Colorectal cancer screening: Comparison of transferrin and immuno fecal occult blood test

AIM: To evaluate the sensitivity and specificity of transfesrrin dipstick test (Tf) in colorectal cancer (CRC) screening and precancerous lesions screening. METHODS: Eight hundreds and sixty-one individuals at high-risk for CRC were recruited. Six hundreds and eleven subsequently received the three fecal occult blood tests and colonoscopy with biopsy performed as needed. Fecal samples were obtained on the day before colonoscopy. Tf, immuno fecal occult blood test (IFOBT) and guaiac fecal occult blood test (g-FOBT) were performed simultaneously on the same stool. To minimize false-negative cases, all subjects with negative samples were asked to provide an additional stool specimen for a second test even a third test. If the results were all negative after testing three repeated samples, the subject was considered a true negative. The performance characteristics of Tf for detecting CRC and precancerous lesions were examined and compared to those of IFOBT and the combination of Tf, IFOBT and g-FOBT. RESULTS: A total of six hundreds and eleven subjects met the study criteria including 25 with CRC and 60 with precancerous lesions. Sensitivity for detecting CRC was 92% for Tf and 96% for IFOBT, specificities of Tf and IFOBT were both 72.0% (95% CI: 68.2%-75.5%; χ2 = 0.4, P > 0.05); positive likelihood ratios of those were 3.3 (95% CI: 2.8-3.9) and 3.4 (95% CI: 2.9-4.0), respectively. In precancerous lesions, sensitivities for Tf and IFOBT were 50% and 58%, respectively (χ 2 = 0.8, P > 0.05); specificities of Tf and IFOBT were 71.5% (95% CI: 67.6%-75.1%) and 72.2% (95% CI: 68.4%-75.8%); positive likelihood ratios of those were 1.8 (95% CI: 1.3-2.3) and 2.1 (95% CI: 1.6-2.7), respectively; compared to IFOBT, g-FOBT+ Tf+ IFOBT had a significantly higher positive rate for precancerous lesions (83% vs 58%, respectively; χ 2 = 9.1, P < 0.05). In patients with CRC and precancerous lesions, the sensitivities of Tf and IFOBT were 62% and 69% (χ 2 = 0.9, P > 0.05); specificities of those were 74.5% (95% CI: 70.6%-78.1%) and 75.5% (95% CI: 71.6%-79.0%); positive likelihood ratios of those were 2.5 (95% CI: 2.0-3.1) and 2.8 (95% CI: 2.3-3.5). Compared to IF-OBT alone, combining g-FOBT, IFOBT and Tf led to significantly increased sensitivity for detecting CRC and cancerous lesions (69% vs 88%, respectively; χ 2 = 9.0, P < 0.05). CONCLUSION: Tf dipstick test might be used as an ad- ditional tool for CRC and precancerous lesions screening in a high-risk cohort.

An AAS Dependent Method for Quantitative Analysis of Essential Trace Elements from Blood Samples of Pakistani Female Breast Cancer Patients

Breast cancer is the second leading cancer in the world. The long-term exposure of some metallic compounds induces different forms of cancer, including breast cancer. Trace elements are essential metals for the physiological functions of the cell on a molecular level and also contribute in treatment of many diseases. The aim of study was to compare the level of essential trace elements, sodium, potassium, calcium, iron, and zinc in breast cancer patients with normal healthy adult women. Total forty-five patients (age range from 25 - 73 years) were included in this study and divided into three groups according to three different stages of breast cancer including tumor-II, tumor-III and tumor-IV. Blood was collected from all participants after taking history, clinical data and taking consent. However, about fifteen non-cancer healthy women in age range from 26 - 69 years were subjected to this study. The elemental concentrations were determined through atomic absorption spectrophotometer subsequent to microwave-induced acid digestion. The results of Na, K, Zn, Fe, Ca, were observed to decrease in blood samples of breast cancer patients as compared to non-cancer subjects. The results are reliable with other numerous literature reported studies, the efficiency, and deficiency of these trace metals may contribute an important role in the progress of breast cancer.

Incidence, Mortality, and Epidemiology of Leukemia in South Asia: An Ecological Study

Background: Nowadays cancer is a buzzword in every corner of the world. Back a few decades, cancer was not that much known to the people of South Asia let alone known of Leukemia. Many countries in the South Asian region are designated as developing countries. Hence, the deficiency of diagnosis system, treatment, management, and lack of knowledge about leukemia in this region are major problems. Therefore, the incidence rate, mortality rate, and several deaths are increasing day by day. Methods: This cross-sectional study is aimed to investigate the incidence and mortality of leukemia in South Asian Countries for the year 2020 by acquiring data from the global cancer project (GLOBOCAN2020) accessible at https://gco.iarc.fr. Results: In South Asia, 1,733,573 cancer cases were documented in 2020 where 62,163 cases were leukemia related. The highest incidence rate was reported in Pakistan (4.3 in 1,000,000) and Sri Lanka (4.1 in 1,000,000) and the lowest in Bangladesh (1.8 in 1,000,000) and Nepal (2.0 in 1,000,000). On the other hand, 1,124,875 death had been reported in 2020, where 45,707 (4.1%) death was associated with leukemia. Pakistan (3.4 in 1,000,000) and Maldives (3.1 in 1,000,000) had the highest death and lowest in Bangladesh (1.4 in 1,000,000) and Nepal (1.5 in 1,000,000). Adults aged from 60 - 85 years old have the highest rate of incidence and mortality rate in all countries except Nepal. Conclusions: Leukemia is one of the major concerning cancer of all ages people in South Asia, the situation and related risk factors information can be helpful to reduce death through proper treatment.

Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening:A meta-analysis

AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literature search in PubMed and Embase was conducted using the following search terms:fecal Tumor M2-PK,faecal Tumour M2-PK,fecal M2-PK,faecal M2-PK,fecal pyruvate kinase,faecal pyruvate kinase,pyruvate kinase stool and M2-PK stool.RESULTS:Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies.The mean faecal M2-PK sensitivity was 80.3%;the specificity was 95.2%.Four studies compared faecal M2-PK head-to-head with guaiacbased faecal occult blood test(gFOBT).Faecal M2PK demonstrated a sensitivity of 81.1%,whereas the gFOBT detected only 36.9% of the CRCs.Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma(n = 554),with the following sensitivities:adenoma < 1 cm in diameter:25%;adenoma > 1 cm:44%;adenoma of unspecified diameter:51%.In a direct comparison with gFOBT of adenoma > 1 cm in diameter,47% tested positive with the faecal M2-PK test,whereas the gFOBT detected only 27%.CONCLUSION:We recommend faecal M2-PK as a routine test for CRC screening.Faecal M2-PK closes a gap in clinical practice because it detects bleeding and nonbleeding tumors and adenoma with high sensitivity and specificity.

Results of National Colorectal Cancer Screening Program in Croatia(2007-2011)

AIM:To study the epidemiologic indicators of uptake and characteristic colonoscopic findings in the Croatian National Colorectal Cancer Screening Program.METHODS:Colorectal cancer(CRC) was the second leading cause of cancer mortality in men(n = 1063,49.77/100 000),as well as women(n = 803,34.89/100 000) in Croatia in 2009.The Croatian National CRC Screening Program was established by the Ministry of Health and Social Welfare,and its implementation started in September,2007.The coordinators were recruited in each county institute of public health with an obligation to provide fecal occult blood testing(FOBT) to the participants,followed by colonoscopy in all positive cases.The FOBT was performed by hypersensitive guaiac-based Hemognost card test(Biognost,Zagreb).The test and short questionnaire were delivered to the home addresses of all citizens aged 50-74 years consecutively during a 3-year period.Each participant was required to complete the questionnaire and send it together with the stool specimen on three test cards back to the institute for further analysis.About 4% FOBT positive cases are expected in normal risk populations.A descriptive analysis was performed.RESULTS:A total of 1 056 694 individuals(born between 1933-1945 and 1952-1957) were invited to screening by the end of September 2011.In total,210 239(19.9%) persons returned the envelope with a completed questionnaire,and 181 102 of them returned it with a correctly placed stool specimen on FOBT cards.Until now,12 477(6.9%),FOBT-positive patients have been found,which is at the upper limit of the expected values in European Guidelines for Quality Assurance in CRC Screening and Diagnosis [European Union(EU) Guidelines].Colonoscopy was performed in 8541 cases(uptake 66%).Screening has identified CRC in 472 patients(5.5% of colonoscopied,3.8% of FOBT-positive,and 0.26% of all screened individuals).This is also in the expected range according to EU Guidelines.Polyps were found and removed in 3329(39% of colonoscopied) patients.The largest number of polyps were found in the left half of the colon:64%(19%,37% and 8% in the rectum,sigma,and descendens,respectively).The other 36% were detected in the proximal part(17% in the transverse colon and 19% in ceco-ascending colon).Small polyps in the rectum(5-10 mm in diameter),sigmoid and descending colon were histologically found to be tubular adenomas in 60% of cases,with a low degree of dysplasia,and 40% were classified as hyperplastic.Polyps of this size in the transverse or ceco-ascending colon in almost 20% had a histologically villous component,but still had a low degree of dysplasia.Polyps sized 10-20 mm in diameter were in 43% cases tubulovillous,and among them,32% had areas with a high degree of dysplasia,especially those polyps in the cecoascending or transverse part.The characteristics of the Croatian CRC Screening National Program in the first 3 years were as follows:relatively low percentage of returned FOBT,higher number of FOBT-positive persons but still in the range for population-based programs,and higher number of pathologic findings(polyps and cancers).CONCLUSION:These results suggest a need for intervention strategies that include organizational changes and educational activities to improve awareness of CRC screening usefulness and increase participation rates.

Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer

AIM:To investigate the association between human papilloma virus(HPV) infection and colorectal cancer.METHODS:Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage Ⅰ,24 stage Ⅱ,21 stage Ⅲ,and 18 stage Ⅳ patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis.Nested-polymerase chain reaction(nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization(ISH).In addition,immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors.To verify whether E6 could inactivate the p53 transcriptional function,the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription(RT)-PCR.RESULTS:Of the 69 colorectal tumors,HPV16 DNA was detected in 11(16%) by nested-PCR,and HPV16 DNA was present in 8 of the 11(73%) tumors which was confirmed by ISH.The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age,gender,smoking status,tumor site;however,HPV16 infection was more common in stage Ⅰ patients than in late-stages patients(Ⅱ,Ⅲ and Ⅳ).We next asked whether HPV16 infection could be linked with colorectal cancer development.Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression.Moreover,we also observed that the adjacent normal tissues including endothelial cells,lymphocytes,fibroblasts,and gland cells in E6-positive tumors had E6 oncoprotein expression.In addition,3 of the 4(75%) E6-positive tumors carrying p53 wild-type had negative immunostaining,but one tumor had less p53 immunostaining.We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity.Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues;as expected,E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues.These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation.CONCLUSION:These results suggest that HPV16 infection may be involved in a subset of colorectal cancer,and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.