Treatment for gastric ‘indefinite for neoplasm/dysplasia' lesions based on predictive factors
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摘要
BACKGROUND Gastric ‘indefinite for neoplasm/dysplasia'(IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.AIM To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.METHODS In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection(n = 134), surgery(n = 22), and follow-up endoscopic biopsy(n = 305) were performed to confirm the diagnosis.The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia(60%) or atypical epithelia(40%)at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.RESULTS Four clinical factors [age ≥ 60 years(2.445, 95%CI: 1.305-4.580, P = 0.005),endoscopic size ≥ 10 mm(3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion(5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding(4.056, 95%CI:1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium(25.575,95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI:1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change(5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.CONCLUSION More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.
BACKGROUND Gastric ‘indefinite for neoplasm/dysplasia'(IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.AIM To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.METHODS In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection(n = 134), surgery(n = 22), and follow-up endoscopic biopsy(n = 305) were performed to confirm the diagnosis.The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia(60%) or atypical epithelia(40%)at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.RESULTS Four clinical factors [age ≥ 60 years(2.445, 95%CI: 1.305-4.580, P = 0.005),endoscopic size ≥ 10 mm(3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion(5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding(4.056, 95%CI:1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium(25.575,95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI:1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change(5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.CONCLUSION More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.
BACKGROUND Gastric ‘indefinite for neoplasm/dysplasia'(IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.AIM To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.METHODS In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection(n = 134), surgery(n = 22), and follow-up endoscopic biopsy(n = 305) were performed to confirm the diagnosis.The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia(60%) or atypical epithelia(40%)at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.RESULTS Four clinical factors [age ≥ 60 years(2.445, 95%CI: 1.305-4.580, P = 0.005),endoscopic size ≥ 10 mm(3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion(5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding(4.056, 95%CI:1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium(25.575,95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI:1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change(5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.CONCLUSION More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.
引文
1 Dixon MF.Gastrointestinal epithelial neoplasia:Vienna revisited.Gut 2002;51:130-131[PMID:12077106 DOI:10.1136/gut.51.1.130]
2 Kim H,Jin SY,Jang JJ,Kim WH,Song SY,Kim KR,Yu ES,Shin HS,Kim HK,Sohn JH,Hong EK.Grading system for gastric epithelial proliferative diseases standardized guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.Korean J Pathol 1997;31:389-400
3 Takao M,Kakushima N,Takizawa K,Tanaka M,Yamaguchi Y,Matsubayashi H,Kusafuka K,Ono H.Discrepancies in histologic diagnoses of early gastric cancer between biopsy and endoscopic mucosal resection specimens.Gastric Cancer 2012;15:91-96[PMID:21814828 DOI:10.1007/s10120-011-0075-8]
4 Schlemper RJ,Riddell RH,Kato Y,Borchard F,Cooper HS,Dawsey SM,Dixon MF,Fenoglio-Preiser CM,Fléjou JF,Geboes K,Hattori T,Hirota T,Itabashi M,Iwafuchi M,Iwashita A,Kim YI,Kirchner T,Klimpfinger M,Koike M,Lauwers GY,Lewin KJ,Oberhuber G,Offner F,Price AB,Rubio CA,Shimizu M,Shimoda T,Sipponen P,Solcia E,Stolte M,Watanabe H,Yamabe H.The Vienna classification of gastrointestinal epithelial neoplasia.Gut 2000;47:251-255[PMID:10896917 DOI:10.1136/gut.47.2.251]
5 Kim JM,Cho MY,Sohn JH,Kang DY,Park CK,Kim WH,Jin SY,Kim KM,Chang HK,Yu E,Jung ES,Chang MS,Joo JE,Joo M,Kim YW,Park DY,Kang YK,Park SH,Han HS,Kim YB,Park HS,Chae YS,Kwon KW,Chang HJ;Gastrointestinal Pathology Study Group of Korean Society of Pathologists.Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists.World J Gastroenterol 2011;17:2602-2610[PMID:21677827 DOI:10.3748/wjg.v17.i21.2602]
6 Jang JS.What Shall We Do for“Atypical Cells and Regenerative Atypia”on Forceps Biopsy Examination.Accessed 2014-03-30.Available from:URL:http://www.gie.or.kr/schedule/old_data/semina/semina/2014_50/seminar/50th_seminar_4.pdf
7 Goldstein NS,Lewin KJ.Gastric epithelial dysplasia and adenoma:historical review and histological criteria for grading.Hum Pathol 1997;28:127-133[PMID:9023391 DOI:10.1016/S0046-8177(97)90095-2]
8 Yu CH,Jeon SW,Kim SK,Lee HS,Heo J,Kwon YH,Kim GY,Kim SZ,Bae HI.Endoscopic resection as a first therapy for gastric epithelial atypia:is it reasonable?Dig Dis Sci 2014;59:3012-3020[PMID:24927801 DOI:10.1007/s10620-014-3249-5]
9 Kim SI,Han HS,Kim JH,Lee KJ,Hong SN,Lee SY,Kim HU,Sung TS,Zheng H,Sung IK,Park HS,Shim CS.What is the next step for gastric atypical epithelium on histological findings of endoscopic forceps biopsy?Dig Liver Dis 2013;45:573-577[PMID:23477869 DOI:10.1016/j.dld.2013.01.015]
10 Sung JK.Diagnosis and management of gastric dysplasia.Korean J Intern Med 2016;31:201-209[PMID:26932397 DOI:10.3904/kjim.2016.021]
11 Stolte M.The new Vienna classification of epithelial neoplasia of the gastrointestinal tract:advantages and disadvantages.Virchows Arch 2003;442:99-106[PMID:12596058 DOI:10.1007/s00428-002-0680-3]
12 Torre LA,Bray F,Siegel RL,Ferlay J,Lortet-Tieulent J,Jemal A.Global cancer statistics,2012.CACancer J Clin 2015;65:87-108[PMID:25651787 DOI:10.3322/caac.21262]
13 Jung KW,Won YJ,Kong HJ,Lee ES.Prediction of Cancer Incidence and Mortality in Korea,2018.Cancer Res Treat 2018;50:317-323[PMID:29566480 DOI:10.4143/crt.2018.142]
14 Information Committee of Korean Gastric Cancer Association.Korean Gastric Cancer Association Nationwide Survey on Gastric Cancer in 2014.J Gastric Cancer 2016;16:131-140[PMID:27752390DOI:10.5230/jgc.2016.16.3.131]
15 Yoshizawa N,Fujisaki J,Suzuki S,Taniguchi C,Horiuchi Y,Matsuo Y,Suganuma T,Ohmae M,Kubota M,Ishiyama A,Hirasawa T,Yamamoto Y,Tsuchida T,Igarashi M.A study on lesions diagnosed as atypical epithelium(new group classification;equivalent to Group 2)at our hospital by stomach biopsy.Prog Dig Endosc 2012;80:42-46[DOI:10.11641/pde.80.2_42]
16 Japanese Gastric Cancer Association.Japanese classification of gastric carcinoma:3rd English edition.Gastric Cancer 2011;14:101-112[PMID:21573743 DOI:10.1007/s10120-011-0041-5]
17 The Paris endoscopic classification of superficial neoplastic lesions:esophagus,stomach,and colon:November 30 to December 1,2002.Gastrointest Endosc 2003;58:S3-S43[PMID:14652541 DOI:10.1016/S0016-5107(03)02159-X]
18 Yakirevich E,Resnick MB.Pathology of gastric cancer and its precursor lesions.Gastroenterol Clin North Am 2013;42:261-284[PMID:23639640 DOI:10.1016/j.gtc.2013.01.004]
19 Rosai J.Rosai and Ackerman’s Surgical Pathology.9th ed.Edinburgh:Mosby,2004.
20 Kim WH,Park CK,Kim YB,Kim YW,Kim HG,Bae HI,Song KS,Chang HK,Chang HJ,Chae YS.Astandardized pathology report for gastric cancer.The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists,Korea.Korean J Pathol 2005;39:106-113
21 Ushiku T,Arnason T,Ban S,Hishima T,Shimizu M,Fukayama M,Lauwers GY.Very welldifferentiated gastric carcinoma of intestinal type:analysis of diagnostic criteria.Mod Pathol 2013;26:1620-1631[PMID:23723017 DOI:10.1038/modpathol.2013.98]
22 Yao T,Utsunomiya T,Oya M,Nishiyama K,Tsuneyoshi M.Extremely well-differentiated adenocarcinoma of the stomach:clinicopathological and immunohistochemical features.World JGastroenterol 2006;12:2510-2516[PMID:16688795 DOI:10.3748/wjg.v12.i16.2510]
23 Kang KJ,Kim KM,Kim JJ,Rhee PL,Lee JH,Min BH,Rhee JC,Kushima R,Lauwers GY.Gastric extremely well-differentiated intestinal-type adenocarcinoma:a challenging lesion to achieve complete endoscopic resection.Endoscopy 2012;44:949-952[PMID:22987215 DOI:10.1055/s-0032-1310161]
24 Lee H,Kim H,Shin SK,Park JC,Lee SK,Lee YC,Kim H,Noh SH.The diagnostic role of endoscopic submucosal dissection for gastric lesions with indefinite pathology.Scand J Gastroenterol 2012;47:1101-1107[PMID:22793876 DOI:10.3109/00365521.2012.704939]
25 Jeon HK,Ryu HY,Cho MY,Kim HS,Kim JW,Park HJ,Kim MY,Baik SK,Kwon SO,Park SY,Won SH.A randomized trial to determine the diagnostic accuracy of conventional vs.jumbo forceps biopsy of gastric epithelial neoplasias before endoscopic submucosal dissection;open-label study.Gastric Cancer2014;17:661-668[PMID:24337434 DOI:10.1007/s10120-013-0322-2]
26 Kim YJ,Park JC,Kim JH,Shin SK,Lee SK,Lee YC,Chung JB.Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.Endoscopy2010;42:620-626[PMID:20623445 DOI:10.1055/s-0030-1255524]
27 Ito E,Saito K,Takizawa T,Koike M.Differential diagnosis of atypical epithelium of biopsied gastric mucosa using immunostaining of Ki-67,p53,hMLH1 and MDM2 expression.J Exp Clin Cancer Res2002;21:527-537[PMID:12636099]
28 Shaheen NJ,Falk GW,Iyer PG,Gerson LB;American College of Gastroenterology.ACG Clinical Guideline:Diagnosis and Management of Barrett’s Esophagus.Am J Gastroenterol 2016;111:30-50;quiz 51[PMID:26526079 DOI:10.1038/ajg.2015.322]
2 Kim H,Jin SY,Jang JJ,Kim WH,Song SY,Kim KR,Yu ES,Shin HS,Kim HK,Sohn JH,Hong EK.Grading system for gastric epithelial proliferative diseases standardized guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.Korean J Pathol 1997;31:389-400
3 Takao M,Kakushima N,Takizawa K,Tanaka M,Yamaguchi Y,Matsubayashi H,Kusafuka K,Ono H.Discrepancies in histologic diagnoses of early gastric cancer between biopsy and endoscopic mucosal resection specimens.Gastric Cancer 2012;15:91-96[PMID:21814828 DOI:10.1007/s10120-011-0075-8]
4 Schlemper RJ,Riddell RH,Kato Y,Borchard F,Cooper HS,Dawsey SM,Dixon MF,Fenoglio-Preiser CM,Fléjou JF,Geboes K,Hattori T,Hirota T,Itabashi M,Iwafuchi M,Iwashita A,Kim YI,Kirchner T,Klimpfinger M,Koike M,Lauwers GY,Lewin KJ,Oberhuber G,Offner F,Price AB,Rubio CA,Shimizu M,Shimoda T,Sipponen P,Solcia E,Stolte M,Watanabe H,Yamabe H.The Vienna classification of gastrointestinal epithelial neoplasia.Gut 2000;47:251-255[PMID:10896917 DOI:10.1136/gut.47.2.251]
5 Kim JM,Cho MY,Sohn JH,Kang DY,Park CK,Kim WH,Jin SY,Kim KM,Chang HK,Yu E,Jung ES,Chang MS,Joo JE,Joo M,Kim YW,Park DY,Kang YK,Park SH,Han HS,Kim YB,Park HS,Chae YS,Kwon KW,Chang HJ;Gastrointestinal Pathology Study Group of Korean Society of Pathologists.Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists.World J Gastroenterol 2011;17:2602-2610[PMID:21677827 DOI:10.3748/wjg.v17.i21.2602]
6 Jang JS.What Shall We Do for“Atypical Cells and Regenerative Atypia”on Forceps Biopsy Examination.Accessed 2014-03-30.Available from:URL:http://www.gie.or.kr/schedule/old_data/semina/semina/2014_50/seminar/50th_seminar_4.pdf
7 Goldstein NS,Lewin KJ.Gastric epithelial dysplasia and adenoma:historical review and histological criteria for grading.Hum Pathol 1997;28:127-133[PMID:9023391 DOI:10.1016/S0046-8177(97)90095-2]
8 Yu CH,Jeon SW,Kim SK,Lee HS,Heo J,Kwon YH,Kim GY,Kim SZ,Bae HI.Endoscopic resection as a first therapy for gastric epithelial atypia:is it reasonable?Dig Dis Sci 2014;59:3012-3020[PMID:24927801 DOI:10.1007/s10620-014-3249-5]
9 Kim SI,Han HS,Kim JH,Lee KJ,Hong SN,Lee SY,Kim HU,Sung TS,Zheng H,Sung IK,Park HS,Shim CS.What is the next step for gastric atypical epithelium on histological findings of endoscopic forceps biopsy?Dig Liver Dis 2013;45:573-577[PMID:23477869 DOI:10.1016/j.dld.2013.01.015]
10 Sung JK.Diagnosis and management of gastric dysplasia.Korean J Intern Med 2016;31:201-209[PMID:26932397 DOI:10.3904/kjim.2016.021]
11 Stolte M.The new Vienna classification of epithelial neoplasia of the gastrointestinal tract:advantages and disadvantages.Virchows Arch 2003;442:99-106[PMID:12596058 DOI:10.1007/s00428-002-0680-3]
12 Torre LA,Bray F,Siegel RL,Ferlay J,Lortet-Tieulent J,Jemal A.Global cancer statistics,2012.CACancer J Clin 2015;65:87-108[PMID:25651787 DOI:10.3322/caac.21262]
13 Jung KW,Won YJ,Kong HJ,Lee ES.Prediction of Cancer Incidence and Mortality in Korea,2018.Cancer Res Treat 2018;50:317-323[PMID:29566480 DOI:10.4143/crt.2018.142]
14 Information Committee of Korean Gastric Cancer Association.Korean Gastric Cancer Association Nationwide Survey on Gastric Cancer in 2014.J Gastric Cancer 2016;16:131-140[PMID:27752390DOI:10.5230/jgc.2016.16.3.131]
15 Yoshizawa N,Fujisaki J,Suzuki S,Taniguchi C,Horiuchi Y,Matsuo Y,Suganuma T,Ohmae M,Kubota M,Ishiyama A,Hirasawa T,Yamamoto Y,Tsuchida T,Igarashi M.A study on lesions diagnosed as atypical epithelium(new group classification;equivalent to Group 2)at our hospital by stomach biopsy.Prog Dig Endosc 2012;80:42-46[DOI:10.11641/pde.80.2_42]
16 Japanese Gastric Cancer Association.Japanese classification of gastric carcinoma:3rd English edition.Gastric Cancer 2011;14:101-112[PMID:21573743 DOI:10.1007/s10120-011-0041-5]
17 The Paris endoscopic classification of superficial neoplastic lesions:esophagus,stomach,and colon:November 30 to December 1,2002.Gastrointest Endosc 2003;58:S3-S43[PMID:14652541 DOI:10.1016/S0016-5107(03)02159-X]
18 Yakirevich E,Resnick MB.Pathology of gastric cancer and its precursor lesions.Gastroenterol Clin North Am 2013;42:261-284[PMID:23639640 DOI:10.1016/j.gtc.2013.01.004]
19 Rosai J.Rosai and Ackerman’s Surgical Pathology.9th ed.Edinburgh:Mosby,2004.
20 Kim WH,Park CK,Kim YB,Kim YW,Kim HG,Bae HI,Song KS,Chang HK,Chang HJ,Chae YS.Astandardized pathology report for gastric cancer.The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists,Korea.Korean J Pathol 2005;39:106-113
21 Ushiku T,Arnason T,Ban S,Hishima T,Shimizu M,Fukayama M,Lauwers GY.Very welldifferentiated gastric carcinoma of intestinal type:analysis of diagnostic criteria.Mod Pathol 2013;26:1620-1631[PMID:23723017 DOI:10.1038/modpathol.2013.98]
22 Yao T,Utsunomiya T,Oya M,Nishiyama K,Tsuneyoshi M.Extremely well-differentiated adenocarcinoma of the stomach:clinicopathological and immunohistochemical features.World JGastroenterol 2006;12:2510-2516[PMID:16688795 DOI:10.3748/wjg.v12.i16.2510]
23 Kang KJ,Kim KM,Kim JJ,Rhee PL,Lee JH,Min BH,Rhee JC,Kushima R,Lauwers GY.Gastric extremely well-differentiated intestinal-type adenocarcinoma:a challenging lesion to achieve complete endoscopic resection.Endoscopy 2012;44:949-952[PMID:22987215 DOI:10.1055/s-0032-1310161]
24 Lee H,Kim H,Shin SK,Park JC,Lee SK,Lee YC,Kim H,Noh SH.The diagnostic role of endoscopic submucosal dissection for gastric lesions with indefinite pathology.Scand J Gastroenterol 2012;47:1101-1107[PMID:22793876 DOI:10.3109/00365521.2012.704939]
25 Jeon HK,Ryu HY,Cho MY,Kim HS,Kim JW,Park HJ,Kim MY,Baik SK,Kwon SO,Park SY,Won SH.A randomized trial to determine the diagnostic accuracy of conventional vs.jumbo forceps biopsy of gastric epithelial neoplasias before endoscopic submucosal dissection;open-label study.Gastric Cancer2014;17:661-668[PMID:24337434 DOI:10.1007/s10120-013-0322-2]
26 Kim YJ,Park JC,Kim JH,Shin SK,Lee SK,Lee YC,Chung JB.Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.Endoscopy2010;42:620-626[PMID:20623445 DOI:10.1055/s-0030-1255524]
27 Ito E,Saito K,Takizawa T,Koike M.Differential diagnosis of atypical epithelium of biopsied gastric mucosa using immunostaining of Ki-67,p53,hMLH1 and MDM2 expression.J Exp Clin Cancer Res2002;21:527-537[PMID:12636099]
28 Shaheen NJ,Falk GW,Iyer PG,Gerson LB;American College of Gastroenterology.ACG Clinical Guideline:Diagnosis and Management of Barrett’s Esophagus.Am J Gastroenterol 2016;111:30-50;quiz 51[PMID:26526079 DOI:10.1038/ajg.2015.322]