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Microsatellite Instability in Sporadic Colorectal Malignancy: A Pilot Study from Northern India

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2279-2288. doi: 10.31557/APJCP.2021.22.7.2279.

ABSTRACT

BACKGROUND: Three molecular pathways are described as the genetic basis of colorectal tumorigenesis. Among these, microsatellite instability (MSI) has shown greatest promise in serving as a biomarker to determine disease aggression by tumour biology, recurrence, and response to chemotherapy.

METHODOLOGY: This prospective observational pilot study included patients of colorectal cancers, in a population subset coming to a tertiary care hospital in northern India, who were operated with curative or palliative intent over a period of one year and followed up for a maximum of 55 months. The post-operative pathological assessment was done for MSI status using PCR technique, and an attempt was made to evaluate its correlation with conventional clinical and histological parameters, early recurrences, disease-free survival and overall survival in comparison to MSS type tumours in sporadic cases of colorectal malignancies.

RESULTS: Out of 38 patients of colorectal cancer, 26 were included in the study. Male to female ratio was 7:6 (n=14:12). Mean age of presentation was 48±14.2 years. Incidence of MSI was n=4 (15.4%). On subgroup analysis, age of presentation (p=0.044) and evidence of perineural invasion (p=0.017) was found to have significant statistical association with MSI tumour biology. Recurrence was seen in seven of the seventeen patients who previously had no synchronous or metastatic disease (41.2%). The mean disease-free survival for MSS was 21.32 months and was 25.25 months for MSI group which was statistically insignificant (p = 0.277). Out of four MSI tumour biology patients one was alive and without recurrence at 47 months. While the other two were alive and without recurrence till 27 months of follow-up. Conclusion: Age and perineural invasion showed statistically significant association with MSI tumour biology. Due to the small sample size statistical significance was not established with site, recurrence rate, DFS and OS.

PMID:34319053 | DOI:10.31557/APJCP.2021.22.7.2279

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Expression of BCL2L12and LIPOCALIN 2 in Adult Patient with Acute Myeloid Leukemia and Correlation with Clinical Response

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2267-2272. doi: 10.31557/APJCP.2021.22.7.2267.

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy arising within the bone marrow (BM), in which leukemic cells proliferate uncontrollably in association with a disruption of normal hematopoiesis.Aim of the work to evaluate the expression of LCN and BCL2L2, in newly diagnosed bone marrow samples from adult with AML and to correlate their expression levels with clinical and Laboratory data of the patients especially that known to have a prognostic feature.

METHODS: This study was carried out on 87 consecutive newly diagnosed adult AML patients of which 75 are evaluated for both LCN, BCL2L12 (All 87 are evaluated for LCN). In addition, 20 donors of matched age and sex healthy individuals from donors for bone marrow transplantation were included as a control group.

RESULTS: No statistical significant correlation was found between LCN over-expression and the control group , there was no statistical significance between its expression and age, sex, hepatomegally, splenomegally and lymphadenopathy, also there was no statistical significance regarding peripheral blood and bone marrow findings, immunophenotyping, cytogenetics or molecular findings and MRD at day 15.No statistical significance was found between BCL2L12 expression and the control group again there was no statistical significance between its expression and age, sex, hepatomegally, splenomegally and lymphadenopathy, also there was no statistical significance regarding peripheral blood and bone marrow findings, immunophenotyping, cytogenetics or molecular findings and MRD at day 15.

CONCLUSION: LCN and BCL2L12 were found to be expressed with non significant difference in AML as in normal subjects; however studies on large number of cases are needed to confirm our finding. The role of LCN and BCL2L12 need to be verified by further large-scale sample and further studies.<br />.

PMID:34319051 | DOI:10.31557/APJCP.2021.22.7.2267

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Factors Influence on Pap Test Screening among Lahu Hill Tribe Women in Remote Area Thailand

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2243-2249. doi: 10.31557/APJCP.2021.22.7.2243.

ABSTRACT

BACKGROUND: Papanicolaou test is widely used to screening cervical cancer but low attend rate. There is one mountainous area found high participation rate.

OBJECTIVE: This study aimed to determine the factors associated with successful Pap test among Lahu hill tribe women.

MATERIALS AND METHODS: The quantitative cross-sectional study was used in this study. Data were collected from 650 Lahu hill tribe women by simple random sampling. The interview forms with reliability coefficient and validity of 0.78 and 0.91 were administered to participants. The data were analyzed by using descriptive statistics and Chi-square test.

RESULTS: The 96.15% of the Lahu hill tribe women had taken Pap test and 74.31% obtained the screening more than once. The contraceptive use and frequency of Pap test obtaining significantly associated with cervical cancer screening (p <0.001). The participants showed good level of knowledge in cervical cancer and the screening test (64.31% and 76.46% respectively). Most of participants received the cervical cancer disease information (87.17%) and screening information (66.92%) from health care professionals, which may influence on well cervical screening co-operation. Conclusions: The suitable health promotion model should provide to promote knowledge, attitude and motivate continuous cooperation in cervical cancer screening among hill tribe women.

PMID:34319048 | DOI:10.31557/APJCP.2021.22.7.2243

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Predictive Value of Marker of Proliferation Ki-67 and Cell Cycle Dependent Protein kinase Inhibitor P16INK4a in Cervical Biopsy to Determine Its Biological Behaviour

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2237-2241. doi: 10.31557/APJCP.2021.22.7.2237.

ABSTRACT

OBJECTIVE: The aim of the study is to analyse the Immuno-histochemical expression of Ki-67 and P16INK4a in CIN and cervical cancer cases and their utility to determine the accuracy of histological diagnosis and prediction of biological behavior of cervical lesion.

METHODOLOGY: A retrospective cross-sectional study was carried in 110 numbers of cervical biopsy that included 25 CIN1, 21 CIN2, 12 CIN3, 26 SCC and 01 adenocarcinoma and 25 non neoplastic lesion. The tissue sections were stained with Ki-67 and P16INK4a.

RESULTS: Ki-67 expression was seen in 55.5% (61/110) cases of cervical lesion., out of which 3.6% (4/110; cervicitis -2/110 and metaplasia-2/110) cases were non dysplaia, 51.8% (57/110) cases were dysplasia /CIN of varying grade including invasive cancer. P16INK4a expression was noted 51.8% (57/110). There was an increasing trend of the intensity of Ki-67 and P16INK4a from focal positivity in low grade lesion to diffuse intensity in higher grade lesion and is statistically significant. There was strong association between the two variables Ki-67 and P16INK4a positive cases with their histologic grade.

CONCLUSION: Though histopathology remains the ”gold standard” for the diagnosis of CIN, both low and high-grade, biomarkers like Ki-67 and P16INK4a have emerged as helpful adjuncts. Their combined use may assist in the histopathologic classification of preinvasive lesions and facilitate the distinction from nondysplasia.

PMID:34319047 | DOI:10.31557/APJCP.2021.22.7.2237

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Diagnostic Accuracy of Fluorescein Sodium for Targeted Cervical Biopsies

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2135-2141. doi: 10.31557/APJCP.2021.22.7.2135.

ABSTRACT

BACKGROUND: Visual inspection methods for cervical cancer screening are widely used in low resource settings. Fluorescent sodium could improve accuracy of cancer screening. This study aimed to assess diagnostic accuracy of fluorescein sodium (FNa) to detect cervical neoplasia.

METHODS: Seventy consecutive patients referred for colposcopy were enrolled prospectively. Acetic acid, Lugol’s iodine, and FNa were used sequentially. Biopsies were taken from all abnormal areas. If there was no obvious abnormality, two random biopsies and endocervical curettage were done. Reference standard was the highest grade lesion on cervical biopsy with a threshold of CIN2+. The patterns of each staining agent were recorded as absent, faint, or distinct. Diagnostic accuracy estimates with 95% confidence intervals were calculated. Correlation between the various tests were also determined using the kappa statistic.

RESULTS: There were 27 cases of CIN2+ (38.6%). The sensitivity of any fluorescence for CIN2+ was 82% (62, 94) and for distinct fluorescence was 59% (39, 78). The specificity was 65% (49, 79) for any fluorescence and 95% (84, 99) for distinct fluorescence, the same as for Swede score > 7. For any fluorescence, the positive likelihood ratio was 2.34 (1.5, 3.65) and the negative likelihood ratio was 0.28 (0.13, 0.65). For distinct fluorescence, the positive likelihood ratio was 12.74 (3.18, 51.1) and the negative likelihood ratio was 0.43 (0.27, 0.68). There was moderate correlation between FNa and the other tests.

CONCLUSION: Distinct fluorescence with FNa was very specific, low cost, and easy to perform and may contribute to confirm CIN2+ disease.

PMID:34319036 | DOI:10.31557/APJCP.2021.22.7.2135

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Assessment of Caregiving Burden of Family Caregivers of Advanced Cancer Patients and Their Satisfaction with the Dedicated Inpatient Palliative Care Provided to Their Patients: A Cross-Sectional Study from a Tertiary Care Centre in South Asia

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2109-2115. doi: 10.31557/APJCP.2021.22.7.2109.

ABSTRACT

BACKGROUND AND OBJECTIVES: Family Caregivers (FCs) of advanced cancer patients often suffer from caregiving burden due to stress arising from the responsibility of caregiving. During the course of their patients palliative therapy, FCs quality of life seems to be influenced by their satisfaction with the quality of patient care. In this study, caregiving burden of FCs and their satisfaction with dedicate Inpatient palliative care (IPC) services provided to their patients were studied.

MATERIAL AND METHODS: This cross-sectional study assessed 211 FCs of advanced cancer patients. Caregiving burden of FCs and their satisfaction with IPC were studied through Zarith Burden Interview (ZBI-12 version) and Family Carer Satisfaction with Palliative Care scale (FAMCARE-2) questionnaires, respectively. Descriptive and correlation analyses were deployed for data analysis.

RESULTS: The summative mean ZBI-12 score for FCs was 20.26±5.92, suggesting moderate to high caregiving burden among FCs. Significantly higher scores were observed among FCs who belonged to below poverty line (BPL) families(p=0.025), revealing higher caregiving burden among this lower income group. FCs who were male, unmarried, unemployed, and residing in rural experienced higher caregiving burden. However, it did not lead to a statistically significant difference. The summative mean FAMCARE-2 scale scores was 74.01±4.34, which suggested FCs high satisfaction with the palliative care services provided to their patients. FAMCARE-2 scale scores were lower for BPL families, but it was not statistically significant.

CONCLUSION: FCs from lower-income groups experienced higher caregiving burden. It seems that IPC unit provided satisfactory services to advanced cancer patients, leading to enhancement of FCs satisfaction and consequently quality of life. <br />.

PMID:34319033 | DOI:10.31557/APJCP.2021.22.7.2109

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Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2069-2077. doi: 10.31557/APJCP.2021.22.7.2069.

ABSTRACT

OBJECTIVE: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications.

METHODS: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed.

RESULTS: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019). Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.

PMID:34319029 | DOI:10.31557/APJCP.2021.22.7.2069

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A Retrospective Hospital-Based Study of HMGCR Expression in HER2 IHC 2+ and 3+ Breast Cancer

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2043-2047. doi: 10.31557/APJCP.2021.22.7.2043.

ABSTRACT

OBJECTIVE: The role of HMG-CoA reductase (HMGCR) in relation to prognostic and treatment predictive information of HER2 positive breast cancer has been newly explored. In this study, we aimed to determine the expression of HMGCR in HER2 immunohistochemistry (IHC) scores of 2+ and 3+ breast cancer and to correlate with the patients’ outcomes.

METHODOLOGY: Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar. IHC staining for HMGCR was performed on paraffin-embedded tissues at the Pathology Laboratory, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian using the standard staining procedure. The results were correlated with the patient’s demographic and clinicopathological data.

RESULTS: A total of 59 cases of HER2 IHC 2+ and 3+ invasive breast carcinoma were identified. The cases were predominant in young Malay women with tumours smaller than 50mm, higher grade and positive for lymphovascular invasion, axillary lymph nodes involvement and ER/PR expressions. HMGCR was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong. Majority of the cases were scored 1+ for HMGCR expression. A low-positive HMGCR was more likely to be associated with less favourable outcomes of patients with HER2 IHC 2+ and 3+. However, the associations were statistically not significant.

CONCLUSION: A study in a larger cohort of tumour samples is needed to further validate HMGCR expression as a potential prognostic biomarker for HER2 positive breast cancer. It is also suggested that all the HER2 IHC 2+ and 3+ cases need to be gene amplified using FISH analysis. <br />.

PMID:34319025 | DOI:10.31557/APJCP.2021.22.7.2043

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Oral and Dental Complications of Radiotherapy for Head and Neck Cancer: Knowledge of Dental Practitioners in Saudi Arabia

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2033-2041. doi: 10.31557/APJCP.2021.22.7.2033.

ABSTRACT

OBJECTIVES: Toxicities of the oral soft and hard tissues due to the radiotherapy of the head and neck cancer can potentially lead to interruptions of cancer treatment and/or dose reduction, resulting in poorer outcomes. The aim of this study was to assess the knowledge of dental practitioners in Saudi Arabia about oral and dental assessment for and complications of radiotherapy of head and neck cancer.

MATERIALS AND METHODS: An online, already validated, self-administered questionnaire was sent via an online link through WhatsApp groups and other Social Media platforms to reach out to the majority of targeted samples (dental practitioners working in Saudi Arabia). Responses were statistically described and analyzed based on the different grouping factors: gender, specialty, working sector, region of work and experience.

RESULTS: There were 370 respondents, 257 (69.5%) of them were males. Most of the respondents were general dental practitioners [144 (38.9%)], The percentages of the correct answers range from as low as 26.2 to as high as 97%. The per cent of correct answers by the respondents in 18 out of 31 questions was above 75%. Females, dental specialists (specifically prosthodontics), working in public sectors and in the central and western regions of Saudi Arabia were associated with higher levels of knowledge.

CONCLUSION: Our results show highly variable knowledge of dental practitioners on oral and dental assessment for, and complications and management of radiotherapy to the head and neck area; that knowledge seems to fluctuate considerably with gender, experience, work sector and specialty.<br />.

PMID:34319024 | DOI:10.31557/APJCP.2021.22.7.2033

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Monitoring Of High-Dose Methotrexate (Mtx)-Related Toxicity and Mtx Levels in Children with Acute Lymphoblastic Leukemia: A Pilot-Study in Indonesia

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2025-2031. doi: 10.31557/APJCP.2021.22.7.2025.

ABSTRACT

The administration of high-dose methotrexate (HD-MTX) requires an accurate monitoring of blood MTX levels to determine the regimen of leucovorin rescue and urine alkalinization to prevent toxicity. However, it is technically and logistically challenging to screen patients routinely in limited-resource settings. This study aimed to evaluate blood MTX levels at 24- and 48-hours from start of infusion in relation to clinical toxicity in childhood ALL.

METHODS: A prospective cohort study was conducted on 32 consecutive children with acute lymphoblastic leukemia (ALL) who had received at least one cycle of 1 g/m2 HD-MTX intravenous infusion as a part of consolidation treatment based on the 2013 Indonesian ALL Protocol. In total, 68 cycles were evaluated. Serum MTX concentrations were measured using enzyme immunoassay. MTX toxicity was categorized using common toxicity criteria (CTCAE) 3.0 version. The association between MTX level and clinical toxicity was assessed by non-parametric analysis.

RESULTS: The 24-hours MTX level was median 29.8 ng/mL (0.065 µmol/L) (IQR 8.1-390.6) with a modest decrease in 48-hours MTX serum level in all cycles (median 28.3 ng/mL and 0.062 µmol/L; IQR 0.35-28.7; p <0.05). The two most common toxicities were hepatotoxicity (32.2%) and neutropenia (30.9%). Nephrotoxicity and febrile neutropenia occurred in 8.8% and 5.8% of patients, respectively, with low percentage of mucositis (4.3%) and thrombocytopenia (5.6%) recorded. No statistically significant association was found between MTX levels and clinical toxicity, except for liver toxicity.

CONCLUSION: Serum MTX levels at 24-hours and 48-hours are low, followed by only 4.4% grade III/IV hepatotoxicity and 26,4% grade III/IV neutropenia. There is no significant association between the clinical toxicity and MTX levels at the two points of measurement. An attempt to increase the MTX dose and/or to introduce a loading dose should be considered in subsequent ALL protocol as supported by further pharmacokinetic MTX studies in the Indonesian population.

PMID:34319023 | DOI:10.31557/APJCP.2021.22.7.2025