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Objective: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1–2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. Methods: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1–2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. Results: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. Conclusions: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs. [ABSTRACT FROM AUTHOR]

Objective: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage. Methods: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design. Results: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC. Conclusions: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate participation and participation patterns in a population-based screening programme for colorectal cancer (CRC) using the faecal immunochemical test (FIT). Methods: All individuals invited to three consecutive screening rounds in the population-based CRC screening between October 2015 and December 2020 in the Stockholm–Gotland Region, Sweden were included. Patterns of participation were assessed. Results: The study included 26 541 individuals which resulted in 79 623 screening events. The overall uptake rate was 71.5% and women had a significantly higher participation rate. The participation rate increased significantly between the first and third screening round for both men and women, and the increase was larger among men than women (66.1 to 70.7% vs. 73.1 to 75.4%). In total, 80.9% participated at least once. Consistent participation was the most common participation pattern (61.0%). The probability of attending all three consecutive rounds after initial participation was 87.7%. Over the three rounds, 17.4% participated after a reminder letter. Screening individuals attending after a reminder letter had a higher proportion of drop-outs in the following screening round compared to initial participants (15.4% vs 6.2%). Conclusion: A constant and high participation rate was observed in population-based FIT-screening for CRC. Initial participation was a strong predictor for continuous participation. The need for a reminder letter before participation was a risk factor for subsequent drop-out. [ABSTRACT FROM AUTHOR]

Objective: To evaluate interval cancer (IC) after two screening rounds of the Swedish population-based screening program of Stockholm–Gotland applying gender-specific cut-off levels in the fecal immunochemical test (FIT). Methods: All 60- to 69-year-olds invited to screening 2015–2019 were included. The cut-off level for a positive test was 40 µg/g in women and 80 µg/g in men. Screening-detected colorectal cancers (SD CRCs) and ICs were verified in the Swedish Colorectal Cancer Register, and the follow-up time was two years from invitation. The test sensitivity, the IC rate (ICs per 10,000 screening negatives) and the IC incidence (ICs per 100,000 person-years) relative to the background CRC incidence were assessed by gender and age. The FIT levels were compared in men and women for CRCs diagnosed within one year of the sample. Results: In the second screening round, 229,187 were invited, and SD CRCs and ICs were diagnosed in 193 and 144, respectively. The IC rate was 8.9 (7.4–10.3) and test sensitivity 0.61 (0.55–0.66), and was similar in men and women. For two screening rounds, the IC rate was significantly higher in men than in women, but the IC incidence/ background CRC incidence was similar in both genders. The FIT levels in female participants with CRC were significantly lower overall, and in early-staged CRCs as compared to men, and proximal localization was more common in women. In multivariable analysis, FIT levels were significantly lower in proximal CRCs. Conclusion: Over two rounds, the IC incidence relative to the background CRC incidence was similar in men and women supporting a gender-specific screening strategy. The results could be explained by lower FIT levels in women due to proximal CRC localization. [ABSTRACT FROM AUTHOR]

Middle ear adenomatous neuroendocrine tumors (MEANT) are rare, mainly benign neoplasms and account for less than 2% of the middle and inner ear neoplasms. There are no specific radiological or clinical findings; therefore, the diagnosis is often difficult. Biopsy prior to surgery is often proposed. The definite treatment is the complete surgical resection. We present an uncommon clinical report of a MEANT, which was treated successfully with surgical excision. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is the fifth leading cancer in the world, and there is a high mortality rate in China. Exploring the relationship between the prognosis of GC and the expression of related genes is helpful to further understand the common characteristics of the occurrence and development of GC and provide a new method for the identification of early GC, so as to provide the best therapeutic targets. Methods: Vascular endothelial growth factor (VEGF) and markers of epithelial-mesenchymal transition (EMT) were investigated immunohistochemically using tumor samples obtained from 196 GC tissues and adjacent tumor tissues. The correlation of the expression level with histopathologic features and survival was investigated. Results: Here, we show that VEGF and EMT markers expression were significantly correlated with depth of tumor invasion and GC stage (P <.05), degree of differentiation and lymph node metastasis (P <.001). We found that the rate of VEGF positivity in GC tissues was 52.05%, which was significantly higher than that in adjacent cancer tissues (16.84%). In GC, the association between VEGF and E-cadherin was negative (r = −0.188, P <.05), whereas VEGF and N-cadherin were positively correlated (r = 0.214, P <.05). Furthermore, the Kaplan-Meier analysis and a Cox regression model were used to analyze the effect of VEGF and EMT marker expression on the survival of the patients. We found that the overall survival of GC patients was correlated with VEGF (P <.001), N-cadherin (P <.001), E-cadherin (P =.002) expression, and some histopathologic features. Conclusions: Vascular endothelial growth factor and EMT markers exist side by side and play a part together in the development of GC, which provides new ideas for evaluating the prognosis of GC and researching targeted drugs. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic significantly impacted the delivery of cancer screening. The resulting decrease in outpatient visits and cancellations of non-urgent procedures have negatively affected colorectal cancer (CRC) screening. We aimed to determine the effect of the pandemic on CRC screening at a safety-net hospital and a private health system based in New York City. Methods: We identified individuals eligible for CRC screening aged 50 to 75 years presenting for outpatient care at a safety-net public hospital and private health system in April through September of 2019 and 2020. The primary outcome was the proportion of screening-eligible patients seen in primary care who underwent CRC screening. Results: The safety-net hospital had 516 (6.1% of screening-eligible individuals) and 269 (4.3%) screening tests completed in 2019 and 2020, respectively (p < 0.01). Fecal immunochemical tests (FIT) accounted for 69.6% of screening in 2019 and 88.1% in 2020. Colonoscopy accounted for 20.3% of screening in 2019 and 11.9% in 2020. The private health system had 39 (0.7%) and 21 (0.6%) screening tests completed in 2019 and 2020, respectively (p = 0.48). FIT accounted for 61.9% of screening in 2019 and 57.1% in 2020. Colonoscopy accounted for 38.1% of screening in 2019 and 42.9% in 2020. Conclusion: Absolute numbers of screening tests decreased for both institutions during the COVID-19 pandemic. We observed a decrease in screening uptake and increase in proportional FIT use in the safety-net hospital but no change in the private health system. [ABSTRACT FROM AUTHOR]

Objective: Colorectal cancer (CRC) is the third most common cancer and the second largest cause of cancer-related death worldwide. Current CRC screening in various countries involves stool-based faecal immunochemical testing (FIT) and/or colonoscopy, yet public uptake remains sub-optimal. This review assessed the literature regarding acceptability of alternative CRC screening modalities compared to standard care in average-risk adults. Method: Systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane and Web of Science were conducted up to February 3rd, 2022. The alternative interventions examined were computed tomography colonography, flexible sigmoidoscopy, colon capsule endoscopy and blood-based biomarkers. Outcomes for acceptability were uptake, discomfort associated with bowel preparation, discomfort associated with screening procedure, screening preferences and willingness to repeat screening method. A narrative data synthesis was conducted. Results: Twenty-one studies met the inclusion criteria. Differences between intervention and comparison modalities in uptake did not reach statistical significance in most of the included studies. The findings do suggest FIT as being more acceptable as a screening modality than flexible sigmoidoscopy. There were no consistent significant differences in bowel preparation discomfort, screening procedure discomfort, screening preference and willingness to repeat screening between the standard care and alternative modalities. Conclusion: Current evidence comparing standard colonoscopy and stool-based CRC screening with novel modalities does not demonstrate any clear difference in acceptability. Due to the small number of studies available and included in each screening comparison and lack of observed differences, further research is needed to explore factors influencing acceptability of alternative CRC modalities that might result in improvement in population uptake within different contexts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer (GC) is the fifth leading cancer in the world, and there is a high mortality rate in China. Exploring the relationship between the prognosis of GC and the expression of related genes is helpful to further understand the common characteristics of the occurrence and development of GC and provide a new method for the identification of early GC, so as to provide the best therapeutic targets. METHODS: Vascular endothelial growth factor (VEGF) and markers of epithelial-mesenchymal transition (EMT) were investigated immunohistochemically using tumor samples obtained from 196 GC tissues and adjacent tumor tissues. The correlation of the expression level with histopathologic features and survival was investigated. RESULTS: Here, we show that VEGF and EMT markers expression were significantly correlated with depth of tumor invasion and GC stage (P < .05), degree of differentiation and lymph node metastasis (P < .001). We found that the rate of VEGF positivity in GC tissues was 52.05%, which was significantly higher than that in adjacent cancer tissues (16.84%). In GC, the association between VEGF and E-cadherin was negative (r = -0.188, P < .05), whereas VEGF and N-cadherin were positively correlated (r = 0.214, P < .05). Furthermore, the Kaplan-Meier analysis and a Cox regression model were used to analyze the effect of VEGF and EMT marker expression on the survival of the patients. We found that the overall survival of GC patients was correlated with VEGF (P < .001), N-cadherin (P < .001), E-cadherin (P = .002) expression, and some histopathologic features. CONCLUSIONS: Vascular endothelial growth factor and EMT markers exist side by side and play a part together in the development of GC, which provides new ideas for evaluating the prognosis of GC and researching targeted drugs. [ABSTRACT FROM AUTHOR]

Objective: How faecal haemoglobin concentrations (f-Hb) vary from one round to the next in a colorectal cancer (CRC) screening programme, and relate to colonoscopy findings, are unknown. Our aim was to use data from the first two rounds of the faecal immunochemical test (FIT) based Scottish Bowel Screening Programme (SBoSP) to explore these issues. Methods: Faecal haemoglobin concentration (f-Hb) percentiles in the second round were compared with those in the first when the first round yielded a negative FIT result (<80 µg Hb/g faeces), a positive FIT but no colonoscopy, CRC, all adenoma, and a negative colonoscopy. In addition, the outcomes in the first and second rounds were compared. Results: The profiles of f-Hb in the first and second rounds differed in (a) those who had had a negative FIT result in the first round and (b) those in whom neoplastic pathology had been found. In contrast, the pattern of difference between profiles in those who had had a negative colonoscopy was very similar to that in those in whom an adenoma had been found. In addition, the risk of CRC being diagnosed in the second round after a negative colonoscopy in the first was 3.0%, not very different to that after a negative test result (4.9%). Conclusions: Adenomas may be rarely the cause of a positive FIT result. An alternative explanation as to why these are detected using FIT is required. In addition, a negative colonoscopy for a positive FIT result does not rule out the finding of significant neoplastic pathology in the next round. [ABSTRACT FROM AUTHOR]

Objective: Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate. Methods: Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when > 20 µg Hb/g faeces; two FIT, positive when either was > 20 µg Hb/g faeces; and two FIT, positive when the mean was > 20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected. Results: In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was > 20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is > 20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT. Conclusions: In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed. [ABSTRACT FROM AUTHOR]

Objective: Evidence of reduction in colorectal cancer (CRC) mortality following CRC screening based on the faecal immunochemical test (FIT) is insufficient. This study aimed to analyse if CRC mortality was reduced after implementing FIT-based screening. Setting: The Danish national CRC screening programme. Methods: This nationwide cohort study included residents aged 50–71 years invited to the prevalence round of the screening programme. Invitation order was decided by randomising on birth month; the first two birth months to be invited were classified as invited and the five last were classified as not-yet-invited and given a pseudo invitation data. Follow-up was from (pseudo)invitation date until 31 December 2017, emigration or death. Relative risk (RR) of CRC death was calculated with 95% confidence intervals (CIs). Results: A total of 897,812 residents were included (29% invited and 71% not-yet-invited). The median follow-up was 3.3 years. The RR of CRC death at end of follow-up was 0.83 (95% CI 0.66; 1.03) among those invited to screening compared with those not yet invited. For men aged 60–71 years, this RR was 0.68 (95% CI 0.49; 0.94). For those participating in screening compared with a similar group of not-yet-invited residents, the RR was 0.71 (95% CI 0.46–1.08). For male participants aged 60–71 years, this RR was 0.49 (95% CI 0.27−0.89). For women and men aged 50–59 years, RRs were small and statistically non-significant. Conclusion: This nationwide study showed that even within a median follow-up of only 3.3 years, implementing FIT-based CRC screening reduced CRC mortality among older men. [ABSTRACT FROM AUTHOR]

The article presents a case of a 73-year-old female who was rushed to an Ear, Nose, and Throat (ENT) clinic due to right-sided nasal obstruction and intermittent pain in the past two years to discuss nasal septum glomus tumor or glomangioma as a rare case of unilateral nasal obstruction. After knowing about her condition, the patient consented for a wide tumor excision.

Objective: To evaluate interval cancers (IC) in the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm-Gotland, which uses gender-specific cut-off levels for the fecal immunochemical test (FIT). Methods: All individuals aged 60–69 in Stockholm-Gotland invited to the screening program in October 2015 to September 2017 were followed up 2 years after invitation. Cut-off level for a positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. Screening-detected CRC (SD-CRC) and IC after negative FIT (FIT-IC) or negative screening colonoscopy (Colonoscopy-IC) were identified in the Swedish colorectal cancer register. The IC rate was calculated as IC/(FIT negatives + negative screening colonoscopies). The IC incidence rate (ICs among negatives per 100,000 person-years) in different sex and age groups was compared to the mean CRC incidence before regional screening implementation. Test sensitivity was defined as SD-CRC/(SD-CRC + FIT-IC). Results: Approximately 214,400 individuals were invited, and in 3521 screening colonoscopies 257(6.3%) SD-CRCs were detected. During follow-up, 124 FIT-IC and 7 Colonoscopy-IC were diagnosed, yielding an IC rate of 12.6 and 6.0 per 10,000 negatives (p = 0.00005) and a test sensitivity of 62% and 75% (p = 0.01) in men and women respectively. The IC incidence rate compared to CRC incidence was non-significantly lower in women. Conclusion: In the population-based screening program of Stockholm-Gotland with a cut-off of 40 µg/g in women and 80 µg/g in men, the test sensitivity was higher and the IC rate was lower in women, which might imply lowering the cut-off level in men. However, the IC incidence rate relative to the CRC incidence was similar in both genders. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer (CRC) screening with a faecal immunochemical test (FIT) has been disrupted in many countries during the COVID-19 pandemic. Performing catch-up of missed screens while maintaining regular screening services requires additional colonoscopy capacity that may not be available. This study aimed to compare strategies that clear the screening backlog using limited colonoscopy resources. Methods: A range of strategies were simulated using four country-specific CRC natural-history models: Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) and MIcrosimulation SCreening ANalysis for CRC (MISCAN-Colon) (both in the Netherlands), Policy1-Bowel (Australia) and OncoSim (Canada). Strategies assumed a 3-month screening disruption with varying recovery period lengths (6, 12, and 24 months) and varying FIT thresholds for diagnostic colonoscopy. Increasing the FIT threshold reduces the number of referrals to diagnostic colonoscopy. Outcomes for each strategy were colonoscopy demand and excess CRC-related deaths due to the disruption. Results: Performing catch-up using the regular FIT threshold in 6, 12 and 24 months could prevent most excess CRC-related deaths, but required 50%, 25% and 12.5% additional colonoscopy demand, respectively. Without exceeding usual colonoscopy demand, up to 60% of excess CRC-related deaths can be prevented by increasing the FIT threshold for 12 or 24 months. Large increases in FIT threshold could lead to additional deaths rather than preventing them. Conclusions: Clearing the screening backlog in 24 months could avert most excess CRC-related deaths due to a 3-month disruption but would require a small increase in colonoscopy demand. Increasing the FIT threshold slightly over 24 months could ease the pressure on colonoscopy resources. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of colonoscopies performed after a positive faecal immunochemical test in the French colorectal cancer screening programme. Methods: Retrospective analysis of all colonoscopies performed between 2015 and 2019 after a positive quantitative faecal immunochemical test in the population-based colorectal cancer screening programme organised in Alsace, part of the French programme. The following indicators were evaluated: annual colonoscopy volume, caecal intubation rate, adenoma detection rate, proximal serrated lesion detection rate and proportion of patients referred directly to surgery for benign polyp management. Endoscopists who performed <30 faecal immunochemical test positive colonoscopies were non-assessable. Results: Overall, 13,455 faecal immunochemical test-positive colonoscopies performed by 116 community gastroenterologists were included, 13,067 of them by 80 assessable endoscopists. The overall caecal intubation, adenoma detection and proximal serrated lesion detection rates were 97.9%, 57.6% and 7.6%, respectively. They were <90%, <45% and <1% for 1.3%, 12.5% and 6.3% of the endoscopists, respectively. Overall, 1028 (7.9%) individuals were examined by 13 low-performing endoscopists and 328 (2.4%) individuals by 33 low-volume non-assessable endoscopists. Among 9133 individuals harbouring polyps, 155 (1.7%) had unwarranted surgery for a benign polyp. Overall, 1487 individuals (11.1%; 95% confidence interval 10.5–11.6) were not given the best possible chances, whereas 5545 individuals (41.2%; 95% confidence interval 40.4–42.0) were offered the best possible chances by 37 endoscopists. Conclusions: At programme level, the key performance indicators evaluated largely exceeded the target standards. At individual level, at least one in nine individuals was not given the best possible chances during faecal immunochemical test-positive colonoscopies by a minority of poor-performing and/or low-volume endoscopists. [ABSTRACT FROM AUTHOR]

Objective: Annual fecal immunochemical tests can reduce colorectal cancer incidence and mortality. However, screening is a multi-step process and most patients do not perfectly adhere to guideline-recommended screening schedules. Our objective was to compare the reduction in colorectal cancer incidence and life-years gained based on US guideline-concordant fecal immunochemical test screening to scenarios with a range of delays. Method: The Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN) microsimulation model was used to estimate the effect of systematic departures from fecal immunochemical test screening guidelines on lifetime screening benefit. Results: The combined effect of consistent modest delays in screening initiation (1 year), repeated fecal immunochemical test screening (3 months), and receipt of follow-up or surveillance colonoscopy (3 months) resulted in up to 1.3 additional colorectal cancer cases per 10,000, 0.4 additional late-stage colorectal cancer cases per 10,000 and 154.7 fewer life-years gained per 10,000. A 5-year delay in screening initiation had a larger impact on screening effectiveness than consistent small delays in repeated fecal immunochemical test screening or receipt of follow-up colonoscopy after an abnormal fecal immunochemical test. The combined effect of consistent large delays in screening initiation (5 years), repeated fecal immunochemical test screening (6 months), and receipt of follow-up or surveillance colonoscopy (6 months) resulted in up to 3.7 additional colorectal cancer cases per 10,000, 1.5 additional late-stage colorectal cancer cases per 10,000 and 612.3 fewer life-years gained per 10,000. Conclusions: Systematic delays across the screening process can result in meaningful reductions in colorectal cancer screening effectiveness, especially for longer delays. Screening delays could drive differences in colorectal cancer incidence across patient groups with differential access to screening. [ABSTRACT FROM AUTHOR]

Objective: There is evidence that colorectal cancer screening using faecal haemoglobin is less effective in women than men. The faecal haemoglobin concentrations were therefore examined in women and men with screen-detected colorectal cancer. Setting: Scottish Bowel Screening Programme, following the introduction of a faecal immunochemical test from November 2017, to March 2020. Methods: Data were collated on faecal haemoglobin concentrations, pathological stage and anatomical site of the main lesion in participants who had colorectal cancer detected. The data in women and men were compared. Results: For the faecal haemoglobin concentrations studied (> 80 µg Hb/g faeces), the distributions indicated lower concentrations in women. Marked differences were found between women and men diagnosed with colorectal cancer. The median faecal haemoglobin concentration for women (n = 720) was 408 µg Hb/g faeces compared to 473 µg Hb/g faeces for men (n = 959) (p = 0.004) and 50.6% of the results were > 400 µg Hb/g faeces in women; in men, this was 57.8%. The difference in faecal haemoglobin concentrations in women and men became less statistically significant as stage advanced from stages I–IV. For right-sided, left-sided and rectal colorectal cancer, a similar gender difference persisted in all sites. Differences in faecal haemoglobin between the genders were significant for left-sided cancers and stage I and approached significance for rectal cancers and stage II, but all sites and stages showed lower median faecal haemoglobin concentrations for women. Conclusions: To minimise gender inequalities, faecal immunochemical test-based colorectal cancer screening programmes should evaluate a strategy of using different faecal haemoglobin concentration thresholds in women and men. [ABSTRACT FROM AUTHOR]

Objectives: Despite several interventions, colorectal cancer (CRC) screening uptake remains below acceptable levels in Italy. Among the potential determinants of screening uptake, only a few studies analysed the role of general practitioners (GPs). The aim was to evaluate the variation in screening uptake of the clusters of subjects assisted by single GPs. Setting: Ancona province, Central Italy. Methods: Cross-sectional study, including all residents aged 50–69 years, who were offered the public screening programme with biannual faecal immunochemical tests. Demographic (of all GPs) and screening data (of all eligible residents) for years 2018–2019 were collected from the official electronic datasets of the Ancona Local Health Unit. The potential predictors of acceptable screening uptake, including GP's gender, age, and number of registered subjects, were evaluated using random-effect logistic regression, with geographical area as the cluster unit. Results: The final sample consisted of 332 GP clusters, including 120,178 eligible subjects. The overall province uptake was 38.0% ± 10.7%. The uptake was lower than 30% in one-fifth of the GP clusters, and higher than 45% in another fifth. At multivariable analysis, the significant predictors of uptake were younger GP age (p = 0.010) and lower number of registered subjects (p < 0.001). None of the GP clusters with 500 subjects or more showed an uptake ≥45%. Conclusions: The wide variation across GPs suggests they might substantially influence screening uptake, highlighting a potential need to increase their commitment to CRC screening. Further research is needed to confirm the role of the number of registered subjects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Triple-negative breast cancer (TNBC) exhibits poor prognosis due to the lack of targets for hormonal or antibody-based therapies, thereby leading to limited success in the treatment of this cancer subtype. Poly (ADP-ribose) polymerase 1 (PARP1) is a critical factor for DNA repair, and using PARP inhibitor (PARPi) is one of the promising treatments for BRCA-mutated (BRCA mut) tumors where homologous recombination repair is impaired due to BRCA1 mutation. Carbon ion (C-ion) radiotherapy effectively induces DNA damages in cancer cells. Thus, the combination of C-ion radiation with PARPi would be an attractive treatment for BRCA mut TNBC, wherein DNA repair systems can be severely impaired on account of the BRCA mutation. Till date, the effectiveness of C-ion radiation with PARPi in BRCA mut TNBC cell killing remains unknown. PURPOSE: Triple-negative breast cancer cell lines carrying either wild type BRCA1, BRCA wt, (MDA-MB-231), or the BRCA1 mutation (HCC1937) were used, and the effectiveness of PARPi, olaparib, combined with C-ion beam or the conventional radiation, or X-ray, on TNBC cell killing were investigated. METHODS: First, effective concentrations of olaparib for BRCA mut (HCC1937) cell killing were identified. Using these concentrations of olaparib, we then investigated their radio-sensitizing effects by examining the surviving fraction of MDA-MB-231 and HCC1937 upon X-ray or C-ion irradiation. In addition, the number of yH2AX (DSB marker) positive cells as well as their expression levels were determined by immunohistochemistry, and results were compared between X-ray irradiated or C-ion irradiated cells. Furthermore, PARP activities in these cells were also observed by performing immunohistochemistry staining for poly (ADP-ribose) polymer (marker for PARP activity), and their expression differences were determined. RESULTS: Treatment of cells with 25 nM olaparib enhanced radio-sensitivity of X-ray irradiated HCC1937, whereas lower dose (5 nM) olapa-rib showed drastic effects on increasing radio-sensitivity of C-ion irradiated HCC1937. Similar effect was not observed in MDA-MB-231, not possessing the BRCA1 mutation. Results of immunohistochemistry showed that X-ray or C-ion irradiation induced similar number of yH2AX- positive HCC1937 cells, but these induction levels were higher in C-ion irradiated HCC1937 with increased PARP activity compared to that of X-ray irradiated HCC1937. Elevated induction of DSB in C-ion irradiated HCC937 may fully activate DSB repair pathways leading to down-stream activation of PARP, subsequently enhancing the effectiveness of PARPi, olaparib, with lower doses of olaparib exerting noticeable effects in cell killing of C-ion irradiated HCC1937. CONCLUSIONS: From this study, we demonstrate that C-ion irradiation can exert significant DSB in BRCA mut TNBC, HCC1937, with high PARP activation. Thus, PARPi, olaparib, would be a promising candidate as a radio-sensitizer for BRCA mut TNBC treatment, especially for C-ion radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: In the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm–Gotland using the fecal immunochemical test (FIT), gender-specific cut-off levels of fecal hemoglobin are applied, since previous studies have indicated a lower sensitivity of FIT for CRC in women. The aim was to evaluate the diagnostic yield and the screening costs overall and per detected CRC of this strategy. Methods: All individuals aged 60–69 invited to screening in 2015–2017 were included. Cut-off level for positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. The yield of CRC and screening cost for the study period were assessed and compared to cut-off levels of 80 µg/g in both genders. Results: Approximately 230,000 individuals were invited. Overall participation rates were 72% in women and 65% in men (p < 0.05). FIT was positive in 4256 individuals (2.7% in both genders). In 3758 colonoscopies, 258 (6.9%) CRCs were detected. The positive predictive value for CRC was significantly higher in men (8.3% vs. 5.8%). In 120 women with CRC, 28 (23%) had FIT < 80 µg/g. Negative colonoscopies were more common in women (24% vs. 17%, p < 0.05). Total costs for the study period were 52,000,000SEK (≈5,200,000€), i.e. 16% higher compared to using cut-off levels of 80 µg/g in both genders, and corresponding to a 3% increment in cost per detected CRC. Conclusion: The high rate of CRC detected in women in the lowest FIT category outweighs the minor reduction in screening costs if the same cut-off level was used as for men. [ABSTRACT FROM AUTHOR]

Objective: Digital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems. Methods: We conducted a systematic review of 30 studies along with key informant surveys and interviews to describe programmatic implementation strategies for selecting patients for CRC screening. PubMed and Embase were searched since inception through December 2018, and hand searches were performed of the retrieved reference lists but none were incorporated (n = 0). No language exclusions were applied. Results: Common criteria for outreach exclusion included: being up-to-date with routine CRC screening (n = 22), comorbidities (n = 20), and personal history (n = 22) or family history of cancer (n = 9). Key informant surveys and interviews were performed (n = 28) to understand data sources and practices for patient outreach selection, and found that 13 studies leveraged electronic medical care records, 10 studies leveraged a population registry (national, municipal, community, health), 4 studies required patient opt-in, and 1 study required primary care provider referral. Broad ranges in fecal immunochemical test completion were observed in community clinic (n = 8, 31.0–59.6%), integrated health system (n = 5, 21.2–82.7%), and national regional CRC screening programs (n = 17, 23.0–64.7%). Six studies used technical codes, and four studies required patient self-reporting from a questionnaire to participate. Conclusion: This systematic review provides health systems with the diverse outreach practices and technical tools to support efforts to automate patient selection for CRC screening outreach. [ABSTRACT FROM AUTHOR]

Objective: Testing for occult blood in faeces is widely used in bowel cancer screening around the world. In many programmes, the faecal immunochemical test (FIT) is replacing the traditional guiaic faecal occult blood test (gFOBT). There have been a number of reports on the clinical impact of making this change; yet, no-one has considered the pre-analytical and analytical impact of moving from a gFOBT to a FIT bowel cancer screening programme. Methods: We interrogated data obtained in a FIT pilot carried out in England in 2014 to assess the timeliness of specimen collection device return time and analysis for gFOBT and FIT, the impact of time to analysis on faecal haemoglobin (f-Hb) concentration, and any differences observed between analyses carried out at two different testing laboratories. Results: FIT kits were returned on average 5.6 days sooner than gFOBT. The time to analysis for FIT leads to an overall rise in f-Hb concentration within the manufacturer's stated 14-day stability period. Conclusion: Both these factors are important considerations for laboratories when considering setting up a bowel cancer screening programme, especially if transitioning from gFOBT to FIT. Our data also support previous evidence of males having a higher f-Hb than females and demonstrate that after adjusting for sex, age and screening hub, neither index of multiple deprivation nor screening episode significantly affected f-Hb. [ABSTRACT FROM AUTHOR]

Based on the theory of social representations, this study aims to identify the main determinants to participation in colorectal cancer screening. Six focus groups (N = 29 participants belonging to the general population) were conducted, followed by a theoretical thematic analysis. Screening obstacles are a lack of test's accessibility, a low preoccupation for prevention and the negative image of colorectal cancer. Conversely, screening facilitators are the ease of the new test, being encouraged to get screened and appointment reminder. This study advances understanding of adherence to screening by addressing the beliefs and knowledge surrounding it. [ABSTRACT FROM AUTHOR]

Objective: To classify interval colorectal cancers as false negatives or newly occurring cases in a biennial Fecal immunochemical test (FIT) screening program and by various interscreening intervals. Setting: Data from the Taiwanese biennial colorectal cancer screening program involving FIT from 2004 to 2014 were used to estimate the incidence rate of asymptomatic colorectal cancer and the rate of its subsequent progression to clinical mode. Methods: The sensitivity of detecting asymptomatic colorectal cancers excluding newly developed colorectal cancers was compared to the conventional estimate of sensitivity, the complementary FIT interval cancer rate as a percentage of the expected incidence rate ((1-I/E)%). The relative contribution of newly developed or false-negative cases to FIT interval colorectal cancers was estimated by age and interscreening intervals. Results: The Taiwanese biennial fecal immunochemical test screening program had a conventional sensitivity estimate of 70.2%. After newly developed colorectal cancers were separated from FIT interval cancers, the ability to detect asymptomatic colorectal cancers increased to 75.5%. FIT interval colorectal cancers from the biennial program mainly resulted from newly developed colorectal cancers (68.8%). The corresponding figures decreased to 61.1% for the annual program but increased to 74.7% for the triennial program. The preponderance of newly developed colorectal cancers among FIT interval cancers was more prominent in screenees aged 50–59 than in those aged 60–69. Conclusions: Newly developed colorectal cancers showed a predominance among the FIT interval colorectal cancers in particular in the younger population screened. It is desirable to identify high-risk individuals to offer them a short interscreening interval or advanced detection methods to reduce their odds of developing interval cancer. [ABSTRACT FROM AUTHOR]

Objectives: The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative haemoglobin concentration provided by FIT in faecal samples with underlying pathology. From this we estimate thresholds required for given levels of sensitivity to CRC and high-risk adenomas (HRA). Methods: Data were collected from a pilot study of FIT in England in 2014, in which 27,238 participants completed a FIT. Those with a faecal haemoglobin concentration (f-Hb) of at least 20 µg/g were referred for further investigation, usually colonoscopy. Truncated regression models were used to explore the relationship between bowel pathology and FIT results. Regression results were applied to estimate sensitivity to different abnormalities for a number of thresholds. Results: Participants with CRC and HRA had significantly higher f-Hb, and this remained unchanged after adjusting for age and sex. While a threshold of 20 μg/g was estimated to capture 82.2% of CRC and 64.0% of HRA, this would refer 7.8% of participants for colonoscopy. The current programme threshold used in England of 120 μg/g was estimated to identify 47.8% of CRC and 25.0% of HRA. Conclusions: Under the current diagnostic policy of dichotomising FIT results, a very low threshold would be required to achieve high sensitivity to CRC and HRA, which would place further strain on colonoscopy resources. The NHS BCSP in England might benefit from a diagnostic policy that makes greater use of the quantitative nature of FIT. [ABSTRACT FROM AUTHOR]