P27KiPl在食管良恶性疾病中的表达及与食管癌淋巴结转移的关系

目的 研究 P27KiPl(Kinase inhibitor proteinl,P27)在食管良恶性病变中的表达及意义。方法 以免疫组织化学SP法检测P27在食管增生的鳞状上皮、食管息肉及食管鳞癌中的表达。结果 P27在食管增生上皮、食管息肉及食管癌中的阳性表达率分别为93.3％、100％及48.0%,三者差异有极显著性(P<0.005),良性病变阳性率显著高于恶性肿瘤(P<0.01),而且P27表达状况与食管癌淋巴转移显著相关(P<0.05)。结论 食管癌中P27表达水平显著下降,且P27低表达与淋巴结转移有关。     

食管鳞癌组织中Survivin、Bcl-2蛋白的表达及意义

目的 探讨食管鳞癌中Survivin、Bcl-2蛋白的表达及其临床意义.方法 应用免疫组织化学SP法检测39例食管鳞癌组织、23例不典型增生组织及39例正常食管黏膜组织中Survivin、Bcl-2蛋白表达情况.结果 Survivin蛋白在癌组织中表达率为59.0%(23/39),Survivin蛋白的表达与肿瘤的临床分期、淋巴转移关系密切(P均＜0.05).Bcl-2蛋白在癌组织、癌旁不典型增生组织中的表达率为69.2%(27/39)、21.7%(5/23),Bel-2蛋白的表达与肿瘤组织的分化程度、临床分期、淋巴结转移有关(P均＜0.05);Survivin蛋白与Bcl-2蛋白表达呈正相关(r=0.46,P＜0.01).结论 Survivin蛋白和Bel-2蛋白的表达在食管癌的发生、发展中起重要作用.     

食管癌发生发展过程中RAR-βmRNA的原位表达

目的:研究RAR-β mRNA在食管癌发生发展过程中的作用,探讨维A酸(RA,retinoid acid)在食管癌高危人群中化学预防和化学治疗中应用的可行性.方法:应用原位杂交方法检测了食管癌70例(原位癌30例,鳞状细胞癌20例,腺癌20例)及增生性病变97例(单纯增生19例,不典型增生Ⅰ-Ⅲ分别为20例,39例,38例)和正常食管黏膜鳞状上皮组织19例中RAR-β mRNA表达情况.结果:在正常食管黏膜上皮、单纯增生、不典型增生上皮总体及其Ⅰ-Ⅲ、原位癌、侵袭性鳞状细胞癌及腺癌中RAR-β mRNA表达的阳性率分别为100%(19/19),94.7%(18/19),90%(18/20),69.2%(27/39),68.4%(26/38),63.3%(19/30),60%(12/20),60%(12/20).正常食管黏膜上皮较不典型增生总体、原位癌和侵袭癌组织均有显著性差异(P＜0.05).结论:RAR-β mRNA达的丢失与食管癌的发生发展有关,用RA对表达RAR-β高危人群进行化学干预可能会得到预期效果.     

食管鳞癌中RECK和MMP-9蛋白表达的相关性及临床病理意义

目的:探讨RECK及基质金属蛋白酶-9(MMP-9)表达与食管癌发生、发展及浸润、转移的关系.方法:应用免疫组化SP法检测62例食管鳞癌组织、31例癌旁不典型增生组织及62例正常食管黏膜组织中RECK及MMP-9蛋白表达.采用X2检验进行统计学分析.结果:食管鳞癌组织中RECK和MMP-9蛋白表达与癌的组织学分级、浸润深度及淋巴结转移密切相关(χ2=10.422,8.550,4.751;χ2=8.447,14.333,5.373;均P＜0.05).在食管鳞癌癌变过程中RECK蛋白表达在癌组织、癌旁不典型增生组织及正常黏膜组织中的表达率依次增高,分别为59.7%,71.0%,85.5%,组间比较有明显差异(P＜0.01);而MMP-9蛋白在癌组织、癌旁不典型增生组织及正常黏膜组织中的表达率依次降低,分别为80.6%,80.6%,27.4%,组间比较有明显差异(P＜0.01).结论:RECK和MMP-9在食管癌的浸润、转移及黏膜上皮癌变过程中起重要作用,RECK及MMP-9的联合检测可望成为食管鳞癌早期诊断和判断预后的分子指标之一.     

基质金属蛋白酶-2和-9在食管鳞状细胞癌中的过表达

目的 探讨人食管鳞癌组织中基质金属蛋白酶(MMP)-2、-9的表达及其临床意义.方法 采用免疫组织化学法,检测57例食管鳞癌及10例食管正常黏膜石蜡标本中MMP-2、-9蛋白的表达情况.结果 食管鳞癌组织中MMP-2及MMP-9阳性表达率(40.3%,61.4%)显著高于正常组织(0.0%,10.0%)(P＜0.05).食管鳞癌组织中MMP-2及MMP-9阳性表达与淋巴结转移和癌组织浸润深度有显著相关性(P＜0.05),而与患者的性别、年龄和组织分化程度无显著相关性(P＞0.05).结论 MMP-2和MMP-9在食管癌中显著高表达,与食管癌的转移及侵袭有关,其异常表达可能共同参与食管癌的发生、发展过程,检测MMP-2、-9可作为食管癌病理学特点的参考指标.     

食管鳞癌组织中p27kip和VEGF的表达及意义

采用免疫组织化学SP法检测118例食管癌组织及20例正常食管黏膜中p27kip和VEGF的表达.结果 食管癌组织中p27kip蛋白阳性表达率为38.13%,显著低于正常食管黏膜的100%(P<0.01),与组织分化程度呈正相关(r=0.65,P<0.01),与淋巴结转移呈负相关(r=-0.55,P<0.01).VEGF在食管癌中的阳性表达率为66.95%,显著高于正常食管黏膜的15.0%(P<0.01),与癌组织浸润深度呈正相关(r=0.75,P<0.01),与淋巴结转移亦呈正相关(r=0.64,P<0.01),与组织分化程度呈负相关(r=-0.65,P<0.01).p27kip在食管癌中的表达与VEGF呈负相关(P<0.01).认为联合检测p27kip、VEGF有助于评估食管癌侵袭转移能力和预后.     

Smad4、MMP-2在食管鳞癌中的表达及其与侵袭转移的关系

目的 旨在探讨Smad4与基质金属蛋白酶-2(MMP-2)在食管癌中的表达及其与侵袭转移的关系.方法 采用SP免疫组化法分别检测80例食管癌组织中Smad4和MMP-2的表达,分析其与肿瘤侵袭、淋巴结转移的关系,同时分析食管鳞癌中Smad4与MMP-2的相关性.结果 Smad4在食管癌组织中的表达显著低于癌旁正常食管组织(P＜0.01),MMP-2在食管癌组织中的表达显著高于癌旁正常食管组织(P＜0.01);食管癌组织中Smad4的表达缺失及MMP-2蛋白高表达均与肿瘤的浸润深度、淋巴结转移及临床分期密切相关(P＜0.05),Smad4和MMP-2在食管癌组织中表达呈负相关(P＜0.05).结论 Smad4蛋白表达缺失和MMP-2蛋白过表达在食管癌的发展及侵袭转移中具有重要作用,Smad4蛋白和MMP-2蛋白在食管癌的发生发展过程中具有协同作用,联合检测食管癌中Smad4蛋白和MMP-2蛋白的表达,比单一检测一种蛋白对评估食管癌的发生、发展及预后更具有意义,也为临床治疗食管癌提供了一条新的思路.     

细胞周期相关基因在食管癌变中的表达及意义

目的 研究细胞周期调控因子细胞周期素25A (cell division cycle 25 A,CDC25A)、转化生长因子-β(TGF-β)、Smad3基因在食管上皮癌变过程中的表达及其意义.方法 利用RT-PCR方法检测44例同一个体的食管癌、食管不典型增生组织、食管正常黏膜组织中CDC25A、TGF-β、Smad3 mRNA的表达.结果 从食管正常黏膜组织到不典型增生组织和食管癌组织,CDC25A基因表达呈逐渐增高趋势,TGF-β、Smad3基因表达呈逐渐下降趋势,三者在食管癌组织和正常组织之间有显著差异(P＜0.05).低分化鳞癌中CDC25A基因表达显著高于中高分化鳞癌(P＜0.05),低分化鳞癌中TGF-β、Smad3基因表达显著低于中高分化鳞癌(P＜0.05).其表达量与年龄和性别无关(P＞0.05).结论 CDC25A、TGF-β、Smad3的表达失衡与食管癌的发生、发展有密切关系,在食管癌变早期即已出现,可以作为早期诊断的指标.     

外周血液CEAmRNA基因表达与食管癌微转移关系的研究

目的探讨靶基因CEAmRNA在食管癌患者外周血中的表达及与肿瘤微转移的关系.方法应用巢式-反转录聚合酶链反应(Nested-RT-PCR)检测50例无远处转移、10例有远处转移的食管癌患者,10例食管良性病变和10例健康成人外周血中癌胚抗原CEAmRNA基因的表达.结果食管癌良性病变者和健康成人的外周血中均未检测出CEAmRNA阳性细胞.50例无远处转移、10例有远处转移的食管癌患者外周血中CEAmRNA阳性率分别为30.2%(16/50)、80.0%(8/10),P＜0.01;食管癌Ⅳ期与Ⅱa、Ⅱb、Ⅲ期者阳性率比较差异有显著性(P均＜0.01),而其他各期之间阳性率比较差异无显著性(P＞0.05);不同程度病理分化者间阳性率比较差异无显著性(P＞0.05).结论食管癌患者临床早期已有癌细胞微转移.应用Nested-RT-PCR检测外周血中CEAmRNA靶基因有助于早期诊断.     

APRIL mRNA在食管鳞癌组织中的表达及意义

应用SYBR GreenⅠ实时荧光定量PCR法检测63份食管鳞癌、30份正常食管上皮、36份单纯增生、29份轻度不典型增生、10份重度不典型增生、4份原位癌组织中APRIL mRNA的表达,并分析其与临床病理特征的关系.结果 食管鳞癌组织APRIL mRNA表达显著高于正常黏膜组织(P<0.05),且在轻度不典型增生、原位癌及浸润癌中的表达均高于正常黏膜组织(P<0.01或P<0.05).APRIL mRNA的表达水平与淋巴结转移相关(P<0.05).提示APRIL mRNA可作为食管癌早期诊断及预后判断的参考指标.     

Association of esophageal cancer and esophageal varices

Of the 312 cases of esophageal cancer seen over 2 years, four patients had associated varices. Three patients gave history of alcohol abuse. All had malnutrition and splenomegaly. Endoscopic biopsies were safe in the presence of varices. External radiation did not have any untoward effect on the varices. Prophylactic sclerotherapy was not required in these patients. The association between esophageal carcinoma and varices could be secondary to alcohol consumption or merely coincidental.     

Influence of smoking and esophageal intubation on esophageal pH-metry

The effect of cigarette smoking on gastroesophageal reflux and the effect of the pH electrode on salivary secretion and swallowing frequency were studied in 30 healthy volunteers (15 habitual smokers, 15 non-smokers) and in 10 smoking patients with proven gastroesophageal reflux disease. Twenty-four-hour pH profiles were measured while the subjects were ambulatory using a combined glass electrode connected to a portable recorder. In 8 of the smoking volunteers, swallowing frequency and salivary secretion were measured, both when smoking and when not. Smokers had more reflux episodes than nonsmokers [median per hour 2.8 (range 0.4-7.1) for the upright body position and 0.5 (range 0.0-1.7) for the supine body position vs. 1.4 (range 0.0-2.1) upright and 0.0 (range 0.0-0.7) supine, p less than 0.01], but the total time of exposure of the esophageal mucosa to acid was affected neither by the status of being a smoker nor by actual smoking. Nasopharyngeal intubation with the pH electrode did not affect the swallowing frequency, but it increased salivary secretion two-to threefold for a period of 4 h. Six hours after introduction of the pH electrode and later, salivary flow was similar to baseline. It is concluded that smoking and nasopharyngeal intubation does not adversely affect the results of 24-h pH-metry.     

Relationship between esophageal achalasia subtypes and esophageal clearance

Esophagus - The diagnosis and pathological evaluation of esophageal achalasia have been improved dramatically by the development of high-resolution manometry. It is currently known to be divided...     

食管静脉及食管、胃粘膜变化预测门脉高压食管静脉曲张出血的价值

为探讨门脉高压症患者内镜下食管静脉(EV)、食管粘膜及胃粘膜变化预测出血的价值,将60例肝硬化门脉高压患者分为出血组(36例)和非出血组(24例),分别观察其EV曲张形态、范围及颜色,炎性表现,胃粘膜改变及有无胃食管返流病(GERD)等.结果出血组EV曲张范围多超过食管中段,呈灰蓝、樱红色,静脉扭曲呈结节状,外径平均6.0±1.6mm;非出血组EV多局限于食管下段,呈灰白或灰蓝色,外径平均4.2±1.2mm;出血组食管炎20例(55.5%),非出血组5例(20.8%).出血组有胃粘膜损害者20例,非出血组为6例(P＜0.01).认为食管静脉曲张超过中段、外径≥6.0mm、有樱红样征;伴有食管炎、GERD及门脉高压性胃病者的出血率明显增加;上述指标预测门脉高压出血具有实用价值.     

Effects of nifedipine on esophageal tone and perception of esophageal distension

The effects of nifedipine (20 mg orally) on esophageal body resting tone and perception of esophageal distension were compared with those of placebo in 10 healthy volunteers, using a double-blind crossover design. A 3-cm silicon balloon positioned 10 cm above the lower esophageal sphincter was inflated with 2–20 ml of air, in 2-ml increments. The subjects scored their chest sensations, while pressure in the balloon was continuously recorded. In each experiment three series of measurements were made, at baseline and 15 and 30 min after administration of nifedipine or placebo. Bench tests were run to determine pressure-to-volume relationships for each of the balloons used in the study. Thirty minutes after nifedipine ingestion, a significant decrease in systolic blood pressure (from 112.6±2.3 to 99.0±2.0 mm Hg) was observed. Amplitude and duration of esophageal peristaltic contractions were significantly decreased by nifedipine (from 128.1±16.7 to 98.7±10.6 mm Hg and from 3.9±0.3 to 3.3±0.2 sec, respectively). With balloon volumes of 8 ml and higher, balloon pressures were higher with the balloon in the esophagus than on the bench, the difference being determined by the compliance of the esophagus. This difference rose from 18.5±6.8 to 40.2±7.2 mm Hg (8–20 ml) with placebo and from 23.1±3.7 to 35.9±5.8 mm Hg with nifedipine. No significant differences between nifedipine and placebo were found. The esophageal sensation scores increased linearly with increasing balloon volume from 6 ml onwards. Nifedipine had no significant effect on the perception of esophageal balloon distension.     

Lower esophageal sphincter pressure, esophageal body motor functioning, and esophageal acid sensitivity

Esophageal acid sensitivity is believed to develop as a result of esophageal acid exposure, contributing factors being gastroesophageal reflux and delayed esophageal acid clearance. The relationship among lower esophageal sphincter pressure, motor functioning of the body of the esophagus, and esophageal acid sensitivity was examined by comparing the results from 912 patients and normal subjects studied with both esophageal manometric and Bernstein acid infusion tests. Positive acid infusions were statistically more closely associated with hypotensive lower esophageal sphincter pressures than with any motor abnormality in the body of the esophagus. Of the several esophageal body motor abnormalities considered, only feeble peristalsis had significantly more positive Bernstein tests than did normal esophageal body motor functioning. The findings from this study demonstrate that hypotensive lower esophageal sphincter pressure is more closely associated with an acid-sensitive esophagus than is impaired esophageal body motor functioning.     

Effects of transdermal nicotine on lower esophageal sphincter and esophageal motility

Cigarette smoking has been shown to decrease lower esophageal sphincter pressure (LESP) by 19–42%. This decrease in LESP may be due to nicotine in the cigarette smoke or substances other than nicotine. The aim of this study was to evaluate the effects of a nicotine patch on esophageal motility since nicotine patches are devoid of all toxins present in the cigarette smoke except the nicotine. Ten healthy nonsmoking volunteers underwent baseline esophageal manometry. Esophageal manometry was repeated after placing a nicotine transdermal patch (Nicotrol) designed to deliver 15 mg of nicotine per day. The parameters that were compared included LESP by rapid pull-through (LESP-RPT) and station pull-through (LESP-SPT), LES relaxation, and velocity, amplitude, and duration of esophageal contractions. Plasma nicotine and cotinine levels were measured prior to baseline manometry and after 12 hr of placing the nicotine patch. the LESP-RPT decreased by 31% from 17.4±6.1 to 12.1±3.3 (P=0.013) and the LESP-SPT by 27% from 13.4±5.4 to 9.8±4.8 (P=0.029) after the nicotine patch. LES relaxation was present in 100% before and after nicotine patch. There were no significant differences in velocity, duration, and amplitude of esophageal contractions after the nicotine patch. Plasma nicotine and cotinine was absent in all subjects at baseline but was significantly elevated after 12 hr of nicotine patch. Transdermal delivery of nicotine results in a significant reduction in LESP in healthy subjects without effecting LES relaxation or esophageal body motility.The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense.This work was published in an abstract form in Gastroenterology 106:A1047, 1994.     

Effect of esophageal erosion on esophageal electrocardiogram

We recorded an esophageal electrocardiogram in a rabbit before and after producing esophageal erosion. The erosion caused an increase in P wave and R wave height and inversion of the T wave. Esophageal erosion can thus cause false positive repolarization changes in the esophageal electrocardiogram.