Oral Fluid, Electrolytes, and Energy Management in Various Adult and Geriatric Illnesses beyond Diarrhea: An Indian Expert Panel Delphi Consensus Recommendation.

BACKGROUND: Dehydration is a highly prevalent clinical challenge in adults which can go undetected. Although dehydration is commonly associated with an increased risk of hospitalization and mortality, only a few international guidelines provide recommendations regarding oral fluids, electrolytes, and energy (FEE) management in adults/geriatrics with dehydration due to nondiarrheal causes. Currently, there is a lack of comprehensive recommendations on the role of oral FEE in nondiarrheal dehydration in adult and geriatric Indian patients. MATERIALS AND METHODS: A modified Delphi approach was designed using an online questionnaire-based survey followed by a virtual meeting, and another round of online surveys was used to develop this consensus recommendation. In round one, 130 statements, including 21 open-ended questions, were circulated among ten national experts who were asked to either strongly agree, agree, disagree, or strongly disagree with statements and provide responses to open-ended questions. The consensus was predefined at 75% agreement (pooling "strongly agree" and "agree" responses). Presentation of relevant literature was done during a virtual discussion, and some statements (the ones that did not achieve predefined agreement) were actively discussed and deliberately debated to arrive at conclusive statements. Those statements that did not reach consensus were revised and recirculated during round two. RESULTS: Consensus was achieved for 130/130 statements covering various domains such as assessment of dehydration, dehydration in geriatrics, energy requirement, impact of oral FEE on patient outcome, and fluid recommendations in acute and chronic nondiarrheal illness. However, one statement was not added as a recommendation in the final consensus (129/130) as further literature review did not find any supporting data. Oral FEE should be recommended as part of core treatment from day 1 of acute nondiarrheal illness and started at the earliest feasibility in chronic illnesses for improved patient outcomes. Appropriately formulated fluids with known electrolyte and energy content, quality standards, and improved palatability may further impact patient compliance and could be a good option. CONCLUSION: These consensus recommendations provide guidance for oral FEE recommendations in Indian adult/geriatric patients with various nondiarrheal illnesses.

Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017-2019.

BACKGROUND: The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. METHODS: Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. RESULTS: There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50-65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100-100); 61% (95% CI: 45-83); 30% (95% CI: 21-43); and 9% (95% CI: 6-13) for stages I-IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39-64), compared to 29% (95% CI: 22-38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6-14) in patients who were palliated (N = 107) (p = <0.0001). CONCLUSION: The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III-IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required.

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.

History of the Growing Burden of Cancer in India: From Antiquity to the 21st Century.

This review traces the growing burden of cancer in India from antiquity. We searched PubMed, Internet Archive, the British Library, and several other sources for information on cancer in Indian history. Paleopathology studies from Indus Valley Civilization sites do not reveal any malignancy. Cancer-like diseases and remedies are mentioned in the ancient Ayurveda and Siddha manuscripts from India. Cancer was rarely mentioned in the medieval literature from India. Cancer case reports from India began in the 17th century. Between 1860 and 1910, several audits and cancer case series were published by Indian Medical Service doctors across India. The landmark study by Nath and Grewal used autopsy, pathology, and clinical data between 1917 and 1932 from various medical college hospitals across India to confirm that cancer was a common cause of death in middle-aged and elderly Indians. India's cancer burden was apparently low as a result of the short life expectancy of the natives in those times. In 1946, a national committee on health reforms recommended the creation of sufficient facilities to diagnose and manage the increasing cancer burden in all Indian states. Trends from the Mumbai population-based cancer registry revealed a four-fold increase in patients with cancer from 1964 to 2012. Depending on the epidemiologic transition level, wide interstate variation in cancer burden is found in India. We conclude that cancer has been recognized in India since antiquity. India's current burden of a million incident cancers is the result of an epidemiologic transition, improved cancer diagnostics, and improved cancer data capture. The increase in cancer in India with wide interstate variations offers useful insights and important lessons for developing countries in managing their increasing cancer burdens.

Prevalence estimation of microsatellite instability in colorectal cancers using tissue microarray based methods - A tertiary care center experience.

AIM: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. METHODS: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. RESULTS: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. CONCLUSION: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.

Investigators' viewpoint of clinical trials in India: Past, present and future.

India's success in producing food and milk for its population (Green Revolution and White Revolution) happened because of scientific research and field trials. Likewise improving the health of Indians needs clinical research and clinical trials. A Large proportion of the sick Indians are poor, illiterate with no access to good health care. They are highly vulnerable to inducement and exploitation in clinical trials. The past two decades saw the rise and fall of clinical trials in India. The rise happened when our regulators created a favorable environment, and Indian investigators were invited to participate in global clinical trials. The gap between the demand and supply resulted in inadequate protection of the trial participants. Reports of abuses of the vulnerable trial participants followed by public interest litigations led to strengthening of regulations by the regulators. The stringent new regulations made the conduct of clinical trials more laborious and increased the cost of clinical trials in India. There was a loss of interest in sponsored clinical trials resulting in the fall in global clinical trials in India. Following repeated appeals by the investigators, the Indian regulators have recently relaxed some of the stringent regulations, while continuing to ensure the adequate patient protection. Clinical trials that are relevant to our population and conducted by well-trained investigators and monitored by trained and registered Ethics Committees will increase in the future. We must remain vigilant, avoid previous mistakes, and strive hard to protect the trial participants in the future trials.

Epidemiology of Non-Hodgkin's Lymphoma in India.

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy. The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively. These are about one fourth of the incidence rates reported from Western Europe or North America. Within India, the incidence is several-fold higher in urban cancer registries compared to rural areas; the incidence being higher in metropolitan cities and Indian immigrants suggesting that urban lifestyles and economic progress may increase the cancer incidence. Compared to developed nations, the key differences in the presentation in India include: median age of 54 years (almost a decade less), higher male to female ratio, higher proportion of patients with B-symptoms (40-60 vs. 20-30%), poor ECOG performance status (≥2) at diagnosis (50 vs. 20-30%), higher frequency of diffuse large B-cell lymphomas (60-70 vs. <40%), lower frequency of follicular NHL (<20 vs. 30-40%) and T-cell type in 10-20 vs. <10%. The estimated mortality rate due to NHL is higher in India than in North America and Western Europe. Diagnostic and treatment delays, incorrect diagnosis and inappropriate or suboptimal treatment may be possible reasons for the poor outcome. Any improvement in the outcomes for NHL in India will require a nationwide approach, e.g. creation of several regional and district-level centers with expertise in lymphoma management. Collection of data on patient- and disease-related characteristics, treatment outcome, development of infrastructure, centralized review of histopathology subtype, novel treatment protocols, rigorous follow-up, training of staff, and financial support towards treatment could be possible strategies to improve the outcome.

Primary liver cancer deaths and related years of life lost attributable to hepatitis B and C viruses in India.

BACKGROUND AND AIMS: More than 25,000 people die of liver cancer annually in India. There is little information about the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to these deaths. We conducted a systematic review of published studies on HBV or HCV infection and liver cancer in India and estimated the population attributable fraction (PAF) of liver cancer deaths caused by these infections and the corresponding annual number of deaths and years of life lost (YLL) in the country. METHODS: We searched the PubMed and Scopus databases, as well as the reference list of relevant articles in the systematic review. For calculation of the number of liver cancer deaths attributable to HBV and HCV, we used two sources of outcome data and two relative risks for the association between HCV and liver cancer. RESULTS: The PAF was 67% for HBV, 17-19% for HCV, and 71-72% for HBV and/or HCV. The annual attributable number of liver cancer deaths was approximately 17,000 for HBV; 4500 for HCV; and 18,500 for HBV and/or HCV, corresponding to approximately 297,000, 75,000, and 315,000 YLL, respectively. There was little difference in these numbers using the two sources of outcome data or the two risk estimates for HCV. CONCLUSIONS: Our findings underscore the importance of primary prevention of HBV and HCV by appropriate measures, including vaccination (HBV only), prevention of transfusion-related infections, and increased awareness of the routes of transmission and long-term health outcomes.

Elevated CA125 Levels in a 72-Year-Old Ethnic Indian Patient: A Diagnostic Pointer Toward Tuberculosis?

Serum CA 125 is widely used as a tumor marker for epithelial ovarian cancer. Our laboratory receives few requests for evaluation of this marker in men. In males an elevation of this marker may occur due to malignant and benign lesions of organs derived from the coelomic epithelium. However, in the absence of evidence of a neoplasm (via clinical examination and other diagnostic modalities), it is useful to consider a diagnosis of tuberculosis, particularly in regions where the disease is endemic. Herein, we describe one such case that we investigated at our medical center in Kolkata, India.

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 India's 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.

Pharmacovigilance Symposium ISCR Annual Conference Jan 5, 2013: Safety aspects of hard endpoint or outcome trials.

The articles describes some highlights of the Pharmacovigilance Symposium held during Annual conference.

An open-label study of the safety and tolerability of pazopanib in combination with FOLFOX6 or CapeOx in patients with colorectal cancer.

BACKGROUND: Although combining targeted agents with conventional, first-line cytotoxic therapy has improved survival outcomes in patients with advanced colorectal cancer, further improvements in outcomes and tolerability are needed. METHODS: This phase I study evaluated the feasibility of combining oral pazopanib, an agent that targets multiple proangiogenic factors, with FOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) or CapeOx (oxaliplatin and capecitabine). This phase I study evaluated the optimally tolerated regimen of daily pazopanib (dose-escalated) plus standard FOLFOX6 or CapeOx in patients with advanced colorectal cancer. At the optimally tolerated regimen, each cohort was expanded to further evaluate safety and clinical response. RESULTS: The optimally tolerated regimens were pazopanib 800 mg plus FOLFOX6 and pazopanib 800 mg plus reduced CapeOx (capecitabine 850 mg/m(2)). The most commonly reported adverse events in the FOLFOX6 cohorts included decreased appetite, neutropenia, diarrhea, peripheral neuropathy, and vomiting. Similarly, the most commonly reported adverse events in the CapeOx cohorts included fatigue, vomiting, and decreased appetite. The overall response rate was 40 % (8/20 patients) in the pazopanib plus FOLFOX6 cohorts and 38 % (8/21 patients) in the pazopanib plus CapeOx cohorts. CONCLUSION: Pazopanib combined with FOLFOX6 or reduced CapeOx was adequately tolerated in this patient population.

Incidence of gastrointestinal cancers by ethnic group in England, 2001-2007.

OBJECTIVE: To compare the incidence of six gastrointestinal cancers (colorectal, oesophageal, gastric, liver, gallbladder and pancreatic) among the six main 'non-White' ethnic groups in England (Indian, Pakistani, Bangladeshi, Black African, Black Caribbean and Chinese) to each other and to Whites. METHODS: We analysed all 378 511 gastrointestinal cancer registrations from 2001-2007 in England. Ethnicity was obtained by linkage to the Hospital Episodes Statistics database and we used mid-year population estimates from 2001-2007. Incidence rate ratios adjusted for age, sex and income were calculated, comparing the six ethnic groups (and combined 'South Asian' and 'Black' groups) to Whites and to each other. RESULTS: There were significant differences in the incidence of all six cancers between the ethnic groups (all p<0.001). In general, the 'non-White' groups had a lower incidence of colorectal, oesophageal and pancreatic cancer compared to Whites and a higher incidence of liver and gallbladder cancer. Gastric cancer incidence was lower in South Asians but higher in Blacks and Chinese. There was strong evidence of differences in risk between Indians, Pakistanis and Bangladeshis for cancer of the oesophagus, stomach, liver and gallbladder (all p<0.001) and between Black Africans and Black Caribbeans for liver and gallbladder cancer (both p<0.001). CONCLUSIONS: The risk of gastrointestinal cancers varies greatly by individual ethnic group, including within those groups that have traditionally been grouped together (South Asians and Blacks). Many of these differences are not readily explained by known risk factors and suggest that important, potentially modifiable causes of these cancers are still to be discovered.