Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

Objective: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors.

Methods: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274].

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

Objectives: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC.

Risk Stratification in Oral Cancer: A Novel Approach.

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines.

Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication.

Background: Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well-established features like perineural invasion (PNI), differentiation, and lymphovascular-invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3-4).

Detection of High-Risk Human Papillomavirus in Oral Cavity Squamous Cell Carcinoma Using Multiple Analytes and Their Role in Patient Survival.

Purpose: Accurate detection of human papillomavirus (HPV) in oral cavity squamous cell carcinoma (OSCC) is essential to understanding the role of HPV in disease prognosis and management of patients. We used different analytes and methods to understand the true prevalence of HPV in a cohort of patients with OSCC with different molecular backgrounds, and we correlated HPV data with patient survival.

Methods: We integrated data from multiple analytes (HPV DNA, HPV RNA, and p16), assays (immunohistochemistry, polymerase chain reaction [PCR], quantitative PCR [qPCR], and digital PCR), and molecular changes (somatic mutations and DNA methylation) from 153 patients with OSCC to correlate p16 expression, HPV DNA, and HPV RNA with HPV incidence and patient survival.

Improving Bethesda Reporting in Thyroid Cytology: A Team Effort Goes a Long Way and Still Miles to Go….

Context: Fine-needle aspiration cytology is the first step in evaluation of thyroid nodules. Although the Bethesda classification for reporting thyroid cytology has been purported that this uniformity in reporting cytology thereby facilitating clinical decision-making, there are also studies indicating that the reporting percentage and the rates of malignancy in each category vary considerably from center to center making the clinical decision more difficult.

Aim And Materials And Methods: We looked at our retrospective cytology and histopathology data of thyroid nodules operated between 2012 and 2014 and then prospectively collected data during 2015-2016.

Sample preparation method considerations for integrated transcriptomic and proteomic analysis of tumors.

Sample processing protocols that enable compatible recovery of differentially expressed transcripts and proteins are necessary for integration of the multiomics data applied in the analysis of tumors. In this pilot study, we compared two different isolation methods for extracting RNA and protein from laryngopharyngeal tumor tissues and the corresponding adjacent normal sections. In Method 1, RNA and protein were isolated from a single tissue section sequentially and in Method 2, the extraction was carried out using two different sections and two independent and parallel protocols for RNA and protein.

The Jugaad Technique for Jaw Reconstruction: Denture Based Inverse Planning.

Aim: The aim of this clinical paper is to introduce a technique to plan for functional maxillofacial reconstructions.

Materials And Methods: Preoperative dental casts were made of the patient and mock surgery performed on the casts. A fibula analogue was then placed in an ideal functional reconstruction position.

Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition.

Chemoresistance leading to disease relapse is one of the major challenges to improve outcome in head and neck cancers. Cancer Stem Cells (CSCs) are increasingly being implicated in chemotherapy resistance, this study investigates the correlation between CSC behavior and acquired drug resistance in in vitro cell line models. Cell lines resistant to Cisplatin (Cal-27 CisR, Hep-2 CisR) and 5FU (Cal-27 5FUR) with high Resistance Indices (RI) were generated (RI ≥ 3) by short-term treatment of head and neck squamous cell carcinoma (HNSCC) cell lines with chemotherapeutic drugs (Cisplatin, Docetaxel, 5FU), using a dose-incremental strategy.

A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes.

Unlabelled: Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of aggressive tumors in the head and neck region that spread early to lymph nodes and have a higher incidence of regional failure. In addition, there is a rising incidence of oral tongue cancer in younger populations. Studies on functional DNA methylation changes linked with altered gene expression are critical for understanding the mechanisms underlying tumor development and metastasis.

Implant supported dental rehabilitation following segmental mandibular reconstruction- quality of life outcomes of a prospective randomized trial.

Purpose: The primary objective of this study was to assess the difference in quality of life (QoL) in patients with dental rehabilitation using two or four implant-supported overdentures following segmental mandibulectomy defect reconstruction with fibula free flap.

Material And Methods: This prospective, parallel designed, randomized clinical study was conducted with a 1:1 ratio. At baseline, all participants already had fibula flap reconstruction for segmental defects of the mandible and rehabilitation with conventional (non-implant supported) removable partial dentures.

Estimation of thyroglobulin in lymph node aspirates: Pilot experience from a tertiary referral cancer center.

Background: Assessment of cervical lymph node involvement in patients with thyroid cancer either during preoperative surgical mapping or detection of recurrences during follow-up is a crucial step in the management of differentiated thyroid cancers (DTCs). In most patients, fine needle aspiration cytology (FNAC) confirms the presence of metastasis in lymph node. However, in cases of paucicellular lymph node aspirate or discordant sonogram and cytology results, thyroglobulin (Tg) measurement in the lymph node aspirate (FNA-Tg) is useful and a value >1 ng/ml is considered consistent with metastatic disease.

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients.

Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) plays a role in the development and progression of epithelial malignancies. Measurements of urinary PGE-M, a stable metabolite of PGE2, reflect systemic PGE2 levels. Here, we investigated whether urinary PGE-M levels were elevated in healthy tobacco users and in patients with oral squamous cell carcinoma (OSCC).

Pathology of advanced buccal mucosa cancer involving masticator space (T4b).

Background: Buccal mucosa cancer involving masticator space is classified as very advanced local disease (T4b). The local recurrence rate is very high due to poor understanding of the extent of tumor spread in masticator space and technically difficult surgical clearance. The objective of this study is to understand the extent of tumor spread in masticator space to form basis for appropriate surgical resection.

Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence.

Oral tongue squamous cell carcinomas (OTSCC) are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs), indels, regions with loss of heterozygosity (LOH), and copy number variations (CNVs) from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV) infection and tumor recurrence.

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.

Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments.

Versatility of adipofascial anterolateral thigh flap for reconstruction of maxillary defects with infratemporal fossa extension.

Tumors arising from the posterior hard palate or posterolateral maxilla may extend to involve the infratemporal fossa (ITF). Resection of these tumors results in infrastructural maxillectomy with ITF defects. In this study, we describe the use of an adipofascial anterolateral thigh flap (ALT) specifically for such defects.

Factors predicting outcome after salvage treatment for stage IV oral squamous cell carcinoma: Evidence of the potential importance of the cyclooxygenase-2-prostaglandin E2 pathway.

Background: We determined the clinicopathological factors that predicted outcome after salvage treatment for stage IV oral squamous cell carcinoma (OSCC). Additionally, the prognostic significance of the cyclooxygenase-2 (COX-2)/microsomal prostaglandin-E synthase-1 (mPGES-1) pathway was evaluated.

Methods: Thirty-one patients who underwent salvage surgery were included.

Inhibition of rapamycin-induced AKT activation elicits differential antitumor response in head and neck cancers.

The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear understanding of the underlying mechanisms in tumor signaling, the biomarker strategy for patient stratification is of limited use.

Reconstruction of large composite buccal defects using single soft tissue flap--analysis of functional outcome.

Resection of advanced gingivo-buccal tumors results in a posterolateral mandibular and large soft tissue defect. Because of large soft tissue requirement, these defects are difficult to reconstruct using a single osteocutaneous flap. A double free flap reconstruction of such defects is recommended.