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Efficacy of Rivaroxaban Use in Solid Tumour Malignancy: Experience from a Tertiary Care Cancer Centre

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3601-3606. doi: 10.31557/APJCP.2021.22.11.3601.

ABSTRACT

OBJECTIVE: Cancer-associated venous thromboembolism (CAT) is a common disease or complication which is associated with reduced survival and incurring a substantial health-care cost. Low molecular weight heparin (LMWH) remained the gold standard treatment option available. Direct oral anticoagulants (DOACs) have recently become more popular in the guidelines, they are still few and inconsistent across the current literature. The aim of this study was to evaluate rivaroxaban in treatment of CAT.

METHODS: In this prospective real-world study, we recruited and followed up patients diagnosed with CAT treated with rivaroxaban or standard of care as a control for 12 months or until death. Baseline characteristics were collected at the study entry. The primary outcomes were recurrent DVT or PE and death within 12 months after treatment initiation. Safety outcomes were composite outcomes of major and minor bleeding. Results: A total of 80 patients confirm CAT with radiological imaging were recruited; 39 patients were evaluated in the control arm and 41 patients in the rivaroxaban arm. The 12 months cumulative CAT recurrence rate was 46.2% in control and 39% in rivaroxaban (p=0.519). The 12-month death was not a statistically significant difference between both arms (20.5% vs. 31.7%, p=0.255). The cumulative rate of composite safety outcomes was similar in both groups (17.9% vs. 12.2%, p=0.471).

CONCLUSION: The result of this small but important real-world evidence proofs that rivaroxaban is an effective and safe alternative to the standard of care for CAT in Malaysia’s cancer population.

PMID:34837918 | DOI:10.31557/APJCP.2021.22.11.3601

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Video-Assisted Breast Surgery (VABS) and Vacuum-Assisted Breast Biopsy (VABB) for Fibroadenoma Mammae on Patients’ Satisfaction: A Preliminary Study

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3615-3621. doi: 10.31557/APJCP.2021.22.11.3615.

ABSTRACT

OBJECTIVE: This study aimed to compare the patients’ satisfaction level after fibroadenoma surgery with Video-Assisted Breast Surgery (VABS) and Vacuum-Assisted Breast Biopsy (VABB) techniques.

METHODS: Patients who underwent VABS or VABB for a diagnosis of fibroadenoma mammae at the Oncology Clinic in Solo, Indonesia were included in this study. Clinical and demographic data were obtained from medical records. Direct or telephone interviews were performed and the patients were asked to complete Universitas Sebelas Maret Breast Satisfaction Questionnaire 8 (UNS-BsQ8) questionnaire.

RESULTS: A total sample of 16 patients with VABS and 26 patients with VABB were recruited. All the patients were confirmed to have fibroadenoma based on the pathological result. The mean total scores for VABS and VABB were 34.50 ± 2.094 and 31.57 ± 3.081, respectively (P= 0.137). Out of 8 questions, only 3 items had statistically significant differences. VABS had higher mean score than VABB in terms of surgery cost (P = 0.002), pain in surgery site (P = 0.006), and pain in shoulder (P = 0.013).

CONCLUSION: There was no significant difference in terms of overall patients’ satisfaction level between both groups. However, VABS had a higher mean score than VABB in terms of cost and pain.

PMID:34837920 | DOI:10.31557/APJCP.2021.22.11.3615

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The Effects of Phyllanthus niruri Linn on Infiltrating Dendritic Cell and Ratio of Neutrophile/Lymphocytes in Chemotherapy of Sprague-Dawley Rats with Colorectal Cancer

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3561-3568. doi: 10.31557/APJCP.2021.22.11.3561.

ABSTRACT

BACKGROUND: Chemotherapy as part of colorectal cancer management can cause death to immunologically active tumor cell, but also it has immune suppressive effect. Phyllanthus niruri Linn is known to has immunomodulatory effect. This study was intended to prove P. niruri Linn effect on infiltrating dendritic cells and Neutrophil/lymphocyte ratios (NLRs) in Sprague-Dawley rats with colorectal cancer which were given capecitabine chemotherapy.

METHODS: The study was randomized post-test only control group design. The samples were 39 Sprague-Dawley male rats, with body weight around 170-220 grams, induced by 1,2-dimetylhydrazine (DMH) 30 mg/kgBW once per week subcutaneously. On 9th,11th and 13th week, there were four induced rats sacrificed each week to detect colorectal cancer (CRC) development. On the 13th week, all of the 4 sacrificed rats developed colon cancer, so the induction had to be stopped. The rest of 27 induced rats were randomly divided into three groups: control-group (K) were left untreated (9 rats), group P1 (9 rats) were given Capecitabine and group P2 (9 rats) were given Capecitabine with combination of P. niruri Linn extract 13.5 mg/kgBW orally. After 17th week, all rats were terminated and tumor lesion of colon were processed to be paraffin blocks and were stained with HE for evaluating the NLRs, and immunohistochemistry (S100) for evaluating infiltrating dendritic cells. Data was analyzed by using Oneway-Anova-test and post-Hoc LSD-test. Considered significant if p was <0.05.

RESULTS: The mean±standard deviation of infiltrating dendritic cells showed increasing value in group P2 (62.11±31.35) compared to group P1 (52.78±29.24) though not statistically significant. The mean of NLRs also showed statistically significant elevation of value in group P2 (0.13±0.05) compared to group P1 (0.04±0.01).

CONCLUSION: Extract of Phyllanthus niruri Linn increasing immunologic status through elevation of infiltrating dendritic cells and NLRs in animal model colorectal cancer with Capecitabine chemotherapy.

PMID:34837913 | DOI:10.31557/APJCP.2021.22.11.3561

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A Clinical Evaluation of Circulating MiR-106a and Raf-1 as Breast Cancer Diagnostic and Prognostic Markers

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3513-3520. doi: 10.31557/APJCP.2021.22.11.3513.

ABSTRACT

OBJECTIVE: MicroRNAs (MiRNAs) regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and serve multiple roles in tumorigenesis and progression. Proto-oncogene serine/threonine-protein kinase (RAF-1) functions as a part of the MAPK/ERK signal transduction pathway. The present study aim was to prospectively evaluate MicroRNA 106a (MiR-106a) and RAF-1 as a diagnostic and prognostic factor in early prediction of breast cancer (BC), recurrence and early detection of distant metastasis as well as to analyses the statistical correlation between MiR-106a and RAF-1 levels and clinical-pathological parameters including tumor size, lymph node, histological type and grading.

METHODS: Sera and plasma of 30 normal women and 50 women with breast carcinoma were assayed for MiR-106a by RT-qPCR as well as levels of Hb, WBCs and platelets count and RAF-1 by solid phase enzyme-linked immunosorbent assay (ELISA).

RESULTS: The patients’ characteristics, they were classified according to grade into 8% grade I, 66% grade II, 22% grade III and 4% grade IV. The stages were classified according to the TNM system as stage II was the highest percentage 66%, while the lowest percentage was 10% for stage I and 24% for stage III. Also, Hb% and RAF-1 levels were significantly decreased in breast cancer patients as compared with healthy control. On the other hand, MiRNA-106a gene expression was non-significantly increased in positive lymph node metastasis patients (FC=3.66) when compared to patients with negative lymph node metastasis (FC=3.51). In addition, MiR-106a was significantly up-regulated in breast cancer patients with a fold of change 3.63 when compared to control samples.

CONCLUSION: Expression of MiR-106a gene can be used as a diagnostic and prognostic noninvasive biomarker which can stimulates breast cancer cell invasion and proliferation through downregulation of Raf-1 levels.<br />.

PMID:34837907 | DOI:10.31557/APJCP.2021.22.11.3513

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Serum Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Patients with Hepatocellular Carcinoma

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3521-3524. doi: 10.31557/APJCP.2021.22.11.3521.

ABSTRACT

OBJECTIVE: To evaluate the clinical value of carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) in predicting the severity of hepatocellular carcinoma(HCC).

METHODS: We evaluated 40 healthy subjects and 40 HCC patients by collecting venous blood for the comparison. Serum CEACAM1 was detected using the Human CEACAM1 ELISA Kit. Other laboratory chemistries were analyzed by standard methods.

RESULTS: The serum level of CEACAM1 was not different between HCC patients and healthy subjects (p=0.0069). There was a correlation between serum CEACAM1 level and total bilirubin, and direct bilirubin. There was also a statistically significant difference among serum CEACAM1 levels stratified by BCLC staging and MELD score at the cut-point of 18. Lower platelet count, higher levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were observed in HCC patients.

CONCLUSION: An increase of serum CEACAM1 level was associated with cholestasis. The role of this molecule in HCC diagnosis was unclear. However, serum CAECAM1 may be useful to predict the severity in HCC patients.

PMID:34837908 | DOI:10.31557/APJCP.2021.22.11.3521

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An Evaluation of Phosphate Buffer Saline as an Alternative Liquid-Based Medium for HPV DNA Detection

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3441-3445. doi: 10.31557/APJCP.2021.22.11.3441.

ABSTRACT

OBJECTIVE: HPV detection has been proposed as part of the co-testing which improves the sensitivity of cervical screening. However, the commercially liquid-based medium adds cost in low-resource areas. This study aimed to evaluate the performance of ice-cold phosphate buffer saline (PBS) for HPV detection.

METHODS: HPV DNA from SiHa cells (with 1-2 copies of HPV16 per cell) preserved in ice-cold PBS or PreserveCyt solution at different time points (24, 36, 48, 72, 120 and 168 h) was tested in triplicate using Cobas 4800. The threshold cycle (Ct) values of both solutions were compared. An estimated false negative rate of PBS was also assessed by using the difference in Ct values between both solutions (∆Ct) and Ct values of HPV16-positive PreserveCyt clinical samples (Ctsample) at corresponding time points. Samples with a (Ctsample+∆Ct) value > 40.5 (the cutoff of HPV16 DNA by Cobas 4800) were considered as false negativity.

RESULTS: The Ct values of HPV16 DNA of SiHa cells collected in PBS were higher than PreserveCyt ranging from 0.43 to 2.36 cycles depending on incubation times. There was no significant difference at 24, 72, 120, and 168 h. However, the Ct values were statistically significantly higher for PBS than PreserveCyt at 36 h (31.00 vs 29.26), and 48 h (31.06 vs 28.70). A retrospective analysis in 47 clinical PreserveCyt collected samples that were positive for HPV16 DNA found that 1 case (2%) would become negative if collected in ice-cold PBS.

CONCLUSIONS: The PBS might be an alternative collecting medium for HPV detection in the low-resource areas. Further evaluations are warranted.

PMID:34837897 | DOI:10.31557/APJCP.2021.22.11.3441

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Determination of β-catenin Expression in Breast Cancer and Its Relationship with Clinicopathologic Parameters

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3493-3498. doi: 10.31557/APJCP.2021.22.11.3493.

ABSTRACT

BACKGROUND: Abnormal activation of the β-catenin signaling pathway is involved in various malignancies, including breast carcinoma.Aberrant expression of β-catenin has been associated with more aggressive behaviors of breast cancer in some previous studies. . In the present study, we intend to evaluate the β-catenin expression in breast cancer specimens and study its relationship with clinicopathological parameters.

MATERIALS AND METHOD: In this cross-sectional study,88 samples diagnosed as invasive ductal breast carcinoma from 2007 to 2017 were evaluated. The slides and paraffin blocks were retrieved from the archive of pathology department. Patients’ clinical characteristics and other information were also extracted from medical documents. Sections from related paraffin blocks through the tissue microarray method were provided, and immunohistochemistry staining for β-catenin was done. Then different patterns of β-catenin expression and the relationship between different patterns and clinicopathological parameters were investigated.

RESULTS: Of the 88 breast cancer samples, 94% were female, and 6% were male. In 70% of the samples, normal membrane expression of β-catenin was observed. Whereas in 30% of them, aberrant expression of β-catenin was observed. A close significant relationship was observed between aberrant β-catenin expression and age over 50 years (p-value: 0.093) and negative HER2 (p-value: 0.07).

CONCLUSION: In the present study, a correlation was observed between aberrant β-catenin expression and age over 50 years in patients and HER2 negativity, although this association was not statistically significant.

PMID:34837904 | DOI:10.31557/APJCP.2021.22.11.3493

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A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma

Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3419-3431. doi: 10.31557/APJCP.2021.22.11.3419.

ABSTRACT

BACKGROUND: In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma.

METHODS: The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software.

RESULTS: A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated.

CONCLUSION: The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

PMID:34837895 | DOI:10.31557/APJCP.2021.22.11.3419

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Arsenic exposure from drinking water and staple food (rice): A field scale study in rural Bengal for assessment of human health risk

Ecotoxicol Environ Saf. 2021 Nov 24;228:113012. doi: 10.1016/j.ecoenv.2021.113012. Online ahead of print.

ABSTRACT

Arsenic is a well-known carcinogen with emerging reports showing a range of health outcomes even for low to moderate levels of exposure. This study deals with arsenic exposure and associated increased lifetime cancer risk for populations in arsenic-endemic regions of rural Bengal, where arsenic-safe drinking water is being supplied at present. We found a median total exposure of inorganic arsenic to be 2. 9 μg/Kg BW/day (5th and 95th percentiles were 1.1 μg/Kg BW/day and 7.9 μg/Kg BW/day); with major contribution from cooked rice intake (2.4 µg/Kg BW/day). A significant number of households drank arsenic safe water but used arsenic-rich water for rice cooking. As a result, 67% participants had inorganic arsenic intake above the JEFCA threshold value of 3 μg/Kg BW/day for cancer risk from only rice consumption when arsenic contaminated water was used for cooking (median: 3.5 μg/Kg BW/day) compared to 29% participants that relied on arsenic-free cooking water (median: 1.0 µg/kg BW/day). Arsenic in urine samples of study participants ranged from 31.7 to 520 µg/L and was significantly associated with the arsenic intake (r = 0.76); confirming the preponderance of arsenic exposure from cooked rice. The median arsenic attributable cancer risks from drinking water and cooked rice were estimated to be 2.4 × 10-5 and 2.7 × 10-4 respectively, which further emphasized the importance of arsenic exposure from staple diet. Our results show that any mitigation strategy should include both drinking water and local staple foods in order to minimize the potential health risks of arsenic exposure.

PMID:34837872 | DOI:10.1016/j.ecoenv.2021.113012

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Rucaparib in patients presenting a metastatic breast cancer with homologous recombination deficiency, without germline BRCA1/2 mutation

Eur J Cancer. 2021 Nov 24;159:283-295. doi: 10.1016/j.ejca.2021.09.028. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer may present genomic alterations leading to homologous recombination deficiency (HRD). PARP inhibitors have proven their efficacy in patients with HER2-negative (HER2-) metastatic breast cancer (mBC) harbouring germline (g) BRCA1/2 mutations in 3 phases III trials. The single-arm phase II RUBY trial included 42 patients, 40 of whom received at least one dose of rucaparib. RUBY study assessed the efficacy of rucaparib in HER2-mBC with either high genomic loss of heterozygosity (LOH) score or non-germline BRCA1/2 mutation.

PATIENTS AND METHODS: The primary objective was the clinical benefit rate (CBR), and the study was powered to see 20% CBR using a 2-stage Simon design.

RESULTS: The primary-end point was not reached with a CBR of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (12 and 28.5 months). Whole-genome analysis was performed on 24 samples, including 5 patients who presented a clinical benefit from rucaparib. HRDetect tended to be associated with response to rucaparib, without reaching statistical significance (median HRDetect responders versus non-responders: 0.465 versus 0.040; p = 0.2135). Finally, 220 of 711 patients with mBC screened for LOH upstream from RUBY presented a high LOH score associated with a higher likelihood of death (hazard ratio = 1.39; 95% CI: 1.11-1.75; p = 0.005).

CONCLUSION: Our data suggest that a small subset of patients with high LOH scores without germline BRCA1/2 mutation could derive benefit from PARP inhibitors. However, the RUBY study underlines the need to develop additional biomarkers to identify selectively potential responders.

PMID:34837859 | DOI:10.1016/j.ejca.2021.09.028