食管癌围手术期严重并发症因素分析及对策

食管癌切除、食管重建为一创伤较大的手术，仍面临一些严重并发症问题，更未杜绝死亡。该文回顾手术治疗食管癌患者３５６例，男性３０８例，女性４８例，年龄３１～８２岁。临床病理分期：０期６例，Ⅰ期３２例，Ⅱ期１４８例，Ⅲ期１７０例。病变位于上段８例，中段２１０例，下段１３８例，所有病例均取胃行食管重建术。其中行颈部吻合２９例，主动脉弓上吻合２５７例，弓下吻合６８例。术后发生严重并发症３５例，占统计病例的９．３％。其中呼吸衰竭１１例，吻合口瘘１３例，颈部３例，胸内１０例，乳糜胸５例，心脏并发症４例，胃穿孔２例。死亡１０例，占统计病例２．８％。分析统计资料可见：６０岁以上年龄组呼吸衰竭发生率明显高于５９岁以下年龄组。呼吸衰竭、吻合瘘大都发生在Ⅱ～Ⅲ期病例，且Ⅲ期高于Ⅱ期，组间比较差异显著（Ｐ＜０．０５）。该组资料还提示，吻合口瘘、心脏并发症、乳糜胸、胃穿孔并发症与病变部位关系密切、组间比较有显著差异（Ｐ＜０．０５）。作者认为，食管癌术后严重并发症一旦发生，常危及生命，需要采取积极有效抢救措施。该文还对食管癌术后严重并发症及因素进行了讨论。

改良Ivor-Lewis手术对胸中段食管鳞癌治疗效果的评价

目的:评价改良Ivor-Lewis手术对胸中段食管鳞癌的治疗效果。方法:对1997年1月～2001年1月间,改良Ivor-Lewis手术治疗的241例胸中段食管鳞癌患者回顾研究。应用Kaplan-Meier法计算生存率;Cox回归分析判定预后的危险因素。结果:围手术期内40例(16.6%)患者有并发症发生,死亡6例(2.5%)。整体5年生存率为31%。Ⅰ、ⅡA、ⅡB和Ⅲ期患者的5年生存率分别为72%、40%、16%和13%(P<0.001)。手术后辅助放疗的T3和N1患者肿瘤局部复发率为23.3%,未完成放疗者的局部复发率为41.3%(P<0.05)。Cox回归分析显示,N1(HR=2.074,P<0.01)和T3(HR=3.493,P<0.01)是独立的预后危险因素。结论:改良Ivor-Lewis手术无严重的手术后并发症。手术后辅助放疗可降低N1和T3患者的肿瘤局部复发率。患者的预后取决于T及N分期。该手术可以治愈多数T1N0M0和T2N0M0胸中段食管鳞癌患者,但是对于T3和N1患者,单纯手术的远期疗效欠佳。

食管癌组织的遗传不稳定性研究

目的:探讨食管癌组织遗传多态性及基因组甲基化改变在其发生或发展中的作用。方法:1)用PCR-AFLP和基因扫描的方法,对食管癌组织与癌旁组织AR基因、Rb基因(intron16、17)、ER基因(PvuII和XbaI)和cbl2基因6个多态位点的检测。2)用HPLC的方法,对食管癌组织与癌旁组织基因组DNA甲基化的水平检测。结果:35例患者中至少一个位点发生改变者占74.29%,在不同级别的食管癌组织中多态性改变各为:Ⅰ:9/12(75%);Ⅱ:13/15(85%);Ⅲ:4/8(50%)。在食管癌早期癌组织基因组甲基化水平比癌旁组织低,随着肿瘤的进程甲基化水平逐渐上升,甚至超过了癌旁组织。结论:从食管癌组织早期基因组低甲基化与大量的多态性改变,推测遗传不稳定性是食管癌发生发展中普遍事件,早期基因组甲基化的降低可能与其遗传不稳定性的产生关系密切。

南方食管癌高、低发区人群总N-亚硝基化合物接触水平

目的 评价南方食管癌高发区和低发区人群总N 亚硝基化合物 (TNOC)的接触水平。方法 在食管癌高发区南澳县和低发区陆丰县各随机选择 12 0名 35～ 6 4岁男性 ,采用双份饭法收集2 4h膳食和 12h尿液 ,测定TNOC、非挥发性亚硝胺和挥发性亚硝胺。结果 高发区膳食TNOC检出率(95 % )、膳食TNOC日摄入量 [(4 2 5± 0 84 ) μmol/d]和尿 12h排出量 [(1 76± 0 2 3)ng/ 12h]、膳食挥发性亚硝胺日摄入量 [(2 6 6± 31 2 ) μg/d]均高于低发区。食管癌死亡率分别与膳食TNOC日摄入量和尿TNOC排泄量呈等级正相关关系。尿非挥发性亚硝胺排泄量两地无差异。

"Layer-to-Layer" Esophagogastric Anastomosis Combined with Intrathoracic Esophageal Mucosal Extention in Patients with Esophageal and Cardia Cancer

Objective: To evaluate the clinical value of intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosa extended varied in plane and to study the effective methods to prevent anastomotic leaking or stricture postoperatively. Methods: From May 1985 to December 2002, 2 240 esophageal and stomach cardia cancer patients treated by intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosa extended varied in plane were retrospectively analyzed. Results: There was no anastomotic leaking and severe stricture in all above cases. Conclusion: Intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosal extended varied in plane is an effective method to prevent anastomotic leaking and stricture postoperatively.

Clinical Application of Exclusive Right-Thoracic Approach in Surgery with or without Laparotomy for Mid-Upper Esophageal Cancer

OBJECTIVE To evaluate the clinical application of a right-thoracic approach with or without laparotomy for mid-upper esophageal cancer. METHODS We retrospectively reviewed the data of 34 esophageal cancer patients who received Belsey surgery or a modified Ivor-Lewis surgery from November 1992 to April 2007. Twenty of the patients underwent a Belsey prodecdure （Group A） from November 1992 to January 2001 and 14 underwent a modified Ivor-Lewis prodecdure （Group B） from May 2001 to April 2007. RESULTS Twenty patients with esophageal cancer received an esophagectomy through an exclusive right-thoracic approach （Belsey surgery）, and 14 patients received an esophagectomy through a right-thoracic approach combined with a laparotomy （modified IvorLewis surgery）. The complication rate was 15% （3/20） and 7.1% （1/14） respectively. The survival rate was 42.9% （5-year survival） and 38.7% （5-year survival） respectively for these two groups. CONCLUSION An exclusive right-thoracic approach （Belsey surgery） is associated with more complications. It is not a routine surgery for cancer of the mid-upper thorax of the esophagus, but can be selectively used as palliative esophagectomy for esophageal cancer patients with poor pulmonary function. Modified Ivor-Lewis surgery can simultaneously be utilized to resect the primary tumor and dissect lymph nodes of the thorax and abdomen. With a shorter time period of surgery and postoperative recovery period, modified Ivor-Lewis surgery can achieve better effects with patients who have midupper esophagus cancer.

Pathologic and Clinical Analysis of Carcinosarcoma of Esophagus (20 Cases)

Objective:Carcinosarcoma of esophagus is an infrequent disease. Here, the pathologic data of larger specimens of this disease are reviewed and analyzed for studying its clinical characteristics in order to provide support information for clinical diagnosis. Methods: To review and study the clinical data of 20 patients of esophageal carcinosarcoma. Results: Most of esophageal carcinosarcoma grew like pileus or polypus in esophagus, a few of them were infiltrating. Microscopic examination of the resected specimens indicated that the tumor is composed of sarcomatous element and carcinomatous element (the main element), and the surface of such tumor was covered mostly by carcinoma tissues. The result of biopsy showed that the tumor is squamous cell carcinoma. X-ray examination indicated that there was polypus-like smooth and tidy filling defect in the esophagus of such patient, and its mucous membrane showed “daubing-trace” like characteristics. Conclusion: Carcinosarcoma of esophagus is a tumor of low invasion, which grows mainly in the esophageal lumen. The clinical symptoms of this tumor are different from those of esophagus carcinoma in certain degree. The “daubing-trace” like characteristics is typical of X-ray picture. The results of most endoscopic biopsies demonstrate squamous cell carcinoma or lower differentiation carcinoma, which are difficult for confirmed diagnosis before operation.

JNK抑制剂对D-氨基葡萄糖衍生物诱导Eca-109细胞Caspase-3活化的影响

目的:观察特异性c-Jun氨基末端激酶(JNK)抑制剂SP600125对D-氨基葡萄糖衍生物(COPADG)诱导的Eca-109细胞Caspase-3激活及细胞凋亡的影响,并探讨COPADG诱导Eca-109细胞凋亡的潜在分子机制。方法:体外培养Eca-109细胞,以COPADG及SP600125与细胞作用,细胞间接免疫荧光染色观察P-JNK蛋白表达的改变,流式细胞术检测细胞凋亡率及Caspase-3活性的变化。结果:经SP600125处理后,COPADG诱导的Eca-109细胞P-JNK蛋白表达明显减弱,凋亡率明显减低,Caspase-3活性显著下调,与COPADG单作用组之间有显著性差异。结论:SP600125能够显著抑制COPADG诱导Eca-109细胞Caspase-3激活以及COPADG诱导Eca-109细胞凋亡,并间接证明JNK信号转导通路在COPADG诱导Eca-109细胞凋亡过程中发挥着重要作用。

Genes Expression Profile Difference in Peripheral Blood Between Esophageal Carcinoma Patients and Normal Subjects

Objective： To study the genes expression profile differences in the peripheral blood between esophageal carcinoma patients and normal subjects using the gene chip technique and screen out the esophageal early conceration associated genes. Methods： The total RNA was extracted and purified in the peripheral blood obtained from the patients with esophageal carcinoma and normal subjects. The first strand of cDNA was synthesized through retro-transcription and labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with a piece of 4096 double dot human whole gene chip. The acquired image was analyzed by microarrav suite software using a digital computer, and the intensity of ttuorescence signal and its ratio were calculated. Results： A total of 92 genes were screened out and its expression difference was more than 2 times in the peripheral blood between the patients with esophageal carcinoma and normal subjects. Among these, the expression difference of 36 genes was more than 3 times. Two human urokinase plasminogen activator surface receptor （UPAR） genes, 80K-L protein gene, human protein tyrosine-phosphatase gent arid proto-oncogene protein mRNA were significantly up-regulated, while the collagen V type （α-2 gene was markedly down-regulated. Conclusion： 80K-L protein gene, tyrosinephophatase gene, proto-oncogene protein arid the collagen V type α-2 gene might be associated with the ontogenesis, development and its metastasis in the esophageal carcinoma. The UPAR gene may play important roles in the diagnosing the micrometastasis in the peripheral blood of esophageal carcinoma.

单体位左胸左颈两切口管型吻合器治疗食管上段癌的疗效

目的:探讨单体位左胸左颈两切口的手术方式在外科治疗食管上段癌中的应用效果。方法:选择2008年1月至2012年4月间我院收治的食管上段癌患者49例,根据手术方法分为研究组(n=19)和对照组(n=30),研究组行单体位左胸左颈两切口管型吻合器治疗,对照组行传统颈、胸、腹三切口方法治疗。观察两组手术时间、术中出血量、清扫淋巴结数、术后引流量和术后并发症等。结果:研究组手术时间显著短于对照组,术中出血量和术后引流量显著低于对照组(P<0.05)。两组清扫淋巴结数比较无统计学差异(P>0.05)。两组患者均全部治愈出院,研究组肺不张、反流性食管炎、吻合口瘘、吻合口狭窄等发生率显著低于对照组(P<0.05)。结论:单体位左胸左颈两切口管型吻合器治疗食管上段癌安全,可靠,省时易行,是一种较好的手术方式,值得推广。

Correlation between c-erbB-2 and P-glycoprotein Expression in Esophageal Carcinoma

Objective： To investigate the correlation between c-erbB-2 and multidrug resistance （MDR） and its clinical significance, Methods： Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein （P-gp） in samples from 46 patients with esophageal carcinoma. Results： The positive expression rate of c-erbB-2 was 26.1% （12/46） in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% （28/46） in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference （P〈0.01） between P-gp expressions with lymph node metastasis （31.09%±5.33%） and without lymph node metastasis （8.04%±3.03%） when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference （P〈0.01） between P-gp expressions in HI Ⅳ stage （33.68%±5.51%）and in Ⅱ stage patients （9.30%±2.78%） when c-erbB-2 expression was positive. The tumor＇s size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion： The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.

The Expression of RECK mRNA and Protein in Esophageal Squamous Cell Carcinoma and Its Clinical Significance

OBJECTIVE To investigate the expression of RECK mRNA and protein in esophageal squamous cell carcinoma （ESCC） and to examine its relationship with the clinicopathologic features. METHODS The expression of RECK mRNA and protein in 62 cases of ESCC, 31 of paraneoplastic atypical hyperplasia （PAH） and 62 normal esophageal mucous membrane specimens was examined, using RT-PCR and immunohistochemistry. RESULTS During canceration of the ESCC, the mRNA of RECK increased sequentially from ESCC tissue to PAH and normal mucous membranes. Values were 1.052±0.078, 1.274±0.235 and 1.306±0.121, respectively, with a significant difference among different groups （F=49.936, P〈0.05）. There was a statistically significant difference in the relative amount of the RECK mRNA among the ESCC tissues at various levels of differentiation, depth of infiltration, and different types of lymph node metastasis （F=5.081, F=26.084, U=24.011, P〈0.05）. In the ESCC tissue and PAH, the positive rates of RECK protein expressions were lower compared to the normal mucosa tissue, i.e. 59.7% （37/62）, 71.0% （22/31） and 85.5% （53/62）, respectively. There was a significant difference among the inter-group comparisons （Х^2=10.331, P〈0.01）. In ESCC, there was a close correlation between the RECK protein expression and the degree of cancer differentiation, and the depth of invasion and the types of ESCC lymph node metastasis （P〈 0.05）. CONCLUSION The decrease in expression of both RECK mRNA and protein in ESCC suggest that these low expressions may relate to ESCC development. Examination of RECK mRNA and protein expression may develop into one of the molecular indices for early ESCC diagnosis and prognosis.

Endoscopic submucosal dissection for gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it:injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en- bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects:(1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.

Nitrosamine and related food intake and gastric and oesophageal cancer risk: A systematic review of the epidemiological evidence

AIM： To study the association between nitrite and nitrosamine intake and gastric cancer （GC）, between meat and processed meat intake, GC and oesophageal cancer （OC）, and between preserved fish, vegetable and smoked food intake and GC. METHODS： In this article we reviewed all the published cohort and case-control studies from 1985-2005, and analyzed the relationship between nitrosamine and nitrite intake and the most important related food intake （meat and processed meat, preserved vegetables and fish, smoked foods and beer drinking） and GC or OC risk. Sixty-one studies, 11 cohorts and 50 case-control studies were included. RESULTS： Evidence from case-control studies supported an association between nitrite and nitrosamine intake with GC but evidence was insufficient in relation to OC. A high proportion of case-control studies found a positive association with meat intake for both tumours （11 of 16 studies on GC and 11 of 18 studies on OC）. A relatively large number of case-control studies showed quite consistent results supporting a positive association between processed meat intake and GC and OC risk （10 of 14 studies on GC and 8 of 9 studies on OC）. Almost all the case-control studies found a positive and significant association between preserved fish, vegetable and smoked food intake and GC. The evidence regarding OC was more limited. Overall the evidence from cohort studies was insufficient or more inconsistent than that from case-control studies.CONCLUSION： The available evidence supports a positive association between nitrite and nitrosamine intake and GC, between meat and processed meat intake and GC and OC, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

Selective cyclooxygenase （COX）-2 inhibitors （coxibs） were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs （NSAIDs）. However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis （FAP）, which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration （FDA） immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

Comparative study of CEA and CA19-9 in esophageal,gastric and colon cancers individually and in combination(ROC curve analysis)

Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods： The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic （ROC） curves were plotted. Results： Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined： in esophageal cancer, sensitivity=28%, negative predictive value （NPV）=61.72%, and AUC=0.742 （SE=0.05）, with a significance level of P〈0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 （SE=0.0S）, with a significance level of P〈0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 （SE=0.04）, with a significance level of P〈0.0001. The sensitivity of CA19-9 was also evaluated： in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 （SE=0.05）, with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 （SE=0.05）, with a significance level of P〈0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.S80 （SE=0.05）, with a significance level ofP=0.1670. The following were the sensitivities of CEA/CA19-9 combined： in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 （95% CI： 0.0159-0.322）; gastric cancer, sensitivity=S8%, NPV=70.42%, SE=0.072 （9$% CI： -0.0866-0.198）; and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 （9S% CI： 0.137-0.415）. Conclusion： CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

Expression of Livin and vascular endothelial growth factor in different clinical stages of human esophageal carcinoma

AIM： To investigate the role of Livin and vascular endothelial growth factor （VEGF） in human esophageal carcinoma, and analyze its relationship to clinical stages.METHODS： Expression of Livin in fresh esophageal cancer tissues was detected by immunohistochemistry （IHC）, Western blotting and reverse transcriptasepolyrnerase chain reaction （RT-PCR）, and VEGF by Western blotting and RT-PCR. All statistical analyses were performed by SPSS version 11.0. RESULTS： Livin positivity was also significantly correlated with tumor stages, increasing with tumor progression. Expression of Livin and VEGF increased with the process of esophageal carcinoma. In the fourth clinical stage, expression of Livin and VEGF was the most significant. Expression of Livin was positively correlated with VEGF. CONCLUSION： Over-expression of Livin and VEGF contributes to the pathogenesis of esophageal carcinoma.