Multimodal treatment for resectable esophageal cancer

Surgical resection has been traditionally the mainstay of treatment for localized esophageal cancers. However, survival after surgery alone for advanced esophageal cancer is not satisfactory. In Japan, the development of multimodal therapy for esophageal cancers has centered mainly on systemic chemotherapy plus surgery to control distant metastasis. Based on the results of the recent Japan Clinical Oncology Group (JCOG) 9907 study, preoperative chemotherapy (consisting of 5-FU and cisplatin) followed by surgery has emerged as the standard treatment. In Western countries, where chemoradiotherapy followed by surgery has been mainly explored for patients with resectable esophageal cancers, two large controlled trials that evaluated the effectiveness of preoperative chemotherapy reported conflicting results. However, a recent meta-analysis reported significant survival benefits for preoperative chemotherapy in patients with adenocarcinoma of the esophagus. We need to find new effective preoperative chemotherapeutic regimens, including molecular target agents, with response rates higher than that of the conventional chemotherapy of 5-FU and cisplatin. However, we also must compare the survival benefits of preoperative chemotherapy with preoperative chemoradiotherapy.     

Multimodal treatment of esophageal cancer

Background

The treatment of localized esophageal cancer has been debated controversially over the past decades. Neoadjuvant treatment was used empirically, but evidence was limited due to the lack of high-quality confirmatory studies. Meanwhile, data have become much clearer due to recently published well-conducted randomized controlled trials and meta-analyses.

Methods

Neoadjuvant and perioperative platinum fluoropyrimidine-based combination chemotherapy has now an established role in the treatment of stage II and stage III esophageal adenocarcinoma and cancer of the esophago-gastric junction. Neoadjuvant chemoradiation is now the standard of care for treating stage II and stage III esophageal squamous cell cancer and can also be considered for treating esophageal adenocarcinoma.

Results

Patients with esophageal squamous cell cancer treated with definitive chemoradiation achieve comparable long-term survival compared with surgery. Short-term mortality is less with chemoradiation alone, but local tumor control is significantly better with surgery.

Conclusion

This expert review article outlines current data and literature and delineates recommendable treatment guidelines for localized esophageal cancer.     

Multimodal treatment of non small cell lung cancer

The primary treatment of lung cancer depends on tumor stage. Chest CT scan and bronchoscopy are used to define the TNM stage and resectability. In case of lung cancer without mediastinal lymph node enlargement or direct mediastinal involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended. The use of adjuvant chemotherapy has to be defined, but will be indicated in stage II and IIIa. Expected 5-year survival achieves 40 to 80 % depending on tumor stage. Exceeds the shorter diameter of mediastinal lymph nodes in chest CT scan more than 1 cm (or in case of positive PET scan) mediastinoscopy is indicated. In case of N2-disease and after tumor response to preoperative chemotherapy (about 60 %) secondary resection of the tumor leads to higher 5-year survival rates (20-40 %) compared to patients without induction therapy (5-20 %). In these patients and after unexpected detection of solitary lymph node metastasis by primary resection adjuvant mediastinal radiotherapy should be added. If the tumor has infiltrated the mediastinum or the upper sulcus (T3/4) and/or mediastinal lymph nodes are obviously tumor burden (e. g. > 3 cm, N2 bulky, N3) radical primary resection may not be possible. In these patients combined radio- and chemotherapy induces a high percentage of tumor regression and can be used before secondary resection (5-year survival 5-20 %). Locally advanced tumors infiltrating the main bronchus close to the carina or the carina itself and tumors with metastases in the same lobe, both without mediastinal lymph node metastases (T3/4N0-1), can be resected by sleeve pneumonectomy and lobectomy with satisfactory results respectively. In patients with resectable lung cancer and no clinical sign of tumor disease (f. e. anemia, weight loss, pain) limited staging procedure with chest CT scan including upper abdomen and bronchoscopy is reasonable. In the remaining patients complete staging is necessary. We recommend an interdisciplinary approach to patients with lung cancer.     

Multimodality treatment strategy for squamous cell oesophageal cancer

Cancer of the oesophagus is notorious for its grave prognosis of an overall 5-year survival rate of 10–20%. Surgical resection with curative intent remains the most effective treatment for this disease. To improve survival, a multimodality treatment strategy was adopted for managing patients with oesophageal cancer. The use of pre-operative adjuvant chemotherapy did not confer any survival benefit to patients with localized oesophageal cancer, as is proven by most randomized studies; however, the preliminary results of pre- operative chemotherapy with radiotherapy is encouraging but needs to be verified in a randomized trial. For patients with incurable diseases, endoscopic stenting offers effective palliation of dysphagia with minimal morbidity and mortality.      

Multimodal treatment of gastric cancer

Gastric cancer is the second leading cause of death from malignant disease worldwide.Although complete surgical resection remains the only curative modality for early stage gastric cancer,surgery alone only provides long-term survival in 20%of patients with advancedstage disease.To improve current results,it is necessary to consider multimodality treatment,including chemotherapy,radiotherapy and surgery.Recent clinical trials have shown survival benefit of combining different neoadjuvant or adjuvant protocols compared with surgery with curative intent.Furthermore,the implementation of chemotherapy with novel targeted agents could play an important role in the multimodal management of advanced gastric cancer.In this paper,we focus on a multidisciplinary approach in the treatment of gastric cancer and discuss future strategies to improve the outcome for these patients.     

关于食管鳞状细胞癌免疫治疗的几点思考

近几年免疫治疗食管鳞状细胞癌取得了很大的进展.但是对于胸外科医生而言,免疫治疗还是个新生事物,缺乏足够的经验.因此,本文试图就一些免疫治疗的热点问题进行探讨,包括免疫治疗的适应证、不良反应、疗效以及疗效的判定等,以期引起胸外科医生的重视.     

Secondary squamous cell prostate cancer after prostate brachytherapy treatment

This report describes the case of a patient with prostate cancerat the age of 59 years, who was treated by interstitial prostate brachytherapy with iodine-125 seeds. Ten years later, he developed a probable secondary squamous cell cancer in his prostate.     

同卵双胞胎食管癌患者的血清蛋白组学研究

目的 观察河南食管癌高发区同卵双胞胎食管癌患者与高发区散发食管癌患者血清蛋白的表达,筛选食管鳞癌相关血清标记物.方法 收集3对同卵双胞胎、5例散发食管癌患者的血清,采用磁珠蛋白组技术对3对同卵双胞胎中的食管癌患者和10对健康同卵双胞胎(对照组)的血清进行蛋白组对比.结果 在3对同卵双胞胎中的3例食管癌患者中,共同表达的差异蛋白为16个.3对同卵双胞胎中的3例食管癌患者和20对健康同卵双胞胎对比差异蛋白为5905.29、5967.68、1779.04 Da(P＜0.05),5例散发食管癌与10对健康人对比差异蛋白为1779.17、1929.57、1866.43、1881.41、5095.48 Da(P＜0.05).结论 应用磁珠蛋白技术在同卵双胞胎中筛选出的差异蛋白可能成为食管癌筛查的血清蛋白标志物.     

Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition.     

Multimodal treatment of pancreatic cancer]

The experience with combined treatment of 122 patients with pancreatic cancer in the clinic of the Institute of Clinical & Experimental Surgery for the period of from 1988 to 1990 is summarized. Radical operations were performed in 54 patients, the palliative ones--in 68. After performance of a palliative operation, the patients underwent polychemotherapy, 5--in combination with UHF-hyperthermia. To study the effect of chemotherapy on the immune system, the immunologic monitoring was carried out. It was established that under the influence of chemotherapy and hyperthermia, the indices of immunity in patients with pancreatic cancer improved. In cancer of the pancreatic head with involvement of pancreatic body, the performance of subtotal pancreatoduodenal resection with subsequent regional chemotherapy is expedient. Chemotherapy and hyperthermia in combination with creation of a shunt permit to improve the results of treatment of inoperable tumors. The use of regional chemotherapy in subtotal resection contributed to increase in 2-year survival of the patients.     

Cluster of 4 cases of esophageal squamous cell cancer developing in adults with surgically corrected esophageal atresia--time for screening to start

BackgroundCurrently, no recommendations exist for the endoscopic screening of patients in adulthood, with surgically corrected esophageal atresia (EA), for the development of esophageal cancer. A small number of individual case reports in the literature have raised concern that these cancers pose an increased risk (2 adenocarcinoma and 3 squamous cell carcinoma).MethodsSt Vincent's hospital has set up an EA clinic to review adult patients previously operated on for correction of EA. These patients underwent clinical review and were offered endoscopic evaluation if they had symptoms of dysphagia or gastroesophageal reflux. Among those patients, 3 have developed esophageal squamous cell carcinoma (SCC). A retrospective review of the EA database from the Royal Children's Hospital (798 patients [309 patients older than 40 years]) was then performed to identify any other cases of esophageal cancer developing in this cohort. One further patient was identified.ResultsTo date, 4 of 309 patients have developed esophageal SCC over the age of 40 years. The cumulative incidence of esophageal SCC in this age group was 50 times that expected in the general population.Conclusions(1) This cluster provides strong evidence that there is a substantial risk of SCC in these adults with surgically repaired EA. (2) We believe that long-term surveillance endoscopy enhanced by advanced imaging techniques is indicated in all adults from the age of 20 years who have had surgical repair of EA.     

全基因组寡核苷酸表达谱筛选哈萨克族食管癌相关靶基因

目的 筛选哈萨克族食管癌与正常食管黏膜的差异表达基因.方法 新鲜标本取自哈萨克族食管鳞癌患者.采用RNA保护技术保护组织标本,分离癌组织、正常食管黏膜组织标本,提取RNA,线性扩增获得足量cRNA,利用基因芯片分别检测癌组织和正常食管黏膜组织基因表达谱,并利用生物信息学方法对检测结果进行分析.结果 癌组织和正常食管黏膜组织比较差异10倍以上共有170个基因,其中表达上调(信号比的对数值>3)有39个,表达下调(信号比的对数值<-3)有131个.表达异常的基因与细胞周期调节、细胞凋亡、细胞骨架、细胞外基质、细胞内信号传递、蛋白质的翻译合成及免疫功能等相关.结论 利用全基因组寡核苷酸芯片可准确、高效地筛选出哈萨克族食管癌相关的候选靶基因170个,这些基因与哈萨克族食管癌的发生、发展有关.     

Postoperative therapy of recurrent esophageal squamous cell carcinoma

Some 218 resected cases and 43 autopsied cases after resection during the last 13 years were analyzed with regard to the mode of recurrence and survival. Several factors were investigated with the following results. 1) Extensive clearance of upper mediastinal lymph nodes during radical surgery may reduce the incidence of tumor recurrence. It is preferable to remove the cervical lymph node, however, after positive metastasis to cervical lymph node. 2) Beginning in 1981, interstitial brachytherapy of 192Ir seed assemblies using afterloading techniques was administered to two patients with esophageal carcinoma infiltrating the aorta and four patients infiltrating the trachea and main bronchus which were not completely resected in either case due to invasion of adjacent organs. No significant difference in life-prolongation was observed, but it may have been effective for prevention of localized recurrence in cases with aortic infiltration and with infiltration of the trachea and bronchus. 3) From 1984, eleven patients with recurrent squamous cell esophageal carcinoma were treated with combination chemotherapy sandwiched with irradiation (CDDP/5FU-RT-CDDP/5FU). Eight patients (73%) had complete or partial response, and six patients survived over one year after combination chemotherapy sandwiched with irradiation. Combination chemotherapy sandwiched with irradiation appears to be effective in the treatment of patients with recurrent squamous cell carcinoma of the esophagus. Toxic effects are moderate and manageable.     

食管鳞癌组织中miR-148a的表达及其临床意义

目的检测食管鳞癌组织中miR-148a的表达水平,探讨miR-148a表达与患者临床病理指标及预后的相关性。 方法收集2009年1至12月在山东大学齐鲁医院胸外科行食管癌切除加系统性淋巴结清扫的75例食管鳞癌患者的肿瘤组织标本,采用实时荧光定量PCR法检测miR-148a的表达。应用SPSS 18.0软件建立数据库并进行统计分析。χ²检验分析miR-148a表达与患者临床病理指标之间的关系;Kaplan-Meier法绘制患者的生存曲线,Log-rank检验比较患者的生存差别,Cox回归多因素分析判定独立的预后因素。 结果有32例患者肿瘤组织中miR-148a为低表达,miR-148a的低表达率为42.7%(32/75),与肿瘤浸润深度(χ²＝8.149,P＝0.017)、淋巴结转移(χ²＝4.151,P＝0.042)及病理分期(χ²＝6.474,P＝0.039)显著相关。患者术后3年的总生存率为70.7%。单因素生存分析结果显示,miR-148a低表达患者的术后3年总生存率显著低于miR-148a高表达患者(53.1%和83.7%,χ²＝9.136,P＝0.003)。Cox多因素回归分析结果显示,肿瘤浸润深度(95%CI为1.015～2.799,P＝0.044)及淋巴结转移(95%CI为1.285～4.796,P＝0.007)分别是判定患者术后3年总生存率的独立预后因素。 结论miR-148a在食管鳞癌组织中存在异常低表达,并与肿瘤进展及患者的不良预后密切相关;miR-148a可作为预测食管鳞癌进展和判定患者不良预后的参考指标。