A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

In the rodent, hippocampal neurogenesis plays critical roles in learning and memory1,2, is tightly regulated by inhibitory neurons3-7 and contributes to memory dysfunction in Alzheimer's disease (AD) mouse models8-10. In contrast, the mechanisms regulating neurogenesis in the adult human hippocampus, the dynamic shifts in the transcriptomic and epigenomic profiles in aging and AD and putative niche interactions within the cellular environment, remain largely unknown. Using single nuclei multi-omics of postmortem human hippocampi we map the molecular mechanisms of hippocampal neurogenesis across aging, cognitive decline, and AD neuropathology. Transcriptomic and epigenetic profiling of neural stem cells (NSCs), neuroblasts and immature neurons suggests that the earliest shift in the characteristics of neurogenesis takes place in NSCs in aging. Cognitive impairment was associated with changes in neuroblast profile. In AD, there was a widespread cessation of the transcription machinery in immature neurons, with robust downregulation of genes regulating ribosomal and mitochondrial function. Further, there was substantial loss of parvalbumin+ inhibitory neurons in the hippocampus in aging. The number of the rest of inhibitory neurons were reduced as a function of age and diagnosis. Notably, a similar system-level effect was observed between immature and inhibitory neurons in the transition from aging to AD, manifested by common molecular pathways that were ultimately lost in AD. The numbers of neuroblasts, immature and GABAergic neurons inversely correlated with extent of neuropathology. Using CellChat and NeuronChat, we inferred the ligands and receptors by which neurogenic cells communicate with their cellular environment. Loss of synaptic adhesion molecules and neurotransmitters, either sent or received by neurogenic cells, was observed in AD. Together, this study delineates the molecular mechanisms and dynamics of human neurogenesis, functional association with inhibitory neurons and a mechanism of hippocampal hyperexcitability in AD.

Role of Perifacial Lymph Node in Nodal Metastasis in Oral Squamous Cell Carcinoma: A Prospective Study.

Nodal involvement in oral squamous cell carcinoma is common due to its lymphatic spread. First echelon group of lymph nodes are to be removed in such scenarios. Perifacial lymph nodes are one of the suspected groups to be affected in metastasis and also missed in dissection due to position. So separate evaluation of this group is important surgically.

Outcomes of Cancer Surgery During the COVID-19 Pandemic: Preparedness to Practising Continuous Cancer Care.

The COVID-19 pandemic has placed unprecedented pressure on healthcare services. Deprioritisation of nonemergency clinical services and growing concerns of adverse outcomes of COVID-19 in cancer patients is having a deleterious impact across oncologic practice. We report cancer surgery outcomes taking into account the acuity of the COVID-19 situation. A prospectively maintained database of the Department of Surgical Oncology was analysed from 1st May to 30th June, 2020, to evaluate the perioperative outcomes, morbidity and mortality following major surgical procedures. A total of 359, preoperatively, tested negative for COVID-19 underwent surgery. Median age was 52 years with 26.7% (n = 96) above the age of 60 years. Sixty-one percent (n = 219) patients were American Society of Anaesthesiology grades II-III. As per surgical complexity grading, 36.8% (n = 132) cases were lower grades (I-III) and 63.2% (n = 227) were complex surgeries (IV-VI). 5.3% (n = 19) had ≥ grade III Clavien-Dindo complication, and the postoperative mortality rate was 0.27% (n = 1). Major complication rates in patients > 60 years were 9.3% in comparison to 4.1% in < 60 years (p = 0·63). The median hospital stay was 1-10 days across subspecialties. Postoperatively, repeat COVID 19 testing in 2 suspected patients were negative. Our study showed that after screening, triaging and prioritisation, asymptomatic cases may undergo cancer surgeries without increased morbidity during COVID-19 pandemic.

Masseter muscle flap for reconstruction of intra-oral defects in patients with early cancer of posterior-inferior parts of the oral cavity / Retalho do músculo masseter para reconstrução de defeitos intraorais em pacientes com câncer inicial de partes póstero‐inferiores da cavidade oral

Abstract Introduction Early carcinomas of the oral cavity in the posterior-inferior regions poses a challenge for reconstruction due to the lack of muscle support underneath and the limited space available to use some of the frequently-used flaps. Objective This study was done to evaluate the efficacy of the superiorly based masseter muscle flap in reconstruction of intra-oral post- ablation defects in patients with early oral carcinoma of the posterior-inferior part of the oral cavity. Methods A superiorly based masseter muscle flap were used to reconstruct the post-surgical intra- oral defect in 60 patients with early squamous cell carcinoma (T < 4 cm) of the posterior-inferior part of the oral cavity. The patients were followed up at 1-week and 1-month postoperatively to check for flap viability, complications, change in mouth opening and deviation of the mandible on mouth opening. To rule out any recurrence in the oral cavity masseter flaps, the patients were followed up for 1 year. Results The flap was viable in all patients and underwent mucosalization. 7/60 patients had postoperative infections, while 2/60 patients developed an oro-cutaneous fistula which required a secondary corrective procedure. The mean ± standard deviation of change in mouth opening at 1 week postoperatively was +1.917 ± 3.36 mm, which increased to +2.633 ± 2.95 mm at 1 month after surgery. The Friedman test revealed that there was a statistically significant change in mouth opening from preoperative period to the1 week and 1 month postoperative periods (p = 0.000). Female patients showed better improvement in mouth opening postoperatively. The ipsilateral deviation of the mandible on mouth opening was between 0-5 mm in 39 patients, 5-10 mm in 17 patients and more than 10 mm in 4 patients. There were no recurrences noted in the masseter flaps used. Conclusion The study infers that the superiorly based masseter muscle flap is a reliable method for reconstruction in early oral cancer patients yielding good functional results and acceptable cosmesis with nominal postoperative complications.

Resumo Introdução Os carcinomas iniciais da cavidade oral nas regiões póstero‐inferiores representam um desafio para a reconstrução devido à falta de suporte muscular abaixo da região e ao espaço limitado disponível para o uso de alguns dos retalhos mais empregados. Objetivo Avaliar a eficácia do retalho do músculo masseter de base superior na reconstrução de defeitos intraorais pós‐ablação em pacientes com carcinoma oral inicial da parte póstero‐inferior da cavidade oral. Método Um retalho do músculo masseter de base superior foi usado para reconstruir o defeito intraoral pós‐cirúrgico em 60 pacientes com carcinoma espinocelular inicial (T < 4 cm) localizado na parte póstero‐inferior da cavidade oral. Os pacientes foram acompanhados após uma semana e um mês de pós‐operatório para verificação da viabilidade do retalho, complicações, alteração na abertura bucal e desvio da mandíbula na abertura bucal. Para descartar recidiva nos retalhos do masseter, os pacientes foram acompanhados por um ano. Resultados O retalho foi viável em todos os pacientes e foi submetido à mucolização; 7/60 pacientes tiveram infecções pós‐operatórias, enquanto 2/60 pacientes desenvolveram uma fístula orocutânea que exigiu um procedimento corretivo secundário. A média ± desvio‐padrão da alteração na abertura da boca em uma semana de pós‐operatório foi + 1,917 ± 3,36 mm, que aumentou para + 2,633 ± 2,95 mm em um mês de pós‐operatório. O teste de Friedman revelou que houve uma alteração estatisticamente significante na abertura da boca do período pré‐operatório para os períodos de uma semana e um mês de pós‐operatório (p = 0,000). Pacientes do sexo feminino apresentaram maior melhoria na abertura da boca no pós‐operatório. O desvio ipsilateral da mandíbula na abertura da boca ficou entre 0 a 5 mm em 39 pacientes, 5 a 10 mm em 17 pacientes e mais de 10 mm em 4 pacientes. Não foram observadas recidivas nos retalhos de masseter usados. Conclusão O retalho do músculo masseter com base superior é um método confiável para reconstrução em casos de câncer oral inicial, produz bons resultados funcionais e resultados cosméticos aceitáveis com complicações pós‐operatórias insignificantes.

Delineating the Neuropathology of Lysosomal Storage Diseases Using Patient-Derived Induced Pluripotent Stem Cells.

Lysosomal storage diseases (LSDs) are inherited metabolic diseases caused by deficiency of lysosomal enzymes, essential for the normal development of the brain and other organs. Approximately two-thirds of the patients suffering from LSD exhibit neurological deficits and impose an escalating challenge to the medical and scientific field. The advent of induced pluripotent stem cell (iPSC) technology has aided researchers in efficiently generating functional neuronal and non-neuronal cells through directed differentiation protocols, as well as in decoding the cellular, subcellular, and molecular defects associated with LSDs using two-dimensional cultures and cerebral organoid models. This review highlights the information assembled from patient-derived iPSCs on neurodevelopmental and neuropathological defects identified in LSDs. Multiple studies have identified neural progenitor cell migration and differentiation defects, substrate accumulation, axon growth and myelination defects, impaired calcium homeostasis, and altered electrophysiological properties, using patient-derived iPSCs. In addition, these studies have also uncovered defective lysosomes, mitochondria, endoplasmic reticulum, Golgi complex, autophagy and vesicle trafficking and signaling pathways, oxidative stress, neuroinflammation, blood-brain barrier dysfunction, neurodegeneration, gliosis, and altered transcriptomes in LSDs. The review also discusses the therapeutic applications such as drug discovery, repurposing of drugs, synergistic effects of drugs, targeted molecular therapies, gene therapy, and transplantation applications of mutation-corrected lines identified using patient-derived iPSCs for different LSDs.

Masseter muscle flap for reconstruction of intra-oral defects in patients with early cancer of posterior-inferior parts of the oral cavity.

INTRODUCTION: Early carcinomas of the oral cavity in the posterior-inferior regions poses a challenge for reconstruction due to the lack of muscle support underneath and the limited space available to use some of the frequently-used flaps. OBJECTIVE: This study was done to evaluate the efficacy of the superiorly based masseter muscle flap in reconstruction of intra-oral post- ablation defects in patients with early oral carcinoma of the posterior-inferior part of the oral cavity. METHODS: A superiorly based masseter muscle flap were used to reconstruct the post-surgical intra- oral defect in 60 patients with early squamous cell carcinoma (T<4cm) of the posterior-inferior part of the oral cavity. The patients were followed up at 1-week and 1-month postoperatively to check for flap viability, complications, change in mouth opening and deviation of the mandible on mouth opening. To rule out any recurrence in the oral cavity masseter flaps, the patients were followed up for 1 year. RESULTS: The flap was viable in all patients and underwent mucosalization. 7/60 patients had postoperative infections, while 2/60 patients developed an oro-cutaneous fistula which required a secondary corrective procedure. The mean±standard deviation of change in mouth opening at 1 week postoperatively was +1.917±3.36mm, which increased to +2.633±2.95mm at 1 month after surgery. The Friedman test revealed that there was a statistically significant change in mouth opening from preoperative period to the1 week and 1 month postoperative periods (p=0.000). Female patients showed better improvement in mouth opening postoperatively. The ipsilateral deviation of the mandible on mouth opening was between 0-5mm in 39 patients, 5-10mm in 17 patients and more than 10mm in 4 patients. There were no recurrences noted in the masseter flaps used. CONCLUSION: The study infers that the superiorly based masseter muscle flap is a reliable method for reconstruction in early oral cancer patients yielding good functional results and acceptable cosmesis with nominal postoperative complications.

Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.

The pathological alterations that manifest during the early embryonic development due to inherited and acquired factors trigger various neurodevelopmental disorders (NDDs). Besides major NDDs, there are several rare NDDs, exhibiting specific characteristics and varying levels of severity triggered due to genetic and epigenetic anomalies. The rarity of subjects, paucity of neural tissues for detailed analysis, and the unavailability of disease-specific animal models have hampered detailed comprehension of rare NDDs, imposing heightened challenge to the medical and scientific community until a decade ago. The generation of functional neurons and glia through directed differentiation protocols for patient-derived iPSCs, CRISPR/Cas9 technology, and 3D brain organoid models have provided an excellent opportunity and vibrant resource for decoding the etiology of brain development for rare NDDs caused due to monogenic as well as polygenic disorders. The present review identifies cellular and molecular phenotypes demonstrated from patient-derived iPSCs and possible therapeutic opportunities identified for these disorders. New insights to reinforce the existing knowledge of the pathophysiology of these disorders and prospective therapeutic applications are discussed.

Integrating Systems Biology and an Ex Vivo Human Tumor Model Elucidates PD-1 Blockade Response Dynamics.

Ex vivo human tumor models have emerged as promising, yet complex tools to study cancer immunotherapy response dynamics. Here, we present a strategy that integrates empirical data from an ex vivo human system with computational models to interpret the response dynamics of a clinically prescribed PD-1 inhibitor, nivolumab, in head and neck squamous cell carcinoma (HNSCC) biopsies (N = 50). Using biological assays, we show that drug-induced variance stratifies samples by T helper type 1 (Th1)-related pathways. We then built a systems biology network and mathematical framework of local and global sensitivity analyses to simulate and estimate antitumor phenotypes, which implicate a dynamic role for the induction of Th1-related cytokines and T cell proliferation patterns. Together, we describe a multi-disciplinary strategy to analyze and interpret the response dynamics of PD-1 blockade using heterogeneous ex vivo data and in silico simulations, which could provide researchers a powerful toolset to interrogate immune checkpoint inhibitors.

Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies - The potential role of p53 and eIF4E as predictive parameters.

BACKGROUND: Recent advances in radiation technology has allowed to significantly reduce toxicity and improve the efficacy of radical radiotherapy in head and neck and oral squamous cell cancers. Insights into molecular biology of carcinogenesis has opened a window for identifying aggressive clinical situations that may benefit with larger clinical target volume (CTV ) margin, broader levels of nodal coverage, or alternative radiation sensitizers. AIM: To evaluate the potential role of eukaryotic translation initiation factor 4E (elF4E) and p53 as predictive biomarkers in resected margins of head and neck and oral cancers. MATERIAL AND METHODS: Forty patients with oral cancers and 26 patients with head and neck cancers were evaluated for p53 and eIF4E in their negative surgical margins, for pattern of distribution and outcome. RESULTS: In oral cancers, 27 patients (67.5%) were positive for p53 and 10 (25%) for eIF4E in surgically negative margins. For head and neck cancer, the values were 13 (50%) for p53 and 9 (34.6%) for eIF4E. Twelve patients with oral cancers and 8 patients with head and neck cancers had local failure or death. The association with these biomarkers did not achieve statistical significance. However, adjuvant radiotherapy had a significant protective value. It improved median survival from 15 to 21 months in patients positive for p53 (P = 0.018) and from 12 to 20 months (P = 0.03) in those with eIF4E. There was no predictive association of subsite, tumor size, or nodal status. CONCLUSION: The overexpression of p53 and eIF4E in pathologically negative margins may represent a subset of patients who would benefit from early initiation of adjuvant radiation and tailored intensity-modulated radiotherapy (IMRT).

Constraint Induced Movement Therapy as a Rehabilitative Strategy for Ischemic Stroke-Linking Neural Plasticity with Restoration of Skilled Movements.

BACKGROUND: Stroke leads to devastating impact on health as well as quality of life making it one of the leading causes of disability. Restoring the functions of upper extremities after ischemic (ISC) stroke is one of the challenges for rehabilitation. Lack of trained professionals and accessibility to rehabilitation centers are limited in many counties. Constraint induced movement therapy (CIMT) has been practiced in regaining the functional activity following stroke. CIMT can be practiced with minimum clinical set up which makes it cost effective. However, the neural plasticity mechanism underlying the recovery with CIMT is not well understood. METHODS: In the current study, we sought to investigate the extent to which CIMT helps in ameliorating neurological deficits in rat model of ISC stroke, induced by Endothelin-1 (ET-1). As well as to understand the cortical plasticity with Golgi-Cox staining and interhemispheric interaction with biotinylated dextran amine (BDA) following CIMT. Neurological deficits were identified within 24 hours of ET-1 infusion. RESULTS: CIMT restored the impaired skilled movements after ISC stroke and improved the quality of fine movements. Golgi-Cox staining showed significant decrease in dendritic arborization in the injured motor cortex following ISC stroke. CIMT was efficient in reversing this effect as indicated by increased dendritic arborization especially in layer III pyramidal neurons. Also, the stroke induced asymmetry in dendritic length across both hemispheres was found to be reduced with CIMT. BDA tracing showed a re-establishment of the axonal connections between the hemispheres after CIMT. CONCLUSIONS: Implications of CIMT can be one of the promising and low cost rehabilitative technique for the individuals with upper limb movement deficits.

Prognostic Indicators of Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide and is the major public health problem in the Indian subcontinent, where it ranks among the top three types of cancer in the country. Here, we aimed to analyze the clinical and tumor characteristics which impact the survival of OSCC patients. METHODS: A retrospective analysis of clinical records of all patients who underwent treatment for OSCC at Kidwai Memorial Institute of Oncology, between January 2009 and January 2012 was analyzed. Age, gender, site of the primary lesion, tumor size (T), nodal status (N), stage of the disease, marginal status, and modality of treatment data were collected and analyzed. RESULTS: Data of 147 patients with OSCC were included in the study and analyzed. Of the patients analyzed 61% were male, with 56% were <65 years, and 40% presented with buccal mucosa cancer followed by 30% with tongue cancer. Of all patients, 30% of them presented with Stage 1 and rest were Stage 2 and above. In our study, 40% underwent surgery only followed by regular follow-up and 60% needed surgery with postoperative adjuvant treatment based on the marginal status, the lymph node status, and T status of the disease. CONCLUSION: Our data suggest that age <65 years, female patients, alveolus lesion and tongue lesion and the early T Stage and N0 and negative margin had a significant positive impact on disease-free and overall survival of oral cancer patients.

Surgical Management of a Rare Case of Massive Compound Odontome Associated with Missing Primary Tooth.

Odontomes are considered to be the most common odontogenic tumours of the jaws. They are benign, mixed tumours arising from the remnants of both odontogenic epithelium and the ectomesenchyme resulting in the deposition of varied propotions of enamel, dentin, cementum and pulp tissues. As these lesions show deficiency only in structural arrangement, some authors consider odontomes as hamartomas or tumour like malformations. Though these lesions are more common in children, very few cases have been reported in less than five years age group. Blood loss is a major issue in paediatric surgery. Careful and safe surgery is the primary goal of the surgeon. The external carorid artery which is the only feeder of blood to the face and oral cavity can be ligated to control bleeding in extensive maxillofacial injuries and orofacial malignancies. Herewith, we report a massive odontome in a three and half-year-old child which was treated by surgical excision along with carotid control to prevent excess bleeding.

Electrophysiological characterization of Nsc-34 cell line using Microelectrode Array.

Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT). Although NSC-34 cell lines have been used to study the effect of various toxicological, neurotrophic and neuroprotective agents, the electrical activity of these cells has not been elucidated. In the current study, we have characterized the electrophysiological properties of NSC-34 cell lines using Micro-Electrode Array (MEA) as a tool. Based on the spike waveform, firing frequency, auto- and cross-correlogram analysis, we demonstrate that NSC-34 cell culture has >2 distinct types of neuronal population: principal excitatory neurons, putative interneurons and unclassified neurons. The presence of interneurons in the NSC-34 culture was characterized by increased expression of GAD-67 markers. Thus, finding an understanding of the electrophysiological properties of different population of neurons in NSC-34 cell line, will have multiple applications in the treatment of neurological disorders.

Variant anatomy of internal jugular vein branching.

The knowledge of both normal and abnormal anatomy of the veins of the neck is important for clinicians performing catheterization and surgeons operating in the region of the neck. The presence of such anomalous communications may also be important for radiologists performing angiographic and sonographic studies. This study presents three cases of variant anatomy in posterior branching and abnormal branching of internal jugular vein found during our routine neck dissection.

No evidence of association of xenotropic murine leukemia virus-related virus with oral cancers: Experience from a tertiary care center in South India.

BACKGROUND: Development of oral cancer, a widely prevalent cancer in India, is multifactorial with increased risk in those habituated to smoking, consuming alcohol and chewing paan and tobacco. This does not preclude other etiological factors in the causation of this cancer. Exploratory studies on several oncogenic viruses have found varied associations with oral cancers. AIM: The aim of this study was to explore the association of xenotropic murine leukemia virus-related virus, (XMRV) a retrovirus recently implicated in oncogenesis in humans, with oral cancers. SETTINGS AND DESIGN: The presence of XMRV proviral deoxyribonucleic acid (DNA) was evaluated by standard nucleic acid amplification from DNA extracted from representative bits of tumor tissues and adjacent normal tissues from surgically resected specimens sent post-operatively for routine histopathological testing. MATERIALS AND METHODS: This prospective study comprised 109 patients with a provisional diagnosis of oral cancer who were operated at the Oral Oncology Department of Kidwai Memorial Institute of Oncology, over a period of 10 months. RESULTS: XMRV was not found in any of the tumor tissues (squamous cell carcinomas - 98; verrucous carcinomas - 4) nor in any of the normal tissues. It is thus important that the absence of this oncogenic virus in all the cases makes the association of XMRV with oral cancers very unlikely. CONCLUSIONS: There is a need to investigate potentially oncogenic viruses in other solid tumors and in larger sample sizes. Any such association could have implications in detecting, preventing and treating these cancers.

A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats.

As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus-amygdala-cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions.

Importance of Serum Copper and Vascular Endothelial Growth Factor (VEGF-A) Levels in Postmenopausal Bleeding.

The main aim of this study is association of serum copper and vascular endothelial growth factor (VEGF-A) in postmenopausal bleeding (PMB) patients. Blood samples were collected from female patients suffering with postmenopausal bleeding (n = 50) as well as healthy females as controls (n = 50). Serum copper levels were estimated by spectrophotometric method and serum VEGF-A by ELISA technique and compared with ultrasonographic measurement of endometrial thickness in both patients and controls. A significant increase in serum copper levels and an almost twofold increase in serum VEGF-A was observed in DUB patients when compared with controls. Correlation (r) between serum VEGF-A levels and endometrial thickness was 0.96. Odds ratio for copper, VEGF-A and combination of copper and VEGF-A was 0.0426, 0.0947 and 0.0313 respectively, in all these cases odds ratio was <1. The abnormal angiogenesis in PMB could be due to increased serum copper levels,which in turn stimulates factors like VEGF-A, thereby causing an increase in endometrial growth.

Use of nasolabial flap in intra and extraoral reconstruction: our experience with 40 cases.

PURPOSE: This article represents the use of inferiorly based nasolabial flap in reconstruction of various intraoral and extraoral defects. PATIENTS AND METHODS: Nasolabial flaps were performed in 40 patients, for reconstruction of buccal mucosa, gingivobuccal sulcus, commissure, lower lip, floor of mouth, upper lip and lower alveolar defects. RESULTS: The most common defect site in the oral cavity was the buccal mucosa. Partial flap necrosis occurred in five patients. Out of 40 cases of carcinoma of lip, commissure and floor of the mouth, all the patients had good speech after complete healing of the wound. None of the patients who had lip or commissure reconstruction developed drooling of saliva due to lip incompetence. CONCLUSION: The inferiorly based nasolabial flap provides reliable coverage of intermediate-sized oral cavity defects when used alone. Minimal donor morbidity is associated with its use. It is especially useful in elderly patients with facial skin laxity and where esthetics is not a major concern.

To operate or not to operate n0 neck in early cancer of the tongue? A prospective study.

Squamous cell carcinoma (SCC) of the tongue is a common cancer across the globe. These cancers have a high predilection for nodal metastasis and a high incidence of occult metastasis. The management of clinically negative neck nodes (N0) remains controversial. We have undertaken a prospective study to evaluate the rate of occult nodal metastasis, the characteristic of metastasis, and assess the usefulness of tumor depth as a predictor of metastasis and as a guide to treat the neck. Prospective study between January 2000 to December 2005. Patients with SCC of the anterior 2/3rd of tongue with N0 neck were included. Wide excision of the primary and subsequent modified radical neck dissection (in patients with tumor depth > 4 mm) was performed. Postoperative radiotherapy was given in patients with lymph node metastasis. Patients who had no node metastasis (p N -ve) were observed. The total number of eligible patients was 180. Occult lymph node metastasis (p N +ve) was seen in 122 (62.2%) patients (p < 0.001), multiple levels of node involvement in 79 (70.5%) patients and extracapsular spread (ECS) in 38 (33.6%) patients. Patients in the p N +ve group who were disease free was 63.1% as compared to 68.2% in the p N -ve group (p = 0.36). Recurrence was seen in 28 (36.8%) patients of p N +ve group and 14 (31.8%) patients of p N -ve group. Early cancer of tongue with tumor depth >4 mm was associated with predominantly high grade tumors, high incidence of occult nodal metastasis, multiple levels of nodal involvement and ECS. The disease free status of patients with occult metastasis who were treated was similar to that of patients with no nodal metastasis. Elective neck dissection appears essential for early oral tongue cancer with tumor depth >4 mm as there is no investigational modality which can reliably identify patients without occult metastasis.

Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer.

BACKGROUND: CYP1A1 is one of the commonest genes which had been widely investigated to find the risk of various malignancies in different ethnic groups. The polymorphism in these genes with a combination of environmental exposure has been hypothesized to confer a differential risk of cancer for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1 activity would be at increased risk of cancer when exposed to high levels of smoke components. The proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by xenobiotics to produce genetic susceptibility for malignancies. PATIENTS AND PROCEDURES: We performed a case-control study in 205 cases with histopathologically confirmed squamous cell carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers especially among smokers of Hyderabad Indian population. Venous blood samples (5 ml) were collected from patients and control groups; genomic DNA was extracted and used for polymerase chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the variant CYP1A1 alleles. RESULTS AND DISCUSSION: CYP1A1m1/m1 genotype (OR=8.12, 95% CI: 3.27-21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly CYP1A1w2/m2 (OR=1.58, 95% CI: 0.94-2.67) and CYP1A1m2/m2 (OR=6.31, 95% CI: 2.74-18.69) genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2 site. CONCLUSION: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2-fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an important determinant in susceptibility to tobacco-induced head and neck carcinogens and there is an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of smoking among Indians. This appears to be a new and important prognostic and diagnostic marker for determining the risk of head and neck cancers genetically.