Apurva Garg

A review of the systemic adverse effects of areca nut or betel nut

Areca nut is widely consumed by all ages groups in many parts of the world, especially south-east Asia. The objective of this review is to systematically review and collate all the published data that are related to the systemic effects of areca nut. The literature search was performed by an electronic search of the Pubmed and Cochrane databases using keywords and included articles published till October 2012. We selected studies that covered the effect of areca nut on metabolism, and a total of 62 studies met the criteria. There is substantial evidence for carcinogenicity of areca nut in cancers of the mouth and esophagus. Areca nut affects almost all organs of the human body, including the brain, heart, lungs, gastrointestinal tract and reproductive organs. It causes or aggravates pre-existing conditions such as neuronal injury, myocardial infarction, cardiac arrhythmias, hepatotoxicity, asthma, central obesity, type II diabetes, hyperlipidemia, metabolic syndrome, etc. Areca nut affects the endocrine system, leading to hypothyroidism, prostate hyperplasia and infertility. It affects the immune system leading to suppression of T-cell activity and decreased release of cytokines. It has harmful effects on the fetus when used during pregnancy. Thus, areca nut is not a harmless substance as often perceived and proclaimed by the manufacturers of areca nut products such as Pan Masala, Supari Mix, Betel quid, etc. There is an urgent need to recognize areca nut as a harmful food substance by the policy makers and prohibit its glamorization as a mouth freshener. Strict laws are necessary to regulate the production of commercial preparations of areca nut.

Harmful effects of nicotine

With the advent of nicotine replacement therapy, the consumption of the nicotine is on the rise. Nicotine is considered to be a safer alternative of tobacco. The IARC monograph has not included nicotine as a carcinogen. However there are various studies which show otherwise. We undertook this review to specifically evaluate the effects of nicotine on the various organ systems. A computer aided search of the Medline and PubMed database was done using a combination of the keywords. All the animal and human studies investigating only the role of nicotine were included. Nicotine poses several health hazards. There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents. The use of nicotine needs regulation. The sale of nicotine should be under supervision of trained medical personnel.

Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography–Tandem Mass Spectrometry

Chewing of areca nut in different forms such as betel quid or commercially produced pan masala and gutkha is common practice in the Indian subcontinent and many parts of Asia and is associated with a variety of negative health outcomes, particularly oral and esophageal cancers. Areca nut-specific alkaloids arecoline, arecaidine, guvacoline, and guvacine have been implicated in both the abuse liability and the carcinogenicity of the areca nut. Therefore, variations in the levels of areca alkaloids could potentially contribute to variations in addictive and carcinogenic potential across areca nut-containing products. Here, we developed an accurate and robust liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for simultaneous quantitation of all four areca alkaloids and applied this method to the analysis of a range of products obtained from India, China, and the United States. The results of the analyses revealed substantial variations in the levels of alkaloids across the tested products, with guvacine being the most abundant (1.39-8.16 mg/g), followed by arecoline (0.64-2.22 mg/g), arecaidine (0.14-1.70 mg/g), and guvacoline (0.17-0.99 mg/g). Substantial differences in the relative contribution of individual alkaloids to the total alkaloid content were also observed among the different products. Our results highlight the need for systematic surveillance of constituent levels in areca nut-containing products and a better understanding of the relationship between the chemical profile and the harmful potential of these products.

Oral sex and human papilloma virus-related head and neck squamous cell cancer: a review of the literature

Head neck squamous cell carcinomas (HNSCCs) are a significant cause of morbidity and mortality all around the world. Just like tobacco and alcohol, Human papilloma virus (HPV) infection is now recognized to play a role in the pathogenesis of a subset of HNSCCs. Unprotected sexual behaviours with the HPV carrier plays an important role in transmission of this virus. The global incidence of head and neck cancers is declining, but the incidence of HPV related head and neck cancers is rapidly increasing over the last few decades. However, most institutions do not mandate documentation of sexual history or counselling of patients regarding sexual practices like they do for tobacco and alcohol addictions in HNSCC patients. The aim of this review of literature is to analyse if there is a strong evidence to correlate oral sex with HPV related HNSCC and counsel the patient’s regarding sexual behaviours.

Prospective study of the pattern of lymphatic metastasis in relation to the submandibular gland in patients with carcinoma of the oral cavity.

The submandibular gland is responsible for 70% to 90% of unstimulated saliva production. Its excision causes a decrease in basal salivary flow resulting in increased symptoms of subjective xerostomia and decreased quality of life. In this study, we have tried to assess the pattern of nodal metastasis in relation to the submandibular gland. With this study, we have tried to find out whether submandibular gland preservation is a viable option in patients with carcinoma of the oral cavity.

A review on harmful effects of pan masala.

Pan masala (PM) is a mixture of areca nut with slaked lime, catechu and other flavoring agents. It is widely available and used by all the sections of the Indian society. It is genotoxic as it increases sister chromatin exchange and chromatin aberrations. Among humans, it is a leading cause of oral submucous fibrosis that often progresses to oral cancer. Among experimental animals, it leads to neoplastic lesions in lung, liver and stomach. It is hepatotoxic leading to increased level of enzymes, deranged carbohydrate and lipid metabolism. It is harmful to kidneys and testes leading to increased creatinine and sperm deformities respectively. PM is a very harmful substance affecting almost all organ systems, and there is immediate need for a national policy on complete ban on the production, storage, sale and marketing of PM.

Diagnosis of tobacco related cancer has impact on consumption of tobacco among family members and friends of patients

Introduction: There is a saying that “cancer cures smoking” as people often quit tobacco after diagnosis of cancer. Very few studies have analyzed the change in tobacco habits of a user after diagnosis of cancer in a relative or friend. Materials and Methods: In this cross-sectional study, 161 friends and relatives of 40 patients treated at Tata Memorial Hospital, Mumbai, India, were interviewed. They were given a questionnaire related to their tobacco habits. The results were analyzed statistically using Wilcoxon signed-rank test and Mann–Whitney test using SPSS. Results: Of the studied individuals, 114 were friends and 47 were blood relatives. 141 used smokeless tobacco, 18 were smokers, and 2 consumed tobacco in both the forms. The mean frequency of tobacco consumption among the friends and relatives before diagnosis of cancer was 12.24 per day and that at the time of interview was 9.76 per day. 35 persons (21.7%) stopped consumption whereas 19 (11.8%) reduced usage after diagnosis of cancer. The difference in mean consumption at median duration of 174 days is statistically significant (P = 0.0005). Conclusions: The diagnosis of tobacco-related cancer has significant impact on the tobacco consumption of friends and relatives. The abstinence rate is comparable to that of various tobacco deaddiction therapies in vogue.

Trends of oral cancer with regard to age, gender, and subsite over 16 years at a tertiary cancer center in India

Introduction: Oral cancers are among the most common cancers in the Indian subcontinent and tobacco is the most common implicated etiologic agent for these cancers. Over last two decades, significant changes have occurred in the lifestyle of people in the subcontinent. Antitobacco legislations have made developed and awareness about the harmful effects of tobacco and related products have increased. We hypothesized that this would lead to change in tobacco use pattern and hence impact the trends of oral cancer in India. Methodology: We analyzed the hospital records of patients having buccal mucosa and tongue cancers at a tertiary care cancer center. We noted the trends of patients presenting with these cancers 4 yearly, over a period of 16 years and in this way tried to assess the impact of legislation and awareness activities upon cancer incidence and trends. Results: This study has shown that the number of patients presenting with tongue and buccal mucosa cancers has not decreased over the years. Increase in buccal mucosa cancers is marginally more than that of the tongue cancer. Proportion of males with respect to females presenting with these cancers has increased. There has been no significant decline in the younger patients presenting with these cancers. Common age of presentation of tongue cancers has come down. Conclusion: The findings of this study highlight the ineffectiveness of current laws and awareness programs in reducing the menace of oral cancer.

Prevention of Oral Cancer

Oral cancer (ICD-10:C00-C08) is now a significant health issue in many parts of the world due to widespread use of tobacco, alcohol, and areca nut [1, 2]. According to GLOBOCON 2012, oral cancer is the 17th most common cancer in the world with about 300,373 new cases and 145,353 deaths in 2012 which is expected to rise to 406,022 and 197,811, respectively, by 2025 [3]. This cancer effects both the developed and developing countries but there is wide global difference in the incidence of this cancer (~20 fold) [2]. It is more common in South Asia (e.g., India, Sri Lanka, Pakistan, Taiwan), Latin America (e.g., Brazil, Uruguay, Puerto Rico and Cuba), Eastern Europe (e.g., Hungary, Slovenia, Slovakia), Western Europe (e.g., Germany, France), and Pacific regions (e.g., Papua New Guinea) [2]. It is the most common cancer among males and overall the 3rd most common cancer in India with age-standardized rate (ASR) of 7.2 but contributes highest to the number of new cases annually [3, 4].

Acute toxicities of adjuvant treatment in patients of oral squamous cell carcinoma with and without submucous fibrosis: A retrospective audit.

OBJECTIVE To assess the severity of acute toxicities of postoperative adjuvant therapy on oral squamous cell carcinoma (OSCC) patients with and without submucous fibrosis (SMF). MATERIALS AND METHODS The study population comprised treatment naïve OSCC patients who underwent curative intent surgical resection from June 2010 to April 2011 followed by adjuvant treatment. Patients whose treatment details including toxicity profile were available were included in the study. One-hundred nine patients met the inclusion criteria of whom 36 had associated SMF and 73 no SMF. Overall, 35 patients received chemotherapy (CT) with radiotherapy (RT) and the rest only RT. Forty-two patients had centralized and 67 lateralized lesions. All patients with centralized lesions and 3 with lateralized lesion received radiation to bilateral face and neck. All others received ipsilateral radiation. The severity of mucositis, xerostomia, and skin toxicity (as per radiation therapy oncology group scale of acute toxicity) was compared between the SMF and non-SMF groups and patients with centralized and lateralized lesions. RESULTS CT in addition to RT did not add significant to the assessed toxicities. Severe mucositis as well as treatment breaks were more in SMF group as compared to non-SMF group (P = 0.001 and <0.001 respectively). Severe mucositis and xerostomia were more in centralized than in lateralized lesions (P = 0.002 and 0.00 respectively). In subgroups of lateralized as well as centralized lesions, severe mucositis was more common in SMF patients than those without SMF (P = 0.01 and 0.02 respectively). CONCLUSION OSCC patients with SMF have worse toxicity with adjuvant therapy and require good supportive care.