參考文獻關于胰腺癌的研究文獻綜述1胰腺癌流行病學胰腺癌（pancreaticcancer,PC）是一種具有高發(fā)病率、高復發(fā)轉移、高死亡率、低早期診斷率、低切除率、低藥物有效率和低生存率的特點的惡性腫瘤ADDINEN.CITEADDINEN.CITE.DATA[6]，5年生存率僅為7.2％，在惡性腫瘤中最低。根據(jù)2018年全球癌癥統(tǒng)計，胰腺癌是世界上發(fā)病率和死亡率較高的惡性腫瘤之一ADDINEN.CITEADDINEN.CITE.DATA[7]。與其他癌癥類型的生存率增加趨勢不同的是，胰腺癌生存率的改善是緩慢的，這很可能與診斷晚期有關。胰腺癌的發(fā)病率隨著年齡的增長而增加，發(fā)病率最高的是70歲以上的患者，而且很少在55歲之前被診斷出來，這種情況男性比女性更常見，非裔美國人比白人更為普遍ADDINEN.CITE<EndNote><Cite><Author>Khoudari</Author><Year>2020</Year><RecNum>121</RecNum><DisplayText><styleface="superscript">[8]</style></DisplayText><record><rec-number>121</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616505225">121</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Khoudari,G.</author><author>Alkhayyat,M.</author><author>AbouSaleh,M.</author><author>Mansoor,E.</author><author>Sarmini,M.T.</author><author>Baidoun,F.</author><author>Vega,K.J.</author><author>Sanaka,M.R.</author></authors></contributors><auth-address>FromtheDepartmentsofHospitalMedicine. Gastroenterology,ClevelandClinic. DepartmentofGastroenterology,CaseWestern/UniversityHospital,Cleveland,OH. DepartmentofGastroenterology,AugustaUniversity,Augusta,GA.</auth-address><titles><title>TheEpidemiologyofPancreaticCancerandtheAssociationWithAcetylsalicylicAcidintheUnitedStates:APopulation-BasedStudy</title><secondary-title>Pancreas</secondary-title><alt-title>Pancreas</alt-title></titles><periodical><full-title>Pancreas</full-title><abbr-1>Pancreas</abbr-1></periodical><alt-periodical><full-title>Pancreas</full-title><abbr-1>Pancreas</abbr-1></alt-periodical><pages>1207-1212</pages><volume>49</volume><number>9</number><edition>2020/09/09</edition><dates><year>2020</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0885-3177</isbn><accession-num>32898007</accession-num><urls></urls><electronic-resource-num>10.1097/mpa.0000000000001659</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[8]。根據(jù)監(jiān)測、流行病學和最終結果18項數(shù)據(jù)分析，2000年至2014年期間，白人的發(fā)病率和死亡率趨勢高于非裔美國人ADDINEN.CITEADDINEN.CITE.DATA[9]。國家癌癥中心于2018年公布了2003-2015年中國17個登記處659732例確診為惡性腫瘤患者流行病學數(shù)據(jù)，其中包括17823例胰腺癌患者，男性9960例，女性7863例，胰腺癌是中國第五大癌癥死亡原因，也是中國第十大最常見的惡性腫瘤ADDINEN.CITEADDINEN.CITE.DATA[10]。根據(jù)美國國家衛(wèi)生統(tǒng)計中心2021年最新公布的數(shù)據(jù)，胰腺癌的發(fā)病率和死亡率均呈上升趨勢，預估美國2021年將出現(xiàn)60430例胰腺癌新病例，48220例胰腺癌死亡病例，成為美國第四大癌癥死亡原因ADDINEN.CITE<EndNote><Cite><Author>Siegel</Author><Year>2021</Year><RecNum>7</RecNum><DisplayText><styleface="superscript">[11]</style></DisplayText><record><rec-number>7</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616497079">7</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Siegel,RebeccaL.</author><author>Miller,KimberlyD.</author><author>Fuchs,HannahE.</author><author>Jemal,Ahmedin</author></authors></contributors><titles><title>CancerStatistics,2021</title></titles><pages>7-33</pages><volume>71</volume><number>1</number><dates><year>2021</year></dates><isbn>0007-9235</isbn><urls><related-urls><url>/doi/abs/10.3322/caac.21654</url></related-urls></urls><electronic-resource-num>/10.3322/caac.21654</electronic-resource-num></record></Cite></EndNote>[11]。WHO預測到2030年，胰腺癌預計將成為美國癌癥相關死亡的第二大原因ADDINEN.CITEADDINEN.CITE.DATA[12]。圖2-1美國2021年估計新癌癥病例和按性別分列的死亡人數(shù)的十大主要癌癥類型2胰腺癌TNM分期自1977年以來，美國癌癥聯(lián)合委員會(AJCC)一直在為常見的實體器官腫瘤制定分期指南，胰腺癌第六版TNM分期2003開始使用，AJCC分別于2010年和2017年公布第七版和第八版TNM分期。從第五版到第六版胰腺癌TNM分期對胰腺癌分期系統(tǒng)進行了3次顯著的改進：T1N0M0和T2N0M0分別分為IA和IB期；T1-3N1M0病從Ⅲ期分到了到ⅡB期，T4NXM0從IVA期轉移到Ⅲ期，并對T分期的定義作了修改，強調了潛在可切除(T3)與局部晚期(T4)疾病之間的區(qū)別ADDINEN.CITE<EndNote><Cite><Author>Bilimoria</Author><Year>2007</Year><RecNum>594</RecNum><DisplayText><styleface="superscript">[13]</style></DisplayText><record><rec-number>594</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616583519">594</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bilimoria,K.Y.</author><author>Bentrem,D.J.</author><author>Ko,C.Y.</author><author>Ritchey,J.</author><author>Stewart,A.K.</author><author>Winchester,D.P.</author><author>Talamonti,M.S.</author></authors></contributors><auth-address>NorthwesternUniversity,DepartmentofSurgery,DivisionofSurgicalOncology,Chicago,IL60611,USA.</auth-address><titles><title>Validationofthe6theditionAJCCPancreaticCancerStagingSystem:reportfromtheNationalCancerDatabase</title><secondary-title>Cancer</secondary-title><alt-title>Cancer</alt-title></titles><periodical><full-title>Cancer</full-title><abbr-1>Cancer</abbr-1></periodical><alt-periodical><full-title>Cancer</full-title><abbr-1>Cancer</abbr-1></alt-periodical><pages>738-44</pages><volume>110</volume><number>4</number><edition>2007/06/21</edition><keywords><keyword>Adenocarcinoma/*pathology</keyword><keyword>DatabasesasTopic/statistics&numericaldata</keyword><keyword>Humans</keyword><keyword>NeoplasmStaging/*methods</keyword><keyword>PancreaticNeoplasms/*pathology</keyword><keyword>Prognosis</keyword><keyword>ProportionalHazardsModels</keyword><keyword>SurvivalAnalysis</keyword><keyword>UnitedStates</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug15</date></pub-dates></dates><isbn>0008-543X(Print) 0008-543x</isbn><accession-num>17580363</accession-num><urls></urls><electronic-resource-num>10.1002/cncr.22852</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[13]。第七版胰腺癌TNM分期基本與第六版基本相同，刪除了Mx分期（遠處轉移無法評估），進一步明確M分期。由于胰腺相對較薄，大多數(shù)會有一些腫瘤成分延伸表面，因此絕大多數(shù)切除的病人被定義為T3腫瘤，同時臨床實踐中難以區(qū)分腫瘤是否累及胰腺以外器官或組織，這導致T分期中T2期和T3期難以區(qū)分。由于T分期的準確性和操作性存在很多爭議，胰腺癌第八版TNM分期T分期刪除了“腫瘤是否累及胰腺以外器官或組織”的相關定義，而是以腫瘤的最大徑作為T分期的標準，該種分類簡便易行，臨床具有較強的可操作性。關于N分期，第六版和第七版胰腺癌TNM分期簡單籠統(tǒng)分成有無淋巴結轉移，沒有反應不同淋巴結轉移個數(shù)對預后的影響，第八版TNM分期增加類似于其他胃腸道疾病部位的N2分類，定義大于等于4個陽性淋巴結為N2分期，同時強調N2期的意義和對預后的價值ADDINEN.CITE<EndNote><Cite><Author>楊尹默</Author><Year>2017</Year><RecNum>85</RecNum><DisplayText><styleface="superscript">[14]</style></DisplayText><record><rec-number>85</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616503393">85</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">楊尹默</style></author></authors></contributors><auth-address><styleface="normal"font="default"charset="134"size="100%">北京大學第一醫(yī)院外科</style><styleface="normal"font="default"size="100%">;</style></auth-address><titles><title><styleface="normal"font="default"size="100%">AJCC</style><styleface="normal"font="default"charset="134"size="100%">第八版及日本胰腺學會第七版胰腺癌</style><styleface="normal"font="default"size="100%">TNM</style><styleface="normal"font="default"charset="134"size="100%">分期的更新要點及內容評介</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">中華外科雜志</style></secondary-title></titles><periodical><full-title>中華外科雜志</full-title></periodical><pages>20-23</pages><volume>55</volume><number>01</number><keywords><keyword>胰腺腫瘤</keyword><keyword>腫瘤分期</keyword><keyword>美國癌癥聯(lián)合會</keyword><keyword>日本胰腺學會</keyword></keywords><dates><year>2017</year></dates><isbn>0529-5815</isbn><call-num>11-2139/R</call-num><urls></urls><remote-database-provider>Cnki</remote-database-provider></record></Cite></EndNote>[14]。AllenPJ等人ADDINEN.CITEADDINEN.CITE.DATA[15]研究了紀念斯隆·凱特林(MSK)、馬薩諸塞州總醫(yī)院(MGH)和約翰·霍普金斯醫(yī)院(JHH)的前瞻性研究中2318例R0切除胰腺癌患者生存資料，證實了AJCC第八版TNM分期中T分期和N分期是有效的，同時T分期的可重復性更強。圖2-2第七版和第八版胰腺癌TNM分期的比較3胰腺癌病理分型胰腺癌是具有多種組織學亞型的復雜腫瘤，胰腺惡性腫瘤目前根據(jù)腫瘤細胞的分化方向（導管、腺泡或神經(jīng)內分泌）和腫瘤的宏觀形態(tài)（實性或囊性）進行分類,其中胰腺導管腺癌是胰腺癌中的最常見的病理類型（約占90%）。胰腺囊性腫瘤最常見四種類型，胰管內乳頭狀黏液性腫瘤(IPMN)、黏液性囊腺瘤(SCN)、漿液性囊腺瘤(MCN)、實性假乳頭狀腫瘤(SPT)ADDINEN.CITEADDINEN.CITE.DATA[16]。而在所有其他惡性胰腺腫瘤如胰腺神經(jīng)內分泌腫瘤(pNET)、實性假乳頭狀腫瘤、腺泡細胞癌(ACC)和胰母細胞瘤中，神經(jīng)內分泌腫瘤最為常見，約占胰腺惡性腫瘤5%，功能性胰腺神經(jīng)內分泌腫瘤因其經(jīng)典的臨床表現(xiàn)而聞名，其中包括Whipple三聯(lián)癥（胰島素瘤）和Zollinger-Ellison綜合征(胃泌素瘤)。2010年世界衛(wèi)生組織(WHO)公布的第４版胰腺腫瘤病理分類中（如表2-1），除了上述胰腺癌病理類型，其他胰腺癌組織學亞型包括腺鱗癌、未分化癌、乳頭狀粘液癌、間質性癌等ADDINEN.CITEADDINEN.CITE.DATA[17]。WHO2019年公布的第5版胰腺腫瘤分類ADDINEN.CITE<EndNote><Cite><Author>于雙妮</Author><Year>2020</Year><RecNum>733</RecNum><DisplayText><styleface="superscript">[18]</style></DisplayText><record><rec-number>733</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1617288520">733</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">于雙妮</style></author><author><styleface="normal"font="default"charset="134"size="100%">陳杰</style></author></authors></contributors><auth-address><styleface="normal"font="default"charset="134"size="100%">中國醫(yī)學科學院北京協(xié)和醫(yī)學院北京協(xié)和醫(yī)院病理科</style><styleface="normal"font="default"size="100%">;</style><styleface="normal"font="default"charset="134"size="100%">中國醫(yī)學科學院北京協(xié)和醫(yī)學院北京協(xié)和醫(yī)院病理科</style></auth-address><titles><title><styleface="normal"font="default"charset="134"size="100%">解讀</style><styleface="normal"font="default"size="100%">2019</style><styleface="normal"font="default"charset="134"size="100%">版</style><styleface="normal"font="default"size="100%">WHO</style><styleface="normal"font="default"charset="134"size="100%">胰腺腫瘤分類</style><styleface="normal"font="default"size="100%"></style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">中華病理學雜志</style></secondary-title></titles><periodical><full-title>中華病理學雜志</full-title></periodical><pages>536-538</pages><number>06</number><keywords><keyword>胰腺腫瘤</keyword><keyword>WHO</keyword></keywords><dates><year>2020</year></dates><isbn>0529-5807</isbn><call-num>11-2151/R</call-num><urls></urls><remote-database-provider>Cnki</remote-database-provider></record></Cite></EndNote>[18]中新增了大細胞癌伴橫紋肌樣亞型和浸潤性微乳頭狀癌亞型，并獨立命名了胰腺導管內乳頭狀黏液性腫瘤（嗜酸細胞亞型）。在胰腺癌的病理分型中腺鱗癌和鱗癌(SCC)是胰腺癌的罕見組織學亞型，BoydADDINEN.CITE<EndNote><Cite><Author>Boyd</Author><Year>2012</Year><RecNum>597</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>597</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616583931">597</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Boyd,C.A.</author><author>Benarroch-Gampel,J.</author><author>Sheffield,K.M.</author><author>Cooksley,C.D.</author><author>Riall,T.S.</author></authors></contributors><auth-address>DepartmentofSurgery,TheUniversityofTexasMedicalBranch,Galveston,TX77555-0541,USA.</auth-address><titles><title>415patientswithadenosquamouscarcinomaofthepancreas:apopulation-basedanalysisofprognosisandsurvival</title><secondary-title>JSurgRes</secondary-title><alt-title>TheJournalofsurgicalresearch</alt-title></titles><periodical><full-title>JSurgRes</full-title><abbr-1>TheJournalofsurgicalresearch</abbr-1></periodical><alt-periodical><full-title>JSurgRes</full-title><abbr-1>TheJournalofsurgicalresearch</abbr-1></alt-periodical><pages>12-9</pages><volume>174</volume><number>1</number><edition>2011/08/06</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Carcinoma,Adenosquamous/*mortality/pathology/surgery</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>MiddleAged</keyword><keyword>NeoplasmStaging</keyword><keyword>PancreaticNeoplasms/*mortality/pathology/surgery</keyword><keyword>Prognosis</keyword><keyword>SurvivalRate</keyword></keywords><dates><year>2012</year><pub-dates><date>May1</date></pub-dates></dates><isbn>0022-4804(Print) 0022-4804</isbn><accession-num>21816433</accession-num><urls></urls><custom2>PMC3210865</custom2><custom6>NIHMS304835</custom6><electronic-resource-num>10.1016/j.jss.2011.06.015</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[4]等證明，腺鱗癌比腺癌更具有侵襲性，更多的出現(xiàn)在胰體尾部，腫瘤更大，分化程度相對較高。胰腺正常狀態(tài)下沒有鱗狀細胞分化，但胰腺標本中普遍存在實質性鱗狀化生，在尸檢相關研究中，17%-48%的病例觀察到鱗狀化生ADDINEN.CITEADDINEN.CITE.DATA[19,20]。盡管鱗狀化生的頻率相對較高，但胰腺鱗狀細胞癌(SCC)是一種罕見的原發(fā)性胰腺惡性腫瘤。Lowry等ADDINEN.CITE<EndNote><Cite><Author>Lowry</Author><Year>1949</Year><RecNum>598</RecNum><DisplayText><styleface="superscript">[21]</style></DisplayText><record><rec-number>598</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616584021">598</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lowry,C.C.</author><author>Whitaker,H.W.,Jr.</author><author>Greiner,D.J.</author></authors></contributors><titles><title>Squamouscellcarcinomaofthepancreas</title><secondary-title>SouthMedJ</secondary-title><alt-title>Southernmedicaljournal</alt-title></titles><periodical><full-title>SouthMedJ</full-title><abbr-1>Southernmedicaljournal</abbr-1></periodical><alt-periodical><full-title>SouthMedJ</full-title><abbr-1>Southernmedicaljournal</abbr-1></alt-periodical><pages>753-7</pages><volume>42</volume><number>9</number><edition>1949/09/01</edition><keywords><keyword>*Carcinoma,SquamousCell</keyword><keyword>Humans</keyword><keyword>*Pancreas</keyword><keyword>*PancreaticNeoplasms</keyword><keyword>*PANCREAS/cancer</keyword></keywords><dates><year>1949</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0038-4348(Print) 0038-4348</isbn><accession-num>18139941</accession-num><urls></urls><electronic-resource-num>10.1097/00007611-194909000-00005</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[21]1949年首次進行了原發(fā)性胰腺鱗癌患者的個案報道，目前發(fā)表的關于胰腺癌鱗癌的數(shù)據(jù)非常有限，主要為個案報告或小病例系列研究ADDINEN.CITEADDINEN.CITE.DATA[22-24]，人們對單純鱗狀細胞胰腺癌的流行病學和臨床過程了解甚少。Makarova-Rusher等ADDINEN.CITE<EndNote><Cite><Author>Makarova-Rusher</Author><Year>2016</Year><RecNum>602</RecNum><DisplayText><styleface="superscript">[25]</style></DisplayText><record><rec-number>602</rec-number><foreign-keys><keyapp="EN"db-id="p0rwrp05g0x5toerpv7xwfd4sf25wd0dfta5"timestamp="1616584201">602</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Makarova-Rusher,O.V.</author><author>Ulahannan,S.</author><author>Greten,T.F.</author><author>Duffy,A.</author></authors></contributors><auth-address>FromtheGastrointestinalMalignancySection,ThoracicandGIOncologyBranch,CenterforCancerResearch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,MD.</auth-address><titles><title>PancreaticSquamousCellCarcinoma:APopulation-BasedStudyofEpidemiology,ClinicopathologicCharacteristicsandOutcomes</title><secondary-title>Pancreas</secondary-title><alt-title>Pancreas</alt-title></titles><periodical><full-title>Pancreas</full-title><abbr-1>Pancreas</abbr-1></periodical><alt-periodical><full-title>Pancreas</full-title><abbr-1>Pancreas</abbr-1></alt-periodical><pages>1432-1437</pages><volume>45</volume><number>10</number><edition>2016/10/18</edition><keywords><keyword>Adenocarcinoma</keyword><keyword>Carcinoma,SquamousCell</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>NeoplasmStaging</keyword><keyword>PancreaticNeoplasms/*epidemiology</keyword><keyword>Prognosis</keyword><keyword>SurvivalRate</keyword></keywords><dates><year>2016</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0885-3177(Print) 0885-3177</isbn><accession-num>27214394</accession-num><urls></urls><custom2>PMC5067965</custom2><custom6>NIHMS769711</custom6><electronic-resource-num>10.1097/mpa.0000000000000658</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[25]回顧性分析了SEER數(shù)據(jù)庫中胰腺鱗癌患者（N=214），發(fā)現(xiàn)低分化的胰腺鱗癌患者的比例高于腺癌患者（73.0％vs43.7％，P<0.001），同時胰腺鱗癌患者的1年生存率（14.0％）低于腺癌患者（24.5％），這些結果表明與胰腺癌相比，男性、黑人和年長的年齡組原發(fā)性鱗狀胰腺癌的發(fā)病率增加，鱗狀細胞癌的組織學表現(xiàn)為低分化率高，生存率較低。表2-12010年第4版WHO消化系統(tǒng)胰腺惡性腫瘤病理分類ADDINEN.CITEADDINEN.CITE.DATA[18,26,27]起源于胰腺導管上皮的惡性腫瘤起源于非胰腺導管上皮的惡性腫瘤導管腺癌腺泡細胞癌腺鱗癌腺泡細胞囊腺癌膠樣癌（粘液性非囊性癌）導管內乳頭狀粘液性腫瘤伴浸潤性癌肝樣腺癌混合性腺泡-導管癌髓樣癌混合性腺泡-神經(jīng)內分泌癌印戒細胞癌混合性腺泡-神經(jīng)內分泌-導管癌未分化癌混合性導管-神經(jīng)內分泌癌未分化癌伴破骨巨細胞樣反應粘液性囊性腫瘤伴浸潤性癌胰母細胞瘤漿液性囊腺癌實性-假乳頭狀腫瘤參考文獻參考文獻[1] SIMONECG,ZULUAGATOROT,CHANE,etal.Characteristicsandoutcomesofadenosquamouscarcinomaofthepancreas[J].Gastrointestinalcancerresearch:GCR,2013,6(3):75-9.[2] 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