Moni Abraham Kuriakose

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of Indias cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population

Oral cancer is a potentially preventable disease due to its association with well-known risk factors and easy detectability. There is a significant deficiency in the awareness of oral cancer and its risk factors among the public. Raising public awareness could effectively contribute to achieving a significant reduction in the incidence of oral cancer. The objective of this study was to evaluate the effectiveness of mouth self-examination (MSE) in improving the awareness of oral cancer and its risk factors as well as test its feasibility as an oral cancer-screening tool. The study was carried out in a high-risk population of 57,704 from India, of which, 34,766 individuals who have met the eligibility criteria formed the study population. MSE brochures and trained health workers were employed for the purpose of health education and cancer screening. The present study compared their efficacy to detect oral lesions. Subjects with suspicious lesions were referred to the trained oral cancer specialist for confirmation. A questionnaire to assess the awareness of oral cancer and its risk factors was developed and validated. SPSS (v.11.0) was used for data analysis. The program identified 216 cases of potentially malignant lesions as well as three cases of oral cancer. The findings of MSE and health workers showed 72% concordance, while that of health workers and oral cancer specialist showed 100% concordance. MSE had a low sensitivity of 18%, while the specificity was 99.9%. Though the technique identified high-risk lesions such as red patches (66.7%) and non-healing ulcers (42.9%), the detection rate of white patches was low (12.7%). Overall awareness of oral cancer and its risk factors after introduction of MSE program was over 80%; but the compliance to seek treatment was poor (32%). Mouth self-examination may be used as an effective tool to improve the awareness of oral cancer and for the early detection of lesions.

Sentinel node biopsy in head and neck squamous cell carcinoma

Purpose of reviewSentinel node biopsy (SNB) is emerging as a potential tool to evaluate neck node metastasis in head and neck cancer. The purpose of this article is to undertake a systemic review of published literature and to outline future directions for further studies. Recent findingsExisting data suggest that the status of the sentinel lymph node (SLN) predicts the pathologic stage of the nodal basin. It has been demonstrated that radiolabeled lymphoscintigraphy is superior to blue dye to localize the SLN in head and neck cancer. SLN biopsy should be recommended only in patients with previously untreated early stage (T1/2) oral cavity and orophparynx cancer with clinical N0 stage. The procedure is technique sensitive. The isolated SLN should be subjected to serial step sectioning at 150 μm and staining by hematoxylin and eosin and immunohistochemistry. Intraoperative frozen section and imprint cytology are not sensitive to identify small foci of micrometastasis and isolated tumor cells within the SLN. The clinical relevance of micrometastasis and isolated tumor cells needs to be established. It is necessary to develop a better method for intraoperative pathological confirmation of SLN metastasis. There exists no randomized clinical trial with adequate power that compares SNB and elective neck dissection in head and neck cancer. SummarySNB in head and neck squamous cell carcinoma should be considered as an investigational tool pending validation by larger randomized clinical trials; therefore, it should not be recommended at present outside a clinical trial setting.

Simultaneously presenting head and neck and lung cancer: a diagnostic and treatment dilemma.

Objectives/Hypothesis Synchronous tumors are defined as malignancies presenting within 6 months of the index tumors. A significant subset of patients present at initial evaluation with malignant tumors of both the head and neck (head and neck squamous cell carcinoma) and the lung, which are termed simultaneous primaries. The management and treatment outcomes in this cohort of patients have not been clearly defined and are the subject of the present review.

Reconstructive indications of simultaneous double free flaps in the head and neck: A case series and literature review

Extensive and complex defects of the head and neck involving multiple anatomical and functional subunits are a reconstructive challenge. The purpose of this study is to elucidate the reconstructive indications of the use of simultaneous double free flaps in head and neck oncological surgery. This is a retrospective review of 21 consecutive cases of head and neck malignancies treated surgically with resection and reconstruction with simultaneous use of double free flaps. Nineteen of 21 patients had T4 primary tumor stage. Eleven patients had prior history of radiotherapy or chemo‐radiotherapy. Forty‐two free flaps were used in these patients. The predominant combination was that of free fibula osteo‐cutaneous flap with free anterolateral thigh (ALT) fascio‐cutaneous flap. The indications of the simultaneous use of double free flaps can be broadly classified as: (a) large oro‐mandibular bone and soft tissue defects (n = 13), (b) large oro‐mandibular soft tissue defects (n = 4), (c) complex skull‐base defects (n = 2), and (d) dynamic total tongue reconstruction (n = 2). Flap survival rate was 95%. Median follow‐up period was 11 months. Twelve patients were alive and free of disease at the end of the follow‐up. Eighteen of 19 patients with oro‐mandibular and glossectomy defects were able to resume an oral diet within two months while one patient remained gastrostomy dependant till his death due to disease not related to cancer. This patient had a combination of free fibula flap with free ALT flap, for an extensive oro‐mandibular defect. The associated large defect involving the tongue accounted for the swallowing difficulty. Simultaneous use of double free flap aided the reconstruction in certain large complex defects after head and neck oncologic resections. Such combination permits better complex multiaxial subunit reconstruction. An algorithm for choice of flap combination for the appropriate indications is proposed.

Pathologic evaluation of sentinel lymph nodes in oral squamous cell carcinoma.

The objective of this study was to determine the relative efficacy of different methods of pathologic evaluation of sentinel lymph nodes.

Lateral arm free flap for oral tongue reconstruction: An analysis of surgical details, morbidity, and functional and aesthetic outcome

The purpose of this study was to report the effectiveness of the lateral arm free flap (LAFF) in the reconstruction of oral tongue defects, the subsite in which it may have advantage over the other donor sites. This is a retrospective analysis of 48 consecutive cases of LAFF used for the reconstruction of partial glossectomy defects for squamous cell carcinoma of the oral tongue. Primary defect and donor-site morbidity and the functional and aesthetic outcomes were assessed in 37 evaluable patients, with a minimum of 6 months follow-up. Patient-reported Visual Analog Scale score from 0 (minimum satisfaction) to 10 (maximum satisfaction) was used to evaluate the aesthetic outcome. The follow-up was for 6 to 52 months (mean, 24 months). The flap was successful in 45 (93.8%) patients. The commonest observed donor-site morbidity was a broad scar, but it did not cause much patient dissatisfaction because it could be covered with appropriate dressing. Speech was normal or near-normal in all patients. Poor functional outcome was associated with adjuvant postoperative radiotherapy. The visual analog scale score for the aesthetic satisfaction (mean [standard deviation]) was 6.58 (1.82) for primary site and 7.13 (1.99) for the donor site. LAFF is an excellent option for the reconstruction of partial glossectomy defects of oral tongue without significant involvement of the floor of mouth and base of tongue.

Human salivary proteome — a resource of potential biomarkers for oral cancer☆

Proteins present in human saliva offer an immense potential for clinical applications. However, exploring salivary proteome is technically challenged due to the presence of amylase and albumin in high abundance. In this study, we used four workflows to analyze human saliva from healthy individuals which involved depletion of abundant proteins using affinity-based separation methods followed by protein or peptide fractionation and high resolution mass spectrometry analysis. We identified a total of 1256 human salivary proteins, 292 of them being reported for the first time. All identifications were verified for any shared proteins/peptides from the salivary microbiome that may conflict with the human protein identifications. On integration of our results with the analyses reported earlier, we arrived at an updated human salivary proteome containing 3449 proteins, 808 of them have been reported as differentially expressed proteins in oral cancer tissues. The secretory nature of 598 of the 808 proteins has also been supported on the basis of the presence of signal sequence, transmembrane domain or association with exosomes. From this subset, we provide a priority list of 139 proteins along with their proteotypic peptides, which may serve as a reference for targeted investigations as secretory markers for clinical applications in oral malignancies. This article is part of a Special Issue entitled: Proteomics in India.

Pectoralis major flap for head and neck reconstruction in era of free flaps

The aim of this study was to evaluate factors affecting the selection of pectoralis major flap in the era of free tissue reconstruction for post ablative head and neck defects and flap associated complications. The records of patients who underwent various reconstructive procedures between July 2009 and December 2010 were retrospectively analysed. 147 reconstructive procedures including 79 free flaps and 58 pectoralis major flaps were performed. Pectoralis major flap was selected for reconstruction in 21 patients (36%) due to resource constrains, in 12 (20%) patients for associated medical comorbidities, in 11 (19%) undergoing extended/salvage neck dissections, and in 5 patients with vessel depleted neck and free flap failure salvage surgery. None of the flaps was lost, 41% of patients had flap related complications. Most complications were self-limiting and were managed conservatively. Data from this study suggest that pectoralis major flap is a reliable option for head and neck reconstruction and has a major role even in this era of free flaps. The selection of pectoralis major flap over free flap was influenced by patient factors in most cases. Resource constraints remain a major deciding factor in a developing country setting.

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.