腸型胃癌和彌漫型胃癌的臨床特點(diǎn)及預(yù)后研究

曹文君，李 敏，李慧娟

·論著·

腸型胃癌和彌漫型胃癌的臨床特點(diǎn)及預(yù)后研究

曹文君1*，李 敏2，李慧娟2

目的 探討腸型胃癌和彌漫型胃癌的臨床特點(diǎn)及預(yù)后。方法 選取2007-01-01至2015-12-30在長(zhǎng)治醫(yī)學(xué)院附屬和平醫(yī)院外科病房手術(shù)治療的胃癌患者392例，其中腸型231例(58.9%)，彌漫型161例(41.1%)。建立胃癌流行病學(xué)調(diào)查問卷，并由經(jīng)過培訓(xùn)的專業(yè)人員按統(tǒng)一標(biāo)準(zhǔn)采集胃癌患者信息，包括基本情況(性別、年齡、身高、體質(zhì)量、文化程度、婚姻狀況、血型、幽門螺桿菌感染、腫瘤家族史)、生活方式及習(xí)慣(吸煙、飲酒、進(jìn)食速度、進(jìn)食燙食、進(jìn)食酸菜/咸菜/泡菜、進(jìn)食油炸食品)及病理診斷與臨床分期等；并由本院中心實(shí)驗(yàn)室具有碩士及以上學(xué)歷人員對(duì)患者進(jìn)行電話隨訪，詢問生存情況，隨訪截至2015-12-30。結(jié)果 腸型與彌漫型胃癌患者性別、體質(zhì)指數(shù)(BMI)、文化程度、婚姻狀況、血型、幽門螺桿菌感染、腫瘤家族史比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；腸型與彌漫型胃癌患者年齡比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。腸型與彌漫型胃癌患者吸煙、飲酒比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；腸型與彌漫型胃癌患者進(jìn)食速度、進(jìn)食燙食、進(jìn)食酸菜/咸菜/泡菜、進(jìn)食油炸食品比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。腸型與彌漫型胃癌患者T期、M期比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；腸型與彌漫型胃癌患者N期比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。340例胃癌患者完成隨訪，隨訪率為86.7%；截至隨訪日期，腸型胃癌患者生存率為66.5%(129/194)，中位生存時(shí)間為24個(gè)月；彌漫型胃癌患者生存率為52.7%(77/146)，中位生存時(shí)間為18個(gè)月。腸型與彌漫型胃癌患者生存曲線比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論 不同Lauren分型胃癌臨床特點(diǎn)和預(yù)后不同。Lauren分型在胃癌治療及預(yù)防中起一定的決策作用。

胃腫瘤；Lauren分型；臨床特點(diǎn)；預(yù)后

曹文君，李敏，李慧娟.腸型胃癌和彌漫型胃癌的臨床特點(diǎn)及預(yù)后研究[J].中國(guó)全科醫(yī)學(xué)，2017，20(13)：1587-1591.[www.chinagp.net]

CAO W J,LI M,LI H J.Clinical characteristics and prognosis of intestinal-type and diffuse-type gastric cancer[J].Chinese General Practice，2017，20(13)：1587-1591.

胃癌是世界上常見惡性腫瘤之一，是癌癥相關(guān)死亡的一個(gè)主要原因[1]。據(jù)國(guó)際癌癥研究機(jī)構(gòu)(IARC)發(fā)布的癌癥統(tǒng)計(jì)數(shù)據(jù)顯示，2012年，全世界范圍內(nèi)有952 000例新增胃癌患者，占癌癥患者的6.8%，其中死亡患者為723 000例，占癌癥總死亡患者的8.8%[2]。全世界有超過70%的胃癌患者在發(fā)展中國(guó)家，其中50%的胃癌患者在亞洲東部(主要是中國(guó))。在我國(guó)城市，胃癌死亡率男性為112.5/10萬，居惡性腫瘤的第3位；女性為50.4/10萬，居惡性腫瘤的第2位[3]。胃癌早期診斷率低，預(yù)后較差，嚴(yán)重影響身體健康。目前，胃鏡是診斷胃癌的金標(biāo)準(zhǔn)，但由于胃鏡靈敏度較低、成本較高，從而使得胃癌的早期診斷受到了一定的限制[4]。此外，由于胃癌早期癥狀不明顯，不易被確診，多數(shù)患者臨床確診時(shí)已到了胃癌晚期，導(dǎo)致胃癌的預(yù)后效果差[5]。當(dāng)前，胃癌仍以手術(shù)治療為主，但術(shù)后仍有50%患者發(fā)生復(fù)發(fā)轉(zhuǎn)移，有研究顯示，胃癌Ⅱ期患者的5年生存率為30%～50%，但是Ⅲ期患者的5年生存率就降為10%～25%[6]。此外，有研究認(rèn)為，約30%的癌癥死亡源自個(gè)體行為[7]。胃癌按照Lauren分型分為腸型和彌漫型[8]，本研究擬通過收集患者的基本情況(年齡、職業(yè)、文化程度等)、生活方式及習(xí)慣(吸煙、飲酒、進(jìn)食速度等)、病理診斷與臨床分期等信息，對(duì)不同分型胃癌的臨床特點(diǎn)和預(yù)后進(jìn)行深入探討，分析個(gè)人行為對(duì)不同分型胃癌發(fā)病風(fēng)險(xiǎn)的影響，以期有效預(yù)防胃癌的發(fā)生，從而降低其發(fā)病率。

1 對(duì)象與方法

1.1 研究對(duì)象 選取2007-01-01至2015-12-30在長(zhǎng)治醫(yī)學(xué)院附屬和平醫(yī)院外科病房手術(shù)治療的胃癌患者392例。納入標(biāo)準(zhǔn)：均經(jīng)手術(shù)病理檢查確診為胃癌。排除標(biāo)準(zhǔn)：認(rèn)知行為異常及伴其他軀體疾病不能參與數(shù)據(jù)采集者。其中男308例(78.6%)，女84例(21.4%)；年齡29～80歲，中位年齡59.0(12.8)歲；已婚378例(96.4%)，未婚/離婚/喪偶14例(3.6%)；BMI為14.2～31.6 kg/m2，平均BMI為(22.2±3.2)kg/m2；腸型231例(58.9%)，彌漫型161例(41.1%)。本研究經(jīng)長(zhǎng)治醫(yī)學(xué)院倫理學(xué)委員會(huì)批準(zhǔn)，患者或其家屬知情同意。

1.2 研究方法

1.2.1 問卷調(diào)查 參照國(guó)內(nèi)外胃癌健康風(fēng)險(xiǎn)因素和相關(guān)文獻(xiàn)[9-11]建立胃癌流行病學(xué)調(diào)查問卷，并由經(jīng)過培訓(xùn)的專業(yè)人員按統(tǒng)一標(biāo)準(zhǔn)采集胃癌患者信息，包括基本情況(性別、年齡、身高、體質(zhì)量、文化程度、婚姻狀況、血型、幽門螺桿菌感染、腫瘤家族史)、生活方式及習(xí)慣(吸煙、飲酒、進(jìn)食速度、進(jìn)食燙食、進(jìn)食酸菜/咸菜/泡菜、進(jìn)食油炸食品)及病理診斷與臨床分期等，將信息錄入已建立的腫瘤信息標(biāo)本庫(kù)。

1.2.2 標(biāo)本判定 手術(shù)標(biāo)本統(tǒng)一由2名具有高級(jí)職稱的病理醫(yī)師進(jìn)行判定。胃癌病理分型按照Lauren分型分為腸型和彌漫型[8]。臨床分期按照美國(guó)癌癥聯(lián)合會(huì)(AJCC)第6版(2002年)TNM分期，TNM是對(duì)腫瘤浸潤(rùn)(T)、淋巴結(jié)轉(zhuǎn)移(N)及遠(yuǎn)端組織(M)進(jìn)行定義[12]。本研究中T分為T1(腫瘤侵犯黏膜基層或下層)、T2(腫瘤侵犯固有肌層或漿膜下層)、T3(腫瘤侵犯漿膜)、T4(腫瘤侵犯鄰近組織結(jié)構(gòu))；N分為N1(1～2個(gè)淋巴結(jié)轉(zhuǎn)移)、N2(3～6個(gè)淋巴結(jié)轉(zhuǎn)移)、N3(7個(gè)及以上淋巴結(jié)轉(zhuǎn)移)；M分為M0(無遠(yuǎn)端轉(zhuǎn)移)、M1(有遠(yuǎn)端轉(zhuǎn)移)。

1.2.3 預(yù)后隨訪 由本院中心實(shí)驗(yàn)室具有碩士及以上學(xué)歷人員對(duì)患者進(jìn)行電話隨訪，隨訪截至2015-12-30。隨訪前進(jìn)行專業(yè)語言培訓(xùn)，詢問患者生存情況，如死亡則記錄死亡時(shí)間，如存活則記錄目前身體狀況，并囑咐其家屬按時(shí)復(fù)查。

1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 19.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析，計(jì)數(shù)資料比較采用χ2檢驗(yàn)；采用Kaplan-Meier法繪制生存曲線，組間比較采用Log-rank檢驗(yàn)。以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 腸型與彌漫型胃癌患者基本情況比較 腸型與彌漫型胃癌患者性別、體質(zhì)指數(shù)(BMI)、文化程度、婚姻狀況、血型、幽門螺桿菌感染、腫瘤家族史比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；腸型與彌漫型胃癌患者年齡比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見表1)。

2.2 腸型與彌漫型胃癌患者生活方式及習(xí)慣比較 腸型與彌漫型胃癌患者吸煙、飲酒比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；腸型與彌漫型胃癌患者進(jìn)食速度、進(jìn)食燙食、進(jìn)食酸菜/咸菜/泡菜、進(jìn)食油炸食品比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05，見表2)。

2.3 腸型與彌漫型胃癌患者臨床分期比較 腸型與彌漫型胃癌患者T期、M期比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；腸型與彌漫型胃癌患者N期比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見表3)。

表1 腸型與彌漫型胃癌患者基本情況比較〔n(%)〕

注：a年齡的分類根據(jù)中位年齡；bBMI的分類參照文獻(xiàn)[13]定義標(biāo)準(zhǔn)；c為數(shù)據(jù)有缺失；BMI=體質(zhì)指數(shù)

表2 腸型與彌漫型胃癌患者生活方式及習(xí)慣比較〔n(%)〕

表3 腸型與彌漫型胃癌患者臨床分期比較〔n(%)〕

2.4 腸型胃癌與彌漫型胃癌患者Kaplan-Meier生存曲線比較 340例胃癌患者完成隨訪，隨訪率為86.7%；截至隨訪日期，腸型胃癌患者生存率為66.5%(129/194)，中位生存時(shí)間為24個(gè)月；彌漫型胃癌患者生存率為52.7%(77/146)，中位生存時(shí)間為18個(gè)月。腸型與彌漫型胃癌患者生存曲線比較，差異有統(tǒng)計(jì)學(xué)意義(χ2=12.415，P<0.001，見圖1)。

圖1 腸型與彌漫型胃癌患者Kaplan-Meier生存曲線比較

Figure 1 Comparison of the Kaplan-Meier survival curve between patients with intestinal-type gastric cancer and patients with diffuse-type gastric cancer

3 討論

有研究報(bào)道，發(fā)展中國(guó)家胃癌的死亡率是發(fā)達(dá)國(guó)家的3.8～7.9倍[14]，而我國(guó)中部的山西省又是胃癌高發(fā)區(qū)[15]。Lauren分型最早于1965年提出，因其簡(jiǎn)單易行、可重復(fù)性強(qiáng)而被大多數(shù)國(guó)家臨床工作者和研究者采用至今。不同胃癌分型健康危險(xiǎn)因素和預(yù)后不同，臨床流行病學(xué)研究發(fā)現(xiàn)，亞洲國(guó)家如中國(guó)、日本腸型胃癌發(fā)病率高于其他國(guó)家[16]。本研究中腸型胃癌患者占58.9%，彌漫型胃癌患者占41.1%。

有研究認(rèn)為，彌漫型胃癌多發(fā)于年輕女性，更易出現(xiàn)淋巴結(jié)轉(zhuǎn)移[17]。本研究結(jié)果顯示，彌漫型胃癌更易發(fā)生距原發(fā)灶邊緣3 cm以外的淋巴結(jié)轉(zhuǎn)移，而不同Lauren分型胃癌的T、M分期無統(tǒng)計(jì)學(xué)意義。有最新研究報(bào)道，幽門螺桿菌陽性與胃癌組織學(xué)分型無關(guān)[17]，本研究結(jié)果進(jìn)一步驗(yàn)證了這一點(diǎn)。此外，多數(shù)研究關(guān)注不同胃癌分型的臨床特點(diǎn)及治療[18-21]，而較少報(bào)道不同胃癌分型患者在個(gè)人行為習(xí)慣方面的差異，本研究結(jié)果顯示，彌漫型胃癌與腸型胃癌在吸煙、飲酒上有差異，而在性別、BMI、文化程度、婚姻狀況、血型、腫瘤家族史、飲食習(xí)慣(進(jìn)食速度、進(jìn)食燙手、進(jìn)食酸菜/咸菜/泡菜、進(jìn)食油炸食品)上無差異。

本研究生存分析結(jié)果顯示，彌漫型胃癌患者預(yù)后差，總體生存率較腸型胃癌患者低，與既往研究報(bào)道結(jié)果一致，即彌漫型胃癌患者5年總生存率(44.1%)低于腸型胃癌患者(52.7%)，且彌漫型胃癌發(fā)生遠(yuǎn)端淋巴結(jié)轉(zhuǎn)移的風(fēng)險(xiǎn)較高[22]。因此Lauren分型在胃癌治療及預(yù)防中起一定的決策作用。

作者貢獻(xiàn)：曹文君進(jìn)行文章的構(gòu)思與設(shè)計(jì)、統(tǒng)計(jì)學(xué)處理、結(jié)果的分析與解釋、撰寫論文、中英文修訂，負(fù)責(zé)文章的質(zhì)量控制及審校，對(duì)文章整體負(fù)責(zé)，監(jiān)督管理；李敏進(jìn)行研究的實(shí)施與可行性分析、數(shù)據(jù)整理；李慧娟進(jìn)行數(shù)據(jù)收集。

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胃癌Lauren分型的病理表現(xiàn)：(1)腸型，一般有腺腔形成，癌細(xì)胞為柱狀或立方形，游離緣常可見刷狀緣，似腸上皮的吸收細(xì)胞，部分癌細(xì)胞似腸化生的杯狀細(xì)胞，癌旁黏膜常伴有廣泛的萎縮性胃炎和腸上皮化生；(2)彌漫型，無腺腔形成，癌細(xì)胞為分化差的小圓形細(xì)胞，細(xì)胞之間黏著力差，彌漫散在，癌旁黏膜無或僅有小片萎縮性胃炎和腸上皮化生；(3)不能分型，難以劃分為腸型或彌漫型或在同一腫瘤內(nèi)含有兩種類型。

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(本文編輯：崔沙沙)

Clinical Characteristics and Prognosis of Intestinal-type and Diffuse-type Gastric Cancer

CAOWen-jun1*,LIMin2,LIHui-juan2

1.DepartmentofEpidemiologyandHealthStatistics,SchoolofPreventiveMedicine,ChangzhiMedicalCollege,Changzhi046000,China2.DepartmentofCentralLaboratory,HepingHospitalAffiliatedtoChangzhiMedicalCollege,Changzhi046000,China

Objective To discuss clinical characteristics and prognosis of intestinal-type and diffuse-type gastric cancer.Methods A total of 392 patients with gastric cancer receiving operative treatment in the surgical ward of Heping Hospital Affiliated to Changzhi Medical College from January 1st2007 to December 30th2015 were selected.Among them,231 (58.9%) were intestinal type and 161 (41.1%) were diffuse type.The epidemiological questionnaire gastric cancer was established.The trained professionals according to unified standards collected the information of patients with gastric cancer.Their basic situation (gender,age,height,body mass,educational level,marital status,blood type,helicobacter pylori infection,family history of cancer);lifestyle and habits (smoking,drinking,eating speed,eating hot food,eating Chinese sauerkraut/pickles/preserved vegetables,eating fried foods);and pathological diagnosis and clinical staging were included in the collected information.The telephone follow-up of patients was made to inquire about survival by people having master degree or above in central lab of the hospital,and would be conducted until December 30th2015.Results There were no significant differences in gender,body mass index (BMI),educational level,marital status,blood type,helicobacter pylori infection and history of cancer between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P>0.05).There were significant differences in age between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P<0.05).There were significant differences in smoking and drinking between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P<0.05).There were no significant differences in eating speed,eating hot food,eating Chinese sauerkraut/pickles/preserved vegetables,eating fried foods between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P>0.05).There was no significant difference in T phase and M phase between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P>0.05).There was significant difference in N phase between patients with intestinal-type cancer and patients with diffuse-type gastric cancer (P<0.05).Three hundred and forty patients with gastric cancer had completed the followed up,the follow-up rate was 86.7%.By the end of follow-up,the survival rate of patients with intestinal-type gastric cancer was 66.5% (129/194),the median survival time was 24 months;and the survival rate was 52.7% (77/146) in patients with diffuse-type gastric cancer,and the median survival time was 18 months.The survival curves between patients with intestinal-type gastric cancer and patients with diffuse-type gastric cancer were significantly different (P<0.05).Conclusion The clinical manifestations and prognosis of Lauren classification were different.Lauren classification plays a decision-making role in the treatment and prevention of gastric cancer.

Stomach neoplasms;Lauren classification;Clinical characteristics;Prognosis

山西省基礎(chǔ)研究計(jì)劃項(xiàng)目(2015021185)；國(guó)家自然科學(xué)基金資助項(xiàng)目(81302518)；山西省長(zhǎng)治醫(yī)學(xué)院創(chuàng)新團(tuán)隊(duì)(CX201403)

R 735.2

A

10.3969/j.issn.1007-9572.2017.13.012

2016-12-08；

2017-03-24)

1.046000山西省長(zhǎng)治市，長(zhǎng)治醫(yī)學(xué)院預(yù)防醫(yī)學(xué)系流行病與衛(wèi)生統(tǒng)計(jì)學(xué)教研室

2.046000山西省長(zhǎng)治市，長(zhǎng)治醫(yī)學(xué)院附屬和平醫(yī)院中心實(shí)驗(yàn)室

*通信作者：曹文君，副教授；E-mail:wjcao16@hotmail.com

*Correspondingauthor:CAOWen-jun,Associateprofessor;E-mail:wjcao16@hotmail.com