原发性食管腺癌外科治疗与病理分析

目的了解原发性食管癌的生物学特性，探讨合理的综合治疗措施。方法对15例原发性食管腺癌者行手术切除并作病理分析。结果其中食管单纯腺癌12例，腺鳞癌3例，1、3、5年生存率分别为73．3％、63．5％、57．1％。结论因食管腺癌粘膜下浸润能力强，恶性程度高，有早期扩散和转移倾向，预后差，手术是其首选的主要治疗手段，以胸段食管全切、食管胃端侧颈部吻合术为宜，同时应最大限度地清除区域淋巴结。     

糜烂性食管炎、Barrett食管及食管腺癌中SOX2、CDX2的表达及其临床意义

目的探讨CDX2、SOX2在糜烂性食管炎、Barrett食管的3种不同组织类型(胃底型、贲门型、肠化生型)及食管腺癌(esophageal adenocarcinoma,EAC)中的表达及意义。方法采用免疫组化Eli Vision两步法检测CDX2和SOX2在35例贲门组、23例胃底组、14例肠化组、10例糜烂性食管炎组、7例EAC组、10例正常食管下段黏膜中的表达情况。结果 CDX2在肠化组及EAC组中的阳性率均为85.7%,显著高于其他四组(P0.05);CDX2阳性率在贲门组(11.4%)、胃底组(0)、糜烂性食管炎组(0)及正常食管组(0)中的差异无显著性(P0.05)。CDX2在贲门组(75%)及EAC组(66.7%)以(+)为主,差异无统计学意义(P0.05),与肠化组(91.7%)以()为主显著不同(P0.05)。SOX2在Barrett食管三组中的阳性率均为100%,显著高于EAC组(28.6%)(P0.05)。SOX2以(++)表达方式在胃底组(95.7%)及贲门组(74.3%)中差异无统计学意义(P0.05);显著高于肠化组(50%)和EAC组(50%)(P0.05)。SOX2和CDX2的表达在肠化型Barrett食管中呈负相关(P0.05),在贲门组、胃底组、EAC组中无明显相关(P0.05)。结论短段贲门型Barrett食管中CDX2的阳性率不高,可能只是一种柱状上皮化生,与EAC的关系不大;CDX2在鳞状上皮向特殊肠上皮化生转化过程中发挥重要作用,SOX2的沉默促进EAC发生。     

Barrett食管的临床病理研究

对3485例胃镜活检标本中的18例Barrett食管(BE)进行病理形态学、组织化学研究,并对其核仁形成区相关嗜银蛋白进行观察。认为先天性柱状上皮残留和后天刺激性柱状上皮化生可能分别为不同病例的病因。BE在胃镜活检中占0.52%,在食管炎活检中占13.3%。胃—食管返流引的化学刺激是炎症的主要原因,弯曲菌感染也可能是其原因。BE有胃底型、责门型和特化型三种组织学类型。在特化型中的肠上皮可是小肠型,也可是大肠型。本组2例见腺体增殖区扩大,6例有上皮异型增生。异型增生细胞AgNORs数量与食管腺癌相近,表明BE上皮受炎症刺激而出现异型增生,是食管腺癌发生的重要原因。     

早期食管原发性腺癌初步病理分析

通过7例早期食管原发性腺癌手术标本系列大切片的观察,证明在早期食管癌中确有原发性腺癌存在。患者平均年龄46岁,较中晚期癌患者年轻约10岁。病理类型以浅表缺损型为主,癌灶平均长度13mm。病理特征为:(1)癌变多起始于食管固有腺腺管上段,可在相邻数个腺体内同时发生;(2)组织学上多表现为腺管癌;(3)癌灶表面和周围覆盖有受压变薄或呈增生性改变的鳞状上皮;(4)多伴有鳞癌成分。     

食管腺癌的细胞学和组织学诊断分析

目的：探讨信用这中段腺癌细胞学诊断意义。方法：对２０例食管腺癌病例的组织切片和细胞学涂片进行形态学对照观察。结果：印戒细胞癌３例,粘液腺癌７例,管状腺癌６例,腺鳞癌２例,粘液表皮样癌２例。其细胞学的共同特征为细胞学涂片中常出现粘液背景或含粘液的癌细胞,细胞学与病理组织学诊断的符合率达９０％。结论：细胞学有助于食管腺癌的诊断食管腺癌可能起地食管固有腺。     

食管腺癌病理组织学,组织化学和免疫组化观察

汕头地区１９７８－１９８８年病理确诊的２４８７例食管癌中，有食管腺癌４８例，占１．９３％，４８例食管腺癌的组织学可分６亚型：高分化普通型腺癌（１０例），低分化普通型腺癌（１１例），腺鳞癌（１８例）。粘液表皮样癌（４例），圆柱瘤样癌（１例），基底细胞样癌（４例）。各型的组化，免疫组化表达及预后均各有特点，提示食管腺癌组织学再分型有意义。     

同一个体先后发生食管鳞状细胞癌和结肠腺癌1例

患者男性,65岁,2002年3月以进食异物感半年就诊。其父亲死于食管癌。电子胃镜显示:距门齿20～23 cm左后壁可见菜花样隆起,黏膜充血、糜烂。胃镜检查报告:食管胸上段隆起性质待定,考虑恶性肿瘤。该处黏膜活检病理诊断为:(食管胸上段)鳞状细胞癌,入院后先行半量放疗,1月后行食管肿瘤切除术。术后未行化疗。2010年11月该患者     

食管腺癌伴其表面上皮原位鳞癌一例

食管腺癌伴其表面上皮原位鳞癌一例王和枚王玉华李维华患者男，５０岁，因进行性吞咽困难６个月入院。术前上消化道造影及纤维胃镜检查、活检病理均诊断食管下段鳞癌。于１９９６年１２月２１日行食管部分切除术。病理检查：切除食管一段，长１０ｃｍ，上切缘周径４ｃｍ，...     

原发性食管腺癌癌基因,抗癌基因的扩增与其蛋白产物的？…

采用免疫组化和原发子杂交技术观察ｐ５３，Ｈ－ｒａｓ，ｃ－ｅｒｂＢ－２，ｃ－ｍｙｃ癌基因和抗癌基因及其蛋白产物在原发性食管腺癌（ＰＥＡ）中的联合表达情况，以探讨ＰＥＡ的发生发展机制，结果表明，ＰＥＡ中的ｐ５３表达较食管鳞癌高，ｃ－ｅｒｂＢ－２变化可能是ＰＥＡ癌变的重要分子学改变；ＰＥＡ与Ｈ－ｒａｓ与ｃ－ｍｙｃ都有基因扩增蛋白产物的过表达，显示两者在ＰＥＡ的癌变过程中有协同作用，ｐ５３，ｃ－ｅｒｂＢ－     

氩离子凝固术治疗Barrett食管67例临床分析

目的 评价内镜下氩离子凝固术(APC)对Barrett食管(BE)的疗效及安全性.方法 内镜下对67例BE施行APC治疗,通常全周型以间隔1周分2～3次治疗,舌型以1次或间隔1周分2次治疗,岛型1次治疗.术后口服质子泵抑制剂奥美拉唑片,治疗时间最少2个月或至反流症状消失.观察疗效及并发症.末次APC治疗后1个月行内镜检查,其后每隔3个月进行一次内镜随访,随访时间持续1年.结果 末次治疗后1个月行内镜检查61例患者BE完全消除(91.0%),无严重并发症发生.随访1年,11例再次发现柱状上皮.结论 APC对BE的治疗安全有效,其长期效果需要大样本试验观察.     

Combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus

Hepatoid adenocarcinoma arising in the esophagus is extremely rare. To date, there are only 3 cases in the world English literature. We report the fourth case here. A 76-year-old Japanese man was admitted to our hospital because of the deterioration of nephritic syndrome. He presented with chest burn, and the endoscopic examination of upper digestive tract disclosed the tumor in the lower esophagus. The subtotal esophagectomy was undertaken because of esophageal cancer. The postoperative histologic examination showed the finding of combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus. Immunohistochemically, hepatoid adenocarcinoma cells were positive for a-fetoprotein, hepatocyte, a1-antitrypsin, a1-antichymotrypsin, and CDX2, but negative for MUC5AC and MUC6. Esophageal hepatoid adenocarcinoma seems to be closely associated with Barrett esophagus and show the intestinal phenotype rather than gastric phenotype.     

Claudin expression in Barrett's esophagus and adenocarcinoma

Claudins (CLDNs) are key molecules in cell adhesion, polarity, and control of paracellular solute transport. Several studies suggested that changes in claudin pattern have a role in cancer development. This study aimed to detect alterations in CLDN 1, 2, 3, 4, and 7 expression patterns in Barrett's esophagus (BE) and adenocarcinoma (ACC) compared with that in foveolar epithelium (FOV), normal squamous epithelium (SQ), and squamous cell carcinoma (SQCC). One hundred twenty five surgically or endoscopically removed, paraffin-embedded cases were studied by immunohistochemistry and analyzed statistically. BE, ACC, and FOV were dissected from 30 paraffin-embedded samples for further mRNA expression analysis. CLDN 7 was the dominating type in all epithelia and carcinomas, but its expression did not differ in normal and altered tissues. CLDN 1 expression was significantly increased in SQCC compared with that in SQ. CLDNs 3 and 4 were significantly elevated both in BE and ACC compared with that in FOV. CLDN 2 expression increased significantly in ACCs compared with that in BE. This is the first report proving similarities and differences regarding claudin expression pattern in BE and ACC compared with that in FOV and SQ. Our data prove a close link in CLDN pattern between BE and ACC, adding further evidence that BE is an alteration preceding esophageal ACC.     

Hepatoid adenocarcinoma in Barrett's esophagus associated with achalasia: first case report

We report an unusual hepatoid adenocarcinoma in Barrett's esophagus with achalasia, which developed in a 44-year-old Japanese woman. The patient received an esophago-gastrectomy after diagnosis of the tumor and achalasia at the lower esophagus, 4 months before her death due to multiple metastatic tumors of the liver. The main granular tumor removed surgically was a hepatoid adenocarcinoma, mainly composed of clear cancer cells (alpha-1 antitrypsin, albumin and alpha-fetoprotein positive), with elements of choriocarcinoma and tubular adenocarcinoma. Non-neoplastic specialized columnar epithelium was present extensively near the oral side of the tumor edge in the esophagus, indicating Barrett's esophagus. This unusual tumor was therefore considered to have originated in Barrett's esophagus. The gastroesophageal reflux was presumed to have occurred for a long period, as there was a well-preserved fundic gland in the stomach and a history of frequent vomiting from the patient's youth, accounting for the appearance of achalasia.     

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus

The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.     

LOH at the sites of the DCC, APC, and TP53 tumor suppressor genes occurs in Barrett's metaplasia and dysplasia adjacent to adenocarcinoma of the esophagus

Barrett's esophagus carries a 30- to 100-fold increased risk of adenocarcinoma, which is thought to develop via a metaplasia-dysplasia-carcinoma progression. A common genetic abnormality detected in Barrett's adenocarcinoma is loss of heterozygosity (LOH) at the sites of known or putative tumor suppressor genes, of which there are at least 9 associated with esophageal adenocarcinoma. The aim of this study was to identify at which histological stage of carcinogenesis LOH at these sites occur. Microdissection of multiple paraffin-embedded tissue blocks from 17 esophagogastrectomy specimens of adenocarcinoma arising in Barrett's esophagus yielded areas of metaplasia, low-, intermediate- and high-grade dysplasia, and carcinoma. LOH analysis of microdissected tissues was performed using a double polymerase chain reaction technique with 11 microsatellite primers shown previously to have LOH in at least 30% of esophageal adenocarcinomas. Identical LOH was detected in premalignant and malignant tissues in 4 of 17 patients, and was located at 5q21-q22 (D5S346 primer), 17p11.1-p12 (TCF2 primer), 17p13.1 (TP53 primer), 18q21.1 (detected in colon cancer tumor suppressor gene [DCC] primer), and 18q23-qter (D18S70 primer). These results suggest that LOH at the sites of the DCC, adenomatous polyposis coli (APC), and TP53 tumor suppressor genes occur before the development of adenocarcinoma in Barrett's esophagus, and so merit further study as potential biomarkers of neoplastic progression in patients with Barrett's esophagus undergoing endoscopic and histological surveillance.     

Cyclooxygenase-2 expression and cell proliferation are increased in MUC2-positive area of columnar-lined esophagus

Columnar-lined esophagus is composed of intestinal type and gastric type epithelium. Only the specialized or intestinal type columnar epithelium is susceptible to the development of esophageal adenocarcinoma. The aim of the present paper was to evaluate the expression of cyclooxygenase (COX) and microsomal prostaglandin E synthase (mPGES) in gastric-type and intestinal-type metaplasia in columnar-lined esophagus and compare these with cell proliferation. Biopsy specimens of 30 columnar-lined esophagus patients were collected, and immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC), COX, mPGES and cell proliferation (Ki-67). The MUC2-positive area had higher COX-2 expression and cell proliferation than the MUC5AC-positive area. There was a close correlation between COX-2 expression and cell proliferation. In contrast, the expression of COX-1, mPGES-1 and -2 was similar between intestinal metaplasia and gastric metaplasia. In conclusion, intestinal-type columnar-lined esophagus possesses COX-2 expression and a higher proliferation potential, suggesting that esophageal adenocarcinoma may arise from specialized columnar-lined esophagus.     

Mucin core polypeptide expression in the progression of neoplasia in Barrett's esophagus

We have previously demonstrated a specific pattern of mucin (MUC) core polypeptide expression in Barrett's esophagus (BE) characterized by MUC1 and MUC6 positivity in goblet cells in a proportion of cases. The aim of this study was to determine the pattern of MUC expression associated with the development and progression of dysplasia in BE. Endoscopic mucosal biopsies from 35 patients with BE (10 with no dysplasia, 6 with indefinite for dysplasia, 12 with low-grade dysplasia [LGD], and 7 biopsies with high-grade dysplasia [HGD]) were immunostained (ABC method) with antibodies against MUC1, MUC2, MUC3, MUC5AC, and MUC6. The extent and pattern of staining for each marker was evaluated in intestinalized Barrett's epithelium and in the various grades of dysplasia. For cases with dysplasia, staining was evaluated separately in nondysplastic epithelium adjacent to (<1 cm) and distant from (>2 cm) areas of dysplasia. In nondysplastic BE, MUC1, MUC2, MUC3, MUC5AC, and MUC6 stained 40%, 100%, 100%, 100%, and 90% of cases, respectively, in goblet or nongoblet columnar epithelium. With the progression of dysplasia (from metaplasia to indefinite, LGD and HGD), there was a significant decrease in expression of MUC1, MUC2, and MUC3, and alterations in the staining patterns of MUC5 and MUC6. In fact, MUC1 and MUC3 were entirely absent from all cases of HGD. Interestingly, BE-associated adenocarcinomas showed an MUC phenotype distinct from that of HGD, with expression of MUC1 and MUC3 in 47% and 67% of cases, and expression of MUC1 in a membranous pattern. There was no significant difference in MUC staining in nondysplastic BE between patients with and without dysplasia. Alterations in MUC expression occur in the progression of dysplasia in BE. However, none of these markers helps identify a subgroup of patients at increased risk for neoplasia.     

Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus

Barrett's esophagus (BE) is a precancerous condition. However, the mechanisms underlying the transformation from metaplastic to dysplastic to adenocarcinomatous epithelium are still poorly understood. As loss of transforming growth factor-beta growth inhibition is considered a hallmark of several human neoplasms, we evaluated the expression of Ski and SnoN (proteins that antagonize transforming growth factor-beta signaling through physical interaction with Smad complex and by recruiting histone deacetylases), as markers of the transforming growth factor-beta signaling pathway, in BE with and without dysplasia. Biopsy samples from 37 patients (26 men, aged 60 +/- 8 years) with histologically proven BE were evaluated; 10 patients had concomitant low-grade dysplasia, 7 high-grade dysplasia (HGD), and 6 HGD associated with adenocarcinoma. Ski and SnoN expression was assessed immunohistochemically. Neither Ski nor SnoN was expressed in normal esophageal epithelium, but both were strongly expressed in BE tissue, with intense cytoplasmic positivity. Expression of these proteins decreased markedly in dysplastic areas in patients with low-grade dysplasia and was absent in those with HGD or HGD/adenocarcinoma. Ski and SnoN proteins are overexpressed in BE and may be involved in abnormal signaling elicited by transforming growth factor-beta in this epithelium, enhancing the tumorigenesis process. These observations might help to elucidate the molecular mechanisms involved in the BE tumorigenesis process.