Breast cancer-related lymphedema in postmastectomy patients receiving adjuvant irradiation: A prospective study

AIM: Inflammation plays a lead role in the tumor microenvironment and promotes metastasis. Single-nucleotide polymorphism (SNP) in the tumor necrosis factor (TNF) gene locus may alter the expression of genes and proteins. The objective of the study is to find the distribution of genetic polymorphism in the sites of TNF-α −308G>A and TNF- β +252A>G in breast cancer and evaluate polymorphism effects on plasma levels. MATERIALS AND METHODS: The study group consisted of 109 invasive ductal primary breast cancer patients and 75 age-matched healthy female controls. Plasma cytokine concentrations were measured by the MILLIPLEX® MAP Human Cytokine/Chemokine Panel magnetic bead kits. The genotyping procedure for SNP included allele-specific polymerase chain reaction for TNFα and restriction fragment length polymorphism for TNFβ. RESULTS: Odds ratio with 95% confidence interval showed that these polymorphisms were not a causative risk factor, and both polymorphisms were consistent with Hardy–Weinberg equilibrium. Plasma TNFα and TNFβ median concentrations were significantly higher in cases when compared to controls (P < 0.01). When plasma TNFα levels were grouped under polymorphic subtypes, patients with mutant TNF- α −308A allele showed significantly higher values (P < 0.001). In addition, plasma TNFα values were significantly elevated in mutant TNF-β +252G allele (P < 0.01). CONCLUSION: This study demonstrated that there is no significant association between SNPs and breast cancer susceptibility in South Indian population. However, plasma TNFα level is significantly elevated with mutant-recessive TNF-α −308 A and TNF-β +252 G alleles of patients.

Compliance to radiotherapy: A tertiary care center experience

CONTEXT: The most commonly prescribed conventional fractionation radiotherapy uses 1.8–2.2 Gy per fraction for five fractions in a week. Many times, unwanted interruptions are encountered, which ultimately affect the local control and overall survival. AIMS: The present retrospective study was carried out to study the compliance to radiotherapy at our institute and to determine various factors related to it. PATIENTS AND METHODS: The present retrospective study was carried out at the department of Radiotherapy, SMS Medical College and attached group of hospitals, Jaipur; in patients who were treated with curative intent with conventional fractionation radiotherapy over telecobalt machine from January 2017 to April 2017. Noncompliance was studied for association with various factors such as age, sex, site of primary disease, stage of tumor, distance patients had to travel to receive treatment, administration of concurrent chemotherapy, and financial burden of the treatment. RESULTS: Of 203 patients, 138 were of head-and-neck cancer, 42 of cervical cancer, and 23 of breast cancer. The cumulative incidence of noncompliance was 12.8% (15.9% for head-and-neck cancer, 7.2% for cervical cancer, and 4.4% for breast cancer). Statistically significant association was found between noncompliance and higher age of the patients (P = 0.07), male gender (P = 0.002), advanced stage (P = 0.004), administration of concurrent chemoradiotherapy (CCRT) (P < 0.001), and greater distance patients had to travel for radiotherapy (P = 0.03). CONCLUSIONS: The factors ith which noncompliance is significantly associated in the present study are higher age, male gender, advanced stage of tumor, administration of CCRT, and greater distance patients had to travel to avail radiotherapy.

Evaluation of a novel decorporation approach to prevent radioactivity uptake by using acidosis in experimental animals.

With an aim to devise a prophylactic and/or therapeutic approach for preventing internalization of radiothallium (201Tl), and more importantly by implication, its chemical analogue radiocesium (137Cs) during any nuclear emergency, different ex vivo and in vivo animal models were created to determine the role of pH in absorption of 201Tl across jejunum/muscle tissue and whole body retention of 201Tl respectively. Movement of Tl+ under simulated pH conditions proved that pH had direct influence on its absorption. Oral intake of acidified water or parenteral administration of lactic acid was able to reduce the body burden of 201Tl by up to 12 and 50% respectively. The results indicate that acidification of gut, within physiological range may be used as an option for decorporation/inhibition of incorporation of radiothallium and radiocesium, particularly in cases of mass casualty.

Transient cell function disruption by low dose acute exposure of ionizing radiation.

Incubation of BMG-1 cells with thallium chloride (201Tl) in the range of diagnostic dose did not show a smooth uptake curve and appeared to have an unsuspected deviation in initial phase. In the present study this unexpected phenomenon was explored, using commonly used radionuclides (viz., 201Tl and 131I). Comparison was made with technetium-99m pertechnetate (99mTcO4-) and technetium-99m labeled methoxyisobutylisonitrile (99mTc-MIBI) that are known to show conventional 2 phase graph representing inflow and outflow segments. Serial in vitro, ex-vivo and in vivo gamma scintigraphy as well as NMR spectroscopy experiments were conducted to corroborate the results. BMG-1 cells demonstrated a four-phase uptake pattern with 201Tl as compared to a conventional biphasic pattern with 99mTc-MIBI. Flow cytometry data however did not reveal any 201Tl induced cell injury. Further, mice tissue extracts injected with 201Tl also showed a transient depression in its uptake. Scintigraphy experiments in rabbits administered with diagnostic dose of 201Tl and 131I confirmed the in vitro and ex vivo findings. Further, proton NMR spectroscopy showed decrease in the level of choline at 3 h and 24 h in 201Tl treated animals as compared to control. Phosphoethanolamine peak firstly decreased at 3 h but reached normal level at 24 h time point. No significant change was observed in the level of betaine. This transient reduction in internalization of 201Tl and 131I may represent a hitherto unknown acute effect of low dose radiation, i.e., transient depression in Na+-K+ ATPase pump activity without any apparent evidence of cell damage, representing a transient cell membrane dysfunction. The phenomenon may present a mechanistical explanation of ‘thyroid stunning’ at cellular level and suggest that it may be more universal in nature than suspected till now.