Efficacy and safety of capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer: An observational study from a tertiary cancer center in South India

Background: 5-fluorouracil (5-FU) was the standard treatment care for colorectal cancer (CRC), however, its efficacy was limited due to safety concerns. Capecitabine and oxaliplatin (CAPOX) treatment was found equivalent to 5-FU in efficacy and preferred now due to easy management and convenience in administration. Hence, the present study aims to determine the efficacy and safety associated with CAPOX treatment in a real world non clinical setting. Methods: 145 treatment-naive and newly diagnosed CRC patients were recruited in the study. Each patient received oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000 mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. Results: In the adjuvant setting, the observed disease-free survival rate was 62% (n=34) in the colon and 67% (n=15) in the rectum cancer patients at 2 years. The observed overall survival rate in the colon and rectal cancer was 80% (n=44) and 83% (n=18) respectively at 2 years. In the palliative setting the observed progression-free survival rate was 28% (n=13) in the colon and 33% (n=7) in rectal cancer patients at 2 years. The observed OSR at 2 years was 64% (n=30) in the colon and 67% (n=14) in the rectal cancer patients. Thrombocytopenia (17, 11.7%) and diarrhea (8, 5.5%) were the most commonly observed grade 3/4 hematological and gastrointestinal toxicities. Hand-foot syndrome and peripheral neuropathy were the major contributors for dose reduction (14, 9.6%), treatment delay (8, 5.4%), and drug discontinuation (9, 6.1%) in the study cohort. Conclusion: CAPOX treatment was found to be effective but associated with several dose-limiting toxicities.

Effect of Arg399Gln single-nucleotide polymorphism in XRCC1 gene on survival rate of Indian squamous cell head-and-neck cancer patients

Background: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%–40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. Materials and Methods: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. Results: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33–39.5), 38.6 (95% CI: 35.3–41.9), 35.8 (95% CI: 28.6–42.9), and 26.4 (95% CI: 13.7–39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4–39.1), 38.2 (95% CI: 34.3–42.1), 32.7 (95% CI: 26.2–39.1), and 22.3 (95% CI: 9.4–35.3) (P = 0.061), respectively. Conclusions: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment

Detection of cancer stem cell-related markers in different stages of colorectal carcinoma patients of Indian origin by immunohistochemistry

Context: Although the incidence rate of colorectal cancer (CRC) in all Indian cancer registries is very close to the lowest rate in the world, westernization has shown an increasing trend in the recent years. Recurrence is reported in CRC because the slowly proliferating stem cells escape the chemotherapeutic regimen. Aim: To detect the presence of CD133 and CD44 in human CRC specimens and to correlate the level of marker expression with tumor staging. Materials and Methods: We included 26 colorectal carcinoma patients between 20 and 70 years of age. Histological and immunohistochemical analysis of CD133 and CD44 was done in sections of 5 μm prepared from paraffin-embedded blocks with most representative areas. Statistical Analysis: All analyses were performed using Microsoft Excel 2010 and SPSS version 22. Results: CD133 expression was seen exclusively on the cell membrane at the glandular luminal surface with dot-like cytoplasmic staining. In the normal mucosa, CD44 expression was seen in the superficial region of the cell, whereas in most of the carcinomas, the staining was localized in the basolateral region of the cell. Both CD133 and CD44 showed significant correlation with tumor stage. Conclusions: In the present study, CD133 and CD44 show significant correlation with tumor staging. Cancer stem cell markers have shown similar pattern of expression in the patients of Indian origin. Using combination of markers for staging is preferred as it increases the sensitivity and specificity

Association of Helicobacter pylori with Parkinson's Disease

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD medications. We aim to investigate the effect of H. pylori infection in Indian PD patients. METHODS: We prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean ‘off’ Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean ‘on’ UPDRS-III score, mean onset time, mean ‘on’ duration, and mean daily ‘on’ time were measured at baseline and at a 3-week follow-up. RESULTS: H. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylori positive patients than in controls (p<0.0001). Controls had a significantly longer ‘on’ duration and daily ‘on’ time, and better ‘on’ UPDRS-III scores. Seropositive patients took a significantly longer time to turn ‘on’ after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean ‘on’ UPDRS-III score, onset time, ‘on’ duration, and daily ‘on’ time. CONCLUSIONS: H. pylori infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.

Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI.

Background & objectives: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations. Methods: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein. Results: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population. Interpretation & conclusions: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI.

Serum 25-Hydroxyvitamin D Deficiency in Ischemic Stroke and Subtypes in Indian Patients / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Vitamin D deficiency is common across all age groups and may contribute to cardiovascular diseases. Serum 25-hydroxyvitamin D deficiency causing ischemic stroke has been documented in recent reports. AIM: To investigate the association of serum 25-hydroxyvitamin D deficiency with ischemic stroke and subtypes. METHODS: We recruited 250 consecutive ischemic stroke patients and 250 age and sex matched controls attending the Department of Neurology, at Yashoda hospital, Hyderabad, India, from January 2011 to December 2012. All ischemic stroke patients underwent stroke subtyping. We measured 25-hydroxyvitamin D by chemiluminescence test, serum calcium, phosphorus, alkaline phosphatase, and C-reactive protein (CRP) in cases and controls. RESULTS: Out of 250 stroke patients, 190 (76%) were men and mean age was 58.4+/-11.1 years (age range-26-89 years). 25-hydroxyvitamin D deficiency was observed in 122 (48.8%) stroke patients and 79 (31.6%) controls (P=0.001). Among stroke patients, serum 25-hydroxyvitamin D deficiency was found in 54.9% (50/91) of patients with large artery atherosclerosis, 54% (20/37) in cardioembolic stroke, 44.4% (20/45) in small artery diseases, 42.8% (15/35) in stroke of other determined etiology and 40.4% (17/42) in stroke of un-determined etiology. Multiple logistic regression analysis showed an independent association of 25-hydroxyvitamin D deficiency with ischemic stroke (odds ratio: 1.6; 95% CI 1.2-2.8). The association was strongest with large artery atherosclerosis (odds ratio: 2.4; 95% CI 1.6-3.5) and cardioembolic stroke (odds ratio: 2.0; 95% CI 1.0-3.2). CONCLUSIONS: We found that 25-hydroxyvitamin D deficiency had an independent association with ischemic stroke. The association was established in large artery arthrosclerosis and cardioembolic stroke.

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients.

Germline mutations of RET gene are pathognomonic of multiple endocrine neoplasia (MEN; MEN 2A/MEN 2B) and familial medullary thyroid carcinoma (FMTC), constituting 25% of medullary thyroid carcinomas (MTCs). We investigated RET gene mutations and polymorphisms at exons 10, 11, 13, 14, 15 and 16 in 140 samples, comprising 51 clinically diagnosed MTC patients, 39 family members of patients and 50 normal individuals. The method of choice was PCR and direct nucleotide sequencing of the PCR products. RET gene mutations were detected in 15 (29.4%) patients, with MEN 2A/FMTC in 13 patients and MEN 2B in 2 patients. Further, 39 family members of seven index cases were analysed, wherein four of the seven index cases showed identical mutations, in 13 of 25 family members. We also examined single nucleotide polymorphisms (SNPs) in RET gene exons in 101 unrelated samples. Significant differences in the allelic frequencies of SNPs at codons 691, 769, 836 and 904 between patient and control groups were not observed. However, SNP frequencies were significantly different in the Indian group as compared with other European groups. We identified two novel, rare and unique SNPs separately in single patients. Our study demonstrated presence of MEN 2A/MEN 2B/FMTC-associated mutations in accordance with the reported literature. Thus, RET gene mutations in exons 10, 11, 13, 14, 15 and 16 constitute a rapid test to confirm diagnosis and assess risk of the disease in familial MEN 2A/MEN 2B/FMTC.