Assessment of Malondialdehyde and Organochlorine Pesticides in Aplastic Anemia Severity Groups: Insights Into Oxidative Stress and Exposure.

Background There is little evidence that pesticide exposure is the primary cause of acquired aplastic anemia (AAA), even though the prevalence of aplastic anemia (AA) is substantially higher in underdeveloped countries than in affluent countries. AA caused by pesticides has not yet been fully understood. This study aimed to examine the potential link between plasma levels of malondialdehyde (MDA) and organochlorine pesticides (OCPs) as risk factors for developing AAA in the North Indian population. Methods This case-control study was conducted at a tertiary care hospital in North India. A total of 99 participants were chosen for the study, of whom 45 were cases of AA. These cases attended the Clinical Hematology department over a period of 1.5 years (May 2018 to November 2019). Forty-five controls were age and sex-matched, apparently healthy subjects. Written informed consent was obtained from each subject before performing the study. Exclusion criteria included patients unwilling to give consent, those using medication to treat AA, those genetically predisposed to AA, those with characteristics including granuloma and dysplasia of bone marrow, any other systemic illness, and subjects with a history of smoking, drinking, or using tobacco in any form. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to evaluate the plasma levels of organochlorines. The estimation of plasma MDA, i.e., the lipid peroxide content, was measured. Results The severity of AA is significantly associated with plasma levels of α-Hexachlorocyclohexane (p = 0.040), Heptachlor (p = 0.006), Aldrin (p < 0.001), p,p'-Dichlorodiphenyldichloroethane (p = 0.004), Endosulfan sulfate (p = 0.010), and Methoxychlor (p = 0.001). There was a statistically non-significant difference in MDA levels between cases and controls (p = 0.145); however, a statistically significant linear increase in MDA levels (p < 0.001) was observed according to the severity of AA. Conclusion Our study suggests that oxidative stress may be linked to the severity of AA. Pesticide exposure (plasma organochlorine levels) could act as a stressor, potentially initiating an alarmin response of oxidative stress in the form of lipid peroxidation (MDA) from damaged tissue, which could then lead to suppression of hematopoiesis and be a possible factor in the development of AA.

Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population.

Background Pesticide exposure might have a contributory role in the development of acquired aplastic anemia (AA). However, the precise mechanisms of pesticide-induced AA remain unknown. In this case-control study, we conducted a comparative analysis of plasma levels of organochlorine pesticides (OCP) and tumor necrosis factor-alpha (TNF-alpha) between Indian patients diagnosed with AA and an age- and sex-matched control group. Methods This is an observational case-control study conducted at a tertiary care hospital in North India. In this study, 90 subjects were included, out of which 45 were diagnosed with AA according to the criteria of the International Agranulocytosis and Aplastic Anemia Study. Cases were compared with 45 controls. A trained interviewer gave all study subjects a questionnaire to collect data regarding demographic details, exposure to pesticides, and clinical history. Physical examination and routine laboratory investigations of each subject were performed. Both cases and controls were tested for their plasma levels of organochlorines as per established protocol by gas chromatography-mass spectrometry. TNF-alpha level was measured by enzyme-linked immunosorbent assay in each subject. Results There was a significant increase in plasma levels of delta hexachlorocyclohexane (delta HCH) (p = 0.02) and heptachlor (p = 0.00) in patients with AA as compared to controls. We observed nonsignificant trends towards higher levels of beta HCH (p = 0.643), aldrin (p = 0.399), and p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) (p = 0.453) in patients with AA when compared to the controls. There were significantly higher TNF-alpha levels (p = 0.024) in cases as compared to the controls. Conclusion Our study concludes that patients with AA exhibited higher levels of delta-HCH, heptachlor, and TNF-alpha in comparison to the control group. There is a significant positive correlation of TNF alpha with OCPs (alpha HCH, lindane, delta HCH, heptachlor, aldrin, p,p'- DDD, and methoxychlor pesticides). These organochlorines may have accumulated in the fatty tissue of bone marrow because of their lipophilic nature. This suggests that they might have served as a neoantigen to trigger an increase in TNF-alpha production, which may have led to disrupted bone marrow function through cell-mediated immunity, leading to AA.

A Retrospective Study of Association of Tumor Budding, Tumor Microenvironment, and Clinicopathological Characteristics of Invasive Breast Carcinoma.

Background Tumor budding (TB) has been identified in many solid cancers and thought to be involved in invasion and is the initial step in the metastatic process. Limited information is available documenting the role of tumor budding in breast carcinoma. With this aim, the present study evaluates the association of tumor budding, tumor microenvironment, and its correlation with clinicopathologic parameters. Materials and Methods A total of 102 cases were archived and evaluated for peripheral and intra tumoral budding along with tumor microenvironment on hematoxylin and eosin (H&E) slides. Statistical Analysis Correlation between tumor budding, tumor microenvironment, and other classical clinicopathological parameters was studied by Chi-square test. A p -value less than 0.05 was considered significant. Results Females constituted 99 cases out of 102 and 3 were males. We found 55.9% and 44.1% of patients in the age group less than or equal to 50 and greater than 50, respectively. Also, 65.6% of cases presented with small tumor size less than or equal to 5 cm, 80.39% with lymph node metastasis, and 76.4% with lympho-vascular emboli. High peripheral tumoral budding (PTB) was seen in 45.10%, low peripheral tumoral budding in 54.9%, high ITB in 53.9%, and low ITB in 46.1%. Necrosis was found only in 39.21%. Significant statistical association of PTB was found with lymph node metastasis, lymphovascular emboli, and tumor necrosis, whereas ITB with tumor grade, lymph node metastasis, lympho-vascular emboli, and necrosis. Both PTB and ITB showed no statistically significant correlation with age and size of the tumor. Conclusion Tumor budding is an independent adverse prognostic factor in invasive breast carcinoma. However, further work is needed to establish a standard method for the quantification of this parameter, which will help in effective stratification of patients in terms of disease-free survival and likely outcome.

Case reports of chronic myeloid leukemia and tuberculosis: Is imatinib the link between the two?

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

Essential Thrombocythemia Presenting with Recurrent Priapism: A Case Report and Review of Literature.

BACKGROUND Priapism is rarely reported as a complication in patients with essential thrombocythemia at presentation. We could find very few such cases of essential thrombocythemia while searching the literature. A combined modality of treatment is used in the form of chemotherapy and procedures like repeated aspiration and instillation of phenylephrine to treat essential thrombocythemia presenting with recurrent priapism. CASE REPORT A 31-year-old man presented to the Urology Department with priapism for the last 24 h. He had previously had multiple similar episodes in the last 20 days and 1 episode of prolonged penile erection 5 months ago. On examination, his penis was erect, swollen, and painful. There was no organomegaly. The priapism was managed with repeated aspiration and instillation of phenylephrine. Routine investigations showed marked thrombocytosis. Subsequent investigations done in the Clinical Hematology Department revealed increased megakaryocytes in bone marrow and presence of JAK2V617F mutation. After confirmation of diagnosis, cytoreductive therapy (hydroxyurea 500 mg twice a day) and acetyl salicylic acid 75 mg once a day was initiated. With this treatment, the platelet count normalized over a period of 2 months and no further episodes of priapism were noted; however, the patient developed erectile dysfunction. CONCLUSIONS Essential thrombocythemia can present with priapism as the first manifestation. Early suspicion, diagnosis, and management is needed to prevent erectile dysfunction. Erectile dysfunction is usually irreversible after long-standing priapism.

Mutation Analysis in Chronic Myeloid Leukemia Patient in Chronic Phase on Imatinib Having Delayed Achievement of Milestones or Loss of Response.

Tyrosine kinase inhibitors (TKI's) are currently the drug of choice for management of chronic myeloid leukemia. Imatinib is the most commonly used first line TKI in India. Mutations leading to resistance to imatinib are the most common cause for imatinib failure. We studied pattern of kinase domain mutations in 40 patients of CML who either lost their response or did not achieve it in defined timepoints. Loss of molecular response was the most common indication for asking mutation analysis. Sixteen patients were found to have detectable mutations. M351T was the most common tyrosine kinase mutation followed by Y253H and H396R. Two patients had 2 mutations simultaneously. M351T is the most common mutation in our patient population.

Epidermal growth factor receptor expression in carcinoma gallbladder: A prospective study in Indian scenario.

AIM: Gallbladder cancer (GBC) is an aggressive disease with poor prognosis and complete surgical resection offering the only cure. Increased epidermal growth factor receptor (EGFR) expression has been noted in various cancers including GBC. Several studies across the world have examined the expression of EGFR in GBC. This study has been done to see the EGFR expression in GBC in Indian context. MATERIALS AND METHODS: Fifty cases of GBC were evaluated histopathologically using hematoxylin and eosin stained sections. Immunohistochemical assessment of EGFR expression was done, and scoring was done as per Kaufman et al. Data were collected, tabulated, and analyzed statistically by SPSS 16.0 version (Chicago, Inc., USA) software. RESULTS: Of 50 cases, 44 revealed EGFR over-expression while 6 were negative. Of the 44 cases, 10 had weak EGFR immunostaining intensity (1+), 26 had moderate (2+), and 8 showed strong EGFR immunostaining (3+). We found that most of the cases showing weak EGFR immunostaining intensity (1+) were well-differentiated tumor (70%) and cases with a strong EGFR immunostaining intensity (3+) were poorly differentiated cases of adenocarcinoma (75%). Moderately differentiated adenocarcinoma showed moderate EGFR immunostaining intensity (2+) in most of the cases (53.8%). CONCLUSION: EGFR is expressed in most of the cases of GBC. In well-differentiated adenocarcinoma, the EGFR expression is less compared to EGFR expression in poorly differentiated tumor, leading to the conclusion that the differentiation of the tumor and EGFR expression is inversely related. Thus, intensity of EGFR expression may correlate with aggressiveness of disease.