Feasibility of Use of the 8th Edition of the American Joint Committee on Cancer Staging for Head and Neck Cancers in Indian Scenario: An Evaluative Study.

INTRODUCTION: Inclusion of depth of invasion (DOI) and a separate classification for human papillomavirus (HPV)-associated Oropharyngeal Cancers (OPCs) are two of the many major changes in the 8th edition of the American Joint Committee on Cancer staging system. After more than 2 years of implementation, the authors found the need to evaluate if the Indian clinicians found it feasible to apply the system in their practice and if the same has influenced their decision-making. METHODS: The survey was done in the form of a questionnaire which was distributed personally and via the internet to 100 clinicians. Seventy-two clinicians responded to the questionnaire. The results were analyzed and frequency distribution was computed. RESULTS: Eighty-three percent of the clinicians experienced that palpation of the tumour was not a reliable method to determine the DOI. The common issues stated by the clinicians were difficulty in assessing DOI in certain subsites of the oral cavity (most commonly retromolar trigone-83%), inability to determine DOI in patients with trismus, and inability to correlate pathological and clinical DOI. Thirteen percent of the clinicians did not rely on radiological tools for measuring the DOI. Seventy percent of the clinicians did not perform a P16 assay for patients with oropharyngeal cancers. Fifty percent of the clinicians preferred chemoradiotherapy for early HPV positive oropharyngeal cancers. DISCUSSION: Based on the results of the survey, the authors recommend a need for more interpretative guidelines and methods for determining the DOI. The authors also emphasize the need for determining HPV status for all oropharyngeal carcinomas.

Validation of a Point-of-Care Optical Coherence Tomography Device with Machine Learning Algorithm for Detection of Oral Potentially Malignant and Malignant Lesions.

Non-invasive strategies that can identify oral malignant and dysplastic oral potentially-malignant lesions (OPML) are necessary in cancer screening and long-term surveillance. Optical coherence tomography (OCT) can be a rapid, real time and non-invasive imaging method for frequent patient surveillance. Here, we report the validation of a portable, robust OCT device in 232 patients (lesions: 347) in different clinical settings. The device deployed with algorithm-based automated diagnosis, showed efficacy in delineation of oral benign and normal (n = 151), OPML (n = 121), and malignant lesions (n = 75) in community and tertiary care settings. This study showed that OCT images analyzed by automated image processing algorithm could distinguish the dysplastic-OPML and malignant lesions with a sensitivity of 95% and 93%, respectively. Furthermore, we explored the ability of multiple (n = 14) artificial neural network (ANN) based feature extraction techniques for delineation high grade-OPML (moderate/severe dysplasia). The support vector machine (SVM) model built over ANN, delineated high-grade dysplasia with sensitivity of 83%, which in turn, can be employed to triage patients for tertiary care. The study provides evidence towards the utility of the robust and low-cost OCT instrument as a point-of-care device in resource-constrained settings and the potential clinical application of device in screening and surveillance of oral cancer.

Metabolically Active Subacute Infarct Masquerading as Metastasis: A Finding not to be overlooked in Asymptomatic Oncology Patients.

A 50-year-old man with carcinoma of the right buccal mucosa underwent staging whole-body 18F-fluorodeoxyglucose positron emission tomography-computed tomography, which revealed a hypermetabolic heterogeneously enhancing lobulated primary lesion in the right buccal region and an incidental finding of subacute stroke. The case highlights the importance of discriminating brain neoplasms mimicking stroke from true ischemic stroke, which is crucial for appropriate management of patients in an oncology setting.

Sternal metastatectomy in a case of papillary thyroid carcinoma.

Thyroid cancer is the most common among endocrine cancers. Over 90% of all thyroid malignancies are differentiated thyroid carcinomas (DTC). However, only 2%-13% of DTC present with bone metastasis. Radioactive iodine ablation (RAI) is the treatment of choice for metastatic DTC. However, RAI therapy is not as effective in bone metastasis as it is in lung and visceral metastases. Only few cases of surgical management of bone metastasis in DTC have been reported in the literature. Here, we report a case of follicular variant of papillary thyroid carcinoma with sternal and lung metastases, for which sternal metastatectomy was performed.

Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers.

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously. The fluorescent PARP1 inhibitor can also detect oral carcinoma in a patient when applied as a mouthwash, and discriminate between fresh biopsied samples of the oral tumour and the surgical resection margin with more than 95% sensitivity and specificity. The PARP1 inhibitor could serve as the basis of a rapid and sensitive assay for the early detection and for the surgical-margin assessment of epithelial cancers of the upper intestinal tract.

A smart tele-cytology point-of-care platform for oral cancer screening.

Early detection of oral cancer necessitates a minimally invasive, tissue-specific diagnostic tool that facilitates screening/surveillance. Brush biopsy, though minimally invasive, demands skilled cyto-pathologist expertise. In this study, we explored the clinical utility/efficacy of a tele-cytology system in combination with Artificial Neural Network (ANN) based risk-stratification model for early detection of oral potentially malignant (OPML)/malignant lesion. A portable, automated tablet-based tele-cytology platform capable of digitization of cytology slides was evaluated for its efficacy in the detection of OPML/malignant lesions (n = 82) in comparison with conventional cytology and histology. Then, an image pre-processing algorithm was established to segregate cells, ANN was trained with images (n = 11,981) and a risk-stratification model developed. The specificity, sensitivity and accuracy of platform/ stratification model were computed, and agreement was examined using Kappa statistics. The tele-cytology platform, Cellscope, showed an overall accuracy of 84-86% with no difference between tele-cytology and conventional cytology in detection of oral lesions (kappa, 0.67-0.72). However, OPML could be detected with low sensitivity (18%) in accordance with the limitations of conventional cytology. The integration of image processing and development of an ANN-based risk stratification model improved the detection sensitivity of malignant lesions (93%) and high grade OPML (73%), thereby increasing the overall accuracy by 30%. Tele-cytology integrated with the risk stratification model, a novel strategy established in this study, can be an invaluable Point-of-Care (PoC) tool for early detection/screening in oral cancer. This study hence establishes the applicability of tele-cytology for accurate, remote diagnosis and use of automated ANN-based analysis in improving its efficacy.

Intra-operative point-of-procedure delineation of oral cancer margins using optical coherence tomography.

OBJECTIVES: Surgical margin status is a significant determinant of treatment outcome in oral cancer. Negative surgical margins can decrease the loco-regional recurrence by five-fold. The current standard of care of intraoperative clinical examination supplemented by histological frozen section, can result in a risk of positive margins from 5 to 17 percent. In this study, we attempted to assess the utility of intraoperative optical coherence tomography (OCT) imaging with automated diagnostic algorithm to improve on the current method of clinical evaluation of surgical margin in oral cancer. MATERIALS AND METHODS: We have used a modified handheld OCT device with automated algorithm based diagnostic platform for imaging. Intraoperatively, images of 125 sites were captured from multiple zones around the tumor of oral cancer patients (n = 14) and compared with the clinical and pathologic diagnosis. RESULTS: OCT showed sensitivity and specificity of 100%, equivalent to histological diagnosis (kappa, ĸ = 0.922), in detection of malignancy within tumor and tumor margin areas. In comparison, for dysplastic lesions, OCT-based detection showed a sensitivity of 92.5% and specificity of 68.8% and a moderate concordance with histopathology diagnosis (ĸ = 0.59). Additionally, the OCT scores could significantly differentiate squamous cell carcinoma (SCC) from dysplastic lesions (mild/moderate/severe; p ≤ 0.005) as well as the latter from the non-dysplastic lesions (p ≤ 0.05). CONCLUSION: The current challenges associated with clinical examination-based margin assessment could be improved with intra-operative OCT imaging. OCT is capable of identifying microscopic tumor at the surgical margins and demonstrated the feasibility of mapping of field cancerization around the tumor.

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. The cell lines (Cal-27 DoxR, Hep-2 DoxR, Hep-2 5FUR) that showed low RI, nevertheless had a high cross resistance to Cisplatin/5FU (P < 0.05). Cal-27 CisR and DoxR showed 12-14% enrichment of CD44+ cells, while CisR/5FUR showed 4-6% increase in ALDH1A1+ cells as compared to parental cells (P < 0.05). Increased expression of stem cell markers (CD44, CD133, NOTCH1, ALDH1A1, OCT4, SOX2) in these cell lines, correlated with enhanced spheroid/colony formation, migratory potential, and increased in vivo tumor burden (P < 0.05). Inhibition of ALDH1A1 in Cal-27 CisR led to down regulation of the CSC markers, reduction in migratory, self-renewal and tumorigenic potential (P < 0.05) accompanied by an induction of sensitivity to Cisplatin (P < 0.05). Further, ex vivo treatment of explants (n = 4) from HNSCC patients with the inhibitor (NCT-501) in combination with Cisplatin showed a significant decrease in proliferating cells as compared to individual treatment (P = 0.001). This study hence suggests an ALDH1A1-driven, CSC-mediated mechanism in acquired drug resistance of HNSCC, which may have therapeutic implications. © 2016 Wiley Periodicals, Inc.

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. New dentures were fabricated on the fibula analogue and drill holes for the placement of implants were placed through the denture. This denture formed as a guide to position the fibula transplant during surgery. RESULTS: This technique was useful in producing functional and rehabilitative outcomes in cases of both maxillary and mandibular reconstructive surgeries. CONCLUSION: The Jugaad technique-denture based inverse planning-is a cost effective method for planning and executing maxillofacial reconstructions using mock surgery on casts and interim dentures.

Implants in free fibula flap supporting dental rehabilitation - Implant and peri-implant related outcomes of a randomized clinical trial.

OBJECTIVES: The objective of this study was to assess the difference in success rates of implants when using two or four implant-supported-overdentures following segmental mandibular reconstruction with fibula free flap. METHODS AND DESIGNS: This prospective, parallel designed, randomized clinical study was conducted with 1:1 ratio. At baseline, all participants already had segmental reconstruction of mandible with free fibula flap. The participants were randomized into two groups: Group-I received implant-supported-overdentures on two tissue-level implants and Group-II received implant-supported-overdentures on four tissue-level implants. Success rates of the implants were evaluated at 3 months, 6 months and 12 months following implant loading using marginal bone level changes as well as peri-implant indices (Buser et al., 1990). RESULTS: 52 patients were randomized into two treatment groups (26 each), out of which 18 patients (36 implants) of Group-I and 17 patients (68 implants) of Group-II were evaluated. One implant in Group-I was lost due to infective complications and one patient in the same group had superior barrel necrosis. There was a statistically significant increase at both time points (p = 0.03, p = 0.04 at 6 months, 12 months) in the amount of marginal bone loss in Group-I (0.4 mm, 0.5 mm at 6 months, 12 months) as compared to Group-II (0.1 mm, 0.2 mm at 6 months, 12 months). There were no clinically significant changes peri-implant parameters between both groups. Peri-implant soft tissue hyperplasia was seen in both groups, 32% of implants at 3-months, 26% at 6-months and 3% at 12-months follow-up. CONCLUSION: The results of this study show that patients with 2-implant-supported-overdentures had higher marginal bone loss as compared to patients with 4-implant-supported-overdentures. There were no clinically significant differences in peri-implant soft tissue factors in patients with 2- or 4-implant-supported-overdentures. Hyperplastic peri-implant tissues are common in the early implant-loading phase and tend to decrease over time under appropriate management.

Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer.

The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance.

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. COX-2 and mPGES-1 levels were quantified by real time polymerase chain reaction (PCR). RESULTS: The 2-year disease-free and overall survival rates were 46% and 53%, respectively. Adequacy of initial treatment, tobacco smoking, and the presence of pathological risk factors were predictive of mortality. In patients who had not received chemotherapy before salvage surgery, high levels of intratumoral COX-2 and mPGES-1 were associated with poor prognosis. By contrast, high intratumoral COX-2 and mPGES-1 after chemotherapy were associated with improved outcomes. CONCLUSION: Clinicopathological factors may inform treatment decisions in patients with stage IV OSCC. Expression patterns of COX-2 and mPGES-1 correlated with outcome and warrant further investigation. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1142-1149, 2015.

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. This case series includes four patients who underwent an infrastructure maxillectomy with ITF clearance and the resultant defects were reconstructed using adipofascial anterolateral thigh flaps. The complications as well as the functional outcomes were assessed. This study included patients with lesions involving the hard palate, posterolateral part of maxilla with extension into the ITF. The mean flap dimension was 150 cm(2) (range, 120-180 cm(2)). All flaps were harvested based on a single perforator. The flap was used to obliterate the ITF defect and also to achieve oroantral separation. All flaps mucosalized well within 6 weeks. All patients were on oral diet and had adequate mouth opening. There were no donor-site complications. Adipofascial ALT is an excellent choice for infrastructural maxillectomy defects with ITF extension. The intraoral part got mucosalized well and provided a smooth and taut surface. A large adipofascial tissue flap helps obliterate the ITF, thus minimizing complications.

Selective neck dissection is effective in N1/N2 nodal stage oral cavity squamous cell carcinoma.

PURPOSE: Although the efficacy of selective neck dissection (SND) in the management of a node-negative neck is established, its utility in the management of node-positive disease remains controversial. The objective of this study was to evaluate the oncologic safety of SND in the management of N1/N2 oral cavity squamous cell carcinoma. MATERIALS AND METHODS: From a prospectively collected electronic database of patients with oral cavity cancer, a retrospective analysis was conducted of patients with nonrecurrent, clinical, and/or pathologic N1/N2 oral cavity squamous cell carcinoma who underwent SND of levels I to III/IV. The patients were stratified into 2 groups: clinical N0 but pathologic N1/N2 (cN0-pN1/N2) and clinical N1/N2 (cN1/N2). The primary outcome variable of the study was the ipsilateral regional recurrence rate. Categorical data were analyzed by the 2-sided Fisher exact test, and 3-year Kaplan-Meier ipsilateral regional control rate, regional recurrence-free survival, disease-free survival, and overall survival were estimated. RESULTS: Forty-nine patients constituted the study sample, with 37 patients in the cN1/N2 group and 12 patients in the cN0-pN1/N2 group. During the follow-up period of 3 years, 2 patients (∼4%) developed ipsilateral neck recurrence, and these patients were in the cN1/N2 group. The 3-year Kaplan-Meier ipsilateral regional control rate was 95%. CONCLUSIONS: SND may produce a satisfactory ipsilateral regional control rate in patients with early-stage node-positive oral squamous cell carcinoma. A prospective, randomized clinical trial comparing SND with modified radical neck dissection may be required for a categorical conclusion of these findings.

Orbital floor reconstruction with free flaps after maxillectomy.

Background The purpose of this study is to evaluate the outcome of orbital floor reconstruction with free flaps after maxillectomy. Methods This was a retrospective analysis of 34 consecutive patients who underwent maxillectomy with orbital floor removal for malignancies, reconstructed with free flaps. A cross-sectional survey to assess the functional and esthetic outcome was done in 28 patients who were alive and disease-free, with a minimum of 6 months of follow-up. Results Twenty-six patients had bony reconstruction, and eight had soft tissue reconstruction. Free fibula flap was the commonest flap used (n = 14). Visual acuity was normal in 86%. Eye movements were normal in 92%. Abnormal globe position resulted in nine patients. Esthetic satisfaction was good in 19 patients (68%). Though there was no statistically significant difference in outcome of visual acuity, eye movement, and patient esthetic satisfaction between patients with bony and soft tissue reconstruction, more patients without bony reconstruction had abnormal globe position (p = 0.040). Conclusion Free tissue transfer has improved the results of orbital floor reconstruction after total maxillectomy, preserving the eye. Good functional and esthetic outcome was achieved. Though our study favors a bony orbital reconstruction, a larger study with adequate power and equal distribution of patients among the groups would be needed to determine this. Free fibula flap remains the commonest choice when a bony reconstruction is contemplated.

Efficacy of per oral access in the surgical management of T2/T3 oral cavity squamous cell carcinoma.

OBJECTIVE: Transcutaneous "access" procedures still continue to be widely employed for surgical management of medium-sized (T2, T3) oral cavity tumors in spite of the almost 4-cm mouth opening available to the surgeon to access the oral cavity. We undertook a retrospective study to objectively evaluate "per oral access" in managing these tumors with regard to the ability to achieve a clear surgical margin and enable reconstruction of resultant defect. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Seventy-nine consecutive patients of oral squamous cell carcinoma excised by per oral approach were analyzed. Multiple patient- and tumor-related factors known to influence status of surgical margins were analyzed. The overall frequency of clear, close, and involved margins was noted, as well as 5-year local control rate. The method of reconstruction employed was evaluated. RESULTS: The close/involved margins were more frequent with larger tumors and tumors exhibiting perineural infiltration, but none were statistically significant (P > .12). The overall frequency of clear, close, and involved margins was 81%, 11%, and 8%, respectively. Tongue and buccal mucosa sites constituted approximately 85% of the cases and had an 85% clear margin rate. Five-year local control rate was 70.35%. Fifty-three free flaps reconstruction were undertaken without any additional "access" procedure. CONCLUSION: Our results demonstrate ability to obtain comparable tumor clearance rates employing per oral access, without compromising ability to perform optimal reconstruction. We suggest per oral access should be the access of choice for medium-sized oral cavity tumors, and additional access procedures should only be considered if the initial access proves inadequate.

The role of preoperative, intratympanic glucocorticoids for hearing preservation in cochlear implantation: a prospective clinical study.

BACKGROUND: Hearing Preservation is becoming increasingly important in cochlear implantation as there is growing evidence that preserving the residual hearing, especially in the low frequencies in combination with the electric stimulation can significantly improve hearing and speech outcomes in noise. Besides the ongoing development of atraumatic implant electrodes and insertion techniques, the implementation of pharmacologic hair cell protection is thought to increase hearing preservation. This study investigates the effects of preoperative intratympanic glucocorticoid application on hearing preservation rates in cochlear implantation. STUDY DESIGN: Prospective interventional study. SETTING: Tertiary neurotology referral center. PATIENTS: Patients undergoing cochlear implantation with measurable preoperative hearing thresholds using either a Flex soft electrode or a Flex EAS electrode depending on the degree of residual low frequency hearing. INTERVENTION: Preoperative intratympanic steroid application during cochlear implantation via round window insertion. MAIN OUTCOME MEASURES: Level of hearing preservation after cochlear implantation; electrode- and frequency-specific hearing preservation rates. RESULTS: Preoperative hearing thresholds were comparable in the control group and the interventional Flex soft group (70.5 db±12.5 dB vs. 73.5 dB±10.5 dB, P=.27). As per selection criteria the low-frequency hearing thresholds were significantly lower in interventional Flex EAS groups when compared to the control group. Hearing preservation was significantly better in the interventional group with no case of complete hearing loss in this group (11 dB±2.5 dB vs. 19.5 dB 3.5 dB, P<.05). The interventional group displayed a higher stability of hearing preservation after implantation (r=.8, P=.03). Level of hearing preservation was higher when a specific hearing preservation electrode was used (r=.85, P<.05). Hearing preservation in the low frequencies was significantly higher than in the high frequencies. CONCLUSIONS: Our study suggests that the additional preoperative use of intratympanic glucocorticoids improves and stabilizes hearing preservations rates in round window cochlear implantation for adults and children with residual hearing.