The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation

BACKGROUND: Esophageal and esophagogastric junction (EGJ) adenocarcinomas frequently have neuroendocrine (NE) differentiation, but the significance of NE differentiation in patients who have undergone preoperative chemoradiation and resection remains unclear. METHODS: The authors evaluated the presence of NE differentiation in esophageal and EGJ adenocarcinomas by immunohistochemistry for chromogranin A and synaptophysin and evaluated the clinical significance of NE differentiation in 83 patients (10 patients who had a complete tumor response and 73 patients who had residual tumor in resection specimens) who received preoperative chemoradiation. RESULTS: Of 73 patients who had residual tumor after preoperative treatment, 52% showed NE differentiation. The proportion of tumor cells with NE differentiation had increased from 6% +/- 18% in pretreatment biopsy specimens to 47% +/- 42% (P = .00003) in posttreatment resection specimens in 30 patients who had paired pretreatment biopsy and resection specimens available. Disease-free survival (P = .002) and overall survival (P = .006) were significantly better in patients who had a complete tumor response than in patients who had residual tumor. Among patients who had residual tumor after preoperative chemoradiation, disease-free survival (P = .03) and overall survival (P = .045) were significantly better in patients who had residual tumor without NE differentiation than in patients who had residual tumor with NE differentiation. In multivariate analysis, the presence of NE differentiation in residual tumor was a prognostic factor for worse disease-free survival (P = .02) independent of pathologic stage and extent of residual tumor. CONCLUSIONS: The results from this study suggested that tumor cells with NE differentiation were more resistant to neoadjuvant chemoradiation in patients with esophageal and EGJ adenocarcinomas. The presence of NE differentiation in residual tumor was associated with poor survival after preoperative neoadjuvant therapy.     

Epidemiology of adenocarcinoma of the esophagogastric junction

The incidence of adenocarcinoma of the esophagogastric junction has increased rapidly in the later half of the twentieth century in the United States and most western countries. Although squamous cell carcinoma of the esophagus used to predominate, adenocarcinoma of the distal esophagus and esophagogastric junction now accounts for more than half of new diagnoses in western countries. There also has been a shift from the development of distal gastric cancers to ones in a more proximal location. These recent epidemiologic shifts have led to controversy regarding the etiology and treatment of adenocarcinoma of the esophagogastric junction. Uncertainty still exists with regards to nomenclature and classification, risk factors, treatment, and screening and surveillance of esophagogastric adenocarcinoma. This article examines the epidemiology and etiologies of adenocarcinoma of the esophagogastric junction.     

食管胃结合部腺癌的手术治疗

There are a variety of surgical treatments of advanced esophagogastric junction cancer, type Ⅰ、Ⅱ mainly by transthoracic approach, part of the type Ⅱ by transabdominal approach, type Ⅲ mainly by left thoracoabdominal approach (LTA) or transabdominal. Intraoperative lymph node dissection is one of the most important factors which affect the postoperative survival rate. The cardia right lymph node (NO.1), the cardia left lymph node (NO.2), gastric lesser curvature (NO.3) and left gastric artery side (NO.7) should do regular cleaning.     

The unique phenotypes of adenocarcinoma of the esophagogastric junction in China

Adenocarcinoma of the esophagogastric junction （AEG） was proposed as a distinct disease for its rapidly increasing incidence. However, most studies of AEG were based primarily on the results of western patients and the studies on Chinese patients were deficient. Recently, some retrospective studies on AEG patients from our hospital show distinct clinical and pathological features compared with American patients （1-3）. In this editorial, we will focus on the unique phenotypes of Chinese AEG patients based on our studies and other reports.     

Current surgical treatment of esophagogastric junction adenocarcinoma

The incidence of esophagogastric junction (EGJ) adenocarcinoma has shown an upward trend over the past several decades worldwide. In this article, we review previous studies and aimed to provide an update on the factors related to the surgical treatment of EGJ adenocarcinoma. The Siewert classification has implications for lymph node spread and is the most commonly used classification. Different types of EGJ cancer have different incidences of mediastinal and abdominal lymph node metastases, and different surgical approaches have unique advantages and disadvantages. Minimally invasive surgeries have been increasingly applied in clinical practice and show comparable oncologic outcomes. Endoscopic resection may be a good therapy for early EGJ cancer. Additionally, there is still a great need for well-designed, large RCTs to forward our knowledge on the surgical treatment of EGJ cancer.     

食管胃交界腺癌的外科治疗

食管胃交界腺癌（ＡＥＧ）指发生于食管远端和胃贲门区域的腺癌,其发生率明显上升。由于两种腺癌发生部位接近、生物学行为相似、预后均较差,多数学者认为ＡＥＧ是一独特的临床病理类型。目前对ＡＥＧ分型采用最广泛的是Ｓｉｅｗｅｒｔ分型方法;在分期方面尚无单独的分期研究,一般根据病灶主体所在部位,按现行ＴＮＭ分期系统,Ⅰ型和Ⅱ、Ⅲ型分别按食管癌和胃癌分期。手术切除是ＡＥＧ最主要的治疗手段,在保证手术安全的前提下应力争达到Ｒ０切除,切缘应距肿瘤边缘５ｃｍ。常规手术径路有经胸、经腹、胸腹联合３种,一般Ⅰ型者多采用经胸途径,Ⅱ、Ⅲ型者多采用经腹途径。对于Ｔ２期以上者应按Ｄ２标准进行淋巴结清扫,扩大切除（联合脾或胰腺体尾切除）仅限于特定的较晚期病例。早期病例（Ｔ１ｂ）可行Ｄ１手术。有关ＡＥＧ综合治疗的研究很少,对病期较晚（Ｔ２分期以上）者可以选择ＥＣＦ为主的新辅助化疗或辅助化疗、化放疗。     

The prognostic relevance of parapyloric lymph node metastasis in Siewert type II/III adenocarcinoma of the esophagogastric junction

Background

The purpose of this study was to evaluate the prognosis of patients with Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG) with parapyloric lymph node (No. 5 and 6 lymph nodes, PLN) metastasis and to determine the need for PLN dissection for patients with type II/III AEG.

胃食管结合部腺癌区域淋巴廓清的临床研究

目的  探讨胃型胃食管结合部腺癌淋巴清扫范围与淋巴结转移区域分布规律。 方法  分析2004年1月至2015年12月,山西省人民医院普外科收治的胃食管结合部癌患者肿瘤数据库,基于Nishi分型选取其中胃型胃食管结合部腺癌肿瘤,直径≤40 mm并R0切除患者相关肿瘤学数据勾勒胃型胃食管结合部腺癌淋巴高频转移站别区域图。 结果  纳入306例胃型胃食管结合部腺癌患者,结果显示：pT4期肿瘤占87％、pN阳性占778％、pTNM分期Ⅲ期占745％;肿瘤直径（2544±1803）mm;腹腔淋巴结转移高频区域依次是贲门左右侧（第1、2组）、小弯侧胃左血管周围（第3组）、胰腺上缘腹腔干（第9组）及其主干分支胃左动脉（第7组）、肝总动脉（第8a组）、脾动脉近端（第11p组）、肝动脉（第12a组）周围以及食管裂孔周围（第19、20组）;胃远端区域转移较为罕见。 结论  瘤体直径≤40 mm胃型胃食管结合部腺癌淋巴清扫区域应集中在贲门左右侧、小弯侧、胰腺上缘腹腔干及其主干分支以及食管裂孔周围,胃远端及大弯侧区域淋巴清扫外科获益价值存疑。     

The optimal lymph node dissection in patients with adenocarcinoma of the esophagogastric junction

Objective

The aim of this study was to refine the optimal lymph node dissection in Western patients with adenocarcinoma of the esophagogastric junction (AEG).

新辅助治疗在食管胃结合部腺癌中的研究进展

食管胃结合部腺癌单纯手术治疗效果并不理想,预后较差,目前尚缺乏专门针对食管胃结合部腺癌的标准治疗方案.新辅助治疗包括新辅助放疗、化疗及新辅助放化疗,它们在食管胃结合部腺癌治疗中的应用及疗效仍存在争议.     

食管-胃结合部腺癌手术治疗的共识与争议

食管-胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)在全球的发病率不断升高,因其特殊的解剖位置、独特的生物学行为被越来越多的临床工作者所重视。目前国内外虽然对AEG的发病、分型等已形成了一定共识,但在更多方面,尤其是外科治疗手段,诸如手术路径、胃的切除范围、淋巴结的清扫范围、消化道重建等方面仍存在较多争议。这些争议不仅限制了对AEG治疗的探索与发展,同时使得对AEG的规范化诊疗变得更加困难。本文结合近些年的相关文献,就目前AEG治疗的国内外相关共识与争议进行综述,以期为临床诊治提供更加合理、有效的方法。     

The prognostic significance of ploidy analysis in operable breast cancer

The nuclear DNA content of 98 operable breast cancers was determined by flow cytometric analysis using paraffin-embedded tissue. All patients were on follow-up and failure of treatment or recurrences were identified. DNA ploidy data in the form of ploidy status and DNA index (DI) has been correlated with various clinical and histopathologic factors. The only significant correlation using univariate analysis exists between the histologic grade and DI (P less than 0.025), recurrence of the disease and ploidy status (P less than 0.005), and recurrence of the disease and DI (P less than 0.005). The absence of correlation of ploidy status with other tumor derived factors indicates the independent nature of ploidy as a prognostic factor. Multivariate analysis showed that in the whole-group ploidy (P less than 0.01), tumor margin (P less than 0.01), and menopausal status (P less than 0.01) were significant factors in the order mentioned. DI with a cut of at 1.29 is not found to be a significant factor in the multivariate analysis. The maximum prognostic value of ploidy status was observed in the postmenopausal group (P less than 0.0005). In the node-negative group ploidy status (P less than 0.05) is the only independent significant factor predicting for early relapse. It is concluded that ploidy status is an independent prognostic factor predicting for recurrence of the disease. In the node-negative subgroup this could be used to identify the subset of patients who may benefit from adjuvant treatment.     

Lymph node metastasis and lymphadenectomy of resectable adenocarcinoma of the esophagogastric junction

Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.     

Frequency and clinical impact of lymph node micrometastasis and tumor cell microinvolvement in patients with adenocarcinoma of the esophagogastric junction

BACKGROUND: Tumor involvement of regional lymph nodes has a crucial impact on the prognosis of patients with adenocarcinoma of the esophagogastric junction (AEG). Although additional tumor cell deposits can be detected by sensitive methods (e.g., immunohistochemistry and polymerase chain reaction), their prognostic significance is uncertain. METHODS: Using immunohistochemistry for cytokeratins (AE1/AE3 antibody), the authors studied 3987 regional lymph nodes from 145 patients with completely resected adenocarcinoma of the esophagus (AEG I; n = 46 patients), cardia (AEG II; n = 79 patients), and subcardial region (AEG III; n = 20 patients). The newly detected cells were categorized with tumor cell microinvolvement (TCM) or with micrometastases (MM) based on tumor size and histology. RESULTS: Of the 75 pathologic lymph node negative (pN0) patients, 3 of 30 patients in the AEG I group (10%) and 8 of 45 patients in the AEG II and III groups (18%) had TCM (no significant difference). MM was found in 2 of 30 tumors in the AEG I group (7%) and in 11 of 45 tumors in the AEG II and III groups (24%), a significantly lower rate that that in the AEG I group (P < 0.05). Neither TCM nor MM showed a significant prognostic impact in AEG I tumors (P > 0.05). For the AEG II and III tumors, MM (new lymph node positive [pN+] cases) had a prognostic impact similar to metastases found by routine methods, with reclassification based on MM resulting in improvement in the pN0 group from 72.8 months to 82.6 months, but almost no change was seen in the pN+ group (49.9-49.2 months). TCM had no adverse impact on survival in any tumor type. CONCLUSIONS: These results highlight important differences between AEG I tumors and AEG II and III tumors and argue for different lymphadenectomy strategies for patients with these tumor types.     

食管胃结合部腺癌外科治疗研究进展

食管胃结合部腺癌作为一类独立的疾病在解剖、发病率等方面与胃其他部位的肿瘤存在明显差异,对其定义、分型、淋巴结转移等方而的研究已基本达成共识,但对于外科治疗的手术路径、切除范围、淋巴结清扫等问题长期以来各学派意见不一.本文就近年来食管胃结合部腺癌外科治疗研究相关的国内外文献复习并加以综述,为临床诊治提供更加合理、有效的方法.     

Analysis of the clinicopathological features and prognostic factors in 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction

Objective

To explore the clinicopathological features and prognostic factors of 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction (AEG).

食管胃交界腺癌和远端胃癌中hMLH1和hMSH2表达及其意义

目的 分析hMLH1和hMSH2在食管胃交界腺癌和远端胃癌中的表达情况,探讨其在不同部位胃癌发生发展中的可能意义.方法 采用免疫组织化学染色法,对比检测52例食管胃交界腺癌和17例远端胃癌hMLH1和hMSH2在蛋白水平上的表达情况,分析表达差异及其临床病理意义.结果 食管胃交界腺癌组织中,hMLH1和hMSH2蛋白表达率分别为55.8％（29/52）和63.5％（33/52）,远端胃癌中hMLH1和hMSH2蛋白的表达率分别为41.2％（7/17）和70.6％（12/17）,两者的阳性表达率差异无统计学意义（P＞0.05）.食管胃交界腺癌和远端胃癌hMLH1和hMSH2的表达与肿瘤的分化程度以及淋巴结转移均无明显相关性（P＞0.05）.结论 hMLH1和hMSH2并不是食管胃交界腺癌和远端胃癌发生机制差异性的关键分子.     

胃食管结合部腺癌术前放疗胃充盈状态与肿瘤分次内动度和分次间动度的关系

目的:探索胃食管结合部腺癌(AEG)术前放疗,胃充盈状态与肿瘤分次内动度和分次间动度的关系。方法:前瞻性纳入2018—2019年间行全新辅助治疗的10例局部晚期AEG患者,均于治疗前在胃镜下标记肿瘤上下界,共获20枚钛夹。全部患者均在定位及治疗期间行空腹和充盈两种状态下的4DCT扫描,每次扫描均由系统自动重建出0%～9...