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Contamination of perfluorinated compounds (PFCs) in Chao Phraya River and Bangpakong River, Thailand

Kunacheva C, Boontanon SK, Fujii S, Tanaka S, Musirat C, Artsalee C, et al.

Water Sci Technol, 2009;60(4):975-82.
PMID: 19700836 DOI: 10.2166/wst.2009.462

Perfluorinated compounds (PFCs) have been used for many years, and are distributed all over the world. This study focused on occurrences of PFCs, especially perfluorooctane sulfonate (PFOS) and perfluorooctonoic acid (PFOA) in Thai rivers and industrial estate discharges, while comparing results with rivers of other Asian countries (Japan, China, and Malaysia). Surveys were conducted in Chao Phraya River, Bangpakong River and three industrial estates. A solid phase extraction (SPE) and HPLC-ESI-MS/MS were used for the analysis of these chemicals. The average concentrations of PFOS and PFOA were 1.9 and 4.7 ng/L, respectively in Chao Phraya River, while lower concentrations were detected in Bangpakong River with the averages of 0.7 ng/L for both PFOS and PFOA. Higher concentrations were detected in all industrial estate discharges with the averages of 64.3 ng/L for PFOA and 17.9 ng/L for PFOS., Total loadings from three industrial estates were 1.93 g/d for PFOS and 11.81 g/d for PFOA. The concentration levels in Thai rivers were less than rivers in Japan, China, and Malaysia. However, PFCs loading rate of Chao Phraya River was much higher than Yodo River (Japan), due to the higher flow rate. The other six PFCs were found above the Limit of Quantification (LOQ) in most samples. PFHxS and PFNA were also highly detected in some river samples.
Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules

Tanaka S, Yoichi S, Ao L, Matumoto M, Morimoto K, Akimoto N, et al.

Phytother Res, 2001 Dec;15(8):681-6.
PMID: 11746860

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.
Impact of adjuvant chemotherapy on survival of women with T1N0M0, hormone receptor negative breast cancer

Bhoo-Pathy NT, Inaida S, Tanaka S, Taib NA, Yip CH, Saad M, et al.

Cancer Epidemiol, 2017 06;48:56-61.
PMID: 28371729 DOI: 10.1016/j.canep.2017.03.007

BACKGROUND: The benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers.
METHOD: All newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score.
RESULTS: Of 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%-94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%-94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14-0.91) in a subgroup of women with high-grade tumors.
CONCLUSION: Adjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.
Fulltext Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions

Hamezah HS, Durani LW, Ibrahim NF, Yanagisawa D, Kato T, Shiino A, et al.

Exp Gerontol, 2017 12 01;99:69-79.
PMID: 28918364 DOI: 10.1016/j.exger.2017.09.008

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.
Fulltext Utility of a standardized training program for endoscopic diagnosis of early gastrointestinal neoplasia

Chiu PW, Sano Y, Uedo N, Singh R, Ng EKW, Aang TL, et al.

Endosc Int Open, 2019 Apr;7(4):E452-E458.
PMID: 30931377 DOI: 10.1055/a-0854-3525

Background and study aims Image enhanced endoscopy (IEE) allows endoscopists to improve recognition and characterization of gastrointestinal neoplasia. The Asian Novel Bio-Imaging and Intervention Group (ANBIG) conducted a standardized training program in endoscopic diagnosis and treatment of early gastrointestinal cancers in Asia. We embarked on a study to investigate the effect of this module on endoscopic diagnosis of early gastrointestinal neoplasia. Methods This prospectively collected database was from workshops conducted on training for endoscopic diagnosis of early gastrointestinal neoplasia. All workshops were conducted in a standardized format, which included a pretest, a learning phase consisting of didactic lectures, case discussion, and live demonstration followed by a post-test to assess knowledge gained. The pretest and post-training tests were standardized questions addressing four domains, including basic knowledge of imaging and diagnosis of esophageal, gastric, and colonic neoplasia. Results From November 2013 to November 2016, 41 ANBIG workshops were conducted in 13 countries. A total of 1863 delegates and 40 faculty participated in these workshops. Of the delegates, 627 completed both tests. There was a significant improvement after training in all domains of the tests. There was a trend in general lack of knowledge across all domains for delegates from "low" healthcare cost countries before training. All delegates demonstrated significant improvement in knowledge of all domains after the workshop irrespective of whether they were from "high" or "low" healthcare cost per capita countries. Conclusion A standardized teaching program on IEE improved the diagnostic ability and quality of endoscopists in recognizing early gastrointestinal neoplasia in Asia.
Fulltext Standards of diagnostic colonoscopy for early-stage neoplasia: Recommendations by an Asian private group

Sano Y, Chiu HM, Li XB, Khomvilai S, Pisespongsa P, Co JT, et al.

Dig Endosc, 2019 May;31(3):227-244.
PMID: 30589103 DOI: 10.1111/den.13330

BACKGROUND AND AIM: In recent years, the incidence of colorectal cancer has been increasing, and it is now becoming the major cause of cancer death in Asian countries. The aim of the present study was to develop Asian expert-based consensus to standardize the preparation, detection and characterization for the diagnosis of early-stage colorectal neoplasia.
METHODS: A professional group was formed by 36 experts of the Asian Novel Bio-Imaging and Intervention Group (ANBI2 G) members. Representatives from 12 Asia-Pacific countries participated in the meeting. The group organized three consensus meetings focusing on diagnostic endoscopy for gastrointestinal neoplasia. The Delphi method was used to develop the consensus statements.
RESULTS: Through the three consensus meetings with debating, reviewing the literature and regional data, a consensus was reached at third meeting in 2016. The consensus was reached on a total of 10 statements. Summary of statements is as follows: (i) Adequate bowel preparation for high-quality colonoscopy; (ii) Antispasmodic agents for lesion detection; (iii) Image-enhanced endoscopy (IEE) for polyp detection; (iv) Adenoma detection rate for quality indicators; (v) Good documentation of colonoscopy findings; (vi) Complication rates; (vii) Cecal intubation rate; (viii) Cap-assisted colonoscopy (CAC) for polyp detection; (ix) Macroscopic classification using indigocarmine spray for characterization of colorectal lesions; and (x) IEE and/or magnifying endoscopy for prediction of histology.
CONCLUSION: This consensus provides guidance for carrying out endoscopic diagnosis and characterization for early-stage colorectal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early-stage colorectal neoplasia.
Fulltext 2019 Seoul Consensus on Esophageal Achalasia Guidelines

Jung HK, Hong SJ, Lee OY, Pandolfino J, Park H, Miwa H, et al.

J Neurogastroenterol Motil, 2020 04 30;26(2):180-203.
PMID: 32235027 DOI: 10.5056/jnm20014

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.
Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, et al.

J Pathol, 2023 Aug;260(5):514-532.
PMID: 37608771 DOI: 10.1002/path.6165

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
Fulltext Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.

J Pathol, 2023 Aug;260(5):498-513.
PMID: 37608772 DOI: 10.1002/path.6155

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Fulltext Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.

J Pathol, 2024 Mar;262(3):271-288.
PMID: 38230434 DOI: 10.1002/path.6238

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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