河北省磁县食管癌普查

[目的]通过内镜普查了解食管癌高发区人群食管及贲门癌和其他各种病变的患病情况，达到早诊早治的目的。[方法]河北省肿瘤研究所于2002年在磁县台城乡进行了电子纤维胃镜辅以碘染色普查，结果采用SPSSl0．0软件进行统计学处理。[结果]食管癌高发区人群中轻度食管炎、中度食管炎、重度食管炎的组织学检出率分别是34．9％、1．6％、0．2％；轻度不典型增生、中度不典型增生、重度不典型增生的组织学检出率分别是8．6％、7．8％、2．6％；食管原位癌、黏膜内癌、浸润性鳞癌的组织学检出率分别是2．5％、0．2％、0．7％。贲门炎的组织学检出率是47．8％；轻度不典型增生、重度不典型增生的组织学检出率分别是2．5％、0．8％；黏膜内腺癌、浸润性腺癌的组织学检出率分别是0．1％、0．8％。内镜普查食管癌的早期发现率为79．4％。普查率达73．8%。[结论]电子纤维胃镜辅以碘染色直接普查较拉网普查的优点是可以得到食管和贲门各种病变的组织学诊断，早期食管癌的检出率高于拉网普查．为二级预防打下基础。     

食管癌高发区的内镜普查研究

目的　通过内镜普查了解食管癌高发区人群食管及贲门癌和其他各级病变的分布情况。方法 :河北省肿瘤研究所于 2 0 0 1年 12月 - 2 0 0 2年 5月在河北省磁县进行了碘染色内镜普查 ,普查结果采用SPSS10 0处理。结果 :食管癌高发区人群中 ,轻、中、重度食管炎的组织学检出率分别是 34 9%、1 6 %、0 2 % ,基底细胞增生、轻、中、重度不典型增生的组织学检出率分别是 0 9%、8 6 %、7 8%、2 6 % ,原位癌、黏膜内癌、浸润性鳞癌的组织学检出率分别是 2 5 %、0 2 %、0 7% ;贲门黏膜非萎缩性胃炎、萎缩性胃炎的组织学检出率分别是 36 3%、11 5 % ,轻、重度不典型增生的组织学检出率分别是2 5 %、0 8% ,黏膜内腺癌、浸润性腺癌的组织学检出率分别是 0 1%、0 8% ;内镜普查食管癌的早期发现率为 79 4 % ,普查率达 73 8%。结论 :本次普查为食管及贲门早期癌的治疗及癌前病变的阻断治疗提供了组织学诊断 ,为今后提高食管癌、贲门癌的治愈率 ,降低食管癌、贲门癌的发病率及死亡率打下了基础     

A Survey of Esophageal Cancer in Cixian County of Hebei Province

OBJECTIVE To characterize the histologic types of esophageal cardiac mucosa by endoscopic survey in a high-risk cancer area of China. METHODS An endoscopic survey with Lugol,s staining was carried out in Cixian County, Hebei Province from December 2001 to May 2002. The data were processed using computer SPSS 10.0 software. RESULTS The incidences of mild esophagitis, moderate esophagitis, and severe esophagitis were for 2013 cases, 34.9%(703), 1.6%(33) and 0.1% (2)respectively; those with mild dysplasia, moderate dysplasia, severe dysplasia of the esophagus were 8.6% (172), 7.8% (157) and 2.6% (53) respectively; those with carcinoma in situ, intramucosal carcinoma, invasive squamous carcinoma of the esophagus were 2.5%(50), 0.2% (4) and 0.7%(14) respectively. The histologic-detecting rates of non-atrophic gastritis, and atrophic gastritis of the cardia were 36.3%(730), 11.5% (232) respectively; those with mild dysplasia, severe dysplasia of the cardia were 2.5%(51), 0.8%(17) respectively; those with intramucosal adenocarcinoma, invasive adenocarcinoma of the cardia were 0.1% (3), 0.8%(17) respectively. The early-detection rate of esophageal cancer was 79.4%(54/68). The survey rate(examined population to covered population) was 73.8% (2013/2725). CONCLUSIONS Esophageal endoscopic screening with Lugol‘s solution staining has an advantage over esophageal balloon cytology, in that the histological diagnoses of esophageal cardiac diseases can be obtained, thus contributing to the prevention of subsequent disease. In using the staining method the detection rate of early esophageal cancer is higher than that revealed by balloon cytology.     

Precursor lesions of esophageal cancer in high-risk populations in Henan Province, China

This report discusses precancerous changes in the esophageal mucosa from three points of view: the histopathologic features of the esophageal mucosa in persons known to be at high risk for esophageal carcinoma (EC); the histopathologic features of the esophageal mucosa of asymptomatic persons randomly selected from areas at high and low risk for EC; and a prospective follow-up of a randomly examined group to determine the impact of esophagitis and dysplasia upon subsequent development of EC. Esophagitis was commonly found at endoscopic examination, but there was no difference in frequency of esophagitis in the randomly selected subjects from high-risk and low-risk areas. Although one third of patients with dysplasia developed cancer over a follow-up period of 30 to 78 months, only 4% of those with esophagitis alone developed EC. The authors conclude that dysplasia, diagnosed by cytologic or histologic examination, is a precancerous state, and that esophagitis is a nonspecific pathologic condition of the esophagus, but moderate and severe types of chronic esophagitis might create an environment favorable for the development of esophageal carcinoma.     

Reliability of balloon-mesh cytology in detecting esophageal carcinoma in a population of US veterans

A catheter, equipped with a terminal balloon covered with nylon mesh, was developed to study the reliability of abrasive cytology for the diagnosis of esophageal carcinoma. Eighty-seven balloon cytology analyses were attempted in 82 subjects. Four patients were unable to swallow the balloon. In the 78 successful attempts, the initial diagnoses were: esophagitis (34) and esophageal carcinoma (13), established by endoscopic examination and histologic sampling; and normal esophagus (31) confirmed histologically in 25. The remaining 6 controls were younger than 40 years old, without any significant history of smoking, drinking and esophageal symptoms. For esophageal carcinoma, the sensitivity of balloon cytology was 91% and the specificity was 94% with four false-positives. Balloon cytology was generally well-tolerated and easily performed. This method is now being tested for screening high-risk patients for esophageal carcinoma.     

山东省肥城市2006-2012年676例食管癌前病变内镜筛查结果分析

[目的]研究食管癌高发地区食管癌前病变转归情况及其影响因素,为食管癌前病变及食管鳞癌的防治工作提供科学依据。[方法]采用历史性队列研究方法对山东省肥城市2006-2012年期间接受筛查未治疗,并进行病理检查随访的受检者资料进行分析,描述首检及随访筛检结果,分析影响癌前病变发生、发展的因素。[结果]676例首检者接受随访,筛检结果为417例(61.7%)发生逆转,157例(23.2%)保持稳定,102例(15.1%)发生进展。102例进展者的病理诊断结果分别为9例食管炎,26例轻度异型增生,27例中度异型增生,30例重度异型增生原位癌,10例食管癌。其中基底细胞增生平均间隔为2.7年,随访结果为食管癌,轻度异常增生为6.3年,中度异常增生为2.9年,重度异型增生/原位癌为1.0年。男性、饮酒、饮茶为癌前病变发生、发展的危险因素,其OR值和95%CI值分别为1.712(1.088~2.694)、1.611(1.058~2.453)、1.784(1.004~3.170);年龄<55岁为癌前病变发生、发展的保护因素。[结论]首检后对基底细胞增生和轻度异型增生应间隔2年复查一次,对中度异型增生和未治疗的重度异型增生/原位癌应间隔半年复查一次,以减少早期癌的漏诊率;对男性、年龄≥55岁、饮酒、饮茶的癌前病变人群应加强筛查力度。     

Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation

BACKGROUND: Anorectal cytology has been increasingly used as a screening method for anal squamous lesions, particularly in high-risk, homosexual, patients with human immunodeficiency virus infection. The diagnostic cytologic, anoscopic, and histologic criteria bear some resemblance to the criteria used in cervicovaginal samples with few differences. It is important to recognize these differences because they can lead to an erroneous diagnosis of dysplasia and unnecessary procedures. METHODS: Seventy-eight anorectal cytology specimens from 51 patients were reviewed blindly. Of the 51 patients, 33 were HIV positive. The cytology specimens consisted of 75 ThinPrep (Cytyc, Boxborough, MA) and 3 conventional Papanicolaou-stained smear specimens. The revised diagnosis was compared with the original diagnosis, corresponding histology specimens, and anoscopic results, when available. RESULTS: Six specimens were unsatisfactory for review. The revised diagnosis was negative in 15 patients, atypical squamous cells of undetermined significance in 3 patients, low-grade squamous intraepithelial lesions in 24 patients, high-grade squamous intraepithelial lesions in 28 patients, and squamous cell carcinoma (SQC) in 2 patients. Five patients with an original diagnosis of SQC had the diagnosis revised upon review of their specimens. It is noteworthy that these five specimens showed the presence of atypical parakeratotic cells. Thirty-two patients had anoscopic evaluation and 30 patients had histologic correlation. Twenty-seven patients with abnormal anoscopic findings had confirmed abnormal histologic findings. Twenty- five of the 32 (78%) patients had abnormal cytology that correlated with abnormal anoscopic findings. CONCLUSIONS: Anorectal cytology is an accurate method for screening patients for anal squamous lesions. Atypical parakeratotic cells represent a potential pitfall. Anoscopy is important in confirming the presence of a lesion, but only a biopsy can accurately determine the grade of a lesion.     

No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: result from a cross-sectional study in a high-risk region of China

Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases.     

p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions

Esophageal squamous cell carcinoma (ESCC) is a common cancer with a very poor prognosis. New methods are needed to screen high-risk populations and identify curable tumors and precursor lesions early. Molecular markers may be useful in such screening efforts. This study was designed to determine the prevalence of p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in patients with ESCC to evaluate the variation of gene methylation across a spectrum of preneoplastic lesions, and assess the feasibility of using gene methylation in a primary screening test utilizing frozen esophageal cells collected by balloon cytology samplers. Samples were obtained from high-risk subjects from north central China. These samples included 11 foci of histologically normal mucosa, 8 foci of low-grade squamous dysplasia, 7 foci of high-grade squamous dysplasia, and 13 foci of ESCC from 6 fully embedded resection specimens; endoscopic biopsies from 6 individuals with no histological evidence of disease; and frozen esophageal balloon samples from 12 asymptomatic subjects. Promoter CpG site-specific hypermethylation status was determined for each gene using real-time methylation-specific PCR (qMS-PCR) based on Taqman chemistry. Of the 6 ESCC patients, 5 showed methylation of at least one gene. For most genes, methylation occurred with increasing frequency during neoplastic progression, with the largest increase found between low- and high-grade dysplasia. There was considerable variation in methylation patterns among different foci of the same histological grade, even within individual patients, but 16/20 (80%) of high-grade dysplastic and cancer foci had >or= 2 methylated genes, while 17/19 (89%) of normal and low-grade dysplastic foci had <2 methylated genes. These genes were rarely methylated in histologically normal mucosa from patients with or without ESCC. Gene methylation was common and easily detectable in the frozen esophageal cells collected by balloon cytology samplers. Our data suggest that methylation of p16, MGMT, RARbeta2, CLDN3, CRBP, and MT1G is common in the esophageal mucosa of patients with ESCC in this high-risk population, and tends to increase in prevalence in foci with increasing histological severity of disease. Methylation data from panels of genes may be able to identify patients with high-grade lesions. Balloon cytology may be able to screen the length of the esophagus effectively for a subset of cells with abnormal methylation, and may be useful in a primary screening test for ESCC and its precursor lesions.     

Endoscopic assessment and management of early esophageal adenocarcinoma

Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion.     

应用内镜下碘染色在食管癌高发区进行普查的意义

背景与目的：食管癌的死亡率一直居高不下,主要是由于其早诊率较低。为提高食管癌的早诊率,本研究探讨在我国食管癌高发区应用直接内镜下碘染色进行普查提高食管癌早诊率的可行性。方法：应用直接内镜下碘染色在我国食管癌高发区对3164名高危人群进行3次普查,每个普查对象均在着色区取一块活检组织,且每例可疑病例也均在食管的不着色区取活检组织作病理检查,然后将食管鳞状上皮的着色情况与其对应的病理检查结果进行对照。结果：（1）早期食管癌100％碘染色阳性,染色级别多为I级。早期食管癌检出率为1．6％－4．59％,中晚期食管癌的检出率为0．29％－1．09％,食管癌的早诊率均在75％以上。（2）食管鳞状上皮重度不典型增生95．6碘染色阳性,其中91．3％病例碘染色级别为I和Ⅱ级。食管鳞状上皮重度不典型增生检出率为4．49％－7．68％。（3）中度不典型增生96．6％碘染色阳性,73．3％病变染色级别为Ⅱ和Ⅲ级。（4）92．3％轻度不典型增生碘染色阳性,86．5％病变染色级别为Ⅱ和Ⅲ级。（5）而只有0．9％的炎症和0．4％的正常组织碘染色级别为I和Ⅱ级,正常组织大多数为阴性或Ⅲ级。结论：在食管癌高发区应用直接内镜下碘染色进行普查,对早期食管癌及其癌前病变有较高的检出率。     

P53 expression in esophageal dysplasia - a possible biomarker for carcinogenesis of esophageal squamous-cell carcinoma

The tumor suppressor gene product p53 has been detected in a high percentage of esophageal squamous cell carcinoma. To evaluate the role of this protein in carcinogenesis, we examined the p53 overexpression both in esophageal dysplasia and in esophageal squamous cell carcinoma in the same patients. Using anti-p53 antibodies pAb1801 and CM-1, we analyzed immunohistochemically 36 dysplastic lesions from 36 patients with esophageal cancer. Nuclear p53 was detected in 14 of 36 dysplasias (39%). From mild to moderate to severe dysplasia, p53 positivity showed tendency to increase in number. Seventeen of the 36 squamous cell carcinomas showed p53 expression (47%). There was a significant concurrent p53 expression in esophageal dysplasia and its related squamous cell carcinoma (p=0.00345). These results indicate that p53 mutation is closely associated with the initiation of this cancer.     

Occurrence of esophageal carcinoma after gastrectomy

A review of data on 548 patients with primary squamous cell carcinoma revealed that 24 (4.4%) had had gastrectomy. Although the interval of the gastrectomy due to peptic ulcer or gastric cancer and esophageal cancer was 13.4 +/- 7.9 and 5.8 +/- 4.2 years, respectively, this difference was thought to be due only to the occurrence of each disease. The incidence of the occurrence of the lower esophageal cancer after gastrectomy was 29.2%, not significantly higher than the 22.4% incidence of lower esophageal cancer in overall cases. Histopathological investigation of the 13 resected esophageal cancer tissues from gastrectomized patients revealed a mild esophagitis in some cases, with no significant histologic characteristics. Thus esophageal squamous cell carcinoma and previous gastrectomy may be incidentally related.     

磁县食管癌高发区高危人群食管癌前状态及病变分析

  目的  了解磁县食管癌高发区居民食管癌前状态及病变的分布情况,为该病的病因及二级预防提供依据。   方法  收集磁县2005年1月至2009年12月完成的40~69岁人群的食管癌早诊早治内镜筛查资料,筛查采用内镜碘染色指示性活检,并对符合对象按性别、年龄组统计食管癌癌前状态及病变的检出率。   结果  纳入分析队列筛查对象11 423例,食管活检率66.90%。食管鳞状上皮轻度、中度、重度异型增生检出率分别为11.84%、2.66%、1.04%,原位癌检出率为0.40%,鳞癌可能有浸润的患者检出率为0.04%、黏膜内鳞状细胞癌为0.37%,浸润性鳞癌为0.17%。平均重度异型增生以上及癌的检出率为2.01%。   结论  磁县食管癌高发区40~69岁人群存在大量无症状癌前病变及癌症患者,年龄和性别与检出率关系密切。      

Associations between oral HPV16 infection and cytopathology: evaluation of an oropharyngeal "pap-test equivalent" in high-risk populations

Human papillomavirus (HPV) is responsible for the rising incidence of oropharyngeal squamous cell cancers (OSCC) in the United States, and yet, no screening strategies have been evaluated. Secondary prevention by means of HPV detection and cervical cytology has led to a decline in cervical cancer incidence in the United States. Here, we explored an analogous strategy by evaluating associations between HPV16 infection, cytopathology, and histopathology in two populations at elevated risk for OSCCs. In the first, a cross-sectional study population (PAP1), cytology specimens were collected by means of brush biopsy from patients presenting with oropharyngeal abnormalities. In the second (PAP2), a nested case-control study, bilateral tonsillar cytology samples were collected at 12-month intervals from HIV-infected individuals. The presence of cytopathologic abnormality in HPV16-positive tonsil brush biopsies (cases) was compared with HPV16-negative samples (controls) matched on age and gender. HPV16 was detected in samples by consensus primer PCR and/or type-specific PCR. Univariate logistic regression was used to evaluate associations. In PAP1, HPV16 alone (OR: 6.1, 95% CI: 1.6-22.7) or in combination with abnormal cytology (OR: 20, 95% CI: 4.2-95.4) was associated with OSCC. In PAP2, 4.7% (72 of 1,524) of tonsillar cytology specimens from HIV-infected individuals without oropharyngeal abnormalities were HPV16 positive. Tonsillar HPV16 infection was not associated with atypical squamous cells of unknown significance (ASCUS), the only cytologic abnormality identified. Therefore, HPV16 was associated with OSCCs among individuals with accessible oropharyngeal lesions but not with cytologic evidence of dysplasia among high-risk individuals without such lesions. An oropharyngeal Pap-test equivalent may not be feasible, likely due to limitations in sampling the relevant tonsillar crypt epithelium.     

A comparative cytopathologic and histologic study of atypia, dysplasia, and adenocarcinoma in Barrett's esophagus.

As a potentially premalignant condition, Barrett's esophagus has stimulated controversy over the need for surveillance of glandular dysplasia and early carcinoma. This prompted the authors to review their experience with endoscopic cytologic brushings and biopsies from patients with Barrett's esophagus. The authors reviewed 65 consecutive specimens from 42 patients with Barrett's esophagus in which both the concurrently obtained esophageal cytologic brushings and companion biopsy specimens were available. In addition, esophagogastrectomy specimens from 9 nine these patients were reviewed. Cytologic and histologic specimens were assigned to one of four diagnostic categories, based on specifically defined criteria: simple Barrett's esophagus with or without inflammatory atypia; dysplasia; adenocarcinoma; or suspicious for dysplasia or carcinoma. Simple Barrett's esophagus was diagnosed in 38 cytologic brushings and 44 biopsy specimens, dysplasia in 4 brushings and 7 biopsy specimens, and carcinoma in 14 brushings and 10 biopsy specimens. Nine brushings and three biopsy specimens were suspicious. In 13 cases, brushings revealed a higher grade lesion than did histology; in 5 cases, biopsy specimens showed a higher grade lesion. Agreement between the two occurred in 72% (47/65) of all specimens. Accuracy was confirmed in the histologic examinations of the resection specimens. The authors conclude that specific criteria, when consistently applied, allow accurate cytologic diagnoses of epithelial changes in Barrett's esophagus. The use of esophageal brush cytology and biopsy specimens provides two complementary techniques, which detect a greater number of serious lesions than either technique alone.     

Alterations of p53, cyclin D1 and pRB expression in the carcinogenesis of esophageal squamous cell carcinoma

Many molecular alterations occur in esophageal carcinogenesis; however, little is known about the molecular genetic events responsible for the development of carcinoma. We investigated the expression of ki67, p53, cyclin D1 and pRB in 105 biopsy specimens using immunohistochemistry from iodine unstained lesions as indicators of carcinogenesis of the esophagus. Also, the genetic alternation of esophageal dysplasia from patients with accompanying esophageal squamous cell carcinoma (ESCC) was examined to study the evidence for field carcinogenesis in the esophagus. The expression of p53, cyclin D1 and pRB was detected in 31, 0 and 51.7% respectively of mild dysplasia; 40, 0 and 70% of moderate dysplasia; 40, 20 and 70% of severe dysplasia; and 48, 32 and 80% of carcinoma specimens. p53 expression was significantly increased in mild dysplasia, whereas cyclin D1 and pRB expression were significantly increased in carcinoma as compared to both normal epithelium and esophagitis. The ki67 LI and the rate of p53 expression were significantly higher in dysplasia with ESCC than in dysplasia without ESCC. Ki67, p53, cyclin D1 and pRB expression may be useful biomarkers for assessing the risk of developing esophageal cancer. Dysplasia observed at screening for secondary lesions has a highly malignant potential and careful follow-up studies are required.     

Screening diagnosis and staging of esophageal cancer

In geographic areas where there is a high risk of esophageal cancer, analysis of cells obtained from the esophagus has been used effectively to detect early lesions. This has been demonstrated on a large scale in studies from China. Using abrasive balloon cytology techniques, 75% of the cancers detected were early lesions, where the 5-year survival after resection was in the range of 90%. Endoscopic followup studies indicate that dysplastic changes in the esophageal mucosa are a common precursor to malignancy. In many cases, the time course from dysplasia to carcinoma in situ to early invasive cancer may take place over many years, allowing a reasonable amount of time for screening. In low-incidence areas, such as the United States, most esophageal cancers are related to the excessive use of tobacco and alcohol. These factors are too common and the incidence of the disease too low, however, to justify screening on this basis. There are smaller groups at higher risk where selective screening by endoscopy with cytology and biopsy is recommended, usually every 1 to 3 years. These include patients with longstanding achalasia, lye strictures, and Plummer- Vinson syndrome. Patients with cancers of the head and neck region and patients with celiac disease may also be considered to be at increased risk. Tylosis is a rare inherited disease with a very high risk of esophageal cancer. There is an increased incidence of adenocarcinoma of the esophagus with Barrett's epithelium, and once identified such patients should be kept under endoscopic surveillance. The finding of severe dysplasia in any of these groups would indicate a shorter screening interval. Most patients with symptoms referable to the esophagus are first tested by barium esophagram. If negative, with persistent symptoms or if a suspicious lesion is identified, endoscopy with cytology and biopsy is recommended. Staging of the cancer is based on the size of the cancer both longitudinally and circumferentially and the presence of extraesophageal spread. At the present time, CT is the best noninvasive method for judging the extent of the cancer. Performance and nutritional status are also determinants of prognosis and should be considered in planning treatment.     

血浆p16和FHIT基因甲基化在食管癌及癌前病变检测的临床意义

目的:研究食管癌及癌前病变患者血浆中p16和FHIT基因甲基化情况,探讨其对食管早期癌和癌前病变诊断的临床应用价值。方法:应用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)方法,对食管癌及癌前病变、慢性食管炎患者组织及血浆标本进行了p16和FHIT基因甲基化检测。结果:在44例癌前病变、14例原位癌、37例浸润癌和10例慢性食管炎共105例患者组织DNA中,分别发现18例、11例、24例和1例p16基因甲基化,15例、9例、25例和0例FHIT基因甲基化。癌前病变和慢性食管炎患者血浆中未发现两基因甲基化。51例食管癌患者血浆中共检出14例p16基因和16例FHIT基因甲基化,其中2例为原位癌。结论:p16及FHIT基因甲基化检测有望将食管癌的筛查提前到原位癌阶段,为食管癌的早期发现提供帮助。     

Immunoreactivity of p16 in anal cytology specimens: histologic correlation

BACKGROUND: Cytology has been proposed as a potential screening tool in the evaluation of squamous anorectal disease in view of the morphologic similarities between anal and cervical squamous lesions. Previous studies have demonstrated that p16 overexpression correlates with the degree of dysplasia in the uterine cervix with promising results. Due to potential diagnostic pitfalls in anal cytology, p16 overexpression in these specimens was studied. METHODS: Patients with anorectal cytology who underwent follow-up biopsy within 1 year were selected. Forty-three anorectal cytologic specimens from 29 patients were selected. One slide of each case was destained. Avidin-biotin immunocytochemical studies with the monoclonal antibody CINtec p16(INK4a) were performed. The results of the p16 immunostaining were correlated with the histologic findings. RESULTS: Twenty-eight of the 43 cases demonstrated the presence of squamous cells immunoreactive for p16 in cytology specimens. The p16-positive cells were identified in cases of low-grade squamous intraepithelial lesion (LSIL) (n = 3 cases), high-grade squamous intraepithelial lesion (HSIL) (n = 22 cases), and invasive squamous carcinoma (n = 1 case), and in 2 cases with negative follow-up biopsies. No cell immunoreactive for p16 was found in 15 cases (5 benign cases and 10 cases with either LSIL or HSIL). The sensitivity and specificity of p16 immunoreactivity in the detection of anal intraepithelial neoplasia or carcinoma were 72% and 71%, respectively. The positive and negative predictive values were 93% and 33%, respectively. CONCLUSIONS: The presence of p16 immunoreactivity is a good predictor of dysplasia in anal specimens. However, the sensitivity and specificity of this marker are not high.