Successful esophagectomy in a patient with combined esophageal cancer and hemophilia B

Patients with esophageal cancer often require esophagectomy with esophagogastrostomy.However,the incidence of complications,such as hemorrhage,during operations for esophageal cancer is high,even with minimally invasive surgery.Without the appropriate interventions,the risk of major intraoperative and postoperative hemorrhage is very high in patients with esophageal cancer and hemophilia.We report the case of a 45-year-old man with esophageal cancer and hemophilia B who underwent a successful hybrid,minimally invasive Ivor-Lewis esophagectomy with appropriate perioperative management.

Proton pump inhibitor responsive esophageal eosinophilia,a distinct disease entity?

Recent studies have suggested the existence of a patient population with esophageal eosinophilia that responds to proton pump inhibitor therapy.These patients are being referred to as having proton pump inhibitor responsive esophageal eosinophilia(PPI-REE),which is currently classified as a distinct and separate disease entity from both gastroesophageal reflux disease(GERD)and eosinophilic esophagitis(EoE).The therapeutic effect of proton pump inhibitor(PPI)on PPI-REE is thought to act directly at the level of the esophageal mucosa with an anti-inflammatory capacity,and completely independent of gastric acid suppression.The purpose of this manuscript is to review the mechanistic data of the proposed immune modulation/anti-inflammatory role of the PPI at the esophageal mucosa,and the existence of PPI-REE as a distinct disease entity from GERD and EoE.

Effects of bile acids on cyclooxygenase-2 expression in a rat model of duodenoesophageal anastomosis

AIM:To examine the expression of cyclooxygenase-2(COX-2)and prostaglandin E2(PGE2)in rat esophageal lesions induced by reflux of duodenal contents.METHODS:Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux.All animals underwent an esophagoduodenal anastomosis(EDA)with total gastrectomy to elicit chronic esophagitis.In ten rats sham operations with only a midline laparotomy were performed(Control).The rats were sacrificed at the 40th week,their esophagi were taken for hematoxylin and eosin staining and for examination of expression of COX2,PGE2,and proliferating cell nuclear antigen(PCNA),and total bile acids in the esophageal lumen was measured.RESULTS:After 40 wk of reflux,columnar dysplasia,squamous cell carcinoma and adenocarcinoma were observed.Total bile acids in the esophageal lumen were significantly increased in the EDA group compared with the sham operated rats.PCNA labelling index and esophageal tissue PGE2 levels were higher in dysplastic and cancer tissues than in control tissues.Overexpression of COX2 was observed in dysplastic and cancer tissues.CONCLUSION:Reflux of duodenal contents induces COX2 expression and increases prostaglandin synthesis in dysplastic and cancer tissues.This result suggests a possible mechanism by which bile acids promote esophageal cancer.

Natural history of Barrett's esophagus

The natural history of Barrett's esophagus (BE) is difficult to quantify because,by definition,it should describe the course of the condition if left untreated.Pragmatically,we assume that patients with BE will receive symptomatic treatment with acid suppression,usually a proton pump inhibitor,to treat their heartburn.This paper describes the development of complications of stricture,ulcer,dysplasia and adenocarcinoma from this standpoint.Controversies over the definition of BE and its implications in clinical practice are presented.The presence of intestinal metaplasia and its relevance to cancer risk is discussed,and the need to measure the extent of the Barrett's epithelium (long and short segments) using the Prague guidelines is emphasized.Guidelines and international consensus over the diagnosis and management of BE are being regularly updated.The need for expert consensus is important due to the lack of randomized trials in this area.After searching the literature,we have tried to collate the important studies regarding progression of Barrett's to dysplasia and adenocarcinoma.No therapeutic studies yet reported show a clear reduction in the development of cancer in BE.The effect of pharmacological and surgical intervention on the natural history of Barrett's is a subject of ongoing research,including the Barrett's Oesophagus Surveillance Study and the aspirin and esomeprazole cancer chemoprevention trial with interesting results.The geographical variation and the wide range of outcomes highlight the difficulty of providing an individualized risk profile to patients with BE.Future studies on the interaction of genome wide abnormalities in Barrett's and their interaction with environmental factors may allow individualization of the risk of cancer developing in BE.

Can high resolution manometry parameters for achalasia be obtained by conventional manometry?

High resolution manometry(HRM) is a new technology that made important contributions to the field of gastrointestinal physiology. HRM showed clear advan-tages over conventional manometry and it allowed the creation of different manometric parameters. On the other side, conventional manometry is still wild available. It must be better studied if the new technology made possible the creation and study of these parameters or if they were always there but the colorful intuitive panoramic view of the peristalsis from the pharynx to the stomach HRM allowed the human eyes to distinguish subtle parameters unknown or uncomprehend so far and if HRM parameters can be reliably obtained by conventional manometry and data from conventional manometry still can be accepted in achalasia studies. Conventional manometry relied solely on the residual pressure to evaluate lower esophageal sphincter(LES) relaxation while HRM can obtain the Integrated Relaxation Pressure. Esophageal body HRM parameters defines achalasia subtypes, the Chicago classification, based on esophageal pressurization after swallows. The characterization of each subtype is very intuitive by HRM but also easy by conventional manometry since only wave amplitudes need to be measured. In conclusion, conventional manometry is still valuable to classify achalasia according to the Chicago classification. HRM permits a better study of the LES.

polβ高表达与食管癌细胞耐药的相关性

目的:建立人食管癌顺铂耐药细胞系及稳定高表达人野生型DNA聚合酶beta(polβ)的食管癌细胞系,分析polβ高表达与食管癌细胞耐药的相关性.方法:顺铂(cDDP)中等浓度、间歇作用法历时9mo建立耐药细胞系Ec9706/cDDP;同时脂质体转染法将人野生型polβ重组绿色荧光蛋白表达载体pEGFP-AC3转染入Ec9706细胞,经G418筛选得到稳定转染细胞系.荧光显微镜观察转染效果,普通倒置显微镜观察细胞形态变化.RT-PCR方法分别检测耐药细胞与转染细胞中polβmRNA的表达水平,MTT法检测各组细胞对cDDP的敏感性.结果:荧光显微镜下转染细胞荧光强,转染效率高,倒置显微镜下耐药细胞与转染前后细胞形态无明显改变.RT-PCR结果表明耐药细胞Ec9706/cDDP中polβ表达较亲本细胞增加,转染细胞的polβ表达较空载体转染细胞、对照细胞也增加.Ec9706/cDDP细胞耐药指数为15.70;转染后细胞对cDDP的敏感性降低,耐药指数为1.78.结论:成功建立了耐药细胞系Ec9706/cDDP与稳定高表达人野生型polβ的Ec9706细胞系,polβ的高表达可引起耐药性的产生,耐药细胞中polβ的表达也增高.polβ的表达与食管癌细胞的耐药性有一定相关性.

手术治疗食管癌放疗后食管狭窄32例

目的 探讨食管癌放射治疗后食管狭窄治疗方法。方法 经上消化道钡餐透视及摄片或泛影葡胺透视及摄片、胸部CT、胃镜、ECT、腹部彩超等检查，选择无远处转移、无影像学外侵、无合并症、体质好的病人32例，采用根治性手术或食管旷置术手术方式治疗食管癌放疗后食管狭窄。结果 手术切除率87．50％，手术相关死亡率9．38％，术后吻合口瘘6．25％，乳糜胸6．25％。根治性切除病人1、3、5、8年总生存率分别为35．71％、21．43％、14．29％、7．14％。食管旷置术病人未及1年生存。结论食管癌放射治疗后食管狭窄手术治疗需严格选择病例，积极处理手术并发症。根治性切除病人疗效好。

胸腹腔镜联合MIILE治疗对中下段食管癌疗效分析

目的探讨胸腹腔镜联合微创Ivor-Lewis手术(MIILE)治疗中下段食管癌患者的临床疗效.方法将95例中下段食管癌患者分为行胸腹腔镜+MIILE的MIILE组(43例)和行微创McKeown术(MIME)的MIME组(52例),对比两组围手术期指标、术后并发症、术后疼痛和术后生存率.结果 MIILE组手术时间、术中出血量、术后进食时间、术后住院时间均低于MIME组(P<0.05);两组清扫淋巴结数、淋巴结转移率、R0切除率、术后拔胸管时间比较差异无统计学意义(P>0.05);MIILE组术后并发症总发生率低于MIME组(P<0.05);MIILE组术后1,7d视觉模拟评分法(VAS)均低于MIME组(P<0.05);两组术后14 d VAS评分差异无统计学意义(P>0.05);MIILE组术后1个月生活质量核心量表(QLQ-30)评分高于MIME组(P<0.05),两组复发或转移率、生存率及术后6个月QLQ-30评分差异无统计学意义(P>0.05).结论胸腹腔镜联合MIILE是治疗中下段食管癌安全有效的微创手术,可减少术后并发症,提高患者早期的生活质量.

全反式维甲酸对食管癌KYSE70细胞增殖、迁移及Notch1、DLL4、VEGF-C表达的影响

目的:探讨全反式维甲酸(ATRA)单独及联合维甲酸受体β(RARβ)激动剂CD2314或抑制剂LE135对食管癌KYSE70细胞增殖、迁移的影响以及可能机制。方法:将KYSE70细胞分为ATRA组、ATRA+CD2314组、ATRA+LE135组和对照组,采用CCK-8法检测各组细胞分别处理24、48、72 h的增殖情况,通过划痕实验测定处理24 h后的迁移能力,采用Western blot方法检测处理48 h后各组细胞Notch1、DLL4和VEGF-C蛋白的表达情况。结果:处理24、48和72 h后,ATRA+CD2314组细胞增殖抑制率高于ATRA组,ATRA+LE135组低于ATRA组(P<0.05);处理24 h后,ATRA组细胞的迁移能力低于对照组,ATRA+CD2314组细胞的迁移能力低于ATRA组(P<0.05),而ATRA+LE135组高于ATRA组(P<0.05);处理48 h后,ATRA组细胞Notch1蛋白表达量高于对照组,DLL4和VEGF-C蛋白表达量低于对照组,ATRA+CD2314组细胞Notch1蛋白表达量高于ATRA组,而DLL4和VEGF-C蛋白的表达量低于ATRA组;ATRA+LE135组细胞Notch1蛋白表达量低于ATRA组,DLL4和VEGF-C蛋白表达量高于ATRA组(P<0.05)。结论:ATRA可能通过上调Notch1蛋白,下调DLL4、VEGF-C蛋白的表达抑制KYSE70细胞增殖和迁移,增强RARβ的表达可进一步增强这一作用。

食管狭窄内支架置入术后的评价

目的:观察食管狭窄患者置入金属内支架后的疗效和并发症。方法:28例食管狭窄置入了内支架,有较完整的随访资料。26例恶性食管狭窄在置入内支架前后均作了放疗和化疗。2例贲门失弛缓症患者球囊扩张后置入支架。内支架置入类型:国产镍钛记忆合金硅胶膜被覆支架27例,Ultreflex支架(美国)1例。结果:1例支架轻度移位,但仍能覆盖病变全长。食管恶性狭窄11例死亡,术后生存时间4～27个月,平均13个月。死亡原因:肿瘤多脏器转移9例,肺部感染1例,其它1例。恶性食管狭窄内支架置入后未发生再狭窄。2例贲门失弛缓患者置入支架后支架上端发生再狭窄,均作了球囊扩张治疗。结论:中晚期食管癌内支架置入是解除吞咽困难有效的姑息治疗方法,应用带膜支架和同时行放、化疗可防止因肿瘤生长而发生再狭窄,延缓患者生命。良性狭窄并发症高,病例选择需慎重。

中上段糜烂的反流性食管炎临床分析

目的:探讨食管中上段糜烂的反流性食管炎的临床和内镜特征。方法:回顾分析2003年1月至2009年9月间31例经胃镜检查证实的食管中上段糜烂的反流性食管炎患者,食管炎分级按洛杉矶标准,探讨其发生机制及其与性别、年龄、伴发疾病等相关因素的关系。结果:食管中上段糜烂的反流性食管炎人数占反流性食管炎人数的3.2%,男女之比为1.58∶1,中位年龄57.63岁,A、B级占83.9%,中重度少见(16.1%),伴发慢性胃炎24例(77.5%),食管裂孔疝5例(16.1%),胃溃疡3例(9.7%),十二指肠球部溃疡2例(6.5%)。结论:食管中上段糜烂的反流性食管炎的胃镜检出率低,患者以男性老年人多见,以轻度糜烂为主;合并胃炎、消化性溃疡、食管裂孔疝可能是发生食管中上段糜烂的反流性食管炎的危险因素,内镜对其诊断具有重要意义。

Advanced gastric cancer:Is there enough evidence to call second-line therapy standard?

Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.

Trends on gastrointestinal bleeding and mortality:Where are we standing?

Bleeding from the gastrointestinal tract and its management are associated with significant morbidity and mortality.The predisposing factors that led to the occurrence of these hemorrhagic instances are largely linked to the life style of the affected persons.Designing a new strategy aimed at educating the publics and improving their awareness of the problem could effectively help in eradicating this problem with no associated risks and in bringing the mortality rates down to almost zero.

贲门失弛缓症发病机制的初步探讨

目的 应用氯苄烷铵(BAC)建立猫贲门失弛缓症模型,探讨贲门失弛缓症发病机制。方法 24只猫随机分为两组,模型组胃镜下LES处环形注射BAC,对照组注射生理盐水,8周后检测食管动力学变化,并取组织进行HE染色、乙酰胆碱酯酶(AChE)免疫组化染色检查和AChE活力测定。结果 模型组下食管括约肌压力较对照组明显升高(P<0.01),两组食管收缩幅度无显著性差异;组织学检查显示模型组环肌层和纵肌层之间可见炎细胞浸润,对照组正常;对照组可见AChE染色阳性神经节,环肌层和纵肌层可见AChE染色阳性产物,模型组AChE染色阳性产物明显减少(P<0.01);模型组乙酰胆碱酯酶活力与对照组比较明显降低(P<0.01)。结论 肌间神经丛的炎性反应和乙酰胆碱酯酶活力降低是贲门失弛缓症的重要发病原因。

一种新型返流诱发食管腺癌动物模型的建立

目的 建立一种既能较好地模拟人类胃食管返流病 (GERD)的病理生理 ,又能快速可靠地诱发Barrett’s食管 (BE)和食管腺癌 (EAC)的动物模型。方法 SD大鼠 65只 ,通过手术产生十二指肠胃食管返流 (DGER)模型 ,分别于术后 1、4、8、12、16、2 0周随机抽取若干只大鼠 ,观察食管下段粘膜病变。结果 DGER模型术后 8、12、16、2 0周BE和EAC的发生率分别为 :33.3%和0 % ,62 .5 %和 12 .5 %、90 .0 %和 30 .0 %、86.6%和 5 3.3%。结论 我们建立的DGER模型能快速可靠地诱发BE和EAC ,是一种研究人类BE和EAC发生机制的较为理想的动物模型。

胃食管反流病的外科治疗策略

胃食管反流病（GERD）是上消化道内容物反流进入食管引起的疾病，欧美国家常见，我国发病率也逐年升高，严重影响患者生命质量。质子泵抑制剂抑酸效果明显，但GERD发病机制复杂，危险因素众多，患者需加大药物剂量或联合其他药物，治疗效果不一。因此，仍有较多GERD患者需行外科治疗，从而摆脱或减少药物治疗。外科医师在掌握手术操作规范化的同时，更应明确手术适应证，全面了解GERD发病机制，制订标准治疗流程，加强多学科团队建设，加强随访工作及数据库建立，从而更好地指导GERD的治疗。

曲古抑菌素A对食管鳞癌细胞迁移影响机制探讨

目的组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors,HDACIs)是一类新型的抗肿瘤药物,抑制食管鳞癌细胞增殖并促进其凋亡,但对食管鳞癌细胞迁移的影响及机制尚不清楚。本研究旨在探讨HDACIs曲古抑菌素A(trichostatin A,TSA)对食管鳞癌细胞迁移能力的影响及其可能的机制。方法培养食管鳞癌细胞KYSE-150和EC9706。单独TSA以及联合NF-κB抑制剂BAY 11-7082、PI3K/Akt信号通路阻断剂LY 294002对食管鳞癌细胞进行处理,Transwell法检测食管鳞癌细胞迁移能力,分为NC组(对照组)、TSA组(200nmol/L TSA组)、BAY组(10μmol/L BAY 11-7082组)、TSA+BAY组(200nmol/L TSA+10μmol/L BAY 11-7082组)、LY组(10μmol/L LY 294002组)和TSA+LY组(200nmol/L TSA+10μmol/L LY 294002组)。蛋白质印迹法检测TSA处理后Vimentin、p-p65和p-Akt等蛋白的表达水平,以及TSA联合BAY、LY后Vimentin、p-p65、p-Akt等蛋白的表达情况。多组间均值差异比较采用两因素析因方差分析,两独立组比较采用t检验。结果 Transwell实验结果表明,TSA处理食管鳞癌细胞24h后细胞迁移能力增加,与对照组比较,KYSE-150细胞中,差异有统计学意义,t=13.687,P<0.01;EC9706细胞中,差异有统计学意义,t=11.917,P<0.01。TSA+BAY组与TSA组比较,迁移能力减弱,KYSE-150细胞中,F=169.896,P<0.01;EC9706细胞中,F=248.813,P<0.01。TSA+LY组与TSA组比较,迁移能力减弱,KYSE-150细胞中,F=56.019,P<0.01;EC9706细胞中,F=93.108,P<0.01。蛋白质印迹实验结果表明,TSA使KYSE-150细胞中Vimentin(t=13.156,P<0.01)、Slug(t=43.866,P<0.01)、p-p65/p65(t=28.866,P<0.01)以及EC9706细胞中Vimentin(t=43.565,P<0.01)、Slug(t=20.810,P<0.01)、p-p65/p65(t=73.525,P<0.01)蛋白表达水平升高,TSA+BAY组与TSA组比较,使KYSE-150细胞中Vimentin(F=49.376,P<0.05)、Slug(F=19.636,P<0.05)、p-p65/p65(F=19.636,P<0.05)以及EC9706细胞中Vimentin(F=14.297,P<0.05)、Slug(F=77.817,P<0.05)、p-p65/p65(F=14.137,P<0.05)蛋白表达水平降低;TSA+LY组与TSA组比较,使KYSE-150细胞中Vimentin(F=110.413,P<0.05)、Slug(F=19.636,P<0.05)、p-p65/p65(F=59.929,P<0.05)、p-pAkt/Akt(F=184.615,P<0.05)以及EC9706细胞中Vimentin(F=94.270,P<0.05)、Slug(F=77.817,P<0.05)、p-p65/p65(F=54.267,P<0.05)、p-pAkt/Akt(F=100.043,P<0.05)蛋白表达水平降低。结论 TSA通过激活PI3K/Akt信号通路,进而调节下游信号分子NF-κB亚基p65,促进食管鳞癌细胞迁移。

病灶18F-FDG摄取PET／CT记分对早期良恶性食管病变的诊断价值

目的探讨病灶18-氟-脱氧葡萄糖（18F-FDG）摄取PET／CT记分对早期良恶性食管病变的诊断价值，为临床诊治提供依据。方法对本院36例癌前或早期恶性食管病变患者与66例食管良性病变患者行18F-FDG摄取PET／CT记分，病变评价记分标准：FDG摄取强度低=0、中=1、高=2；FDP摄取表现同心圆=0、偏心圆形=1；FDG摄取能力弥散=0、弧形=1、局灶型=2；CT检查显示食管正常=0、增厚=1、团块=2；部位位于食管近端1／3=0，中1／3=1、远端1／3=2。结果早期恶性病变组FDG摄取强度记分≥2分者15例（41．8％）、FDG摄取偏心率≥1分者20例（55．6％），良性病变组≥2分者12例（18．2％）、≥1分者7例（10．6％），两组间比较差异均有统计学意义（X2=16．22，24．18，P〈0．01）。早期恶性病变组CT检查食管厚度记分≥2分者占22．2％（8／36），良性病变组为12．1％（8／66），两组比较差异无统计学意义（P〉0．05）。早期恶性病变组SUV最大值高于良性病变组（3．3±0．9vs5．3±4．1，t=11．04，P〈0．01）。应用局灶一偏心性记分阈≥2分，区别良或恶性病变的敏感度为83．3％、特异度为68．3％。结论FDG摄取能力和偏心率对区别食管良恶性病变有一定价值。