Publications by authors named "Tony Hsiu-Hsi Chen"

158 Publications

Imaging biomarkers of breast cancers originating from the major lactiferous ducts: Ductal adenocarcinoma of the breast, DAB.

Eur J Radiol 2022 Jun 4;154:110394. Epub 2022 Jun 4.

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Wuxing Street, Taipei 110, Taiwan.

Purpose: As we have previously demonstrated, breast cancers originating in the major lactiferous ducts and propagating through the process of neoductgenesis are a distinct subtype of invasive breast cancers, although by current practice they are placed within the group termed ductal carcinoma in situ (DCIS) and are consequently underdiagnosed and undertreated. Imaging biomarkers provide a reliable indication of the site of origin of this breast cancer subtype (Ductal Adenocarcinoma of the breast, DAB) and have excellent concordance with long-term patient outcome. In the present paper, the imaging biomarkers of DAB are described in detail to encourage and facilitate its recognition as a distinct, invasive breast cancer subtype.

Methods: Correlation of breast imaging biomarkers with the corresponding histopathological findings using large format technology, with additional evidence from subgross, thick section histopathology to demonstrate the complex three-dimensional structure of the newly formed duct-like structures, neoducts.

Results: There are six imaging biomarkers (mammographic tumour features) of DAB. Four subgroups have characteristic malignant-type calcifications on the mammogram. Two of these are characterized by intraluminal necrosis producing fragmented or dotted casting type calcifications on the mammogram; another two subgroups are characterized by intraductal fluid production which may eventually calcify, producing skipping stone-like or string of pearl-like calcifications. A fifth DAB subgroup presents with bloody or serous nipple discharge and is usually occult on mammography but is detectable with galactography and magnetic resonance imaging (MRI). The sixth subgroup presents as architectural distortion on the mammogram without associated calcifications.

Conclusions: Radiologists can use these well-defined imaging biomarkers to readily detect Ductal Adenocarcinoma of the Breast, DAB. Immunochemical biomarkers are generally not determined from the DAB itself, due to the erroneous assumption that DAB is non-invasive. MRI plays a crucial role in determining disease extent and guiding surgical management. The accumulating evidence that this disease subtype is, in fact, an invasive cancer, necessitates an urgent re-evaluation of the diagnostic and management criteria for this poorly understood malignancy.
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http://dx.doi.org/10.1016/j.ejrad.2022.110394DOI Listing
June 2022

Breast cancers originating from the major lactiferous ducts and the process of neoductgenesis: Ductal Adenocarcinoma of the Breast, DAB.

Eur J Radiol 2022 Aug 18;153:110363. Epub 2022 May 18.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 17 Hsuchow Road, Taipei 100, Taiwan.

Purpose: To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion.

Method: All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome.

Results: Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article.

Conclusions: Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.
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http://dx.doi.org/10.1016/j.ejrad.2022.110363DOI Listing
August 2022

Breast cancers originating from the terminal ductal lobular units: In situ and invasive acinar adenocarcinoma of the breast, AAB.

Eur J Radiol 2022 Jul 10;152:110323. Epub 2022 May 10.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 17 Hsuchow Road, Taipei, Taiwan 100.

Purpose: To use mammographic tumour features (imaging biomarkers) to identify and investigate breast cancers originating from the terminal ductal lobular units (TDLUs) of the breast in order to overcome the confusion arising from the current histopathology terminology, which calls cancers arising from the TDLUs either "ductal" or "lobular".

Method: Prospectively collected data from a randomized controlled mammography screening trial with more than four decades of follow up, and data from the subsequent population-based service screening program in Dalarna County, Sweden, provided the database necessary for studying nonpalpable, primarily screen-detected breast cancer cases in their earliest detectable phases. Large format thick (subgross) and thin section histopathologic images of breast cancers originating from the TDLUs were correlated with their mammographic tumour features (imaging biomarkers) and long-term patient outcome.

Results: This systematic correlation indicates that imaging biomarkers can reliably determine the site of origin of breast cancers arising from the terminal ductal lobular units (TDLUs). This breast cancer subgroup has four specific mammographic tumour features: the in situ carcinomas developing from the TDLUs appear as powdery or crushed stone-like calcifications, while the invasive carcinomas appear as stellate/spiculated or circular/oval shaped tumour masses. These features are easily identified with breast imaging, either alone or in combination, unifocal or multifocal. We propose calling breast cancers of TDLU origin acinar adenocarcinoma of the breast (AAB).

Conclusions: The era of early detection necessitates rectifying the current, confusing histopathological nomenclature to one that is based on the anatomical site of origin of breast cancers. Invasive cancers originating from the TDLUs are either stellate/spiculated or circular, irrespective of the complex WHO histopathologic terminology. The mortality reduction accomplished by participation in mammography screening is mostly accomplished by identifying and treating the AABs in their non-palpable, early phase. AABs detected when < 15 mm diameter with no associated carcinoma originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB) have a good to excellent long-term outcome, irrespective of the current terminology, which tends to lead to overtreatment of these early invasive tumours. The conventionally used prognostic factors, including immunohistochemical biomarkers, fail to identify those 1-14 mm invasive AABs tumours that are eventually fatal. This identification can be made preoperatively by including the characteristic mammographic tumour features, imaging biomarkers, in primary diagnosis, treatment planning, and predicting long-term patient outcome. Forthcoming articles will address breast malignancies originating from structures of the breast other than the TDLUs.
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http://dx.doi.org/10.1016/j.ejrad.2022.110323DOI Listing
July 2022

Evaluating the effectiveness of population-based breast cancer service screening: an analysis of parsimonious patient survival information with the time-varying Cox model.

Int J Epidemiol 2022 May 13. Epub 2022 May 13.

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

Background: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial.

Methods: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated.

Results: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets.

Conclusion: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data.
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http://dx.doi.org/10.1093/ije/dyac096DOI Listing
May 2022

A pre-symptomatic incubation model for precision strategies of screening, quarantine, and isolation based on imported COVID-19 cases in Taiwan.

Sci Rep 2022 04 11;12(1):6053. Epub 2022 Apr 11.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Facing the emerging COVID viral variants and the uneven distribution of vaccine worldwide, imported pre-symptomatic COVID-19 cases play a pivotal role in border control strategies. A stochastic disease process and computer simulation experiments with Bayesian underpinning was therefore developed to model pre-symptomatic disease progression during incubation period on which we were based to provide precision strategies for containing the resultant epidemic caused by imported COVID-19 cases. We then applied the proposed model to data on 1051 imported COVID-19 cases among inbound passengers to Taiwan between March 2020 and April 2021. The overall daily rate (per 100,000) of pre-symptomatic COVID-19 cases was estimated as 106 (95% credible interval (CrI): 95-117) in March-June 2020, fell to 37 (95% CrI: 28-47) in July-September 2020 (p < 0.0001), resurged to 141 (95% CrI: 118-164) in October-December 2020 (p < 0.0001), and declined to 90 (95% CrI: 73-108) in January-April 2021 (p = 0.0004). Given the median dwelling time, over 82% cases would progress from pre-symptomatic to symptomatic phase in 5-day quarantine. The time required for quarantine given two real-time polymerase chain reaction (RT-PCR) tests depends on the risk of departing countries, testing and quarantine strategies, and whether the passengers have vaccine jabs. Our proposed four-compartment stochastic process and computer simulation experiments design underpinning Bayesian MCMC algorithm facilitated the development of precision strategies for imported COVID-19 cases.
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http://dx.doi.org/10.1038/s41598-022-09863-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998162PMC
April 2022

A new approach to breast cancer terminology based on the anatomic site of tumour origin: The importance of radiologic imaging biomarkers.

Eur J Radiol 2022 Apr 9;149:110189. Epub 2022 Feb 9.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 17 Hsuchow Road, Taipei 100, Taiwan.

Purpose: To use mammographic tumour features (imaging biomarkers) to classify breast cancer according to its apparent anatomic site of origin in the new era where tumours are found at their nonpalpable, earliest detectable phase.

Method: Large format, subgross, three-dimensional histopathologic images of breast cancer subtypes and their corresponding imaging biomarkers were correlated with large format thin section histopathology and long-term patient outcome.

Results: This systematic correlation indicates that breast cancers arise from three separate fibroglandular tissue components: the terminal ductal lobular units (TDLUs), the major lactiferous ducts, and in the stem cells of the mesenchyme. The resulting three cancer subgroups have distinctly different clinical, histopathological and mammographic presentations and different long-term outcomes. The relative frequency of these three breast cancer subgroups is approximately 75%, 20% and 5%, respectively. Classification of breast cancers according to their anatomic site of origin, as demonstrated with breast imaging and confirmed by subgross histopathology, correlates closely with the long-term patient outcome.

Conclusions: Classification of breast cancers according to their site of origin helps overcome the inconsistencies in the current histopathologic terminology with its ductal-lobular dichotomy. The ability of the imaging biomarkers to determine the site of tumour origin and serve as a prognostic indicator emphasizes the increasingly crucial role of breast imaging in the management of breast cancer. Basing breast cancer management upon anatomically relevant terminology challenges the conventional mindset. Our proposals are based on research results from an unprecedented number of prospectively collected nonpalpable breast cancers diagnosed at their earliest detectable phases and followed up for several decades. This article is a general introduction to a series of forthcoming articles describing in detail the breast malignancies originating from the three sites of origin.
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http://dx.doi.org/10.1016/j.ejrad.2022.110189DOI Listing
April 2022

Modelling the impacts of COVID-19 pandemic on the quality of population-based colorectal cancer screening.

Prev Med 2021 10 30;151:106597. Epub 2021 Jun 30.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

COVID-19 pandemic has severely affected regular public health interventions including population-based cancer screening. Impacts of such screening delays on the changes in structure and screening process and the resultant long-term outcomes are unknown. It is therefore necessary to develop a systematic framework to assess theses impacts related to these components of quality. Using population-based cancer screening with fecal immunochemical test (FIT) as an illustration, the main analysis was to assess how various scenarios of screening delays were associated with the capacity for primary screening and full time equivalent (FTE) for colonoscopy and impact long-term outcomes based on a Markov decision tree model on population level. The second analysis was to quantify how the extent of COVID-19 epidemic measured by social distancing index affected capacity and FTE that were translated to delays with an exponential relationship. COVID-19 epidemic led to 25%, 29%, 34%, and 39% statistically significantly incremental risks of late cancer for the delays of 0.5-year, 1-year,1.5-year, and 2-year, respectively compared with regular biennial FIT screening. The corresponding statistically findings of four delayed schedules for death from colorectal cancer (CRC) were 26%, 28%, 29%, and 30%, respectively. The higher social distancing index led to a lower capacity of uptake screening and a larger reduction of FTE, resulting in longer screening delay and longer waiting time, which further impacted long-term outcomes as above. In summary, a systematic modelling approach was developed for demonstrating the strong impact of screening delays caused by COVID-19 epidemic on long-term outcomes illustrated with a Taiwan population-based FIT screening of CRC.
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http://dx.doi.org/10.1016/j.ypmed.2021.106597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241682PMC
October 2021

Evaluating Clinical Efficacy of Antiviral Therapy for COVID-19: A Surrogate Endpoint Approach.

Infect Dis Ther 2021 Jun 18;10(2):815-825. Epub 2021 Mar 18.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 533, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan.

Introduction: Efficient evaluation with an early surrogate endpoint, taking into account the process of disease evolution, may not only clarify inconsistent or underpowered results but also provide a new insight into the exploration of a new antiviral therapy for treating COVID-19 patients.

Methods: We assessed the dynamics of COVID-19 disease spectrum, commencing from low-risk (no or low oxygen supplement), medium-risk (non-invasive ventilator or high oxygen supplement), and high-risk (extracorporeal membrane oxygenation or invasive ventilator) risk state on enrollment, and then the subsequent progression and regression of risk states until discharge or death. The efficacy of antiviral therapy in altering the dynamics was assessed by using the high-risk state as a surrogate endpoint based on the data retrieved from the two-arm Adaptive Covid-19 Treatment Trial.

Results: Using the high-risk state as a surrogate endpoint, remdesivir treatment led to a decrease in the high-risk COVID-19 state by 34.8% (95% CI 26.7-42.0%) for a 14-day period and 29.3% (95% CI 28.8-29.8%) up to 28 days, which were consistent with a statistically significant reduction of death by 30.5% (95% CI 6.6, 50.9%) up to a 28-day period. The estimates of numbers needed to be treated were 100.9 (95% CI 88.1, 115.7) for using the high-risk COVID-19 state as a surrogate endpoint for a 14-day period and 133.3 (95% CI 112.5, 158.0) were required for averting one death from COVID-19 up to 28 days.

Conclusions: We demonstrate the expedient use of the high-risk COVID-19 disease status as a surrogate endpoint for evaluating the primary outcome of the earliest death.
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http://dx.doi.org/10.1007/s40121-021-00431-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972010PMC
June 2021

Likelihood function for estimating parameters in multistate disease process with Laplace-transformation-based transition probabilities.

Math Biosci 2021 05 15;335:108586. Epub 2021 Mar 15.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Multistate statistical models are often used to characterize the complex multi-compartment progression of the disease such as cancer. However, the derivation of multistate transition kernels is often involved with the intractable convolution that requires intensive computation. Moreover, the estimation of parameters pertaining to transition kernel requires the individualized time-stamped history data while the traditional likelihood function forms are constructed. In this paper, we came up with a novel likelihood function derived from Laplace transformation-based transition probabilities in conjunction with Expectation-Maximization algorithm to estimate parameters. The proposed method was applied to two large population-based screening data with only aggregated count data without relying on individual time-stamped history data.
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http://dx.doi.org/10.1016/j.mbs.2021.108586DOI Listing
May 2021

Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan.

J Hepatol 2021 07 6;75(1):132-141. Epub 2021 Mar 6.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background & Aims: Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period.

Methods: Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates.

Results: Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively.

Conclusions: Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

Lay Summary: Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.
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http://dx.doi.org/10.1016/j.jhep.2021.02.029DOI Listing
July 2021

Effectiveness of a 30-year periodontist's primary care for 1946 patients during five-year follow-up.

Oral Dis 2022 May 17;28(4):1250-1260. Epub 2021 Mar 17.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Objective: To evaluate the effect of the periodontal primary care (PPC) on the improvement of periodontal probing depth based on a periodontist's 30-year practice.

Materials And Methods: We enrolled a total of 2,894 patients who underwent periodontal basic treatment between 1987 and 2017 with 84.5% retention rate. The study population was composed of 80% (n = 1,946) of retained patients with complete re-evaluation up to five-year follow-up. The outcome was measured by the improvement of probing depths (graded as 1:1-3 mm; 2:4-6 mm; 3: ≥7 mm) before and after PPC on both sextant and patient levels. Whether a better improvement was seen in the surgical group and the non-smoker group opposed to their comparators was assessed with various multi-variable regression models.

Results: On patient (sextant) level, 82% (38%) improved, 13% (59%) unchanged, and 5% (3%) deteriorated. Adjusted better improvement of probing depth was noted for the surgical group by 63% and non-smoker by 31% compared with their counterparts. The similar findings were found for the outcomes based on continuous probing depth scores.

Conclusions: We demonstrate the improvement of probing depth scores with a periodontal primary care offered for the retained patients and larger effect for the surgical group and non-smoker patients.
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http://dx.doi.org/10.1111/odi.13822DOI Listing
May 2022

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Radiology 2021 06 2;299(3):541-547. Epub 2021 Mar 2.

From the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, England (S.W.D., R.M.); Department of Mammography, Falun Central Hospital, Falun, Sweden (L.T.); School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan (A.M.F.Y., S.L.S.C.); Department of Diagnostic Radiology, University of Turku, Turku, Finland (P.B.D.); Department of Cancer Control Sciences, American Cancer Society, Atlanta, Ga (R.A.S.); Regional Cancer Center, Umeå University, Umeå, Sweden (H.J.); Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden (S.T.); Department of Health Care Management, College of Management, Chang Gung University, Taoyuan, Taiwan (S.Y.H.C.); Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (S.Y.H.C.); Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan (S.Y.H.C., G.H.H.J., M.M.S.K., C.Y.H., T.H.H.C.); Regional Cancer Center, Uppsala University Hospital, Uppsala, Sweden (J.A.); Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, England (L.H.); and Department of Surgical Sciences, Uppsala University, Uppsala, Sweden (L.H.).

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. See also the editorial by Stephen A. Feig in this issue.
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http://dx.doi.org/10.1148/radiol.2021203935DOI Listing
June 2021

Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers.

Gut 2021 12 25;70(12):2321-2329. Epub 2021 Jan 25.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

Objective: To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.

Design: A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.

Results: FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).

Conclusion: A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.
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http://dx.doi.org/10.1136/gutjnl-2020-322545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588305PMC
December 2021

Community-Based Gastric Cancer Screening Coupled With a National Colorectal Cancer Screening Program: Baseline Results.

Gastroenterology 2021 05 11;160(6):2159-2161.e4. Epub 2021 Jan 11.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.01.008DOI Listing
May 2021

Sojourn-time-corrected receiver operating characteristic curve (ROC) for prostate specific antigen (PSA) test in population-based prostate cancer screening.

Sci Rep 2020 11 26;10(1):20665. Epub 2020 Nov 26.

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

Evaluating the performance of serum prostate-specific antigen (PSA) test in population-based screening with receiver operating characteristics (ROC) curve often neglects the time dimension. Asymptomatic cases with negative PSA test would have been missed if sojourn time is not taken into account to allow for cases surfacing into the clinical phase. Data included 20,796 men with PSA test at the first screening round was used from population-based Finnish prostate cancer screening trial during 1996-1999. Cancers detected at the first screen, together with interval cancers ascertained during 4-year follow-up were expediently used to estimate sensitivity and specificity. A sojourn-time-corrected model was applied to estimating the possible false negative cases for those with PSA < 4 ng/ml for correcting the ROC curve. The estimated sensitivity estimate was reduced from 94.4% without correction to 68.8% with correction but the estimated specificity was identical (89.4% vs. 89.2%) at cutoff of 3 ng/ml. The corrected area under curve (AUC) [77.0% (74.9-79.1%)] of the PSA test was significantly lower than the uncorrected AUC [95.9% (95.3-96.6%)]. The failure of considering the time since last negative screen due to incomplete ascertainment for asymptomatic cancer led to the overestimation of PSA test performance that further affects the cut-off value of PSA tests for population-based prostate cancer screening.
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http://dx.doi.org/10.1038/s41598-020-77668-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691355PMC
November 2020

Effect of epidural analgesia on cancer prognosis after colon cancer resection: a single-centre cohort study in Taiwan.

BMJ Open 2020 10 22;10(10):e036577. Epub 2020 Oct 22.

Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan

Objectives: Whether epidural analgesia affects cancer outcomes remains controversial. Most previous investigations ignored the confounding potential of important pathological factors on cancer outcomes. This study aimed to assess the association between epidural analgesia and cancer recurrence or death after resections for colon cancer.

Design: Retrospective cohort study.

Setting: A single-medical centre in Taiwan.

Participants: Patients with stage I through III colon cancer undergoing bowel resection and receiving either epidural analgesia or intravenous opioid analgesia from 2005 to 2014.

Primary And Secondary Outcome Measures: Primary outcome was postoperative recurrence-free survival and secondary outcome was overall survival.

Results: A total of 2748 and 1218 patients were analysed before and after propensity score matching. Cox regression analyses did not demonstrate any association between epidural analgesia and recurrence or death after matching (HR 0.89, 95% CI 0.65 to 1.21 for recurrence; 0.72, 95% CI 0.48 to 1.09 for death). Independent prognostic factors for cancer recurrence and death were higher level of preoperative carcinoembryonic antigen, perioperative blood transfusion, advanced cancer stage and pathological lymphovascular invasion.

Conclusions: No definite association was found between epidural analgesia and risk of recurrence or death in patients undergoing colon cancer resection.
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http://dx.doi.org/10.1136/bmjopen-2019-036577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583069PMC
October 2020

Effect of metabolic syndrome on incidence of oral potentially malignant disorder: a prospective cohort study in Taiwan.

BMJ Open 2020 10 14;10(10):e041971. Epub 2020 Oct 14.

Oral Health Care Research Center, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

Objectives: We aimed to assess the effect of metabolic syndrome (MetS) on incident oral potentially malignant disorder (OPMD).

Design: We conducted a prospective cohort study of the Changhua community-based integrated screening (CHCIS) programme and nationwide oral cancer screening programme during the period between 2005 and 2014.

Setting: CHCIS, Taiwan.

Participants: We enrolled 17 590 participants aged 30 years and older.

Main Outcomes And Measures: We assessed the impact of MetS on the outcome measured by incident OPMD.

Results: The incidences of OPMD among subjects with and without MetS were 7.68 ‰ and 5.38 ‰, respectively. After adjusting for confounders, subjects with MetS exhibited a statistically greater risk of developing OPMD compared with those who were free of MetS by 33% (adjusted rate ratio, aRR=1.33, 95% CI 1.14 to 1.55). Individual components of MetS still remained significant, including central obesity (aRR=1.22, 95% CI 1.04 to 1.44), hypertriglyceridaemia (aRR=1.26, 95% CI 1.07 to 1.49) and hyperglycaemia (aRR=1.20, 95% CI 1.02 to 1.41). Central obesity and hypertriglyceridaemia were also statistically associated with a subtype of OPMD, namely, leukoplakia.

Conclusion: The temporal influence of MetS on the risk of incident OPMD was noted in our prospective cohort study. Therefore, promoting an MetS prevention and control programme might reduce the occurrence of OPMD and oral cancer.
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http://dx.doi.org/10.1136/bmjopen-2020-041971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559119PMC
October 2020

Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a population-based screening programme.

Gut 2021 07 28;70(7):1318-1324. Epub 2020 Sep 28.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Objective: Subjects with a positive faecal immunochemical test (FIT) have a much higher likelihood of advanced neoplasms than the general population. Whether FIT-positive subjects with negative colonoscopy should receive subsequent FIT screening remain unclear.

Design: Subjects with a negative colonoscopy after positive FIT in the first screening in the Taiwanese Colorectal Cancer (CRC) Screening Program 2004-2009 were followed until the end of 2014. CRC incidence was compared between those who did and did not receive subsequent FIT screening. Cox regression analysis was conducted, adjusting for major confounders to investigate whether subsequent FIT was associated with lower risk of incident CRC.

Results: The study cohort was comprised of 9179 subjects who had negative diagnostic colonoscopy after positive FIT in 2004-2009, of whom 6195 received subsequent FIT during the study period. The CRC incidence (per 1000 person years) was 1.34 in those who received subsequent FIT and 2.69 in those who did not, with corresponding adjusted HR (aHR) of 0.47 (95% CI 0.31 to 0.71). Lower adenoma detection rate of diagnostic colonoscopy was associated with higher risk of incident CRC but became non-significant in multivariable analysis after adjustment for subsequent FIT. Higher baseline faecal haemoglobin concentration (FHbC, μg haemoglobin/g faeces) was associated with increased risk of incident CRC (reference: FHbC=20-39; aHR=1.93 (1.04-3.56), 0.95 (0.45-2.00), 2.26 (1.16-4.43) and 2.44 (1.44-4.12) for FHbC=40-59, 60-99, 100-149 and ≥150, respectively).

Conclusion: Subsequent FIT should be scheduled after negative colonoscopy to detect missed neoplasms and reduce the risk of incident CRC in a national FIT screening programme.
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http://dx.doi.org/10.1136/gutjnl-2020-320761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223654PMC
July 2021

Impact of the COVID-19 pandemic on a population-based breast cancer screening program.

Cancer 2020 12 11;126(24):5202-5205. Epub 2020 Sep 11.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

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http://dx.doi.org/10.1002/cncr.33180DOI Listing
December 2020

An Index for Lifting Social Distancing During the COVID-19 Pandemic: Algorithm Recommendation for Lifting Social Distancing.

J Med Internet Res 2020 09 17;22(9):e22469. Epub 2020 Sep 17.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Background: Implementing and lifting social distancing (LSD) is an urgent global issue during the COVID-19 pandemic, particularly when the travel ban is lifted to revive international businesses and economies. However, when and whether LSD can be considered is subject to the spread of SARS-CoV-2, the recovery rate, and the case-fatality rate. It is imperative to provide real-time assessment of three factors to guide LSD.

Objective: A simple LSD index was developed for health decision makers to do real-time assessment of COVID-19 at the global, country, region, and community level.

Methods: Data on the retrospective cohort of 186 countries with three factors were retrieved from a publicly available repository from January to early July. A simple index for guiding LSD was measured by the cumulative number of COVID-19 cases and recoveries, and the case-fatality rate was envisaged. If the LSD index was less than 1, LSD can be considered. The dynamic changes of the COVID-19 pandemic were evaluated to assess whether and when health decision makers allowed for LSD and when to reimplement social distancing after resurgences of the epidemic.

Results: After large-scale outbreaks in a few countries before mid-March (prepandemic phase), the global weekly LSD index peaked at 4.27 in March and lasted until mid-June (pandemic phase), during which most countries were affected and needed to take various social distancing measures. Since, the value of LSD has gradually declined to 0.99 on July 5 (postpandemic phase), at which 64.7% (120/186) of countries and regions had an LSD<1 with the decile between 0 and 1 to refine risk stratification by countries. The LSD index decreased to 1 in about 115 days. In addition, we present the results of dynamic changes of the LSD index for the world and for each country and region with different time windows from January to July 5. The results of the LSD index on the resurgence of the COVID-19 epidemic in certain regions and validation by other emerging infectious diseases are presented.

Conclusions: This simple LSD index provides a quantitative assessment of whether and when to ease or implement social distancing to provide advice for health decision makers and travelers.
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http://dx.doi.org/10.2196/22469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505695PMC
September 2020

Association between faecal haemoglobin concentration and the risk of cardiovascular diseases among Taiwanese adults in a community-based screening cohort.

BMJ Open 2020 06 15;10(6):e032633. Epub 2020 Jun 15.

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

Objectives: The role of faecal haemoglobin as a colorectal cancer screening tool has been demonstrated. However, the association between the faecal haemoglobin concentration and the risk of cardiovascular disease events and deaths is still unclear.

Design: Cohort study design.

Setting: Population-based organised integrated service screening in Keelung City, Taiwan PARTICIPANTS: A total of 33 355 healthy individuals aged over 40 years who were free of cardiovascular disease at study entry were followed up.

Main Outcomes And Measures: Newly diagnosed cardiovascular disease events and deaths.

Results: After a median follow-up of 2.39 years, a total of 2768 participants developed cardiovascular events, and after a median follow-up of 8.43 years, 317 cases of cardiovascular deaths occurred. The risk of cardiovascular disease increased with baseline faecal haemoglobin in a dose-response manner, yielding a significant elevated risk of cardiovascular disease in parallel with the incremental concentration of faecal haemoglobin (adjusted HRs=1.04, 1.10, 1.40 and 1.23 for faecal haemoglobin concentrations of 1-19, 20-49, 50-99 and ≥100 ng/mL, trend test, p<0.0001, as compared with the reference group with undetectable faecal haemoglobin concentrations). A similar pattern was observed for the risk of cardiovascular disease deaths. In addition, the faecal haemoglobin improved the prediction performance of the model for the risk of cardiovascular diseases; the integrated discrimination improvement was 0.3% (p<0.001) for cardiovascular events and 0.1% (p=0.020) for cardiovascular deaths.

Conclusions: Our data support that faecal haemoglobin concentrations may be associated with the risk of cardiovascular diseases. The biological mechanisms underlying the role of faecal haemoglobin as health outcomes should be investigated.
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http://dx.doi.org/10.1136/bmjopen-2019-032633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299009PMC
June 2020

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

Cancer 2020 07 11;126(13):2971-2979. Epub 2020 May 11.

Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.

Methods: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.

Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]).

Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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http://dx.doi.org/10.1002/cncr.32859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318598PMC
July 2020

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

J Med Screen 2021 03 5;28(1):34-38. Epub 2020 May 5.

Regional Cancer Center Stockholm Gotland, Stockholm, Sweden.

Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome.

Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.

Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range.

Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.
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http://dx.doi.org/10.1177/0969141320921210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905745PMC
March 2021

Impact of varying anatomic sites on advanced stage and survival of oral cancer: 9-year prospective cohort of 27 717 cases.

Head Neck 2019 05 16;41(5):1475-1483. Epub 2019 Jan 16.

Department of Otolaryngology - Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan.

Background: To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer.

Methods: A total of 27 717 oral cancers mainly from a population-based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012.

Results: Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92-2.51) for tongue, 2.60 (2.28-2.97) for buccal, 2.68 (2.20-3.28) for floor of mouth, 2.96 (2.52-3.47) for hard palate, 6.04 (5.17-7.05) for gingiva, and 10.83 (9.20-12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31-1.67) in buccal, 1.61 (1.43-1.82) in tongue, 1.68 (1.41-1.99) in floor of mouth, 1.79 (1.57-2.05) in gingiva, 1.97 (1.71-2.26) in hard palate, and 2.15 (1.89-2.45) in oropharynx.

Conclusion: Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance.
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http://dx.doi.org/10.1002/hed.25579DOI Listing
May 2019

The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening.

Cancer 2019 02 8;125(4):515-523. Epub 2018 Nov 8.

Center for Cancer Prevention, Queen Mary University of London, London, United Kingdom.

Background: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate?

Methods: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection.

Results: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants.

Conclusions: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.
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http://dx.doi.org/10.1002/cncr.31840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588008PMC
February 2019

Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community-based Cohort Study.

J Clin Gastroenterol 2019 May/Jun;53(5):e186-e193

Institute of Public Health, National Yang-Ming University, Taipei.

Goals: The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort.

Background: Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk.

Study: Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators.

Results: Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I <30 μg/L and PG-I <30 μg/L or PG-I/II ratio <3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases.

Conclusion: This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.
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http://dx.doi.org/10.1097/MCG.0000000000000992DOI Listing
August 2020

Effect of Mammography Screening on Mortality by Histological Grade.

Cancer Epidemiol Biomarkers Prev 2018 02 17;27(2):154-157. Epub 2017 Nov 17.

Queen Mary University of London, London, United Kingdom.

It has been asserted that mammography screening preferentially benefits those with less aggressive cancers, with lesser or no impact on more rapidly progressing and therefore more life-threatening tumors. We utilized data from the Swedish Two-County Trial, which randomized 77,080 women ages 40 to 74 to invitation to screening and 55,985 for usual care. We tabulated cancers by histologic grade and then compared mortality from cancers specific to histologic grade between the invited and control group using Poisson regression, with specific interest in the effect on mortality from grade 3 cancers. We used incidence-based mortality from tumors diagnosed within the screening phase of the trial. Finally, we cross-tabulated grade with tumor size and node status, to assess downstaging within tumor grades. There was a major reduction in mortality from grade 3 tumors (RR = 0.65; 95% CI, 0.53-0.80; < 0.001), and more deaths prevented from grade 3 tumors ( = 95) than grade 1 and 2 tumors combined ( = 48) in the invited group. The proportions of tumors ≥15 mm or larger and node-positive tumors were substantially reduced in the grade 3 tumors in the invited group. The combination of prevention of tumors progressing to grade 3 and detection at smaller sizes and lesser rates of lymph node metastases within grade 3 tumors results in a substantial number of deaths from grade 3 cancers being prevented by invitation to mammographic screening. Mammography screening prevents deaths from aggressive cancers. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0487DOI Listing
February 2018

Preliminary Results: Colorectal Cancer Screening Using Fecal Immunochemical Test (FIT) in a Thai Population Aged 45-74 Years: A Population-Based Randomized Controlled Trial

Asian Pac J Cancer Prev 2017 10 26;18(10):2883-2889. Epub 2017 Oct 26.

Epidemiology and Biostatistics Department, Faculty of Public Health, Khon Kaen University, Thailand.

Objective: The aim of this paper is to provide some details and the results to date of a colorectal cancer screening trial using a fecal immunochemical test (FIT). Methods: A population-based randomized controlled trial began in May, 2016. All people aged 45 to 74 years living in Nam Phong District, Khon Kaen Province, Thailand, and willing to participate are being recruited using an outreach method. Enrolled participants are randomly allocated by a computer-generated randomization program either to a study arm (receive sample kit for FIT) or to a control arm (no provision of kit). Positive FIT cases are subsequently confirmed by a colonoscopy examination, and negative FIT cases are re-tested with FIT every two years. The preliminary results to date were analysed using descriptive statistics. Results: A total of 1,060 enrolled participants provided a complete set of data. Of those randomly assigned to the study arm and tested by FIT, 92 (8.7%) were found to be positive, 39 (11.5%) males and 53 (7.4%) females. The f-Hb concentrations at the 75th, 90th and 95th percentiles for all age groups were higher in males than in females, and the distributions of f-Hb concentration varied with age, especially at the 95th percentile where f-Hb concentrations increased with age. Conclusion: The preliminary results of our screening trial have indicated that the prevalence of positive FIT cases is higher than in a similar recent and, at the time unique, previous study in Thailand. This finding is especially the case for males and those in the older age groups.
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http://dx.doi.org/10.22034/APJCP.2017.18.10.2883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747418PMC
October 2017

The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a hospital-based matched case-control study.

BMC Cancer 2017 Oct 11;17(1):680. Epub 2017 Oct 11.

Institute of Epidemiology and Prevention Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Background: Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population.

Methods: Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression.

Results: The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR , 3.7; 95%CI, 1.30-10.72) compared with Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer was modified by both a high intake of vegetable oils and salt (p = 0.036 and p = 0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no additive effects on the risk of stomach cancer between variants of the XRCC1gene and smoking,alcohol or pork oil consumption.

Conclusions: The effect of the XRCC1 gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was elevated by a high intake of vegetable oils and salt.
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http://dx.doi.org/10.1186/s12885-017-3675-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637079PMC
October 2017
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