnlva-005: Open-label, phase II study of ladiratuzumab vedotin (LV) for advanced aerodigestive tract malignancies.

TPS469 Background: LIV-1 is a transmembrane protein with putative zinc transporter and metalloproteinase activity. It has been linked to the epidermal-to-mesenchymal transition that leads to malignant progression and metastasis. Ladiratuzumab vedotin (LV), also known as SGN-LIV1A, is an investigational antibody-drug conjugate (ADC) targeting LIV-1 that is composed of a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. MMAE-linked ADCs can induce mitotic arrest and immunogenic cell death. In a phase 1 study, LV was well tolerated and showed antitumor activity in heavily pretreated patients (pts) with metastatic breast cancer (Modi et al 2017). The current study was initiated to evaluate LV in previously treated pts with advanced upper aerodigestive tract malignancies. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy (2.5 mg/kg IV every 3 weeks) for pts with the following advanced malignancies: gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer (NSCLC)-squamous, NSCLC-nonsquamous, and head and neck squamous cell carcinoma. Up to approximately 30 pts with unresectable locally advanced or metastatic disease, measurable disease per RECIST v1.1, an ECOG score of 0 or 1, and adequate organ function are enrolling in each of the cohorts. Pts in the gastric and GEJ adenocarcinoma and esophageal squamous cell carcinoma cohorts must have received no more than 1 prior line of platinum-based cytotoxic chemotherapy and pts in the gastric and GEJ adenocarcinoma cohort should have received prior anti-PD(L)1 therapy if indicated. The study consists of a 2-stage design that includes a Bayesian predictive probability of success approach to determine futility criteria. Study objectives include objective response rate (primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study enrollment is ongoing in North America. Pts will also enroll in Europe and Asia. Clinical trial information: NCT04032704.

Demography and Pattern of Tobacco Usage in Carcinoma of Upper Aerodigestive Tract.

Upper aerodigestive tract (UADT) malignancies account for significant proportion of all malignancies. The aim of the study is to know the demography and patterns of tobacco consumption and the proportion of non-tobacco consumers in patients with UADT carcinoma. Patient diagnosed with primary UADT carcinoma visiting outpatient department in a tertiary centre from February 2009 to May 2011 were included in the study. 150 patients were documented with UADT carcinoma and analysed. Among these 133 were males and 17 were female. 40% of them had smoking, 25% had smokeless tobacco, 13% had both smoking and smokeless tobacco and 22% hadn't had any form of tobacco. Carcinoma larynx is the most common site and glottis is the commonest subsite. Most individuals who developed UADT carcinoma have used tobacco in some form. The high proportion of UADT carcinoma in non-tobacco consumer is alarming.

Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction.

Biliary reflux has been considered a potential risk factor in upper aerodigestive tract malignancies. It is not yet clearly known how pH affects the bile‐induced activation of NF‐κB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applications of conjugated primary bile acids with unconjugated secondary bile acid, deoxycholic acid (DCA), on human hypopharyngeal primary cells reveal that strongly acidic pH (4.0) optimally enhances the tumorigenic effect of bile, by inducing activation of NF‐κB, STAT3 nuclear translocation, bcl‐2 overexpression and significant overexpression of the oncogenic mRNA phenotype, compared to weakly acidic pH (5.5) or neutral pH (7.0). As the pH becomes less acidic the partially activated primary bile acids and activated DCA begin to exert their influence; however, with significantly less intensity compared to bile acids at strongly acidic pH. Our findings suggest that biliary tumorigenic effect is strongly pH dependent. Controlling pH during reflux events may be therapeutically effective in reducing the potential risk of bile‐induced hypopharyngeal cancer.

Improving target localization during trans-oral surgery with use of intraoperative imaging.

Trans-oral surgery provides a less invasive means for the surgical management of upper aerodigestive tract malignancies but is limited in its ability to readily assess submucosal tumor extent and location of critical structures intraoperatively. We sought to determine surgeons' baseline target localization accuracy during operative laryngoscopy with preoperative imaging alone and then assess for improvement in localization accuracy when presented with intraoperative CT imaging capturing soft tissue deformation. Fiducial beads were placed submucosally in four cadaver heads. "Preoperative" (PO) and "intraoperative" (IO) neck CTs were acquired before and during suspension laryngoscopy using a CT-compatible laryngoscopy system. Surgeons attempted to localize submucosal fiducials beads using pins based on sequential review of PO and IO images. Mean total error (TE) decreased from 12.8 ± 9.9 to 10 ± 7.5mm from PO to IO (P < 0.001), respectively. TE for base of tongue and vallecula decreased by 1.7 ± 6.7mm (P = 0.015). Right-sided structures were most exposed by scope positioning and experienced a TE reduction of 4.8 ± 9.3mm (P < 0.001). Task completion time decreased from PO to IO by 26% (P < 0.001). Intraoperative imaging significantly improves localization accuracy and task efficiency when targeting submucosal beads in cadaver heads during operative laryngoscopy.