活检病理为食管黏膜中度不典型增生病变内镜下切除治疗的可行性研究

目的：对食管上皮不典型增生病变内镜下表现进行量化评分,并结合活检病理以期更能准确反映出病变真实程度,并及时给予相应的处理措施。方法作者回顾性分析有明确病理诊断的180例食管上皮不典型增生患者的内镜下表现,找寻其中规律以此为基础制定出内镜下评分标准,再应用此评分标准,分析活检病理为食管上皮中度不典型增生患者84例内镜下评分与术后病理的关系。结果84例活检病理为中度不典型增生患者,活检病理诊断与内镜下食管黏膜切除术（EMR）后病理诊断一致50例,活检病理诊断不足22例,EMR 术后病理不足诊断中度不典型增生（轻度不典型增生或炎症）12例。内镜下评分≥8分者36例（43%）,EMR 术后中度不典型增生者18例（21%）,EMR 术后重度不典型增生者18例（21%）,重度不典型增生与中度不典型增生的比值为1：1。结论活检病理存在一定的局限性,不能完整反映食管癌前病变的严重程度,内镜下评分可以在一定程度上反映病变的严重程度,且能指导内镜下治疗。内镜下评分≥8分可作为活检病理为中度不典型增生病变行 EMR 治疗的标准。     

胃镜活检与内镜下黏膜切除病理诊断比较

摘 要：［目的］ 探讨胃镜活检在食管早期癌及其癌前病变诊断中的价值以及影响其准确性的因素。［方法］ 对在河南省林州市肿瘤医院实施内镜下黏膜切除(EMD)的618例食管早期癌及癌前病变的诊断结果进行回顾性分析。比较分析内镜活检病理结果与EMD术后病理诊断的一致性。［结果］ 术前活检病理和EMD术后病理诊断的总体一致率为58.09%（359/618）,其中轻度、中度、重度不典型增生完全一致率分别为50.00%（6/12）、49.35%（38/77）、59.83%（210/351）,原位癌和早期癌诊断的一致率分别为50.42%（60/119）和77.19%（44/57）。2例活检为炎症的病例,术后1例诊断为重度不典型增生。术后病理诊断较活检病理病变程度减轻的有64例（10.36%,64/618）,加重的有195例（31.55%,195/618）。影响活检准确性的因素主要有内镜咬检因素、病理诊断差异和病情转化。［结论］ 活检病理诊断与EMD术后病理诊断结果存在较大差异,EMD术后病理是活检病理的补充,为临床规范治疗提供可靠依据。     

内镜下黏膜剥离术治疗早期食管癌及癌前病变的临床应用

目的探讨内镜黏膜剥离术（ESD）在早期食管癌及癌前病变治疗中的应用价值与意义。方法选取2007年1月至2010年1月57例行内镜检查取活检经病理学确诊的早期食管癌及癌前病变并行ESD治疗的患者,进行内镜下黏膜剥离术,对照术前与术后的病理结果,并对手术并发症、治疗效果及预后进行观察。结果57例行ESD治疗的早期食管癌及癌前病变患者,术后病理学诊断黏膜内癌12例（21．1％）,原位癌22例（38．6％）,重度不典型增生18例（31．6％）,中度不典型增生5例（8．8％）。术前术后病理学诊断符合率为87．6％,其中有10例不相符的患者为术前活检病理级别低于术后病理级别。结论对于病理学活检、染色内镜及超声内镜确诊为直径〈30mm无肿瘤转移的早期食管癌及中重度异型增生患者进行内镜下黏膜切除术效果良好。黏膜下剥离术是这类早期食管癌及癌前病变治疗的有效方法,且创伤小,能有效提高患者术后生活质量,值得临床推广应用。     

病理相关因素对内镜黏膜切除食管癌前病变影响的分析

目的：探讨病理活检及相关因素对内镜下黏膜切除术（ EMR）或内镜下黏膜剥离术（ESD）等内镜黏膜切除术切除食管早期癌前病变的影响。方法收集进行 EMR 或 ESD 等内镜粘膜切除术的早期食管癌前病变的患者,均有术前及术后病理诊断结果,并进行随访。结果术前活检诊断高级别鳞状上皮内瘤变的75例食管患者采取 EMR 或 ESD,其术后病理结果并不一致,显示低级别上皮内瘤变10例,高级别上皮内瘤变49例,黏膜内及黏膜下癌16例,说明术前活检诊断与术后诊断不完全一致性。这受主观和客观多种因素的影响：病理医生对术前活检结果的诊断标准、内镜医生钳去的组织完整性及深度、组织的处理步骤、癌变组织具有异质性或多态性。这些因素都会最终影响活检病理结果,从而导致不同的手术方式。结论EMR 和ESD 等内镜黏膜切除术创伤性轻、并发症少、治疗效果好,具有很大的优越性,适合广泛运用及推广,但是其治疗方式易受术前病理活检及相关因素的制约。     

河南林县食管癌防治研究现场普查工作中X线诊断早期食管癌的经验

 1984年，中国医学科学院肿瘤研究所医务人员在河南林县食管癌高发区进行了食管癌普查，X线检查177例，均为细胞学发现有鳞癌细胞者。X线诊断早期癌122例，高度可疑早期癌21例，X线阴性34例。食管镜及病理证实早期癌160例，食管上皮不典型增生17例。所有病例作了X线与食管镜的对照观察。X线诊断的准确性为81.4%，敏感性为84.3%，假阳性为4.4%，假阴性14.1%。以上结果表明X线检查在早期食管癌的诊断中有较重要的作用，但是最后的诊断需内镜与病理证实。     

触诊阴性乳腺病灶术中冰冻诊断的可行性分析

 目的 探讨触诊阴性乳腺病灶活检术中冰冻诊断的准确性与可行性。方法 由钼靶发现的触诊阴性乳腺病灶158例，采用金属线定位技术切除活检，术中进行冰冻切片与诊断，以石蜡组织学诊断为准，评价冰冻诊断的准确性。结果 158例标本中，病理巨检时仅80例（50．6％）发现肉眼可见的异常病灶，平均长径1．2cm。石蜡组织学诊断乳腺浸润癌15例，微小浸润导管癌15例，原位癌12例，导管上皮不典型增生5例，占29．7%（47／158）。术中冰冻对乳腺浸润癌诊断的准确率为93．3％，对微小浸润癌、原位癌、导管上皮不典型增生诊断的准确率分别为60％、58．3％与60％，误诊均为假阴性与低估诊断，无假阳性与过度诊断，原因主要为切片误差与解释错误。结论 冰冻切片对浸润性乳腺癌诊断的准确率高，可用于指导触诊阴性乳腺病灶活检术中手术方案的选择，而对微小浸润癌、原位癌及导管上皮不典型增生常出现假阴性与低估诊断，应待石蜡组织学诊断后再决定手术方案。     

食管癌及癌前病变组织P53蛋白表达的研究

对１９７例食管内窥镜活检组织中Ｐ５３蛋白的免疫组化分析表明，约３８．８％的食管轻度不典型增生，５２．０％的中重度不典型增生，６１．１％的原位癌和６２．５％食管浸润癌组织中有高表达的Ｐ５３蛋白。正常食管鳞状上皮和慢性皮炎症食管上皮中很少有Ｐ５３蛋白聚积，对１４例食管癌病人癌及癌旁不典型增生组织中Ｐ５３蛋白的免疫组化分析表明，９例Ｐ５３蛋白高表达的食管癌中，８例癌旁不典型增生组织也有高表达的Ｐ５３基因     

内镜下黏膜切除术联合氩离子血浆凝固术治疗早期食管癌及其癌前病变

[目的]探讨内镜下黏膜切除术（endoscopic mucosal resection,EMR）联合氩离子血浆凝固术（Argon plasma coagulation,APC）在食管癌高发区治疗早期食管癌及其癌前病变的意义。[方法]应用透明帽法对食管癌高发区普查中发现的84例早期食管癌及食管癌前病变行EMR治疗,并联合应用APC治疗残留及复发病灶。术后2、6个月进行内镜复查。[结果]2004～2008年间共有84例患者成功行EMR,治疗成功率为100%。并发症：术中出血3例,术后出血2例,经内镜下治疗或保守治疗均成功止血;无一例穿孔、狭窄等并发症发生。随访：84例中,5例早期食管癌,49例原位癌/重度不典型增生术后半年随访时对原切除部位行内镜下活检,病理诊断5例重度不典型增生、8例中度不典型增生和19例轻度不典型增生,均内镜下APC治疗。平均随访21个月,无一例复发。[结论]应用透明帽法内镜下黏膜切除联合氩离子凝固术治疗早期食管癌及其癌前病变是食管癌二级预防的有效方法。     

内镜技术在早期食管癌诊断中的应用

色素内镜、超声内镜（EUS）、放大内镜、荧光内镜等技术在检出早期食管癌和食管癌前病变如Barrett食管、上皮不典型增生等方面显示出比常规内镜更高的敏感性和特异性，尤其超声内镜，对于判断食管原位癌、癌灶浸润深度以及局部淋巴结转移状况极具临床应用价值。同时，这些技术各自也存在不足之处。     

食管贲门重复癌及重复高级别上皮内瘤变患病队列分析

 目的从经典的重复癌诊断和WHO肿瘤新分类两个标准，分析食管癌高发区食管贲门重复癌和重复高级别上皮内瘤变患病情况。方法选择河北省磁县2013例40-69岁队列人群为样本。根据WHO新分类标准，将食管鳞状上皮的重度不典型增生、原位癌和贲门腺上皮重度不典型增生、粘膜内癌划为高级别上皮内瘤变（HIN）。对食管和贲门病理同时为HIN的作为重复HIN诊断；食管贲门重复癌仍采用Warren标准。结果以Warren的诊断标准统计，食管贲门重复癌患病率为0．01％（2／2013），占食管贲门原位癌、粘膜内癌和早期浸润癌总检出的2．2％（2／88）；重复HIN患病率0．2％（4／2013），占HIN总检出的3．3％（4／123）。结论磁县40-65岁人群食管贲门重复癌和重复HIN患病率相对较高。     

食管上皮高度不典型增生的处理

Objective： Early detection and treatment in patients with esophageal cancer is the most effective way to improve the prognosis. Patients with high-grade dysplasia （HGD） in esophageal mucosa might be involved with early esophageal cancer, but the management of the disease is controversial. The purpose of our study was to explore the management of esophageal mucosa with HGD. Methods： We retrospectively analyzed 10 patients with HGD in esophageal mucosa, who underwent esophagectomy in Cancer Hospital of Fudan University from 1999 to 2006. The surgical approach, postoperative morbidity, in-hospital complications and pathological results of the patients were analyzed. Basing on our data together with other studies, we aimed at looking for an appropriate management for patients with HGD. Results： Of the 10 patients who received esophagectomy, the pathological results showed that 2 （20%） cases were in situ carcinoma and 8 （80%） cases were invasive cancer with no regional lymph nodes involved. 30-day mortality was 0. One patient experienced cervical anastomotic leakage, but healed in 2 weeks. There was no pulmonary complication. Conclusion： Most patients with HGD actually have occult carcinoma. High percentage of patients with HGD would develop into cancer during their lifetime. Esophagectomy is now a selective approach for the treatment of the patients with HGD.     

Nonsurgical management of Barrett's esophagus with high-grade dysplasia

Endoscopic management options for BE with high-grade dysplasia consist of either surveillance methods or endoscopic mucosal ablative therapies. Intensive surveillance once a person is diagnosed with high-grade dysplasia may avoid an unneeded esophagectomy because it appears that most patients with high-grade dysplasia may not progress to esophageal adenocarcinoma. Only a single study has been presented that demonstrates that this approach does not lead to missed opportunities for intervention before progression to advanced stage disease [20]. This study excluded patients with cancer detected within 1 year of diagnosis of high-grade dysplasia; thus, patients who wish to proceed with an observation approach should be aware that the rate of missed esophageal adenocarcinomas ranges from 38% to 73%. The ability to observe a patient with high-grade dysplasia, however, does have appeal because a number of these patients appear to lose the high-grade dysplasia over time. The other endoscopic management option for Barrett's esophagus with high-grade dysplasia is endoscopic mucosal ablative therapies. These include the KTP:YAG laser, the Nd:YAG laser, photodynamic therapy, and endoscopic mucosal resection. All ablative therapies are used in combination with control of gastroesophageal reflux. This allows the esophageal tissue to heal in an environment that is conducive to squamous mucosa. Although most are relatively small series with short durations of observation, they all have shown some promise in treating BE with high-grade dysplasia. These approaches have the advantage of eliminating the problem. The patient who is being observed must live with the thought of developing cancer. Patients who undergo successful ablation are returned to a normal life. The combination of therapies such as EMR with PDT may be the most promising approach to BE with high-grade dysplasia; however, the long-term effects of ablative therapy are not known and continued surveillance is still advised for this group of patients. The choice of a nonsurgical approach for the management of BE with high-grade dysplasia is ultimately up to the individual patient. All patients must be carefully informed of the treatment effects, possible outcomes, and the surgical alternative. Most patients who select nonsurgical approaches are either elderly or are not good surgical candidates. The choice is often affected by local expertise, as surgical procedures should be performed in centers with surgeons expert in esophagectomy. Nonsurgical approaches should also be performed by physicians who are familiar with their application. Future advances in nonsurgical techniques such as new photosensitizers in PDT and improvements in diagnostic techniques may allow patients a greater opportunity to preserve their esophagus.     

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.     

Treatment of Barrett’s esophagus with high-grade dysplasia

The incidence of esophageal adenocarcinoma is increasing in the USA, now accounting for at least 4% of US cancer-related deaths. Barrett’s esophagus is the main risk factor for the development of esophageal adenocarcinoma. The annual incidence of development of adenocarcinoma in Barrett’s esophagus is approximately 0.5% per year, representing at least a 30–40-fold increase in risk from the general population. High-grade dysplasia is known to be the most important risk factor for progression to adenocarcinoma. Traditionally, esophagectomy has been the standard treatment for Barrett’s esophagus with high-grade dysplasia. This practice is supported by studies revealing unexpected adenocarcinoma in 29–50% of esophageal resection specimens for high-grade dysplasia. In addition, esophagectomy employed prior to tumor invasion of the muscularis mucosa results in 5-year survival rates in excess of 80%. Although esophagectomy can result in improved survival rates for early-stage cancer, it is accompanied by significant morbidity and mortality. Recently, more accurate methods of surveillance and advances in endoscopic therapies have allowed scientists and clinicians to develop treatment strategies with lower morbidity for high-grade dysplasia. Early data suggests that carefully selected patients with high-grade dysplasia can be managed safely with endoscopic therapy, with outcomes comparable to surgery, but with less morbidity. This is an especially attractive approach for patients that either cannot tolerate or decline surgical esophagectomy. For patients that are surgical candidates, high-volume centers have demonstrated improved morbidity and mortality rates for esophagectomy. The addition of laparoscopic esophagectomy adds a less invasive surgical resection to the treatment armanentarium. Esophagectomy will remain the gold-standard treatment of Barrett’s esophagus with high-grade dysplasia until clinical research validates the role of endoscopic therapies. Current treatment strategies for Barrett’s esophagus with high-grade dysplasia will be reviewed.     

Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression

PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions. PCNA, in contrast, stains the nuclei of cells in the parabasal and basal layers. We examined 201 regions from 47 patients that represented different stages of esophageal neoplasia, comprising 34 areas of normal mucosa, 18 of dysplasia in squamous epithelium (DYS/SC), 39 squamous cell carcinoma (SCCA), 29 areas of Barrett's esophagus, 48 of Barrett's dysplasia (DYS/BAR) and 33 areas of adenocarcinoma (AC). The immunostaining patterns of esophagin and PCNA were evaluated and graded for level of expression. There was loss of esophagin expression in the high- and low-grade dysplasias compared to normal epithelia. In the squamous dysplasias, there was more intense staining (of esophagin) in the atypical nuclei and superficial squamous epithelial cells than in the basal cells. PCNA staining was increased in intensity in the high-grade dysplasias relative to normal basal layer cells. Combined analysis of esophagin and PCNA appears to reveal an inverse relationship between proliferation and differentiation during esophageal neoplastic progression. Moreover, this combined staining approach also offers promise for detecting esophageal cancer in early, precancerous stages.     

高龄食管癌68例外科治疗体会

目的:探讨高龄食管癌患者的外科治疗经验。方法:回顾性分析68例70岁以上食管癌外科治疗临床资料。结果:68例患者中手术切除65例,切除率95.6％,并发症发生率44％,其中肺部感染9例,吻合口瘘2例,心功能不全7例,心律失常10例,切口愈合不良2例,死亡2例,1例死于吻合口瘘,1例死于呼吸衰竭,死亡率2.9%。结论:严格掌握手术指征,选择合理的手术方式、加强围手术期处理,是减少高龄食管癌患者术后并发症的关键。     

Endoscopic therapy of dysplasia and early-stage cancers of the esophagus

Endoscopic treatments have become a viable alternative for some patients with early-stage esophageal neoplasia. Although esophagectomy remains the standard of care for high-grade dysplasia and superficial cancers, surgical morbidity and mortality may deter patients who are medically unfit or reluctant to undergo surgery. Photodynamic therapy (PDT) and endoscopic mucosal resection (EMR) are the best-studied nonsurgical approaches at present. PDT has been reported to eradicate high-grade dysplasia (HGD) and early Barrett's cancers at rates ranging from 75% to 100% and 17% to 100%, respectively, and a recent randomized controlled trial confirmed that PDT may prevent progression of HGD to cancer. Complete remission rates greater than 90% have also been reported with EMR and other mucosa-ablating interventions, although recurrence rates necessitate close endoscopic surveillance and retreatment in some patients. In addition to PDT and EMR, several emerging endoscopic treatment options for superficial esophageal neoplasia may provide attractive alternatives to surgery.     

全量放疗后复发性食管癌的外科治疗

目的:探讨全量放疗后食管癌复发的外科手术治疗的可行性。方法:回顾性分析从1995年1月至2004年12月76例全量放疗后复发的食管癌施行外科手术治疗的临床资料。结果:手术切除率86.0%,并发症40.8%,死亡率17.1%。切除组术后1,3,5年生存率分别为63.1%、23.7%、14.5%。结论:对全量放疗后复发性食管癌行外科手术是可行的,但手术适应症应严格掌握。     

185例70岁以上老年人食管癌的外科治疗

[目的]分析70岁以上老年人食管癌的手术适应证、围手术期并发症、死亡以及围手术期处理,探讨降低围手术期死亡的方法。[方法]回顾性分析2000年1月～2005年1月间,在我科行食管癌根治术的年龄大于70岁的185例老年食管癌患者的临床资料,采用单因素和多因素分析围手术期死亡的危险因素。[结果]全组无手术死亡,手术切除率100%。26例（14.1%）手术时间大于5h。术后并发症发生率为28.6%,围手术期死亡率为8.1%。围手术期死亡主要原因为肺部并发症、吻合口瘘和心脑血管并发症。Logistic回归分析显示术前伴发病、肺功能差、手术时间长及喉返神经损伤与围手术期死亡明显相关。[结论]70岁以上老年人食管癌术后围手术期死亡率相对较高,严格选择手术适应证和合理周密的围手术期处理对降低围手术期死亡有重要意义。     

成束蛋白和膜联蛋白I在食管鳞状细胞癌癌前病变中的表达

背景与目的：研究食管鳞状细胞癌癌变早期异常改变的蛋白质以发现与食管癌早期病变相关的特征性标志分子。探讨了成束蛋白和膜联蛋白Ⅰ在食管癌癌前病变中的表达情况。方法：应用免疫组化方法分析食管癌高发现场癌前病变样本中成束蛋白和膜联蛋白Ⅰ的表达水平，用X^2检验对比成束蛋白和膜联蛋白Ⅰ在不同程度癌前病变和食管癌中的表达差异。其中包括，食管鳞状细胞癌癌前病变54例、正常食管上皮8例和中晚期食管癌9例成束蛋白的表达水平；以及食管鳞状细胞癌前病变52例、正常食管上皮11例和中晚期食管癌7例的膜联蛋白Ⅰ表达水平。结果：与正常食管鳞状上皮相比，成束蛋白在食管癌及其癌前病变中表达增强，其表达阳性率为低度癌前病变（轻度和中度不典型增生）85．7％（24／28）、高度癌前病变（重度不典型增生和原位癌）84．6％（22／26）和中晚期食管癌88．9％（8／9）。然而，膜联蛋白Ⅰ在食管癌及其癌前病变中表达降低或丢失，其表达阳性率分别为低度癌前病变14．3％（4／28）、高度癌前病变8．3％（2／24）和中晚期食管癌0％（0／7）。与正常食管上皮相比，成束蛋白和膜联蛋白Ⅰ在食管低度癌前病变中表达程度的异常均具有显著意义，P值分别为0．003和0．000。结论：成束蛋白异常增强和膜联蛋白Ⅰ的丢失与食管癌癌前病变相关。