今日の臨床サポート

癌検診

著者: 米田博輝 弘前大学 総合地域医療推進学講座

監修: 名郷直樹 武蔵国分寺公園クリニック

著者校正済:2021/12/01
現在監修レビュー中
参考ガイドライン:
患者向け説明資料

概要・推奨   

  1. 便潜血(2回法)による大腸癌検診は、グアヤック法、免疫法ともに大腸癌による死亡を減少させるため、強く推奨される(推奨度1)。
  1. S状結腸鏡による大腸癌検診は、大腸癌による死亡を減少させる可能性が高いものの、検査範囲が制限されること、検査が簡便でないこと、検査による副作用のリスクがあることから、患者が希望すれば行ってもよい(推奨度3)。
  1. 全大腸内視鏡による大腸癌検診は、大腸癌による死亡を減少させる可能性が高いものの、検査が簡便でないこと、検査による副作用のリスクがあることから、患者が希望すれば行ってもよい(推奨度3)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
米田博輝 : 特に申告事項無し[2021年]
監修:名郷直樹 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、癌検診の各項目ついて加筆修正を行った。

まとめ

スクリーニングの基本事項  
  1. 癌検診には対策型検診と任意型検診がある。対策型検診は死亡率を下げることを目的に、主に公共政策として行うものである。任意型検診は人間ドックに代表され、利益・不利益を個人で判断して受けるものである。
  1. 癌検診により目的とする癌の早期発見ができ、死亡率低下が期待できる。その反面、過剰な二次検査、検査による副作用、費用、精神的・肉体的苦痛などの不利益は避けられない。
  1. デメリットの具体例として、胃癌や大腸癌の精査として行われる消化管内視鏡は出血や穿孔、薬剤に対するアレルギー、まれに死亡のリスクがある。前立腺癌の精査で施行される針生検のような侵襲的検査では出血や感染などのリスクがある。また、CTをはじめとする放射線診断機器による被ばくは発癌リスクや遺伝的影響の可能性を考慮する必要がある。一般に、検診は感度の高い検査が選択されることが多いため偽陽性は避けられず、精査の結果が判明するまで“癌があるかもしれない”という心理的な負担を強いられる。そもそも、通常の癌との区別は困難であるが、検診では生命予後に影響しない癌を発見する可能性もあり、本来必要のない検査と治療が行われる可能性があることも考慮に入れる。
  1. 対策型検診では全体の利益と不利益のバランスを考慮することが必須だが、任意型検診では適切な情報を提供したうえで、個人に判断させる。
  1. 一般に、罹病率の低い若年者と、癌の発見による利益が相対的に低い高齢者とでは同じ検査でも有効性が異なるため、対策型検診の対象には一定の年齢範囲が示される。
  1. 次々に開発されている新しい検査方法は、理論的有効性は高くても、死亡率減少のエビデンスは不足している。
  1. USPSTF(U.S. Preventive Services Task Force)とは米国予防医療サービス専門作業部会のこと。スクリーニング、カウンセリング、予防投薬など予防に関するヘルスケアサービスについて、エビデンスに基づく推奨を行う機関である。
スクリーニングのポイント  
  1. 対策型検診と任意型検診の違いを理解する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: P Hewitson, P Glasziou, L Irwig, B Towler, E Watson
雑誌名: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001216. doi: 10.1002/14651858.CD001216.pub2. Epub 2007 Jan 24.
Abstract/Text BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality, especially in the Western world. The human and financial costs of this disease have prompted considerable research efforts to evaluate the ability of screening tests to detect the cancer at an early curable stage. Tests that have been considered for population screening include variants of the faecal occult blood test, flexible sigmoidoscopy and colonoscopy. Reducing mortality from colorectal cancer (CRC) may be achieved by the introduction of population-based screening programmes.
OBJECTIVES: To determine whether screening for colorectal cancer using the faecal occult blood test (guaiac or immunochemical) reduces colorectal cancer mortality and to consider the benefits, harms and potential consequences of screening.
SEARCH STRATEGY: Published and unpublished data for this review were identified by: Reviewing studies included in the previous Cochrane review; Searching several electronic databases (Cochrane Library, Medline, Embase, CINAHL, PsychInfo, Amed, SIGLE, HMIC); and Writing to the principal investigators of potentially eligible trials.
SELECTION CRITERIA: We included in this review all randomised trials of screening for colorectal cancer that compared faecal occult blood test (guaiac or immunochemical) on more than one occasion with no screening and reported colorectal cancer mortality.
DATA COLLECTION AND ANALYSIS: Data from the eligible trials were independently extracted by two reviewers. The primary data analysis was performed using the group participants were originally randomised to ('intention to screen'), whether or not they attended screening; a secondary analysis adjusted for non-attendence. We calculated the relative risks and risk differences for each trial, and then overall, using fixed and random effects models (including testing for heterogeneity of effects). We identified nine articles concerning four randomised controlled trials and two controlled trials involving over 320,000 participants with follow-up ranging from 8 to 18 years.
MAIN RESULTS: Combined results from the 4 eligible randomised controlled trials shows that participants allocated to screening had a 16% reduction in the relative risk of colorectal cancer mortality (RR 0.84, CI: 0.78-0.90). In the 3 studies that used biennial screening (Funen, Minnesota, Nottingham) there was a 15% relative risk reduction (RR 0.85, CI: 0.78-0.92) in colorectal cancer mortality. When adjusted for screening attendance in the individual studies, there was a 25% relative risk reduction (RR 0.75, CI: 0.66 - 0.84) for those attending at least one round of screening using the faecal occult blood test.
AUTHORS' CONCLUSIONS: Benefits of screening include a modest reduction in colorectal cancer mortality, a possible reduction in cancer incidence through the detection and removal of colorectal adenomas, and potentially, the less invasive surgery that earlier treatment of colorectal cancers may involve. Harmful effects of screening include the psycho-social consequences of receiving a false-positive result, the potentially significant complications of colonoscopy or a false-negative result, the possibility of overdiagnosis (leading to unnecessary investigations or treatment) and the complications associated with treatment.

PMID 17253456  Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001216. d・・・
著者: H Saito, Y Soma, J Koeda, T Wada, H Kawaguchi, T Sobue, T Aisawa, Y Yoshida
雑誌名: Int J Cancer. 1995 May 16;61(4):465-9.
Abstract/Text Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.

PMID 7759151  Int J Cancer. 1995 May 16;61(4):465-9.
著者: Jennifer S Lin, Margaret A Piper, Leslie A Perdue, Carolyn M Rutter, Elizabeth M Webber, Elizabeth O'Connor, Ning Smith, Evelyn P Whitlock
雑誌名: JAMA. 2016 Jun 21;315(23):2576-94. doi: 10.1001/jama.2016.3332.
Abstract/Text IMPORTANCE: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States.
OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC.
DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016.
STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events.
RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings.
CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

PMID 27305422  JAMA. 2016 Jun 21;315(23):2576-94. doi: 10.1001/jama.20・・・
著者: Aasma Shaukat, Steven J Mongin, Mindy S Geisser, Frank A Lederle, John H Bond, Jack S Mandel, Timothy R Church
雑誌名: N Engl J Med. 2013 Sep 19;369(12):1106-14. doi: 10.1056/NEJMoa1300720.
Abstract/Text BACKGROUND: In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex.
METHODS: In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008.
RESULTS: Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction).
CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

PMID 24047060  N Engl J Med. 2013 Sep 19;369(12):1106-14. doi: 10.1056・・・
著者: Geir Hoff, Tom Grotmol, Eva Skovlund, Michael Bretthauer, Norwegian Colorectal Cancer Prevention Study Group
雑誌名: BMJ. 2009 May 29;338:b1846. Epub 2009 May 29.
Abstract/Text OBJECTIVE: To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy.
DESIGN: Randomised controlled trial.
SETTING: Population based screening in two areas in Norway-city of Oslo and Telemark county (urban and mixed urban and rural populations).
PARTICIPANTS: 55 736 men and women aged 55-64 years.
INTERVENTION: Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913).
MAIN OUTCOME MEASURES: Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years.
RESULTS: No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016).
CONCLUSIONS: A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years' follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias.
TRIAL REGISTRATION: Clinical trials NCT00119912.

PMID 19483252  BMJ. 2009 May 29;338:b1846. Epub 2009 May 29.
著者: Wendy S Atkin, Rob Edwards, Ines Kralj-Hans, Kate Wooldrage, Andrew R Hart, John M A Northover, D Max Parkin, Jane Wardle, Stephen W Duffy, Jack Cuzick, UK Flexible Sigmoidoscopy Trial Investigators
雑誌名: Lancet. 2010 May 8;375(9726):1624-33. doi: 10.1016/S0140-6736(10)60551-X. Epub 2010 Apr 27.
Abstract/Text BACKGROUND: Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality.
METHODS: This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761.
FINDINGS: 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11.2 years (IQR 10.7-11.9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0.77, 95% CI 0.70-0.84) and mortality by 31% (0.69, 0.59-0.82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0.67, 0.60-0.76) and mortality by 43% (0.57, 0.45-0.72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0.50, 0.42-0.59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145-277) and 489 (343-852), respectively.
INTERPRETATION: Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit.
FUNDING: Medical Research Council, National Health Service R&D, Cancer Research UK, KeyMed.

Copyright 2010 Elsevier Ltd. All rights reserved.
PMID 20430429  Lancet. 2010 May 8;375(9726):1624-33. doi: 10.1016/S014・・・
著者: Hermann Brenner, Christian Stock, Michael Hoffmeister
雑誌名: BMJ. 2014 Apr 9;348:g2467. Epub 2014 Apr 9.
Abstract/Text OBJECTIVES: To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths.
DESIGN: Systematic review and meta-analysis of randomised controlled trials and observational studies.
DATA SOURCES: PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings.
ELIGIBILITY CRITERIA: Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk.
RESULTS: For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only.
CONCLUSIONS: Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.

© Brenner et al 2014.
PMID 24922745  BMJ. 2014 Apr 9;348:g2467. Epub 2014 Apr 9.
著者: Nancy N Baxter, Meredith A Goldwasser, Lawrence F Paszat, Refik Saskin, David R Urbach, Linda Rabeneck
雑誌名: Ann Intern Med. 2009 Jan 6;150(1):1-8. Epub 2008 Dec 15.
Abstract/Text BACKGROUND: Colonoscopy is advocated for screening and prevention of colorectal cancer (CRC), but randomized trials supporting the benefit of this practice are not available.
OBJECTIVE: To evaluate the association between colonoscopy and CRC deaths.
DESIGN: Population-based, case-control study.
SETTING: Ontario, Canada.
PATIENTS: Persons age 52 to 90 years who received a CRC diagnosis from January 1996 to December 2001 and died of CRC by December 2003. Five controls matched by age, sex, geographic location, and socioeconomic status were randomly selected for each case patient.
MEASUREMENTS: Administrative claims data were used to detect exposure to any colonoscopy and complete colonoscopy (to the cecum) from January 1992 to an index date 6 months before diagnosis in each case patient and the same assigned date in matched controls. Exposures in case patients and controls were compared by using conditional logistic regression to control for comorbid conditions. Secondary analyses were done to see whether associations differed by site of primary CRC, age, or sex.
RESULTS: 10 292 case patients and 51 460 controls were identified; 719 case patients (7.0%) and 5031 controls (9.8%) had undergone colonoscopy. Compared with controls, case patients were less likely to have undergone any attempted colonoscopy (adjusted conditional odds ratio [OR], 0.69 [95% CI, 0.63 to 0.74; P < 0.001]) or complete colonoscopy (adjusted conditional OR, 0.63 [CI, 0.57 to 0.69; P < 0.001]). Complete colonoscopy was strongly associated with fewer deaths from left-sided CRC (adjusted conditional OR, 0.33 [CI, 0.28 to 0.39]) but not from right-sided CRC (adjusted conditional OR, 0.99 [CI, 0.86 to 1.14]).
LIMITATION: Screening could not be differentiated from diagnostic procedures.
CONCLUSION: In usual practice, colonoscopy is associated with fewer deaths from CRC. This association is primarily limited to deaths from cancer developing in the left side of the colon.

PMID 19075198  Ann Intern Med. 2009 Jan 6;150(1):1-8. Epub 2008 Dec 15・・・
著者: A D Müller, A Sonnenberg
雑誌名: Arch Intern Med. 1995 Sep 11;155(16):1741-8.
Abstract/Text BACKGROUND: Although several clinical and epidemiologic studies suggest that timely diagnostic procedures of the large bowel may reduce mortality from colorectal cancer, the evidence for this relationship is primarily circumstantial.
METHODS: A case-control study was conducted among hospitalized US military veterans to investigate whether diagnostic procedures of the large bowel were performed in the period preceding the diagnosis of colorectal cancer less frequently in patients dying of colorectal cancer than in control patients. Data files of a total of 4411 veterans dying of colorectal cancer between 1988 and 1992 were extracted from the records of the US Department of Veterans Affairs, Washington, DC. Data of four living control patients and four dead control patients without colorectal cancer were matched by age, sex, and race to each case patient. The case and the two control populations were compared by conditional logistic regression, calculating odds ratios, and their 95% confidence interval.
RESULTS: Diagnostic procedures of the large bowel reduced mortality from colorectal cancer, the odds ratio being 0.41 (range, 0.33 to 0.50) for the comparison with living control patients. The protective effects of proctosigmoidoscopy, colonoscopy, and polypectomy lasted for 5 years. The procedures were protective against death from cancer of the colon, as well as cancer of the rectum. The most protective influence was associated with removal of tissue through biopsy, fulguration, and polypectomy. Similar influences were found comparing case patients with dead control patients.
CONCLUSION: Removal of tissue represents the most effective means to reduce mortality from cancers of the large bowel. It retains its efficacy over a time period of 5 years.

PMID 7654107  Arch Intern Med. 1995 Sep 11;155(16):1741-8.
著者: Jun Pan, Lei Xin, Yi-Fei Ma, Liang-Hao Hu, Zhao-Shen Li
雑誌名: Am J Gastroenterol. 2016 Mar;111(3):355-65. doi: 10.1038/ajg.2015.418. Epub 2016 Jan 12.
Abstract/Text OBJECTIVES: Observational studies have shown that colonoscopy reduces colorectal cancer (CRC) incidence and mortality in the general population. We aimed to conduct a meta-analysis quantifying the magnitude of protection by colonoscopy, with screening and diagnostic indications, against CRC in patients with non-malignant findings and demonstrating the potentially more marked effect of screening over diagnostic colonoscopy.
METHODS: PubMed, EMBASE, and conference abstracts were searched through 30 April 2015. The primary outcomes were overall CRC incidence and mortality. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models.
RESULTS: Eleven observational studies with a total of 1,499,521 individuals were included. Pooled analysis showed that colonoscopy was associated with a 61% RR reduction in CRC incidence (RR: 0.39; 95% CI: 0.26-0.60; I(2)=93.6%) and a 61% reduction in CRC mortality (RR: 0.39; 95% CI: 0.35-0.43; I(2)=12.0%) in patients with non-malignant findings, although there was high heterogeneity for the outcome of CRC incidence. After excluding one outlier study, there was low heterogeneity for the outcome of incidence (I(2)=44.7%). Subgroup analysis showed that the effect of screening colonoscopy was more prominent, corresponding to an 89% reduction in CRC incidence (RR: 0.11; 95% CI: 0.08-0.15), in comparison with settings involving diagnostic colonoscopy (RR: 0.51; 95% CI: 0.43-0.59; P<0.001).
CONCLUSIONS: On the basis of this meta-analysis of observational studies, CRC incidence and mortality in patients with non-malignant findings are significantly reduced after colonoscopy. The effect of screening colonoscopy on CRC incidence is more marked than diagnostic colonoscopy.

PMID 26753884  Am J Gastroenterol. 2016 Mar;111(3):355-65. doi: 10.103・・・
著者: S M Scheitel, D A Ahlquist, P C Wollan, P T Hagen, M D Silverstein
雑誌名: Mayo Clin Proc. 1999 Dec;74(12):1207-13. doi: 10.4065/74.12.1207.
Abstract/Text OBJECTIVE: To examine the effectiveness of screening proctosigmoidoscopy, barium enema radiography, and the fecal occult blood test (FOBT) in decreasing colorectal cancer mortality in a community setting.
PATIENTS AND METHODS: In this population-based case-control study, cases comprised 218 Rochester, Minn, residents who died of colorectal cancer between 1970 and 1993. Controls were 435 age- and sex-matched residents who did not have a diagnosis of colorectal cancer. Screening proctosigmoidoscopy, barium enema radiography, and FOBT results were documented for the 10 years prior to and including the date of diagnosis of fatal colorectal cancer in cases and for the same period in matched controls. History of general medical examinations and hospitalizations was also recorded.
RESULTS: Within the 10 years prior to diagnosis, the percentages of cases vs controls with at least 1 screening proctosigmoidoscopy were 23 (10.6%) of 218 cases vs 43 (9.9%) of 435 controls; at least 1 screening barium enema radiographic study was done in 12 (5.5%) of 218 vs 25 (5.7%) of 435. Within 3 years prior to diagnosis, the percentages of cases vs controls with at least 1 screening FOBT were 27 (12.4%) of 218 vs 44 (10.1%) of 435. Adjusted odds ratios were 1.04 (95% confidence interval [CI], 0.21-5.13) for proctosigmoidoscopy (distal rectosigmoid cancers only), 0.67 (95% CI, 0.31-1.48) for barium enema radiography, and 0.83 (95% CI, 0.45-1.52) for FOBT over the above time periods.
CONCLUSION: In this case-control study within a community setting, a colorectal cancer-specific mortality benefit could not be demonstrated for screening by FOBT, proctosigmoidoscopy, or barium enema radiography. Screening frequency was low, which may have contributed to the lack of measurable effects.

PMID 10593348  Mayo Clin Proc. 1999 Dec;74(12):1207-13. doi: 10.4065/7・・・
著者: Heidi D Nelson, Kari Tyne, Arpana Naik, Christina Bougatsos, Benjamin K Chan, Linda Humphrey, U.S. Preventive Services Task Force
雑誌名: Ann Intern Med. 2009 Nov 17;151(10):727-37, W237-42. doi: 10.7326/0003-4819-151-10-200911170-00009.
Abstract/Text BACKGROUND: This systematic review is an update of evidence since the 2002 U.S. Preventive Services Task Force recommendation on breast cancer screening.
PURPOSE: To determine the effectiveness of mammography screening in decreasing breast cancer mortality among average-risk women aged 40 to 49 years and 70 years or older, the effectiveness of clinical breast examination and breast self-examination, and the harms of screening.
DATA SOURCES: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2008), MEDLINE (January 2001 to December 2008), reference lists, and Web of Science searches for published studies and Breast Cancer Surveillance Consortium for screening mammography data.
STUDY SELECTION: Randomized, controlled trials with breast cancer mortality outcomes for screening effectiveness, and studies of various designs and multiple data sources for harms.
DATA EXTRACTION: Relevant data were abstracted, and study quality was rated by using established criteria.
DATA SYNTHESIS: Mammography screening reduces breast cancer mortality by 15% for women aged 39 to 49 years (relative risk, 0.85 [95% credible interval, 0.75 to 0.96]; 8 trials). Data are lacking for women aged 70 years or older. Radiation exposure from mammography is low. Patient adverse experiences are common and transient and do not affect screening practices. Estimates of overdiagnosis vary from 1% to 10%. Younger women have more false-positive mammography results and additional imaging but fewer biopsies than older women. Trials of clinical breast examination are ongoing; trials for breast self-examination showed no reductions in mortality but increases in benign biopsy results.
LIMITATION: Studies of older women, digital mammography, and magnetic resonance imaging are lacking.
CONCLUSION: Mammography screening reduces breast cancer mortality for women aged 39 to 69 years; data are insufficient for older women. False-positive mammography results and additional imaging are common. No benefit has been shown for clinical breast examination or breast self-examination.

PMID 19920273  Ann Intern Med. 2009 Nov 17;151(10):727-37, W237-42. do・・・
著者: Peter C Gøtzsche, Margrethe Nielsen
雑誌名: Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001877. doi: 10.1002/14651858.CD001877.pub4. Epub 2011 Jan 19.
Abstract/Text BACKGROUND: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary.
OBJECTIVES: To assess the effect of screening for breast cancer with mammography on mortality and morbidity.
SEARCH STRATEGY: We searched PubMed (November 2008).
SELECTION CRITERIA: Randomised trials comparing mammographic screening with no mammographic screening.
DATA COLLECTION AND ANALYSIS: Both authors independently extracted data. Study authors were contacted for additional information.
MAIN RESULTS: Eight eligible trials were identified. We excluded a biased trial and included 600,000 women in the analyses. Three trials with adequate randomisation did not show a significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42) for the two adequately randomised trials that measured this outcome; the use of radiotherapy was similarly increased.
AUTHORS' CONCLUSIONS: Screening is likely to reduce breast cancer mortality. As the effect was lowest in the adequately randomised trials, a reasonable estimate is a 15% reduction corresponding to an absolute risk reduction of 0.05%. Screening led to 30% overdiagnosis and overtreatment, or an absolute risk increase of 0.5%. This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false positive findings. It is thus not clear whether screening does more good than harm. To help ensure that the women are fully informed of both benefits and harms before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk.

PMID 21249649  Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001877. d・・・
著者: Heidi D Nelson, Rochelle Fu, Amy Cantor, Miranda Pappas, Monica Daeges, Linda Humphrey
雑誌名: Ann Intern Med. 2016 Feb 16;164(4):244-55. doi: 10.7326/M15-0969. Epub 2016 Jan 12.
Abstract/Text BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years.
PURPOSE: To review studies of the effectiveness of breast cancer screening in average-risk women.
DATA SOURCES: MEDLINE and Cochrane databases to 4 June 2015.
STUDY SELECTION: English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes.
DATA EXTRACTION: Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus.
DATA SYNTHESIS: Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10,000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10,000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10,000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome.
LIMITATIONS: Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited.
CONCLUSION: Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID 26756588  Ann Intern Med. 2016 Feb 16;164(4):244-55. doi: 10.7326・・・
著者: A B Miller, T To, C J Baines, C Wall
雑誌名: J Natl Cancer Inst. 2000 Sep 20;92(18):1490-9.
Abstract/Text BACKGROUND: Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer. However, the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known. This study was designed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only. Breast self-examination was taught to all participants.
METHODS: This trial randomly and individually assigned 39 405 women aged 50-59 years, recruited from January 1980 through March 1985, to one of the study arms. The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Database to December 31, 1993, and by active follow-up of breast cancer patients to June 30, 1996.
RESULTS: Randomization achieved virtually equal distribution of demographic and breast cancer risk variables. At the first annual screen, 21% of the cancers found by mammography alone (in the mammography plus physical examination group) were 20 mm or more in size compared with 46% of those found by physical examination in the mammography plus physical examination group and 56% in the physical examination-only group. The corresponding percentages for screens 2-5 were 10%, 42%, and 50%, respectively. Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group. By December 31, 1993, 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group, and 610 and 16 were ascertained in the physical examination-only group. At 13-year follow-up, with 107 and 105 deaths from breast cancer in the respective groups, the cumulative rate ratio was 1.02 (95% confidence interval = 0.78-1.33).
CONCLUSION: In women aged 50-59 years, the addition of annual mammography screening to physical examination has no impact on breast cancer mortality.

PMID 10995804  J Natl Cancer Inst. 2000 Sep 20;92(18):1490-9.
著者: Noriaki Ohuchi, Akihiko Suzuki, Tomotaka Sobue, Masaaki Kawai, Seiichiro Yamamoto, Ying-Fang Zheng, Yoko Narikawa Shiono, Hiroshi Saito, Shinichi Kuriyama, Eriko Tohno, Tokiko Endo, Akira Fukao, Ichiro Tsuji, Takuhiro Yamaguchi, Yasuo Ohashi, Mamoru Fukuda, Takanori Ishida, J-START investigator groups
雑誌名: Lancet. 2016 Jan 23;387(10016):341-8. doi: 10.1016/S0140-6736(15)00774-6. Epub 2015 Nov 5.
Abstract/Text BACKGROUND: Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography.
METHODS: Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757.
FINDINGS: Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034).
INTERPRETATION: Adjunctive ultrasonography increases sensitivity and detection rate of early cancers.
FUNDING: Ministry of Health, Labour and Welfare of Japan.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26547101  Lancet. 2016 Jan 23;387(10016):341-8. doi: 10.1016/S014・・・
著者: Janie M Lee, Robert F Arao, Brian L Sprague, Karla Kerlikowske, Constance D Lehman, Robert A Smith, Louise M Henderson, Garth H Rauscher, Diana L Miglioretti
雑誌名: JAMA Intern Med. 2019 May 1;179(5):658-667. doi: 10.1001/jamainternmed.2018.8372.
Abstract/Text Importance: Whole-breast ultrasonography has been advocated to supplement screening mammography to improve outcomes in women with dense breasts.
Objective: To determine the performance of screening mammography plus screening ultrasonography compared with screening mammography alone in community practice.
Design, Setting, and Participants: Observational cohort study. Two Breast Cancer Surveillance Consortium registries provided prospectively collected data on screening mammography with vs without same-day breast ultrasonography from January 1, 2000, to December 31, 2013. The dates of analysis were March 2014 to December 2018. A total of 6081 screening mammography plus same-day screening ultrasonography examinations in 3386 women were propensity score matched 1:5 to 30 062 screening mammograms without screening ultrasonography in 15 176 women from a sample of 113 293 mammograms. Exclusion criteria included a personal history of breast cancer and self-reported breast symptoms.
Exposures: Screening mammography with vs without screening ultrasonography.
Main Outcomes and Measures: Cancer detection rate and rates of interval cancer, false-positive biopsy recommendation, short-interval follow-up, and positive predictive value of biopsy recommendation were estimated and compared using log binomial regression.
Results: Screening mammography with vs without ultrasonography examinations was performed more often in women with dense breasts (74.3% [n = 4317 of 5810] vs 35.9% [n = 39 928 of 111 306] in the overall sample), in women who were younger than 50 years (49.7% [n = 3022 of 6081] vs 31.7% [n = 16 897 of 112 462]), and in women with a family history of breast cancer (42.9% [n = 2595 of 6055] vs 15.0% [n = 16 897 of 112 462]). While 21.4% (n = 1154 of 5392) of screening ultrasonography examinations were performed in women with high or very high (≥2.50%) Breast Cancer Surveillance Consortium 5-year risk scores, 53.6% (n = 2889 of 5392) had low or average (<1.67%) risk. Comparing mammography plus ultrasonography with mammography alone, the cancer detection rate was similar at 5.4 vs 5.5 per 1000 screens (adjusted relative risk [RR], 1.14; 95% CI, 0.76-1.68), as were interval cancer rates at 1.5 vs 1.9 per 1000 screens (RR, 0.67; 95% CI, 0.33-1.37). The false-positive biopsy rates were significantly higher at 52.0 vs 22.2 per 1000 screens (RR, 2.23; 95% CI, 1.93-2.58), as was short-interval follow-up at 3.9% vs 1.1% (RR, 3.10; 95% CI, 2.60-3.70). The positive predictive value of biopsy recommendation was significantly lower at 9.5% vs 21.4% (RR, 0.50; 95% CI, 0.35-0.71).
Conclusions and Relevance: In a relatively young population of women at low, intermediate, and high breast cancer risk, these results suggest that the benefits of supplemental ultrasonography screening may not outweigh associated harms.

PMID 30882843  JAMA Intern Med. 2019 May 1;179(5):658-667. doi: 10.100・・・
著者: David B Thomas, Dao Li Gao, Roberta M Ray, Wen Wan Wang, Charlene J Allison, Fan Liang Chen, Peggy Porter, Yong Wei Hu, Guan Lin Zhao, Lei Da Pan, Wenjin Li, Chunyuan Wu, Zakia Coriaty, Ilonka Evans, Ming Gang Lin, Helge Stalsberg, Steven G Self
雑誌名: J Natl Cancer Inst. 2002 Oct 2;94(19):1445-57.
Abstract/Text BACKGROUND: Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer.
METHODS: From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided.
RESULTS: There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group.
CONCLUSIONS: Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.

PMID 12359854  J Natl Cancer Inst. 2002 Oct 2;94(19):1445-57.
著者: J P Kösters, P C Gøtzsche
雑誌名: Cochrane Database Syst Rev. 2003;(2):CD003373. doi: 10.1002/14651858.CD003373.
Abstract/Text BACKGROUND: Breast self-examination and clinical breast examination have been promoted for many years as general screening methods to diagnose breast cancer at an earlier stage in order to decrease morbidity and or mortality. The possible benefits and harms remain unclear.
OBJECTIVES: To determine whether screening for breast cancer by regular self-examination or clinical breast examination reduces breast cancer mortality and morbidity.
SEARCH STRATEGY: The Cochrane Library and Medline were searched for randomised trials; date of last search October 2002. The specialised register maintained by the Cochrane Breast Cancer Group was searched.
SELECTION CRITERIA: Randomised clinical trials, including cluster randomised trials.
DATA COLLECTION AND ANALYSIS: Decisions on which trials to include were taken independently by the reviewers based on the methods of trial. Disagreements were resolved by discussion. Intention to treat analyses were conducted using a fixed effect model with 95% confidence intervals.
MAIN RESULTS: Two large population-based studies (388,535 women) from Russia and Shanghai that compared breast self-examination with no intervention were included. There was no statistically significant difference in breast cancer mortality, relative risk 1.05 (95% confidence interval (CI) 0.90 to 1.24) (587 deaths in total). In Russia, more cancers were found in the breast self-examination group than in the control group (relative risk 1.24, 95% CI 1.09 to 1.41), while this was not the case in Shanghai (relative risk 0.97, 95% CI 0.88 to 1.06). Almost twice as many biopsies (3406) with benign results were performed in the screening group compared to the control group (1856), relative risk 1.89, 95% CI 1.79 to 2.00.
REVIEWER'S CONCLUSIONS: Data from two large trials do not suggest a beneficial effect of screening by breast self-examination whereas there is evidence for harms. There were no randomised trials of clinical breast examination. At present, breast self-examination cannot be recommended.

PMID 12804462  Cochrane Database Syst Rev. 2003;(2):CD003373. doi: 10.・・・
著者: A Fukao, Y Tsubono, I Tsuji, S HIsamichi, N Sugahara, A Takano
雑誌名: Int J Cancer. 1995 Jan 3;60(1):45-8.
Abstract/Text Although a screening program for gastric cancer, using barium X-ray examination, has been carried out widely in Japan for the past 3 decades, there is insufficient evidence to confirm its effectiveness in terms of reducing mortality. To evaluate the effectiveness of the screening, a population-based case-control study was carried out in Miyagi Prefecture, Japan. Case subjects, who had died from gastric cancer (198) and control subjects matched in age, sex and residence (577) were selected from among members of the National Health Insurance. Their screening histories during 5 years before the cases were diagnosed were surveyed on the basis of records of the regional cancer registry and the cancer-detection center. The odds ratio (OR) of death from gastric cancer for the persons who participated in the screening at least once during 5 years was 0.41. For those who participated only once during 5 years the OR was 0.43, and for those whose last participation was 5 years earlier it was 0.30. Our data suggest that screening for gastric cancer at 5-year intervals might reduce mortality by 60%, and that the effect might remain for at least 5 years.

PMID 7814150  Int J Cancer. 1995 Jan 3;60(1):45-8.
著者: Tetsuya Mizoue, Takesumi Yoshimura, Noritaka Tokui, Yoshiharu Hoshiyama, Hiroshi Yatsuya, Kiyomi Sakata, Takaaki Kondo, Shogo Kikuchi, Hideaki Toyoshima, Norihiko Hayakawa, Akiko Tamakoshi, Yoshiyuki Ohno, Yoshihisa Fujino, Satoshi Kaneko, Japan Collaborative Cohort Study Group
雑誌名: Int J Cancer. 2003 Aug 10;106(1):103-7. doi: 10.1002/ijc.11183.
Abstract/Text Although screening for stomach cancer is a widespread community service in Japan, the benefits of the screening program remain unclear. Our study investigated prospectively the relation between participation in stomach-cancer screening during the past 12 months and subsequent deaths. Data was derived from the Japan Collaborative Cohort Study, in which 480 stomach-cancer deaths were identified during an 8-year follow-up period. Cox proportional hazard regression was used to estimate the relative risk of death from stomach cancer and that from other causes while adjusting for potential confounding factors. In men, screening participation was associated significantly with a reduced risk of death from stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41-0.70). The extent of the risk reduction was greater than potential health selection (for deaths other than stomach, RR = 0.71). The adjustment for potential confounding variables, however, attenuated the difference in risk of death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the magnitude of the association between screening participation and death from stomach cancer (RR = 0.74; 95% CI = 0.52-1.07) was equal to that for deaths from non-stomach cancers (RR = 0.74). Subgroup analysis showed that women with a parental history of stomach cancer had a reduced risk of death from stomach cancer associated with screening (RR = 0.32; 95% CI = 0.12-0.87). The present results underline the potential for selection bias in observational studies, and thus it remains an open question whether screening for stomach cancer is effective.

Copyright 2003 Wiley-Liss, Inc.
PMID 12794764  Int J Cancer. 2003 Aug 10;106(1):103-7. doi: 10.1002/ij・・・
著者: A Oshima, N Hirata, T Ubukata, K Umeda, I Fujimoto
雑誌名: Int J Cancer. 1986 Dec 15;38(6):829-33.
Abstract/Text In order to evaluate the effectiveness of a mass screening program for stomach cancer, a case-control study was conducted in Nose town in Osaka, Japan. The case series consisted of all deaths from stomach cancer during the period 1969-1981 (54 in males and 37 in females). For each case, 3 controls of the same sex and from the same precinct as the case, and born within 5 years of the case birth-year, were selected at random from Nose town residents alive at the date of death of the relevant case. We then investigated whether each case and corresponding controls had ever had screening tests before the date of diagnosis of the case. From the matched analysis of the distribution of screening in case-control combination, the odds ratio of screened vs. unscreened among those who died from stomach cancer compared to those who did not was calculated as 0.595 (90% confidence interval: 0.338-1.045) among males and 0.382 (0.185-0.785) among females. When the screening tests conducted within 12 months of diagnosis were ignored on the presumption that they were symptom-related, the odds ratio was calculated as 0.519 (0.297-0.905) among males and 0.486 (0.239-0.986) among females. These data strongly suggest that the mass screening program is effective in reducing stomach cancer mortality.

PMID 3793262  Int J Cancer. 1986 Dec 15;38(6):829-33.
著者: S Inaba, H Hirayama, C Nagata, Y Kurisu, N Takatsuka, N Kawakami, H Shimizu
雑誌名: Prev Med. 1999 Aug;29(2):102-6. doi: 10.1006/pmed.1999.0507.
Abstract/Text BACKGROUND: Systematic population-based screening for gastric cancer is widely spread in Japan. However, the case-control study method has been the main method used to evaluate the effectiveness of the screen ing to reduce gastric cancer mortality in Japan.
METHODS: This article presents a population-based cohort study. A questionnaire about lifestyles and dietary habits was distributed to 36,990 residents in a city of Japan. The response rate to the questionnaire was 92.0%. After ineligible responders had been excluded, 24,134 subjects were classified into screened and un screened groups according to their self-reports of participation in the screening the previous year. We followed them up for 40 months and linked resident death records in the city. We compared mortality from gastric cancer and all other causes between the groups by us ing the Cox proportional hazard model.
RESULTS: The follow-up period was 78,156.6 person-years from September 1992 to December 1995. The multivariate relative risks for gastric cancer death of the screened group in comparison with the unscreened group were 0.72 (95% CI 0.31-1.66) among males and 1.46 (95% CI 0.43-4.90) among females.
CONCLUSION: Although our data are preliminary, we were unable to demonstrate a large contribution of the present screening program to decreasing gastric cancer mortality. Further follow-up is needed to in crease the precision.

Copyright 1999 American Health Foundation and Academic Press.
PMID 10446035  Prev Med. 1999 Aug;29(2):102-6. doi: 10.1006/pmed.1999.・・・
著者: B Riecken, R Pfeiffer, J L Ma, M L Jin, J Y Li, W D Liu, L Zhang, Y S Chang, M H Gail, W C You
雑誌名: Prev Med. 2002 Jan;34(1):22-8. doi: 10.1006/pmed.2001.0925.
Abstract/Text BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China.
METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey.
RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females.
CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.

Copyright 2002 American Health Foundation and Elsevier Science.
PMID 11749093  Prev Med. 2002 Jan;34(1):22-8. doi: 10.1006/pmed.2001.0・・・
著者: Xing Zhang, Meng Li, Shuntai Chen, Jiaqi Hu, Qiujun Guo, Rui Liu, Honggang Zheng, Zhichao Jin, Yuan Yuan, Yupeng Xi, Baojin Hua
雑誌名: Gastroenterology. 2018 Aug;155(2):347-354.e9. doi: 10.1053/j.gastro.2018.04.026. Epub 2018 Apr 30.
Abstract/Text BACKGROUND & AIMS: It is not clear how endoscopic screening for gastric cancer affects incidence or mortality. We performed a systematic review and meta-analysis to evaluate the relationship between endoscopic screening for gastric cancer and mortality and incidence.
METHODS: We conducted a systematic search of PubMed and EMBASE for published cohort and case-control studies of adults without gastric cancer who underwent endoscopic screening at least once that included a comparator and reported outcomes of mortality or incidence through March 8, 2018. Two investigators independently reviewed the included studies and extracted relevant data. The effect estimate of interest was the relative risk (RR). We used a random effects model to combine RRs and 95% confidence intervals (Cis).
RESULTS: Our final analysis included 6 cohort studies and 4 nested case-control studies comprising 342,013 individuals, all from Asia. The combined result (RR, 0.60; 95% CI, 0.49-0.73) indicated that endoscopic screening was associated with a 40% RR reduction in gastric cancer mortality. We did not observe an association between endoscopic screening and incidence (RR, 1.14; 95% CI, 0.93-1.40). Subgroup analysis showed significant reductions in gastric cancer mortality after endoscopic screening compared with no screening (RR, 0.58; 95% CI, 0.48-0.70) or radiographic screening (RR, 0.33; 95% CI, 0.12-0.91). However, endoscopic screening did not significantly reduce mortality compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16).
CONCLUSIONS: In a systematic review and meta-analysis, we found that endoscopic screening may reduce the risk of death from gastric cancer and not affect incidence in Asian countries. Population-based prospective cohort studies are warranted to confirm our findings.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 29723507  Gastroenterology. 2018 Aug;155(2):347-354.e9. doi: 10.1・・・
著者: T Sobue, T Suzuki, S Hashimoto, N Yokoi, I Fujimoto
雑誌名: Jpn J Cancer Res. 1988 Dec;79(12):1269-75.
Abstract/Text In the small town of Nose in Osaka, Japan, a population-based screening program for cervical cancer by Papanicolaou smear has been conducted since 1965. In order to evaluate the effectiveness of screening in terms of the reduction of the mortality and the incidence of invasive cervical cancer, two types of case-control studies were carried out. In the first study, the case series consisted of all women who died of cervical cancer under 80 years of age at the time of diagnosis in 1965-1987 (N = 15). For each case, 10 controls were chosen from living residents, matched by year of birth. It showed that the odds ratio (OR) of dying of cervical cancer for screened versus non-screened women was 0.22 (95% CI = 0.03-1.95). In the second study, the case series consisted of all women who were diagnosed as having invasive cancer under 80 years of age at the time of diagnosis in the same period (N = 28). For each case, 10 controls were chosen from living residents without invasive cancer, matched by year of birth and according to whether or not they were screened at the year of the diagnosis of the matched case. It showed that the OR of getting invasive cancer for screened versus non-screened women was 0.41 (95%CI = 0.13-1.29). From these results, it was estimated that 78% of cervical cancer mortality and 59% of invasive cervical cancer incidence among non-screened women could be prevented by cervical cancer screening.

PMID 3148596  Jpn J Cancer Res. 1988 Dec;79(12):1269-75.
著者: Khandoker Aklimunnessa, Mitsuru Mori, M M H Khan, Fumio Sakauchi, Tatsuhiko Kubo, Yoshihisa Fujino, Sadao Suzuki, Shinkan Tokudome, Akiko Tamakoshi, JACC Study Group, Yutaka Motohashi, Ichiro Tsuji, Yosikazu Nakamura, Hiroyasu Iso, Haruo Mikami, Yutaka Inaba, Yoshiharu Hoshiyama, Hiroshi Suzuki, Hiroyuki Shimizu, Hideaki Toyoshima, Kenji Wakai, Yoshinori Ito, Shuji Hashimoto, Shogo Kikuchi, Akio Koizumi, Takashi Kawamura, Yoshiyuki Watanabe, Tsuneharu Miki, Chigusa Date, Kiyomi Sakata, Takayuki Nose, Norihiko Hayakawa, Takesumi Yoshimura, Akira Shibata, Naoyuki Okamoto, Hideo Shino, Yoshiyuki Ohno, Tomoyuki Kitagawa, Toshio Kuroki, Kazuo Tajima
雑誌名: Jpn J Clin Oncol. 2006 Aug;36(8):511-8. doi: 10.1093/jjco/hyl060. Epub 2006 Jul 14.
Abstract/Text BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study.
METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment.
RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias.
CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

PMID 16844732  Jpn J Clin Oncol. 2006 Aug;36(8):511-8. doi: 10.1093/jj・・・
著者: Leslea Peirson, Donna Fitzpatrick-Lewis, Donna Ciliska, Rachel Warren
雑誌名: Syst Rev. 2013 May 24;2:35. doi: 10.1186/2046-4053-2-35. Epub 2013 May 24.
Abstract/Text BACKGROUND: The systematic review on which this paper is based provided evidence for the Canadian Task Force on Preventive Health Care to update their guideline regarding screening for cervical cancer. In this article we highlight three questions covered in the full review that pertain to the effectiveness of screening for reducing cervical cancer mortality and incidence as well as optimal timing and frequency of screening.
METHODS: We searched MEDLINE, Embase and Cochrane Central from 1995 to 2012 for relevant randomized controlled trials and observational studies with comparison groups. Eligible studies included women aged 15 to 70 years who were screened using conventional cytology, liquid-based cytology or human papillomavirus DNA tests. Relevance screening, data extraction, risk of bias analyses and quality assessments were performed in duplicate. We conducted a meta-analysis using a random-effects model on the one body of evidence that could be pooled.
RESULTS: From the 15,145 screened citations, 27 papers (24 studies) were included; five older studies located in a United States Preventive Services Task Force review were also included. A randomized controlled trial in India showed even a single lifetime screening test significantly decreased the risk of mortality from and incidence of advanced cervical cancer compared to no screening (mortality: risk ratio 0.65, 95% confidence interval 0.47, 0.90; incidence: relative risk 0.56, 95% confidence interval 0.42, 0.75). Cytology screening was shown to be beneficial in a cohort study that found testing significantly reduced the risk of being diagnosed with invasive cervical cancer compared to no screening (risk ratio 0.38; 95% confidence interval 0.23, 0.63). Pooled evidence from a dozen case-control studies also indicated a significant protective effect of cytology screening (odds ratio 0.35; 95% confidence interval 0.30, 0.41). This review found no conclusive evidence for establishing optimal ages to start and stop cervical screening, or to determine how often to screen; however the available data suggests substantial protective effects for screening women 30 years and older and for intervals of up to five years.
CONCLUSIONS: The available evidence supports the conclusion that cervical screening does offer protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality.

PMID 23706117  Syst Rev. 2013 May 24;2:35. doi: 10.1186/2046-4053-2-35・・・
著者: Rengaswamy Sankaranarayanan, Bhagwan M Nene, Surendra S Shastri, Kasturi Jayant, Richard Muwonge, Atul M Budukh, Sanjay Hingmire, Sylla G Malvi, Ranjit Thorat, Ashok Kothari, Roshan Chinoy, Rohini Kelkar, Shubhada Kane, Sangeetha Desai, Vijay R Keskar, Raghevendra Rajeshwarkar, Nandkumar Panse, Ketayun A Dinshaw
雑誌名: N Engl J Med. 2009 Apr 2;360(14):1385-94. doi: 10.1056/NEJMoa0808516.
Abstract/Text BACKGROUND: In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India.
METHODS: In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.
RESULTS: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women.
CONCLUSIONS: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

2009 Massachusetts Medical Society
PMID 19339719  N Engl J Med. 2009 Apr 2;360(14):1385-94. doi: 10.1056/・・・
著者: Motoyasu Sagawa, Tomio Nakayama, Hiroko Tsukada, Kenji Nishii, Takashi Baba, Yuzo Kurita, Yasuki Saito, Masahiro Kaneko, Tsutomu Sakuma, Takaichiro Suzuki, Shigefumi Fujimura
雑誌名: Lung Cancer. 2003 Jul;41(1):29-36.
Abstract/Text The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

PMID 12826309  Lung Cancer. 2003 Jul;41(1):29-36.
著者: P M Marcus, E J Bergstralh, R M Fagerstrom, D E Williams, R Fontana, W F Taylor, P C Prorok
雑誌名: J Natl Cancer Inst. 2000 Aug 16;92(16):1308-16.
Abstract/Text BACKGROUND: The Mayo Lung Project (MLP) was a randomized, controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983. The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years; the usual-care arm was advised at trial entry to receive the same tests annually. No lung cancer mortality benefit was evident at the end of the study. We have extended follow-up through 1996.
METHODS: A National Death Index-PLUS search was used to assign vital status and date and cause of death for 6523 participants with unknown information. The median survival for lung cancer patients diagnosed before July 1, 1983, was calculated by use of Kaplan-Meier estimates. Survival curves were compared with the log-rank test.
RESULTS: The median follow-up time was 20.5 years. Lung cancer mortality was 4.4 (95% confidence interval [CI] = 3.9-4.9) deaths per 1000 person-years in the intervention arm and 3.9 (95% CI = 3.5-4.4) in the usual-care arm (two-sided P: for difference =.09). For participants diagnosed with lung cancer before July 1, 1983, survival was better in the intervention arm (two-sided P: =.0039). The median survival for patients with resected early-stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm.
CONCLUSIONS: Extended follow-up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm. Similar mortality but better survival for individuals in the intervention arm indicates that some lesions with limited clinical relevance may have been identified in the intervention arm.

PMID 10944552  J Natl Cancer Inst. 2000 Aug 16;92(16):1308-16.
著者: R L Manser, L B Irving, C Stone, G Byrnes, M Abramson, D Campbell
雑誌名: Cochrane Database Syst Rev. 2004;(1):CD001991. doi: 10.1002/14651858.CD001991.pub2.
Abstract/Text BACKGROUND: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer.
OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality.
SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials.
SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest.
DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used.
MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT.
REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

PMID 14973979  Cochrane Database Syst Rev. 2004;(1):CD001991. doi: 10.・・・
著者: Martin M Oken, Willam G Hocking, Paul A Kvale, Gerald L Andriole, Saundra S Buys, Timothy R Church, E David Crawford, Mona N Fouad, Claudine Isaacs, Douglas J Reding, Joel L Weissfeld, Lance A Yokochi, Barbara O'Brien, Lawrence R Ragard, Joshua M Rathmell, Thomas L Riley, Patrick Wright, Neil Caparaso, Ping Hu, Grant Izmirlian, Paul F Pinsky, Philip C Prorok, Barnett S Kramer, Anthony B Miller, John K Gohagan, Christine D Berg, PLCO Project Team
雑誌名: JAMA. 2011 Nov 2;306(17):1865-73. doi: 10.1001/jama.2011.1591. Epub 2011 Oct 26.
Abstract/Text CONTEXT: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown.
OBJECTIVE: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed.
INTERVENTION: Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009.
MAIN OUTCOME MEASURES: Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality.
RESULTS: Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10,000 person-years in the intervention group and 19.2 per 10,000 person-years in the usual care group (rate ratio [RR]; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10).
CONCLUSION: Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00002540.

PMID 22031728  JAMA. 2011 Nov 2;306(17):1865-73. doi: 10.1001/jama.201・・・
著者: Maurizio Infante, Silvio Cavuto, Fabio Romano Lutman, Giorgio Brambilla, Giuseppe Chiesa, Giovanni Ceresoli, Eliseo Passera, Enzo Angeli, Maurizio Chiarenza, Giuseppe Aranzulla, Umberto Cariboni, Valentina Errico, Francesco Inzirillo, Edoardo Bottoni, Emanuele Voulaz, Marco Alloisio, Anna Destro, Massimo Roncalli, Armando Santoro, Gianluigi Ravasi, DANTE Study Group
雑誌名: Am J Respir Crit Care Med. 2009 Sep 1;180(5):445-53. doi: 10.1164/rccm.200901-0076OC. Epub 2009 Jun 11.
Abstract/Text RATIONALE: Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies.
OBJECTIVES: To explore the effect of screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability.
METHODS: Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only.
MEASUREMENTS AND MAIN RESULTS: A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively.
CONCLUSIONS: The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.

PMID 19520905  Am J Respir Crit Care Med. 2009 Sep 1;180(5):445-53. do・・・
著者: Zaigham Saghir, Asger Dirksen, Haseem Ashraf, Karen Skjøldstrup Bach, John Brodersen, Paul Frost Clementsen, Martin Døssing, Hanne Hansen, Klaus Fuglsang Kofoed, Klaus Richter Larsen, Jann Mortensen, Jakob Fraes Rasmussen, Niels Seersholm, Birgit Guldhammer Skov, Hanne Thorsen, Philip Tønnesen, Jesper Holst Pedersen
雑誌名: Thorax. 2012 Apr;67(4):296-301. doi: 10.1136/thoraxjnl-2011-200736. Epub 2012 Jan 27.
Abstract/Text BACKGROUND: The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial.
METHODS: 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice.
RESULTS: Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs. 24, p<0.001), and more were low stage (48 vs 21 stage I-IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA-IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428).
CONCLUSION: CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

PMID 22286927  Thorax. 2012 Apr;67(4):296-301. doi: 10.1136/thoraxjnl-・・・
著者: National Lung Screening Trial Research Team, Denise R Aberle, Amanda M Adams, Christine D Berg, William C Black, Jonathan D Clapp, Richard M Fagerstrom, Ilana F Gareen, Constantine Gatsonis, Pamela M Marcus, JoRean D Sicks
雑誌名: N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.
Abstract/Text BACKGROUND: The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.
METHODS: From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.
RESULTS: The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02).
CONCLUSIONS: Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

PMID 21714641  N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/N・・・
著者: Harry J de Koning, Carlijn M van der Aalst, Pim A de Jong, Ernst T Scholten, Kristiaan Nackaerts, Marjolein A Heuvelmans, Jan-Willem J Lammers, Carla Weenink, Uraujh Yousaf-Khan, Nanda Horeweg, Susan van 't Westeinde, Mathias Prokop, Willem P Mali, Firdaus A A Mohamed Hoesein, Peter M A van Ooijen, Joachim G J V Aerts, Michael A den Bakker, Erik Thunnissen, Johny Verschakelen, Rozemarijn Vliegenthart, Joan E Walter, Kevin Ten Haaf, Harry J M Groen, Matthijs Oudkerk
雑誌名: N Engl J Med. 2020 Feb 6;382(6):503-513. doi: 10.1056/NEJMoa1911793. Epub 2020 Jan 29.
Abstract/Text BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers.
METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants.
RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9.
CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).

Copyright © 2020 Massachusetts Medical Society.
PMID 31995683  N Engl J Med. 2020 Feb 6;382(6):503-513. doi: 10.1056/N・・・
著者: Gerald L Andriole, E David Crawford, Robert L Grubb, Saundra S Buys, David Chia, Timothy R Church, Mona N Fouad, Edward P Gelmann, Paul A Kvale, Douglas J Reding, Joel L Weissfeld, Lance A Yokochi, Barbara O'Brien, Jonathan D Clapp, Joshua M Rathmell, Thomas L Riley, Richard B Hayes, Barnett S Kramer, Grant Izmirlian, Anthony B Miller, Paul F Pinsky, Philip C Prorok, John K Gohagan, Christine D Berg, PLCO Project Team
雑誌名: N Engl J Med. 2009 Mar 26;360(13):1310-9. doi: 10.1056/NEJMoa0810696. Epub 2009 Mar 18.
Abstract/Text BACKGROUND: The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality.
METHODS: From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained.
RESULTS: In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings.
CONCLUSIONS: After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.)

2009 Massachusetts Medical Society
PMID 19297565  N Engl J Med. 2009 Mar 26;360(13):1310-9. doi: 10.1056/・・・
著者: Fritz H Schröder, Jonas Hugosson, Monique J Roobol, Teuvo L J Tammela, Stefano Ciatto, Vera Nelen, Maciej Kwiatkowski, Marcos Lujan, Hans Lilja, Marco Zappa, Louis J Denis, Franz Recker, Antonio Berenguer, Liisa Määttänen, Chris H Bangma, Gunnar Aus, Arnauld Villers, Xavier Rebillard, Theodorus van der Kwast, Bert G Blijenberg, Sue M Moss, Harry J de Koning, Anssi Auvinen, ERSPC Investigators
雑誌名: N Engl J Med. 2009 Mar 26;360(13):1320-8. doi: 10.1056/NEJMoa0810084. Epub 2009 Mar 18.
Abstract/Text BACKGROUND: The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer.
METHODS: We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006.
RESULTS: In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90).
CONCLUSIONS: PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

2009 Massachusetts Medical Society
PMID 19297566  N Engl J Med. 2009 Mar 26;360(13):1320-8. doi: 10.1056/・・・
著者: Jonas Hugosson, Sigrid Carlsson, Gunnar Aus, Svante Bergdahl, Ali Khatami, Pär Lodding, Carl-Gustaf Pihl, Johan Stranne, Erik Holmberg, Hans Lilja
雑誌名: Lancet Oncol. 2010 Aug;11(8):725-32. doi: 10.1016/S1470-2045(10)70146-7. Epub 2010 Jul 2.
Abstract/Text BACKGROUND: Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.
METHODS: In December, 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243.
FINDINGS: In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI 1.50-1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17-0.64), from 0.90% in the control group to 0.50% in the screening group. The rate ratio for death from prostate cancer was 0.56 (95% CI 0.39-0.82; p=0.002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death.
INTERPRETATION: This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs.
FUNDING: The Swedish Cancer Society, the Swedish Research Council, and the National Cancer Institute.

2010 Elsevier Ltd. All rights reserved.
PMID 20598634  Lancet Oncol. 2010 Aug;11(8):725-32. doi: 10.1016/S1470・・・
著者: Joshua J Fenton, Meghan S Weyrich, Shauna Durbin, Yu Liu, Heejung Bang, Joy Melnikow
雑誌名: JAMA. 2018 May 8;319(18):1914-1931. doi: 10.1001/jama.2018.3712.
Abstract/Text Importance: Prostate cancer is the second leading cause of cancer death among US men.
Objective: To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force.
Data Sources: Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018.
Study Selection: English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers.
Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.
Main Outcomes and Measures: Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms.
Results: Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]).
Conclusions and Relevance: PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.

PMID 29801018  JAMA. 2018 May 8;319(18):1914-1931. doi: 10.1001/jama.2・・・
著者: K E Richert-Boe, L L Humphrey, A G Glass, N S Weiss
雑誌名: J Med Screen. 1998;5(2):99-103.
Abstract/Text BACKGROUND: Prostate cancer is the second most common cause of death from cancer in men in the United States. Digital rectal examination is the oldest and most commonly used screening test for prostate cancer, but as yet there are no studies which demonstrate its effectiveness.
METHODS: A case-control study was conducted among members of a large health maintenance organisation to estimate the effect of screening digital rectal examination on mortality from prostate cancer. 150 men, aged 40-84 when cancer was diagnosed, who developed fatal prostate cancer, and 299 male controls matched for age who did not die from prostate cancer were studied. A history of screening digital rectal examination during the 10 years before the date on which cancer was-diagnosed was determined from medical records.
RESULTS: A similar proportion of men who died from prostate cancer and controls had undergone at least one screening digital rectal examination during the 10 year interval (odds ratio = 0.84, 95% confidence interval 0.48 to 1.46). Similar results were obtained when a shorter interval (such as five years before diagnosis) during which screening histories were evaluated was considered, or in analyses in which men with a history of benign prostatic hypertrophy were excluded.
CONCLUSIONS: The data suggest that screening digital rectal examination does not reduce mortality from prostate cancer to any appreciable degree.

PMID 9718529  J Med Screen. 1998;5(2):99-103.
著者: S J Jacobsen, E J Bergstralh, S K Katusic, H A Guess, C H Darby, M D Silverstein, J E Oesterling, M M Lieber
雑誌名: Urology. 1998 Aug;52(2):173-9.
Abstract/Text OBJECTIVES: Although digital rectal examination (DRE) for the detection of prostate cancer has been recommended by many professional groups and has become part of the general physical examination, no randomized clinical trial has demonstrated the efficacy or effectiveness of this practice. We conducted a population-based case-control study to evaluate the association between DRE and prostate cancer mortality.
METHODS: With the resources of the Rochester Epidemiology Project, all 173 men who died of prostate cancer in Olmsted County from 1976 to 1991, who were resident at the time of diagnosis, were identified. For each case, two control patients were drawn from the population, matched for residence at the time of diagnosis in the case, birth date, and duration of medical record in Olmsted County. Trained nurse abstractors reviewed the community medical records for up to 10 years before the date of diagnosis in the case for mention of DRE and specific findings associated with each mention.
RESULTS: Case subjects were less likely than control subjects to have had any DRE in the 10 years before diagnosis (matched odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.31, 0.84). When limited to DREs without mention of signs or symptoms that might raise suspicion of prostate cancer, the association was even stronger (OR = 0.31; 95% CI = 0.19, 0.49). Adjustment for educational attainment, marital status, and comorbid conditions did little to alter the associations.
CONCLUSIONS: These results demonstrate a strong inverse association between DRE and prostate cancer mortality. If further research concludes this association to be causal, screening DREs may have prevented as many as 50% to 70% of deaths due to prostate cancer that might have occurred in the absence of screening.

PMID 9697778  Urology. 1998 Aug;52(2):173-9.
著者: Saundra S Buys, Edward Partridge, Amanda Black, Christine C Johnson, Lois Lamerato, Claudine Isaacs, Douglas J Reding, Robert T Greenlee, Lance A Yokochi, Bruce Kessel, E David Crawford, Timothy R Church, Gerald L Andriole, Joel L Weissfeld, Mona N Fouad, David Chia, Barbara O'Brien, Lawrence R Ragard, Jonathan D Clapp, Joshua M Rathmell, Thomas L Riley, Patricia Hartge, Paul F Pinsky, Claire S Zhu, Grant Izmirlian, Barnett S Kramer, Anthony B Miller, Jian-Lun Xu, Philip C Prorok, John K Gohagan, Christine D Berg, PLCO Project Team
雑誌名: JAMA. 2011 Jun 8;305(22):2295-303. doi: 10.1001/jama.2011.766.
Abstract/Text CONTEXT: Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality.
OBJECTIVE: To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010.
MAIN OUTCOME MEASURES: Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures.
RESULTS: Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06).
CONCLUSIONS: Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

PMID 21642681  JAMA. 2011 Jun 8;305(22):2295-303. doi: 10.1001/jama.20・・・
著者: Clare J Reade, John J Riva, Jason W Busse, Charlie H Goldsmith, Laurie Elit
雑誌名: Gynecol Oncol. 2013 Sep;130(3):674-81. doi: 10.1016/j.ygyno.2013.06.029. Epub 2013 Jun 30.
Abstract/Text OBJECTIVE: We performed a systematic review and meta-analysis to quantify risks and benefits of screening asymptomatic women for ovarian cancer.
METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL, without language restrictions, from January 1, 1979 to February 5, 2012. Eligible studies randomly assigned asymptomatic women to screening or usual care. Two reviewers independently screened studies for eligibility, extracted data using a standardized, piloted extraction form, and assessed bias and strength of inference for each outcome using the GRADE framework. Chance-corrected agreement was calculated at each step, and disagreements were resolved through consensus.
RESULTS: Ten randomized trials proved eligible. Screening did not reduce all-cause mortality (relative risk (RR)=1.0, 95% confidence interval (CI) 0.96-1.06), ovarian cancer specific mortality (RR=1.08, 95% CI 0.84-1.38), or risk of diagnosis at an advanced stage (RR of diagnosis at FIGO stages III-IV=0.86, 95% CI 0.68-1.11). Transvaginal ultrasound resulted in a mean of 38 surgeries per ovarian cancer detected (95% CI 15.7-178.1) while screening with CA-125 led to 4 surgeries per ovarian cancer detected (95% CI 2.7-4.5). Surgery was associated with severe complications in 6% of women (95% CI 1%-11%). Quality of life was not affected by screening; however, women with false-positive results had increased cancer-specific distress compared to those with normal results (odds ratio (OR)=2.22, 95% CI 1.23-3.99).
CONCLUSIONS: Screening asymptomatic women for ovarian cancer does not reduce mortality or diagnosis at an advanced stage and is associated with unnecessary surgery.

© 2013.
PMID 23822892  Gynecol Oncol. 2013 Sep;130(3):674-81. doi: 10.1016/j.y・・・
著者: Ian J Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K Kalsi, Nazar N Amso, Sophia Apostolidou, Elizabeth Benjamin, Derek Cruickshank, Danielle N Crump, Susan K Davies, Anne Dawnay, Stephen Dobbs, Gwendolen Fletcher, Jeremy Ford, Keith Godfrey, Richard Gunu, Mariam Habib, Rachel Hallett, Jonathan Herod, Howard Jenkins, Chloe Karpinskyj, Simon Leeson, Sara J Lewis, William R Liston, Alberto Lopes, Tim Mould, John Murdoch, David Oram, Dustin J Rabideau, Karina Reynolds, Ian Scott, Mourad W Seif, Aarti Sharma, Naveena Singh, Julie Taylor, Fiona Warburton, Martin Widschwendter, Karin Williamson, Robert Woolas, Lesley Fallowfield, Alistair J McGuire, Stuart Campbell, Mahesh Parmar, Steven J Skates
雑誌名: Lancet. 2016 Mar 5;387(10022):945-56. doi: 10.1016/S0140-6736(15)01224-6. Epub 2015 Dec 17.
Abstract/Text BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.
METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032.
FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS.
INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening.
FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Copyright © 2016 Jacobs Menon et al. Open Access article published under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
PMID 26707054  Lancet. 2016 Mar 5;387(10022):945-56. doi: 10.1016/S014・・・
著者: Usha Menon, Aleksandra Gentry-Maharaj, Matthew Burnell, Naveena Singh, Andy Ryan, Chloe Karpinskyj, Giulia Carlino, Julie Taylor, Susan K Massingham, Maria Raikou, Jatinderpal K Kalsi, Robert Woolas, Ranjit Manchanda, Rupali Arora, Laura Casey, Anne Dawnay, Stephen Dobbs, Simon Leeson, Tim Mould, Mourad W Seif, Aarti Sharma, Karin Williamson, Yiling Liu, Lesley Fallowfield, Alistair J McGuire, Stuart Campbell, Steven J Skates, Ian J Jacobs, Mahesh Parmar
雑誌名: Lancet. 2021 Jun 5;397(10290):2182-2193. doi: 10.1016/S0140-6736(21)00731-5. Epub 2021 May 12.
Abstract/Text BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS.
METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032.
FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.
INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.
FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 33991479  Lancet. 2021 Jun 5;397(10290):2182-2193. doi: 10.1016/S・・・
著者: Alexander C Ford, David Forman, Richard H Hunt, Yuhong Yuan, Paul Moayyedi
雑誌名: BMJ. 2014 May 20;348:g3174. Epub 2014 May 20.
Abstract/Text OBJECTIVES: To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals.
DESIGN: Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES: Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years.
MAIN OUTCOME MEASURES: Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.
RESULTS: The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.
CONCLUSIONS: These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.

© Ford et al 2014.
PMID 24846275  BMJ. 2014 May 20;348:g3174. Epub 2014 May 20.
著者: Wei-cheng You, Linda M Brown, Lian Zhang, Ji-you Li, Mao-lin Jin, Yun-shen Chang, Jun-ling Ma, Kai-feng Pan, Wei-dong Liu, Yuanreng Hu, Susan Crystal-Mansour, David Pee, William J Blot, Joseph F Fraumeni, Guang-wei Xu, Mitchell H Gail
雑誌名: J Natl Cancer Inst. 2006 Jul 19;98(14):974-83. doi: 10.1093/jnci/djj264.
Abstract/Text BACKGROUND: Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions.
METHODS: Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided.
RESULTS: H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements.
CONCLUSION: H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.

PMID 16849680  J Natl Cancer Inst. 2006 Jul 19;98(14):974-83. doi: 10.・・・
著者: Benjamin Chun-Yu Wong, Shiu Kum Lam, Wai Man Wong, Jian Shun Chen, Ting Ting Zheng, Rui E Feng, Kam Chuen Lai, Wayne Hsing Cheng Hu, Siu Tsan Yuen, Suet Yi Leung, Daniel Yee Tak Fong, Joanna Ho, Chi Kong Ching, Jun Shi Chen, China Gastric Cancer Study Group
雑誌名: JAMA. 2004 Jan 14;291(2):187-94. doi: 10.1001/jama.291.2.187.
Abstract/Text CONTEXT: Although chronic Helicobacter pylori infection is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown.
OBJECTIVE: To determine whether treatment of H pylori infection reduces the incidence of gastric cancer.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, placebo-controlled, population-based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province, China, recruited in July 1994 and followed up until January 2002. A total of 988 participants did not have precancerous lesions (gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry.
INTERVENTION: Patients were randomly assigned to receive H pylori eradication treatment: a 2-week course of omeprazole, 20 mg, a combination product of amoxicillin and clavulanate potassium, 750 mg, and metronidazole, 400 mg, all twice daily (n = 817); or placebo (n = 813).
MAIN OUTCOME MEASURES: The primary outcome measure was incidence of gastric cancer during follow-up, compared between H pylori eradication and placebo groups. The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions, compared between the 2 groups.
RESULTS: Among the 18 new cases of gastric cancers that developed, no overall reduction was observed in participants who received H pylori eradication treatment (n = 7) compared with those who did not (n = 11) (P =.33). In a subgroup of patients with no precancerous lesions on presentation, no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo (0 vs 6; P =.02). Smoking (hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.3-16.5; P<.001) and older age (HR, 1.10; 95% CI, 1.05-1.15; P<.001) were independent risk factors for the development of gastric cancer in this cohort.
CONCLUSIONS: We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China. In the subgroup of H pylori carriers without precancerous lesions, eradication of H pylori significantly decreased the development of gastric cancer. Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted.

PMID 14722144  JAMA. 2004 Jan 14;291(2):187-94. doi: 10.1001/jama.291.・・・
著者: Il Ju Choi, Chan Gyoo Kim, Jong Yeul Lee, Young-Il Kim, Myeong-Cherl Kook, Boram Park, Jungnam Joo
雑誌名: N Engl J Med. 2020 Jan 30;382(5):427-436. doi: 10.1056/NEJMoa1909666.
Abstract/Text BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.
METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period.
RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).
CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

Copyright © 2020 Massachusetts Medical Society.
PMID 31995688  N Engl J Med. 2020 Jan 30;382(5):427-436. doi: 10.1056/・・・
著者: Takeichi Yoshida, Jun Kato, Izumi Inoue, Noriko Yoshimura, Hisanobu Deguchi, Chizu Mukoubayashi, Masashi Oka, Mika Watanabe, Shotaro Enomoto, Toru Niwa, Takao Maekita, Mikitaka Iguchi, Hideyuki Tamai, Hirotoshi Utsunomiya, Nobutake Yamamichi, Mitsuhiro Fujishiro, Masataka Iwane, Tatsuya Takeshita, Toshikazu Ushijima, Masao Ichinose
雑誌名: Int J Cancer. 2014 Mar 15;134(6):1445-57. doi: 10.1002/ijc.28470. Epub 2013 Oct 3.
Abstract/Text Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

© 2013 UICC.
PMID 24009139  Int J Cancer. 2014 Mar 15;134(6):1445-57. doi: 10.1002/・・・
著者: Hiroshi Ohata, Shintaro Kitauchi, Noriko Yoshimura, Kouichi Mugitani, Masataka Iwane, Hideya Nakamura, Akiyoshi Yoshikawa, Kimihiko Yanaoka, Kenji Arii, Hideyuki Tamai, Yasuhito Shimizu, Tatsuya Takeshita, Osamu Mohara, Masao Ichinose
雑誌名: Int J Cancer. 2004 Mar;109(1):138-43. doi: 10.1002/ijc.11680.
Abstract/Text We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.

Copyright 2003 Wiley-Liss, Inc.
PMID 14735480  Int J Cancer. 2004 Mar;109(1):138-43. doi: 10.1002/ijc.・・・
著者: Teruhiko Terasawa, Hiroshi Nishida, Katsuaki Kato, Isao Miyashiro, Takaki Yoshikawa, Reo Takaku, Chisato Hamashima
雑誌名: PLoS One. 2014;9(10):e109783. doi: 10.1371/journal.pone.0109783. Epub 2014 Oct 14.
Abstract/Text BACKGROUND: To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H. Pylori antibodies, and a risk-prediction model based on these two tests. To investigate whether these tests accurately predict gastric cancer development, we conducted a systematic review and meta-analysis.
METHODS: PubMed and other electronic databases were searched for cohort studies published in English or Japanese from January 1985 through December 2013. Six reviewers identified eligible studies, and at least two investigators extracted data on population and study-design characteristics, quality items, and outcomes of interest. Meta-analyses were performed on non-overlapping studies.
RESULTS: Nine prospective cohorts from Eastern Asia reported in 12 publications, including 33,741 asymptomatic middle-aged participants of gastric cancer screening, were eligible. For discriminating between asymptomatic adults at high and low risk of gastric cancer, the pepsinogen test (summary hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.7-4.7; I2 = 0%) and H. pylori antibodies (summary HR, 3.2; 95% CI, 2.0-5.2; I2 = 0%) were statistically significant predictors as standalone tests. Although the risk-prediction model was in general moderately accurate in separating asymptomatic adults into four risk groups (summary c-statistic, 0.71; 95% CI: 0.68-0.73; I2 = 7%), calibration seemed to be poor. The study validity was generally limited.
CONCLUSIONS: The serum pepsinogen test, H. pylori antibodies, and the four-risk-group model for predicting gastric cancer development seem to have the potential to stratify middle-aged presumptively healthy adults. Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests. Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.

PMID 25314140  PLoS One. 2014;9(10):e109783. doi: 10.1371/journal.pone・・・

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