Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Analytical and clinical evaluation of the cobas Epstein-Barr virus test at a tertiary care cancer hospital.

BACKGROUND: Epstein-Barr Virus (EBV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Cobas EBV test (Roche Molecular, Pleasanton, CA) has recently been FDA-cleared for the monitoring of EBV viral loads in plasma samples of transplant patients. In this study, we compared the viral loads obtained by a laboratory-developed test (EBV LDT) using Altona Analyte specific reagents (ASR) to those obtained on the Cobas EBV test. METHODS: The analytical performance of the assay was established using the EBV verification panel from Exact Diagnostics and the EBV ATCC strain B95-8. The clinical evaluation was performed using 343 plasma samples initially tested on the EBV LDT. RESULTS: The analytical sensitivity (<18.8 IU/mL), precision (SD < 0.17 log) and linear range (35.0 IU/mL to 1E + 08 IU/mL) of the Cobas EBV assay established by the manufacturers were confirmed. The strength of the qualitative agreement was substantial between the cobas EBV and the EBV LDT (85.6 %; κ = 0.71) and almost perfect when discordant results were resolved (96.4 %; κ = 0.93). The quantitative agreement was moderate (82.9 %; κ = 0.53) with the viral load obtained on the Cobas EBV test being lower across the linear range of the two tests (mean log difference of 1.0). While the absolute values of the viral loads were markedly different, the overall trends observed in patients with multiple consecutive results were similar between the two tests. CONCLUSIONS: The Cobas EBV test provides an accurate and valid, in vitro diagnostic (IVD) option for monitoring of EBV viral loads in transplant patients and should provide an opportunity for increased standardization and commutability of tests results across laboratories.

Confined within a sugarcane monoculture: A participatory assessment of water pollution and potential health risks in the community of El Tiple, Colombia.

Communities neighboring monoculture plantations are vulnerable to different forms of pollution associated with agro-industrial operations. Herein, we examine the case of El Tiple, a rural Afro descendant community embedded within one of the largest sugarcane plantations in the Americas. We implemented a participatory approach to assess water pollution, exposure via water ingestion, and non-carcinogenic health risks associated with the use of local water sources available to the community. We conducted household surveys to unveil demographic characteristics and family dynamics linked to water consumption. Additionally, we measured water quality parameters and assessed the concentration glyphosate, its major metabolite (aminomethylphosphonic acid) and metals and metalloids. Drinking water El Tiple households is sourced from three primary sources: the local aqueduct system, water delivery trucks, and private deep wells. Tests on water samples from both the local aqueduct and delivery trucks showed no traces of pesticides, metals, or metalloids surpassing regulatory limits set by Colombian or EPA standards. However, we found concentration of contaminants of primary concern, including mercury (up to 0.0052 ppm) and lead (up to 0.0375 ppm) that exceed the permissible regulatory thresholds in water from groundwater wells. Residents of the peripheric subdivisions of El Tiple are four times more reliant on well water extraction than residents of the central area of the town due to lack of access to public drinking water and sanitation infrastructure. Finally, adult women and school-age children have a higher health risk associated with exposure to local pollutants than adult men due to their constant presence in the town. We conclude that expanding the coverage of clean water and sanitation infrastructure to include all households of the community would be the most recommended measure to minimize exposure and risk via ingestion of water pollutants.

Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series.

PURPOSE: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. EXPERIMENTAL DESIGN: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. RESULTS: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response-associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. CONCLUSIONS: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer.

Transposable elements (TEs) are abundant in the human genome, and they provide the sources for genetic and functional diversity. The regulation of TEs expression and their functional consequences in physiological conditions and cancer development remain to be fully elucidated. Previous studies suggested TEs are repressed by DNA methylation and chromatin modifications. The effect of 3D chromatin topology on TE regulation remains elusive. Here, by integrating transcriptome and 3D genome architecture studies, we showed that haploinsufficient loss of NIPBL selectively activates alternative promoters at the long terminal repeats (LTRs) of the TE subclasses. This activation occurs through the reorganization of topologically associating domain (TAD) hierarchical structures and recruitment of proximal enhancers. These observations indicate that TAD hierarchy restricts transcriptional activation of LTRs that already possess open chromatin features. In cancer, perturbation of the hierarchical chromatin topology can lead to co-option of LTRs as functional alternative promoters in a context-dependent manner and drive aberrant transcriptional activation of novel oncogenes and other divergent transcripts. These data uncovered a new layer of regulatory mechanism of TE expression beyond DNA and chromatin modification in human genome. They also posit the TAD hierarchy dysregulation as a novel mechanism for alternative promoter-mediated oncogene activation and transcriptional diversity in cancer, which may be exploited therapeutically.

Relations between Glucose and d-Amino Acids in the Modulation of Biochemical and Functional Properties of Rodent Islets of Langerhans.

The cell-to-cell signaling role of d-amino acids (d-AAs) in the mammalian endocrine system, particularly in the islets of Langerhans, has drawn growing interest for their potential involvement in modulating glucose metabolism. Previous studies found colocalization of serine racemase [produces d-serine (d-Ser)] and d-alanine (d-Ala) within insulin-secreting beta cells and d-aspartate (d-Asp) within glucagon-secreting alpha cells. Expressed in the islets, functional N-methyl-d-aspartate receptors are involved in the modulation of glucose-stimulated insulin secretion and have binding sites for several d-AAs. However, knowledge of the regulation of d-AA levels in the islets during glucose stimulation as well as the response of islets to different levels of extracellular d-AAs is limited. In this study, we determined the intracellular and extracellular levels of d-Ser, d-Ala, and d-Asp in cultures of isolated rodent islets exposed to different levels of extracellular glucose. We found that the intracellular levels of the enantiomers demonstrated large variability and, in general, were not affected by extracellular glucose levels. However, significantly lower levels of extracellular d-Ser and d-Ala were observed in the islet media supplemented with 20 mM concentration of glucose compared to the control condition utilizing 3 mM glucose. Glucose-induced oscillations of intracellular free calcium concentration ([Ca2+]i), a proxy for insulin secretion, were modulated by the exogenous application of d-Ser and d-Ala but not by their l-stereoisomers. Our results provide new insights into the roles of d-AAs in the biochemistry and function of pancreatic islets.

Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study.

Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1-3) enemas 43.67 (25-50) mL total, retained for an average of 60.78 (10-145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.

Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.

Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.

Imaging and Management of Internal Mammary Lymph Nodes.

Internal mammary lymph nodes (IMLNs) account for approximately 10%-40% of the lymphatic drainage of the breast. Internal mammary lymph nodes measuring up to 10 mm are commonly seen on high-risk screening breast MRI examinations in patients without breast cancer and are considered benign if no other suspicious findings are present. Benign IMLNs demonstrate a fatty hilum, lobular or oval shape, and circumscribed margins without evidence of central necrosis, cortical thickening, or loss of fatty hilum. In patients with breast cancer, IMLN involvement can alter clinical stage and treatment planning. The incidence of IMLN metastases detected on US, CT, MRI, and PET-CT ranges from 10%-16%, with MRI and PET-CT demonstrating the highest sensitivities. Although there are no well-defined imaging criteria in the eighth edition of the American Joint Committee on Cancer Staging Manual for Breast Cancer, a long-axis measurement of ≥ 5 mm is suggested as a guideline to differentiate benign versus malignant IMLNs in patients with newly diagnosed breast cancer. Abnormal morphology such as loss of fatty hilum, irregular shape, and rounded appearance (which can be quantified by a short-axis/long-axis length ratio greater than 0.5) also raises suspicion for IMLN metastases. MRI and PET-CT have good sensitivity and specificity for the detection of IMLN metastases, but fluorodeoxyglucose avidity can be seen in both benign conditions and metastatic disease. US is helpful for staging, and US-guided fine-needle aspiration can be performed in cases of suspected IMLN metastasis. Management of suspicious IMLNs identified on imaging is typically with chemotherapy and radiation, as surgical excision does not provide survival benefit and is performed only in rare cases.

Abbreviated Breast MRI: Road to Clinical Implementation.

Breast MRI offers high sensitivity for breast cancer detection, with preferential detection of high-grade invasive cancers when compared to mammography and ultrasound. Despite the clear benefits of breast MRI in cancer screening, its cost, patient tolerance, and low utilization remain key issues. Abbreviated breast MRI, in which only a select number of sequences and postcontrast imaging are acquired, exploits the high sensitivity of breast MRI while reducing table time and reading time to maximize availability, patient tolerance, and accessibility. Worldwide studies of varying patient populations have demonstrated that the comparable diagnostic accuracy of abbreviated breast MRI is comparable to a full diagnostic protocol, highlighting the emerging role of abbreviated MRI screening in patients with an intermediate and high lifetime risk of breast cancer. The purpose of this review is to summarize the background and current literature relating to abbreviated MRI, highlight various protocols utilized in current multicenter clinical trials, describe workflow and clinical implementation issues, and discuss the future of abbreviated protocols, including advanced MRI techniques.