Bilateral Microvascular Submandibular Gland Transfer with Implantation of Wharton's Duct in Superior Conjunctival Fornix: A Vision-Saving Procedure for Severe Dry Eye Disease.

Dry eye can initially cause mild symptoms of irritation and may rapidly progress to corneal scarring and blindness. Tear substitutes can only help for mild cases. With the advancement in microsurgical techniques, an option of transferring vascularized salivary glands has shown positive results. We present a case of a 5-year-old boy with congenital alacrimia with ocular surface damage. Vascularized autologous submandibular gland transfer was considered as a viable option for this patient. We performed the gland transfer in two separate stages for the two eyes (1 year 5 months apart). The patient was evaluated for up to 2 years for the right eye and for 7 months for the left eye. Dry eye workup showed drastic improvement (right > left). Biochemical analysis showed gradual transition to resemble that of natural tears. This procedure can result in significant symptomatic improvement and can be a promising treatment option for cases of severe dry eye.

Volume and Location of the Defect as Predictors of Swallowing Outcome After Glossectomy: Correlation with a Classification.

This study aimed to characterize the swallowing outcomes after glossectomy and analyze factors affecting them. An attempt is made to propose a classification system and corroborate it to the results. This is a cross-sectional study to assess swallowing in carcinoma tongue patients treated surgically with or without reconstruction, followed by adjuvant therapy as indicated. One hundred and six patients were evaluated with videofluoroscopy (VFS). Volume defects were classified as I: less than one-third, II: one-third to half, III: half to two-thirds, IV: two-thirds to total glossectomy. Location was assigned as lateral, tip, and sulcus defects. Predictors were T stage, surgical approach, volume, location, and adjuvant radiotherapy. Chi-square and logistic regression were used for statistical analysis. Defects were Class I, II, III, and IV in 36, 42, 16, and 12 patients, respectively. Adjuvant radiotherapy was given in 40% of cases. Mean evaluation time was 14 months from treatment. On, Functional Oral Intake Scale (FOIS) score, as the Class of the defect increased, the percentage of patients with low scores (poor swallowing outcomes) showed an increasing trend (p < 0.001). Defect volume, T stage, approach, and radiotherapy correlated significantly with an abnormality of all VFS parameters (p < 0.001). On multivariate analysis, defect volume remained an independent predictor for oral parameters; radiotherapy emerged as the only independent predictor for pharyngeal parameters. The incremental volume of the defect is a significant independent predictor of swallowing. Based on this, we propose a classification for glossectomy.

Estimation of Health Utility and Quality Adjusted Life Years in Bilateral Hand Transplantation: A Time Trade-off Study.

BACKGROUND: Hand transplantation and advances in the field of prostheses have opened new frontiers in the restoration of hand function among bilateral hand amputees (BHA). There is only scarce literature evaluating the health utility (HU) and quality adjusted life years (QALY) gained by bilateral hand composite tissue allotransplantation (CTA) or prosthesis over amputation. The study was focused on BHA restored with prosthesis or CTA. METHODS: The HU of three different health states (HS) namely, BHA, using prosthesis or with CTA and net QALYs gained by hand transplantation or prosthesis over amputation were computed by time trade-off (TTO) method among 236 study participants. RESULTS: Among 236 study participants, medical professional (120), general public (89), BHA (23), and bilateral hand transplant recipients (4) were included. The mean HU by TTO method among the study participants (n = 232) as BHA, using prosthesis or CTA was 0.34 (±0.24), 0.50 (±0.26) and 0.69 (±0.26) respectively. Bilateral hand CTA imparted an expected gain of 12.57 (±11.43) mean QALYs over amputation among the study participants. The subgroup analysis displayed higher mean HU in hand CTA recipient HS along with maximum QALY gained by CTA over amputation. CONCLUSIONS: Bilateral hand CTA HS stands above the other 2 HSs, namely BHA and prosthesis, in terms of the health utility. As demonstrated by QALY gain of 12.57, participants' valuation of health utility is notably higher for CTA with acceptance of lifelong immunosuppressant rather than for a state of uncompromised physical health with a bilateral hand amputation.

Tracheal Allotransplantation-Lessons Learned.

Reconstruction of long tracheal defects still proves to be a challenge. Free fasciocutaneous flaps with cartilaginous struts or an allotransplant trachea have been reported but not been widely performed. This article reports with the experience of using a tracheal allotransplant in such a defect. A 43-year-old lady presented with adenoid cystic carcinoma involving the entire trachea from subglottic area up to the carina, leading to a life-threatening airway occlusion. After preliminary stenting, allotransplant trachea obtained from a brain-dead individual was revascularized in the forearm of the patient after mechanical decellularization to reduce the immune load and fulfil the need for immunosuppression in the background of active cancer. Subsequently, the trachea and larynx were resected. The vascularized neotrachea was transferred successfully into the neck. The patient did well initially but succumbed to a fatal hemorrhage due to innominate vein aneurysmal rupture on the 22nd day after the transplant. The technical details of resection, fabrication of the neotrachea, its transfer, and the lessons learnt in this tracheal allotransplant are described.

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

BACKGROUND: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control. METHODS: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems. RESULTS: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively. CONCLUSION: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.

"Deep Extrinsic Muscle Involvement" Is a Fallacy in the American Joint Committee on Cancer's Seventh Edition of Tumor Staging of Oral Cavity Cancers.

PURPOSE: The seventh edition of tumor staging by the American Joint Committee on Cancer (AJCC) includes extrinsic muscle involvement to define stage T4a tongue carcinomas. The anatomic location of extrinsic muscles predisposes them to early involvement even in superficial tumors. The purpose of this study was to expose a fallacy in this staging system for extrinsic muscle involvement. MATERIALS AND METHODS: This was a prospective cohort study of 87 patients with oral tongue squamous cell carcinoma. Magnetic resonance imaging (MRI) parameters were 1) the distance of the extrinsic muscles from the surface measured on the normal side in millimeters (range, mean, and standard deviation); 2) maximum transverse, craniocaudal, and anteroposterior tumor dimensions (range, mean, and standard deviation); and 3) tumor involvement of the muscles recorded on the involved side for the number and percentage of each muscle involved. Histopathologic depth of invasion also was recorded. RESULTS: Sixty-seven patients were men and 20 were women (age range, 18 to 74 yr; mean age, 51 yr). The mean distances of the most superficial part of the muscle to the normal surface at MRI for the genioglossus (anteroventral), hyoglossus, and styloglossus were 3.98, 2.13 and 0.66 mm, respectively. The patterns of extrinsic muscle involvement showed hyoglossus, styloglossus, and genioglossus involvement in 79 (90.8%), 58 (66.76%), and 31 (35.6%), respectively. In patients with a pathologic depth of invasion shallower than 10 mm, involvement of the hyoglossus, styloglossus, and genioglossus was seen in 80, 35, and 15%, respectively. CONCLUSION: The extrinsic muscles of the tongue are not deep. Even superficial thin tumors can involve these muscles. The eighth edition of tumor staging by the AJCC, which includes tumor thickness in the staging system, is in the process of being implemented. The present study justifies the removal of extrinsic muscle involvement in defining stage T4 of the oral cavity.

Factors Affecting Survival in Surgically Salvaged Locoregional Recurrences of Squamous Cell Carcinoma of the Tongue.

PURPOSE: To determine the factors affecting outcomes in surgically salvaged, locoregionally recurrent squamous cell carcinoma of the tongue (SCCT). MATERIALS AND METHODS: In a retrospective cohort of patients who underwent successful salvage of locoregionally recurrent SCCT, we performed this observational analytical study to determine survival and its determinants. Details extracted from our database were patient characteristics (age, gender, tobacco use), treatment characteristics, and characteristics of recurrent disease (stage and adverse pathologic features [APFs] such as grade, perineural invasion, and lymphovascular invasion). Overall survival (OS) curves were plotted using the Kaplan-Meier method. A Cox proportional hazards model was used to determine the impact of patient, disease, and treatment characteristics on OS. RESULTS: Of 52 patients with locoregional recurrences of surgically treated SCCT, 25 (48.1%) underwent surgical salvage with curative intent. The median overall OS for this cohort was 26 months. Factors predictive of worse OS were previous adjuvant therapy (P = .016) and increasing APFs in recurrent tumor histology (P = .008). Lymphovascular invasion in recurrent tumor histology and patients with a disease-free interval of less than 6 months showed worse survival (P = .008 and P = .058, respectively). CONCLUSIONS: Among patients with locoregional recurrence, the number who are eligible for curative-intent surgical salvage is small. Those who received previous adjuvant therapy and those with increasing APFs in recurrent tumors had poor outcomes despite attempts at surgical salvage, particularly patients with early recurrence.

Interdisciplinary Telemedicine in the Management of Dysphagia in Head and Neck.

The study considered the feasibility and impact of interdisciplinary telemedicine discussions in the management of post-treatment dysphagia in patients with head and neck tumors. This is a retrospective analysis of patients with persistent dysphagia after treatment for head and neck pathology, at an institute in India. The cases were discussed in the telemedicine meeting conducted between host institute and a second unit in the United States. A monthly meeting was organized, using an internet-based video conference system. The ongoing swallowing problems and management were presented, and through discussions, a plan for further management was formulated and carried out. The Functional Oral Intake Scale (FOIS) was measured before and after the implementation of the plan. Twenty-six patients were discussed, out of which, 22 were head and neck malignancies. The recommendations concurred with that of the host unit in 18, differed for three and additive in five patients. The pre-treatment mean FOIS was 1.46 with a standard deviation of 0.989 and post-treatment mean improved to 3.92 with a standard deviation of 1.809 (p < 0.0001). The present study supports the success of an interdisciplinary telemedicine meeting to manage difficult cases of dysphagia in head and neck. The outcome in terms of the FOIS score improved significantly after implementing them. In addition to the direct patient benefits, the meeting helped to facilitate interdepartmental collaboration between two units treating similar sets of patients across the globe, in specialized clinical areas like dysphagia management.

Outcomes following pharyngeal reconstruction in total laryngectomy - Institutional experience and review of literature.

BACKGROUND: Pharyngeal reconstruction is a challenging aspect of reconstruction after resections for head-and-neck cancer. The goals of reconstruction are to restore the continuity of the pharyngeal passage to enable oral alimentation and rehabilitation of speech wherever possible. This study was performed to determine the outcomes following pharyngeal reconstruction in total laryngectomy (TL) using different reconstructive options and to determine the predictors of pharyngocutaneous fistula (PCF) and swallowing dysfunction. MATERIALS AND METHODS: Retrospective analysis of patient data between 2003 and 2010 of patients undergoing TL with partial or total pharyngectomy. Demographic and treatment details were collected and analysed. Univariate analysis was performed to determine predictors of PCF and swallowing dysfunction. RESULTS: Fifty-seven patients underwent pharyngeal reconstruction following TL, 31 of whom had received prior treatment. Following tumour resection, 31 patients had circumferential defects and 26 patients had partial pharyngeal defects. The flaps used include pectoralis major myocutaneous flap (n = 29), anterolateral thigh flap (n = 8), gastric pull-up (n = 13) and free jejunal flap (n = 7). PCF was seen in 20 patients, of which 15 (75%) were managed conservatively and 5 required another surgery. At last follow-up, 99 patients (68%) were on full oral alimentation. Tracheo-oesophageal puncture and prosthesis insertion was done in 20 patients, of whom 17 (85%) developed satisfactory speech. Partial pharyngeal defects were associated with a higher risk of PCF on univariate analysis (P = 0.006) but were not significant on multivariate analysis. Post-operative swallowing dysfunction was significantly higher with hypopharyngeal involvement by tumour (P = 0.003). CONCLUSION: Pharyngeal reconstruction in TL is feasible with good results. Majority of the patients swallow and regain acceptable swallowing function within 3 months.

Soft embalming of cadavers for training purposes: Optimising for long-term use in tropical weather.

BACKGROUND: Surgical and anatomical training has been found to be most optimally simulated in a cadaver than any other available methods. Soft embalming methods have made the bodies more 'lifelike' and better suited for training. The widely accepted soft embalming techniques, including Thiel embalming, are designed for temperate climates. Their use in tropical locations has been found to be associated with poor short-term and long-term preservation of the bodies. In fact, adequate reports from tropical countries on effective methods for soft embalming are lacking. MATERIALS AND METHODS: This article details the modifications made in the Thiel embalming technique over a period of 2 years which has enabled us to preserve the anatomical features of bodies in an optimal way for longer periods in tropical conditions. This study was carried out in a tertiary care referral centre located in a tropical climate zone. A total of 13 frozen and thawed cadavers were used over a period of 2 years for developing such soft embalming technique. The efficacy of the technique was tested using these cadavers for varying types of surgical exercises on multiple occasions. RESULTS: The conventionally described technique of Thiel embalming did not provide desired results. Hence, various modifications to this technique were instituted which helped us to get superior quality of soft-embalmed cadavers. In the final year, these cadavers were used successfully for workshops in flap dissection. Head and neck access surgery, arthroscopic and laparoscopic procedures as well as mock face and hand transplant dissections. CONCLUSIONS: The Theil embalming technique for obtaining soft embalmed cadavers, even though found to be best in many centres in the world, has not been found to be suitable to tropical weather. By modifying it, we have succeeded in developing a technique suitable to the tropical weather. This technique yields cadavers suitable for various surgical simulation exercises. This technique also allows the body to be optimally used over several months in multiple occasions. These modifications are very simple and have been described in detail enabling it to be adopted by any surgical skill laboratory in the tropical countries.

Comparison between Sialendoscopy and Conventional Methods in the Treatment of Sialolithiasis.

BACKGROUND: Sialendoscopy is gaining in popularity in treating calculus disease. The delicacy of the instrument and the diameter of the salivary ducts are factors that limit the ability to achieve complete success. There is also continued speculation regarding the utility of the procedure, especially among clinicians who are masters of conventional methods like sialadenectomy and sialodochotomy. OBJECTIVE: To assess the efficacy of sialendoscopy over conventional methods in treating sialolithiasis. METHODS: A prospective case control study was conducted in a tertiary care centre; this study involved 50 patients of sialolithiasis, and it extended over a 36-month period. All had undergone treatment, either by conventional methods or interventional sialendoscopy. All patients with nonpalpable calculi smaller than 6 mm underwent interventional sialendoscopy. Failed sialendoscopies and larger nonpalpable calculi were removed through sialadenectomy. The outcome variables studied included calculus removal, postoperative symptoms, and gland preservation. RESULTS: The success rate in terms of calculus removal by sialendoscopy was 88%, versus 100% by sialadenectomy. The salivary gland was preserved in 88% of the cases in the sialendoscopy group. Only 12% of patients were symptomatic. CONCLUSION: Sialendoscopy was effective in removing calculi of various sizes; it was definitely superior to conventional methods. Sialadenectomy should be reserved for cases either not suitable for sialendoscopy or in which there was an intervention failure.

Challenges in the reconstruction of bilateral maxillectomy defects.

PURPOSE: Bilateral maxillectomy defects, if not adequately reconstructed, can result in grave esthetic and functional problems. The purpose of this study was to investigate the outcome of reconstruction of such defects. MATERIALS AND METHODS: This is a retrospective case series. The defects were analyzed for their components and the flaps used for reconstruction. Outcomes for flap loss and functional indices, including oral diet, speech, and dental rehabilitation, also were evaluated. RESULTS: Ten consecutive patients who underwent bilateral maxillectomy reconstruction received 14 flaps. Six patients had malignancies of the maxilla, and 4 patients had nonmalignant indications. Ten bony free flaps were used. Four soft tissue flaps were used. The fibula free flap was the most common flap used. Three patients had total flap loss. Seven patients were alive and available for functional evaluation. Of these, 4 were taking an oral diet with altered consistency and 2 were on a regular diet. Speech was intelligible in all patients. Only 2 patients opted for dental rehabilitation with removable dentures. CONCLUSIONS: Reconstruction after bilateral maxillectomy is essential to prevent esthetic and functional problems. Bony reconstruction is ideal. The fibula bone free flap is commonly used. The complexity of the defect makes reconstruction difficult and the initial success rate of free flaps is low. Secondary reconstructions after the initial flap failures were successful. A satisfactory functional outcome can be achieved.

Objective analysis of microtia reconstruction in Indian patients and modifications in management protocol.

INTRODUCTION: An ideal ear, with representation of all anatomic landmarks, is the aim of any reconstructive surgeon embarking on reconstructing the ear in a microtia patient. The literature is abundant with the description of techniques, but these have been reported mainly in Caucasian and Oriental population. There have been very few publications on results in the population belonging to the Indian subcontinent. In spite of strictly adhering to the recommended techniques of reconstruction, the results obtained in these patients have often been marred by problems that are not reported with the Oriental or Caucasian populations. This may necessitate a relook into the management strategy of these cases. Hindering the assessment of the results, their reporting and auditing the improvement obtained by such change in the management strategy, is the lack of a standardized method for assessment of the outcome. Hence, an attempt was made in a series of patients who underwent microtia reconstruction to assess the outcome using a new tool based on the attained definition of anatomical components of the reconstructed pinna. Further effort was made to document the modifications in the technical execution of the reconstruction during the period of the study. MATERIALS AND METHODS: A retrospective review of 44 patients and a prospective analysis of 11 patients, who underwent ear reconstruction for microtia from December 2003 to September 2014 at a tertiary care teaching hospital, was undertaken. Taking a cue from Nagata's description of an 'ideal reconstructed ear' which should show all the anatomical components, we developed an objective grading system to assess our results. The technique had undergone several changes during these years combining the principles of three universally accepted methods, that is, those described by Nagata, Brent, and Firmin. These changes, as well as the reasons behind them, were documented. RESULTS: On objectively measuring and analysing the replication of normal morphologic characteristics of the reconstructed ears, we documented progressive improvement of our results. Good or excellent results could be achieved in 70% of cases in the second group compared to a poor outcome in more than 2/3(rd) of the cases carried out during the initial period. Based on these results and the changes adopted in our practice we propose suggestions for management of microtia cases in the Indian population. CONCLUSIONS: An objective, weighted grading system has further enabled us to critically evaluate the outcomes and to further improve upon the existing results. Our amalgamation of the salient features of the established techniques as well as changes made based on our experience has enabled us to get good results more consistently in our attempts at microtia reconstruction. We believe that the adoption of such amalgamated methods will be more suitable in Indian patients.

Anatomic basis for an algorithmic approach for free fibula flap donor side selection in composite oro-mandibular defects.

INTRODUCTION: Head and neck oncological resections may result in composite oro-mandibular defects involving the oral mucosa (lining), mandibular bone and the skin (cover). Reconstructive options for such defects have evolved over a period. Free fibula flap reconstruction is currently accepted the world over as the gold standard for oro-mandibular defect reconstruction. Existing literature provides conflicting views about the use of a particular side and orientation of the fibula flap for achieving the optimal outcome. The purpose of this study is to confirm anatomically the effect of bone, soft tissue and vessel orientation on the ease of doing reconstruction. MATERIALS AND METHODS: This is a cadaveric study. A mandibular model with a defect was used. This was pre plated to maintain continuity. Composite fibula flaps of the same dimension were harvested from both legs of a fresh cadaver. The harvested flaps were used to reconstruct the mandibular defect in different orientations and the best configuration for each reconstructive requirement was assessed. RESULTS: Keeping the peroneal surface for plating, that is, facing outwards, four different configurations of the fibula flap are possible for a given mandibular defect. With a posterior vascular pedicle ipsilateral fibula is suitable for skin cover and contralateral for mucosal lining and the reverse for an anteriorly placed pedicle. CONCLUSION: The algorithm based selection of appropriate sided fibula flap facilitates complex mandibular reconstruction by placing the right kind of tissue at the right place and helps in reducing the donor site morbidity by allowing the surgeon to harvest only the required amount of skin.

Defect components and reconstructive options in composite orbitomaxillary defects with orbital exenteration.

PURPOSE: The conventional way of reconstructing an orbital exenteration defect associated with a maxillectomy is to cover it with a soft tissue free flap and camouflage it with a spectacle-mounted orbital prosthesis. Also, there are some reports on the use of bone flaps. The objective of this study was to review the reconstructive options for a defect resulting after orbital exenteration and maxillectomy. MATERIALS AND METHODS: This study concerns a retrospective case series of 20 patients. Electronic medical records, including clinical details, operative notes, and follow-up data, were analyzed. Defects were analyzed for their reconstructive components. The reconstructive methods used were studied by the types of flap used, bony versus soft tissue types of reconstruction, and the prosthetic method used to rehabilitate the eye. Outcomes were analyzed for flap success rate. Descriptive methods for data analysis were used. RESULTS: Fourteen patients underwent a soft tissue reconstruction alone and 6 underwent bony reconstruction. The free rectus abdominis was the commonest soft tissue flap used. This article presents the outcome of reconstruction in such patients and the utility of individual flaps for their ability to replace different components of the defect. CONCLUSIONS: Ideal reconstruction should address all individual defect components of facial contour, orbital, palatal, skull base, and skin defects. The free rectus abdominis flap remains the common choice. When a composite socket reconstruction is to be achieved, the innovative free tensor fascia lata flap with the iliac crest bone and internal oblique muscle is an option.

Maxillary reconstruction: Current concepts and controversies.

Maxillary reconstruction is still an evolving art when compared to the reconstruction of the mandible. The defects of maxilla apart from affecting the functions of the speech, swallowing and mastication also cause cosmetic disfigurement. Rehabilitation of the form and function in patients with maxillary defects is either by using an obturator prosthesis or by a surgical reconstruction. Literature is abundant with a variety of reconstructive methods. The classification systems are also varied, with no universal acceptance of any one of them. The oncologic safety of these procedures is still debated, and conclusive evidence in this regard has not emerged yet. Management of the orbit is also not yet addressed properly. Tissue engineering, that has been hyped to be one of the possible solutions for this vexing reconstructive problem, has not come out with reliable and reproducible results so far. This review article discusses the rationale and oncological safety of the reconstructing the maxillary defects, critically analyzes the classification systems, offers the different reconstructive methods and touches upon the controversies in this subject. The management of the retained and exenterated orbit associated with maxillectomy is reviewed. The surgical morbidity, complications and the recent advances in this field are also looked into. An algorithm, based on our experience, is presented.

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. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

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]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

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.