韋存志 肖世強(qiáng) 王建洪
同部位舌癌的不同厚度與頸淋巴結(jié)轉(zhuǎn)移間的相關(guān)性
韋存志 肖世強(qiáng) 王建洪
目的探討同部位舌癌厚度與頸淋巴結(jié)轉(zhuǎn)移的關(guān)系。方法回顧性分析手術(shù)切除的T1、T2期舌癌手術(shù)標(biāo)本98例,測量舌癌厚度,對(duì)舌癌進(jìn)行病理分級(jí)和TMN分期;探討患者頸淋巴結(jié)轉(zhuǎn)移與臨床病理因素的關(guān)系,重點(diǎn)分析舌癌厚度與頸淋巴結(jié)轉(zhuǎn)移的關(guān)系;檢測患者血清血管內(nèi)皮細(xì)胞生長因子(VEGF)水平。結(jié)果舌癌組織頸淋巴結(jié)轉(zhuǎn)移與病理分級(jí)、舌癌厚度相關(guān),而與病程、部位、面積、T分期和N分期無相關(guān)。隨著舌癌厚度增加,頸淋巴結(jié)轉(zhuǎn)移率呈現(xiàn)逐漸升高,在厚度為7~10 mm時(shí),轉(zhuǎn)移率最高;舌癌厚度大于7 mm時(shí),頸淋巴結(jié)轉(zhuǎn)移率均明顯高于3~5 mm和5~7 mm組,比較差異有統(tǒng)計(jì)學(xué)意義(P<0.01,P<0.05);舌癌厚度大于10 mm組與7~10 mm組比較,頸淋巴結(jié)轉(zhuǎn)移率變化不明顯。舌癌厚度≥7 mm組患者血清VEGF含量明顯高于<7 mm組(P<0.01)。結(jié)論舌癌厚度測量對(duì)評(píng)估早期舌癌頸淋巴結(jié)轉(zhuǎn)移有重要意義,可能與患者VEGF水平升高相關(guān)。
舌癌;頸淋巴結(jié);轉(zhuǎn)移;血管內(nèi)皮細(xì)胞生長因子
(The Practical Journal of Cancer,2015,30:1146~1148)
口腔癌為臨床常見惡性腫瘤,其中舌癌發(fā)病率為口腔癌之首;舌癌具有惡性程度高、頸部轉(zhuǎn)移率高和致死率高等特點(diǎn)。隨著人們飲食生活習(xí)慣的改變,舌癌的發(fā)病率正呈現(xiàn)逐漸升高趨勢[1],且患者年齡也逐步趨于年輕化[2]。舌癌的臨床治療以手術(shù)為主,而手術(shù)治療的效果在一定程度上取決于術(shù)前有無淋巴結(jié)轉(zhuǎn)移發(fā)生。研究表明,對(duì)于術(shù)前無頸部等或其他區(qū)域淋巴結(jié)轉(zhuǎn)移患者,5年的生存率達(dá)到50%以上,而對(duì)術(shù)前發(fā)生了淋巴結(jié)轉(zhuǎn)移的患者,5年的生存率僅為30%[3]。當(dāng)前,對(duì)于診斷舌癌頸部轉(zhuǎn)移淋巴結(jié)尚無有效方法。在本研究中,我們回顧性分析98例舌癌的厚度對(duì)其頸淋巴結(jié)轉(zhuǎn)移的影響。
1.1 一般資料
回顧性分析2009年9月至2014年12月我院頜面-頭頸外科手術(shù)切除的T1、T2期舌癌手術(shù)標(biāo)本98例,男性68例,女性30例;年齡40~70歲,平均(60.56±8.21)歲。所有病例均為首次手術(shù),術(shù)前均
未進(jìn)行化療和放療,經(jīng)病理診斷均為舌鱗狀細(xì)胞癌。所有患者病例資料齊全,所有舌癌組織獲得均得到患者或患者家屬知情同意。TNM分期根據(jù)2002年國際抗癌聯(lián)盟(UICC)擬定標(biāo)準(zhǔn)[4]進(jìn)行;舌癌組織病理學(xué)分級(jí)依據(jù)1997年WHO關(guān)于口腔鱗狀細(xì)胞癌分級(jí)標(biāo)準(zhǔn)進(jìn)行[5]。所有淋巴結(jié)轉(zhuǎn)移均經(jīng)病理檢查確診。
1.2 舌癌厚度測量
參照國際測量標(biāo)準(zhǔn)[6]進(jìn)行,舌癌厚度為舌癌組織上皮至最深部基質(zhì)或肌肉長度,對(duì)于癌組織表面形成潰瘍者,厚度應(yīng)為潰瘍底到舌癌最深部長度。
1.3 血清VEGF水平測定
于空腹下抽取所有患者靜脈血,離心,取上清,-20℃保存待測;采取Elisa法檢測,試劑盒由上海廣銳生物科技有限公司提供。
1.4 統(tǒng)計(jì)學(xué)方法
2.1 舌癌頸淋巴結(jié)轉(zhuǎn)移與臨床病理因素的關(guān)系
98例舌癌患者頸淋巴結(jié)轉(zhuǎn)移49例。舌癌組織頸淋巴結(jié)轉(zhuǎn)移與病理分級(jí)、舌癌厚度相關(guān),而與病程、部位、面積、T分期和N分期無關(guān),見表1。
表1 舌癌頸淋巴結(jié)轉(zhuǎn)移與臨床病例因素的關(guān)系(例,%)
2.2 不同舌癌厚度下頸淋巴結(jié)轉(zhuǎn)移率比較
隨著舌癌厚度增加,頸淋巴結(jié)轉(zhuǎn)移率逐漸升高,在厚度為>7~10 mm時(shí),轉(zhuǎn)移率最高;舌癌厚度>7 mm時(shí),頸淋巴結(jié)轉(zhuǎn)移率均明顯高于3~5 mm和>5~7 mm組比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.01;P<0.05);而>5~7 mm組患者的頸淋巴結(jié)轉(zhuǎn)移率與3~5 mm組比較,差異無統(tǒng)計(jì)學(xué)意義;舌癌厚度>10 mm組與>7~10 mm組比較,頸淋巴結(jié)轉(zhuǎn)移率變化不明顯,見表2。
表2 不同舌癌厚度下頸淋巴轉(zhuǎn)移率比較(例,%)
2.3 患者血清VEGF含量比較
>7 mm組患者血清VEGF含量為(552.85± 95.27)pg/mL,明顯高于≤7 mm組的(197.81± 49.31)pg/mL,差異有統(tǒng)計(jì)學(xué)意義(t=21.65,P<0.01)。
舌癌作為口腔頜面部最常見惡性腫瘤,淋巴結(jié)轉(zhuǎn)移是其重要的生物學(xué)特性,是影響臨床手術(shù)療效的主要因素之一,其中頸淋巴結(jié)轉(zhuǎn)移是舌癌的主要轉(zhuǎn)移方式,目前國內(nèi)外對(duì)舌癌的頸淋巴結(jié)轉(zhuǎn)移研究報(bào)道較多。如FDG PET的早期診斷,然而也有研究認(rèn)為PET的診斷存在一定局限性,在評(píng)估舌癌頸淋巴結(jié)轉(zhuǎn)移方面無顯著優(yōu)勢[7]。因此,探尋早期診斷舌癌頸淋巴結(jié)轉(zhuǎn)移的有效方法是當(dāng)前口腔科亟待解決的重要臨床難題。
近年,部分研究認(rèn)為直接對(duì)頸淋巴結(jié)探查、癌組織的浸潤深度和病理分級(jí)均可作為評(píng)估淋巴結(jié)轉(zhuǎn)移的有效方法[8-9]。然而,上述方法均存在主觀性大的特點(diǎn),對(duì)評(píng)估結(jié)果可能存在較大誤差,故用于臨床疾病診斷不可為良好方法。部分學(xué)者認(rèn)為可通過術(shù)前MRI診斷,但是這些方法操作復(fù)雜、價(jià)格昂貴,不能適用于普通臨床和人群。本研究采取測量舌癌厚度方法檢測頸淋巴結(jié)轉(zhuǎn)移情況。
結(jié)果顯示,舌癌組織頸淋巴結(jié)轉(zhuǎn)移與病理分級(jí)、舌癌厚度相關(guān),而與病程、部位、面積、T分期和N分期無關(guān)。隨著舌癌厚度增加,頸淋巴結(jié)轉(zhuǎn)移率逐漸升高,在
厚度為>7~10 mm時(shí),轉(zhuǎn)移率最高;舌癌厚度>7 mm時(shí),頸淋巴結(jié)轉(zhuǎn)移率均明顯高于3~5 mm和>5~7 mm組,比較差異有統(tǒng)計(jì)學(xué)意義;舌癌厚度>10 mm組與>7~10 mm組比較,頸淋巴結(jié)轉(zhuǎn)移率變化不明顯;以上結(jié)果與以往研究相近[6,10]。提示,在上述影響舌癌淋巴結(jié)轉(zhuǎn)移的因素中,病理分級(jí)和舌癌厚度起到重要作用,結(jié)合以往研究,我們認(rèn)為相對(duì)于病理分級(jí)存在主觀性大的缺點(diǎn),舌癌厚度可更好地早期評(píng)估頸淋巴結(jié)轉(zhuǎn)移,可能是臨床診治舌癌的較好方法。
腫瘤轉(zhuǎn)移是一個(gè)動(dòng)態(tài)的、復(fù)雜過程,依賴于新的血管生成,豐富的血管可以供給腫瘤組織血液和氧氣,而VEGF對(duì)腫瘤血管生成起到重要調(diào)節(jié)作用[11]。腫瘤組織能夠分泌VEGF等因子,促進(jìn)血管生成的同時(shí)也降解血管基膜和組織基質(zhì),從而癌細(xì)胞可快速進(jìn)入血液循環(huán)和周圍組織,導(dǎo)致轉(zhuǎn)移發(fā)生[12]。目前,在肝癌、乳腺癌和胃癌中均已證實(shí)VEGF與癌細(xì)胞的轉(zhuǎn)移及其患者的預(yù)后存在直接相關(guān)性[13]。近年,關(guān)于VEGF對(duì)舌癌淋巴結(jié)轉(zhuǎn)移的研究也有報(bào)道[14],然而關(guān)于舌癌厚度是否與外周血VEGF水平相關(guān)尚不清楚。本研究結(jié)果顯示,舌癌厚度≥7 mm組患者血清VEGF含量明顯高于<7 mm組,比較差異有統(tǒng)計(jì)學(xué)意義。提示在舌癌發(fā)生頸淋巴結(jié)轉(zhuǎn)移過程中,血液中VEGF水平增加,促進(jìn)血管生成;因此,患者舌癌得到更多營養(yǎng)物質(zhì),因?yàn)楹穸仍黾?同時(shí)過多的營養(yǎng)和血管生成,也有利于淋巴結(jié)轉(zhuǎn)移,這可能是兩者間相互作用的機(jī)制之一。
綜上,隨著舌癌組織厚度的增加,患者頸淋巴結(jié)轉(zhuǎn)移的發(fā)生率也逐漸升高,本研究結(jié)果和以往國內(nèi)外學(xué)者研究結(jié)果相近。此外,本研究也發(fā)現(xiàn)舌癌組織厚度增加引起的頸淋巴結(jié)轉(zhuǎn)移發(fā)生可能與患者機(jī)體或癌組織分泌過多VEGF有關(guān),為臨床診治舌癌提供了更多研究依據(jù)。
[1]Wade J,Smith H,Hankins M,et al.Conducting oral examinations for cancer in general practice:What are the barriers?〔J〕.Fam Pract,2010,27(1):77-84.
[2]Sano K,Kitai R,Yoshimura H,et al.Frontal meningioma incidentally detected in the routine preoperative assessment of tongue cancer:a case report and literature review〔J〕.J Oral Maxillofac Surg,2013,71(12):2195.e1-6.
[3]Zhang T,Ord RA,Wei WI,et al.Sublingual lymph node metastasis of early tongue cancer:report of two cases and review of the literature〔J〕.Int J Oral Maxillofac Surg,2011,40(6):597-600.
[4]International Union Against Cancer.TMN classification of malignant tumours〔M〕.6th ed.NewYork:Wiley,2002: 102.
[5]Pindborg JJ,Reichart PA,Smith CJ,et al.Histological typing of cancer and precancer of the oral mucosa〔M〕.2nd E-dition.New York:Springer-Verlag Berlin heideberg,1997: 11-12.
[6]Matos LL,Manfro G,Santos RV,et al.Tumor thickness as a predictive factor of lymph node metastasis and disease recurrence in T1N0 and T2N0 squamous cell carcinoma of the oral tongue〔J〕.Oral Surg Oral Med Oral Pathol Oral Radiol,2014,118(2):209-217.
[7]Iwai T,Baba J,ShⅠBasaki M,et al.18F-fluorodeoxyglucose-positive Warthin tumor in a contralateral cervical lymph node mimicking metastasis in tongue cancer staging with PET/CT〔J〕.J Craniofac Surg,2012,23(5):e507-509.
[8]Lloyd S,Yu JB,Wilson LD,et al.The prognostic importance of midline involvement in oral tongue cancer〔J〕.Am J Clin Oncol,2012,35(5):468-473.
[9]Sparano A,Weinstein G,Chalian A,et al.Multivariate predictors of occult neck metastasis in early oral tongue cancer〔J〕.Otolaryngol Head Neck Surg,2004,131(4):472-476.
[10]周輝紅,徐秋華,胡永杰,等.舌鱗狀細(xì)胞癌厚度與區(qū)域淋巴結(jié)轉(zhuǎn)移的超聲研究〔J〕.上??谇会t(yī)學(xué),2008,17 (5):465-470.
[11]Shen Z,Kauttu T,Sepp?nen H,et al.Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs〔J〕.Med Oncol,2012,9(4):2718-2726.
[12]Huang TH,Chiu YH,Chan YL,et al.Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor(VEGF)and matrix metalloproteinases(MMPs)in lewis tumor-bearing mice〔J〕.Mar Drugs,2015,13(4):1882-1900.
[13]Bilgi? CI,Tez M.Serum VEGF levels in gastric cancer patients:correlation with clinicopathological parameters〔J〕.Turk J Med Sci,2015,45(1):112-117.
[14]黃欣,溫玉明,李龍江.外周血VEGF表達(dá)水平與舌癌頸淋巴結(jié)轉(zhuǎn)移關(guān)系的臨床研究〔J〕.實(shí)用口腔醫(yī)學(xué)雜志,2004,20(3):329-331.
Correlation between Thickness of Tongue Cancer and Cervical Lymph Node Metastasis
WEI Cunzhi,XIAO Shiqiang,WANG Jianhong.Yibin First People's Hospital,Yibin,644000
ObjectiveTo study the correlation between thickness of tongue cancer and cervical lymph node metastasis.Methods98 cases with T1 and T2 tongue cancer were retrospectively analyzed.Thickness of tongue cancer was measured,and pathological grading and TMN stage were analyzed.The relationship between cervical lymph node metastasis and clinicopathological parameters,especially between thickness of tongue cancer and cervical lymph node metastasis were analyzed.Serum level of vascular endothelial growth factor(VEGF)in all patients was detected.ResultsCervical lymph nodes metastasis of tongue cancer was highly correlated with histological grade and thickness of tongue cancer,but not with course of disease,position,area,T stage,and N stage.Metastasis rate was increased following raise of thickness of tongue cancer,and metastasis rate was highest at 7~10 mm.When thickness of tongue cancer was bigger than 7 mm,metastasis rate of cervical lymph node was higher than that of 3~5 mm group and 5~7 mm group,there had statistical difference(P<0.01,P<0.05).Cervical lymph node metastasis had no statistical difference between>10 mm group and 7~10 mm group.Serum level of VEGF in thickness of tongue cancer≥7 mm group was obviously higher than that<7 mm group(P<0.01).ConclusionThickness of tongue cancer can play an important role in evaluating cervical lymph node metastasis,which may be related with increase of serum VEGF level.
Tongue cancer;Cervical lymph node;Metastasis;VEGF
10.3969/j.issn.1001-5930.2015.08.012
R739.86
A
1001-5930(2015)08-1146-03
2015-05-13
2015-06-29)
(編輯:甘艷)
四川省宜賓市衛(wèi)生局科研基金項(xiàng)目(編號(hào):2012400007)
644000四川省宜賓市第一人民醫(yī)院