Controversies on the classification of esophagogastric junction carcinoma?a modified classi-fication based on esophageal invasion length / 中华消化外科杂志

Due to the particularity of tumor location, the surgery of esophagogastric junc-tion(EGJ) carcinoma needs to meet the safety of negative tumor margin, lymph node dissection and digestive tract reconstruction at the same time, which attracted more and more attention of esopha-gogastric surgeons. The current Siewert and Nishi classifications are based on the tumor epicenter, which is difficult to be accurately evaluated and measured before and during operation, and also lack of significance in determining the surgical methods and approach and lymph node dissection. The authors systematically analyze the limitations of Siewert and Nishi classification, discuss the relationship between esophageal invasion length and mediastinal lymph node metastasis and the role of esophageal invasion length on selection of surgical approach, and propose a modified classi-fication based on esophageal invasion length, including (1) malignant tumors with the upper or lower edge of tumor involving the zone of EGJ are defined as EGJ carcinoma; (2) EGJ carcinoma with the upper edge of tumor located 3.0 cm above the EGJ is classified as type Ⅰ; (3) EGJ carcinoma with the upper edge of tumor located 0?3.0 cm above the EGJ is classified as type Ⅱ; (4) EGJ carcinoma with the upper edge of tumor located 0?2.0 cm below the EGJ is classified as type Ⅲ.

Treatment of Siewert type II adenocarcinoma of the esophagogastric junction: the perspectives from thoracic surgery / 中华胃肠外科杂志

A greater controversy remains in clinical diagnosis and treatment of Siewert type II adenocarcinoma of esophagogastric junction (AEG), compared with Siewert type I and III AEG. In 2018, the first edition of Chinese Expert Consensus on the Surgical Treatment for Adenocarcinoma of Esophagogastric Junction was published in the Chinese Journal of Gastrointestinal Surgery. In the past few years, the advance in minimally invasive thoracoscopic surgery has been proven to reduce thoracic trauma in Siewert type II AEG. Meanwhile, distal thoracic esophagectomy can achieve more complete resection, and upper abdomen-right thoracic approach can ensure the mediastinal lymph node dissection and improve long-term survival. The concept and practice of endoscopic surgery and the comprehensive treatment also give new supplements to the treatment regimen of Siewert type II AEG. More clinical researches should be conducted to address the surgical residual safety and lymph node dissection issues.

Analysis of Siewert classification, microsatellite instability and HER2 expression in 242 cases of adenocarcinoma of esophagogastric junction / 国际外科学杂志

Objective:To explore the characteristics of Siewert classification and microsatellite instability(MSI) and HER2 expression in adenocarcinoma of esophagogastric junction (AEG).Methods:The clinicopathological data of gastric adenocarcinoma from May 2019 to November 2020 were retrospectively analyzed. The patients were divided into two groups: AEG group and non AEG group. The composition ratio of Siewert type of AEG was counted, and the relationship between tumor size and Siewert type was analyzed. The MSI status and HER2 expression status of AEG and non AEG were statistically compared. The measurement data of normal distribution were expressed as mean ± standard deviation( Mean± SD), the comparison between groups were by t test, the comparison of count data between groups were by Chi-square test. Results:A total of 328 consecutive cases of gastric adenocarcinoma were collected, including 242 cases of AEG and 86 cases of non AEG. The Siewert classification of AEG was mainly type Ⅱ (151 cases, 62.40%), followed by type Ⅲ (86 cases, 35.54%) and type Ⅰ (5 cases, 2.07%). The analysis of the relationship between the size of the tumor length and the number of Siewert type showed that the number of Siewert type Ⅱ cases decreased and the number of Siewert type Ⅲ cases increased with the increase of the tumor size. MSI status was detected non selectively in 192 cases of gastric adenocarcinoma (140 cases of AEG and 52 cases of non AEG). There were 12 cases of MSI (6.25%), 2 cases of MSI-H (1.04%) and 10 cases of MSI-L (5.21%). There was no significant difference in MSI ratio between AEG group and non AEG group ( P>0.05). All MSI cases were negative or weakly positive for PMS2. The expression of HER2 was detected by immunohistochemistry in 313 cases of gastric adenocarcinoma, except 15 cases of PTIS/T1a. There were 30 cases (9.58%) with HER2 expression 3+ . Thirty-two cases (10.22%) expressed HER2 (2+ ), of which 7 cases were detected by fluorescence in situ hybridization (FISH), and 3 cases were positive. The proportion of HER2 (3+ ) in AEG was significantly higher than that in non AEG group ( P<0.05). Conclusions:The main type of AEG was Siewert type Ⅱ. AEG may mostly occur between 1 cm above the esophagogastric junction and 2 cm below the esophagogastric junction; For endoscopic screening of early AEG, more attention should be paid to this area of stomach. Siewert type Ⅲ may be derived from the development of Siewert type Ⅱ. The incidence of microsatellite instability in gastric cancer is low. Compared with other gastric adenocarcinoma, AEG has no specificity in MSI. The MSI of AEG was mainly the expression defect of PMS2. Compared with other gastric adenocarcinoma, there are more HER2 overexpression in AEG.

Treatment strategies for adenocarcinoma of esophagogastric junction based on Siewert classification / 中华消化外科杂志

In recent years,the incidence of gastric cancer has been decreasing year by year in the world,but the incidence of adenocarcinoma of esophagogastric junction (AEG) has shown a significant upward trend,especially in western countries such as Europe and America.The prognosis of AEG is poor,therefore,it is extremely necessary to establish AEG's best diagnosis and treatment strategies to improve the long-term outcome of AEG.Nowadays,the most commonly used AEG classification is the Siewert classification proposed by German scholars in 1987,which is based on the anatomical features of the esophagogastric junction.It provides guidance for the choice of surgical methods.Compared with European and American countries,Siewert type Ⅱ or type Ⅲ are more common in Asian countries,and are mainly treated as the proximal gastric cancer.Compared with gastric tumors in other areas,AEG has obvious differences and specialities in anatomy,physiology and pathology,and there is still much controversy in the field of surgical and comprehensive treatment.

Surgical Treatment of Gastroesophageal Junction Cancer

Although the incidence of gastroesophageal junction (GEJ) adenocarcinoma has been increasing worldwide, no standardized surgical strategy for its treatment has been established. This study aimed to provide an update on the surgical treatment of GEJ adenocarcinoma by reviewing previous reports and propose recommended surgical approaches. The Siewert classification is widely used for determining which surgical procedure is used, because previous studies have shown that the pattern of lymph node (LN) metastasis depends on tumor location. In terms of surgical approaches for GEJ adenocarcinoma, a consensus was reached based on two randomized controlled trials. Siewert types I and III are treated as esophageal cancer and gastric cancer, respectively. Although no consensus has been reached regarding the treatment of Siewert type II, several retrospective studies suggested that the optimal treatment strategy includes paraaortic LN dissection. Against this background, a Japanese nationwide prospective trial is being conducted to determine the proportion of LN metastasis in GEJ cancers and to identify the optimal extent of LN dissection in each type.

Expression and its clinical significance of gastric and intestinal phenotypic markers in 47 Siewert type Ⅱ and type Ⅲ early gastroesophageal junctional cancers / 中华消化杂志

Objective To investigate the expression of gastric and intestinal phenotypic markers in Siewert typeⅡand Ⅲ early gastroesophageal junction(GEJ) cancer, and to explore its correlation with clinic-pathological features.Methods From April 2010 to July 2015, 53 cases diagnosed as early GEJ cancer were enrolled.The gastric and intestinal phenotypic markers such as mucin5AC(MUC5AC),mucin6(MUC6),mucin2(MUC2),caudal related homeodomain transcription 2(CDX2) and cluster of differentiation 10(CD10) were detected, and then the patients were divided into gastric type, gastrointestinal type, intestinal type and non-classified type according to the results of immunohistochemical staining.Combined with Siewert classification the clinicopathological features were analyzed.Chi square test or Fisher′s exact test was performed for statistical analysis.Results In the cancer tissues of 47 patients with Siewert type Ⅱand Ⅲ early GEJ cancer, the case numbers of positive expression of MUC5AC,MUC6,MUC2, CDX2 and CD10 were 21(44.7%),19(40.4%),31(66.0%),27(57.4%) and 17(36.2%),respectively;the case numbers of gastric type, gastrointestinal type, intestinal type and non-classified type were 11(23.4%),14(29.8%),21(44.7%) and one(2.1%), respectively.The positive expression rates of MUC5AC and MUC6 in Siewert typeⅡwere 55.9%(19/34) and 50.0%(17/34),which were higher than those of Siewert typeⅢ(2/13), and the positive expression rate of MUC2 was 55.9%(19/34), which was lower than that of Siewert typeⅢ(12/13), and the differences were statistically significant (x2=6.240,4.679 and 4.053;all P<0.05).In Siewert typeⅡ, the proportion of intestinal type was 32.4%(11/34), which was lower than that of Siewert typeⅢ(10/13), and the differences were statistically significant (x2=7.142,P=0.010).In patients with Siewert typeⅡand Ⅲ early cancer, males predominated in intestinal type which were mostly well differentiated type with less submucosal carcinoma.The maximum diameter of tumor was less than those of gastric type and gastrointestinal type.In paracancerous mucosal tissues, the incidences of intestinal metaplasia in gastrointestinal type and intestinal type were 11/14 and 81.0%(17/21), which were higher than that of gastric type (3/11);the incidences of atrophy in gastrointestinal type and intestinal type were 12/14 and 85.7%(18/21),which were higher than that of gastric type (4/11),and the differences were statistically significant (Fisher′s exact test,all P<0.05).Conclusions Siewert typeⅡand Ⅲ early GEJ cancer can directly originated not only from gastric mucosa, but also from gastrointestinal and intestinal mucosa.Atrophy and intestinal metaplasia could exist before cancer genesis.

Efficacy and prognosis of different surgical approach in siewert Ⅱ and Ⅲ gastroesophageal junction adenocarcinoma / 中国综合临床

Objective To investigate the surgical approach of Siewert Ⅱ and Ⅲ gastroesophageal junction adenocarcinoma.Methods A total of 148 cases with Siewert Ⅱ,Ⅲ type patients were prospectively studied.The patients were divided into two groups,including transthoracic approach group (58 cases) and transabdominal approach group(90 cases).The results of surgery were compared.Patients were followed up for 2 years and survival rate were compared.Results In transthoracic approach group and transabdominal approach group,operative time ((329.5 ± 84.3) min vs.(202.4± 84.5) min,t =15.431,P ＜ 0.001),the positive rate margin stump (8.62％ vs.1.11％,x2 =5.763,P =0.012),pleural effusion (13.79％ vs.2.22％,x2 =10.462,P ＜0.001) and pulmonary infection rate (15.52％ vs 1.11％,x2 =12.574,P＜ 0.001) were significantly higher than transabdominal approach group,and number of lymph node dissection ((16.7 ± 4.3) vs.(22.6± 5.5),t =6.321,P =0.004) was significantly less than transabdominal approach group.In incidence of blood loss,tumor diameter,anastomotic leakage (or bleeding) and discharge time,there was no significant difference (P ＞0.05).One-year survival rate of transthoracic approach group was 73.24％,and 2-year survival rate was 53.43％.Oneyear survival rate of transabdominal approach group was 78.42％,and 2-year survival rate was 57.51％.Survival rate of two groups showed no significant difference (P =0.453,0.311).Conclusion Transabdominal surgical approach in Siewert Ⅱ,Ⅲ patients is better than transthoracic approach,can better carry out abdominal lymph node dissection,does not destroy the integrity of the chest,and avoid the occurrence of related complications.

Adenocarcinoma of esophago-gastric junction / 国际外科学杂志

The incidence of gastroesophageal junction cancers is rapidly increasing, the Year' s upwards rate being more than 5％ ～ 10％. Siewert in 1987 proposed a definition for adenocarcinoma of the esophagogastric junction (AEG), as a adenocarcinoma within 5 cm of the gastroesophageal junction (GEJ), and divided AEG in to three types. The majority of patients with AEG in Asian countries have type Ⅱ and Ⅲ cancers, and no obvious differences have been reported in 5-year survival rates between patients with different types of AEG. In contrast, in western countries, the distribution of each type of AEG is nearly equal,patients with AEG type Ⅰ cancer have the best prognosis, whereas the overall survival of patients with type Ⅲ cancer is the worst. Now people presume that the AEG is a special type of carcinoma which is not same as carcinoma of esophagus and stomach. The surgical routes and operative methods and the extent of lymph node dissection of AEG are still not completely clear, and AEG lacks also a independent TNM system for itself. We will summarize the actuality of diagnosis and therapy of AEG.

Cardia Cancer: Personal Experience

PURPOSE: Due to the biological characteristics of cardia cancer, prognosis is poor. It is therefore essential to achieve a sufficient proximal resection margin to maximize survival. The authors studied gastric cardia cancer, focusing on adenocarcinoma. METHODS: One-hundred fifty patients who were diagnosed with gastric cardia cancer and underwent surgery between January 1990 and December 2006 by a single surgeon were included in this study. RESULTS: Of the 150 cases, 141 were adenocarcinomas, 4 were carcinomas, and 3 were leiomyosarcomas. In the adenocarcinoma group, the male-to-female ratio was 2.62:1. There were 2, 60, and 79 (56.0%) cases of adenocarcinoma type I, II, and III, respectively, and there were 32 (22.7%), 18 (12.8%), 70 (49.6%), and 21 (14.9%) cases of stage I, II, III, and IV tumors, respectively. The mean distance from the proximal tumor to the resection margin was 1.93+/-2 cm pathologically, and there was tumor invasion of the resection margin in 4 cases (2.8%). In the 10 cases of extended surgery in type II, the mean distance was 5.85+/-3.67 cm, with no tumor invasion of the resection margin. Recurrence occurred in 30 (21.3%) cases, and 5 of those cases were local anastomotic site recurrences. Cumulative survival was 81.3%, 77.8%, 51.4%, and 28.6% for stage I, II, III, and IV tumors, respectively. CONCLUSION: Although it is possible to remove the tumor with an appropriate resection margin by only an abdominal incision, the surgeon should always keep in mind the possibility of a thoracoabdominal incision when operating on a patient with esophageal infiltration.

The Clinicopathological Characteristics of Adenocarcinoma of the Gastro-esophageal Junction

PURPOSE: Siewert's classification of adenocarcinoma of the esophagogastric junction (AEG) has been widely adopted, but there is a wide discrepancy of the clinicopathological features of AEG of the Asian patients as compared to that of the Western patients. The aim of this study was to investigate the clinicopathological characteristics of AEG according to the Siewert classification. MATERIALS AND METHODS: Among the patients who underwent surgery for gastric carcinoma in our institution between May 2004 and February 2008, the AEG patients were selected based on their operation records and the photographs according to Siewert's classification. RESULTS: There were 70 AEG patients (3.9%) among the total of 1,778 patients. There were 3 patients (4.3%) with type I, 30 patients (42.8%) with type II and 37 patients (52.8%) with type III. Curative resection (R0) was achieved in 68 cases (97.1%). No significant differences in gender, stage, Barrett's esophagus and the proximal margin were found between the patients with type II and type III AEG. The patients with type III were younger than the patients with type II (59 vs 64 years, respectively, P=0.049). Well differentiated histology (P=0.045) and the intestinal type (P=0.055) were significantly more frequent in the patients with type II as compared with that in the patients with type III. CONCLUSION: There was a striking difference of the Asian patients from the Western patients for the incidence of AEG (and especially type I). Some of the differences between type II and type III patients were similar to those of the previous Western studies. A large study is needed to investigate whether these features are typical in the Korean population.

Surgical Option for Sufficient Safety Margine in Locally Advanced Type II Cardia Cancer-Left Colon Interposition

PURPOSE: Radical surgery is the standard therapy for patients with resectable cardia cancer. In the case of type II disease with esophageal invasion, a transhiatal extended radical total gastrectomy is needed or a gastroesophagectomy through an abdomino-thoracotomy, depending on the extent of the esophageal invasion. We analyzed the indications and outcome of left colon interposition as an esophageal substitution. MATERIALS AND METHODS: Between 1 January 1994 and 31 December 2006, 10 patients underwent left colon interposition after gastroesophagectomy through an abdomino-thoracotomy or the tanshiatal approach for type II cardia cancer at the Department of surgery, Yonsei University College of Medicine. The outcomes of these patients were reviewed and compared, with those who underwent a Roux-en-Y, by gender and age matched analysis, retrospectively. RESULTS: There were nine males and one female with a mean age of 52.5 (range, 16~72). The operation time was 449.00+/-87.39 minutes. The mean distance between the proximal resection margin and the cancer was 6.56+/-3.65 cm; the maximum size of the tumor was 9.90+/-3.97 cm. These measures differed significantly from patients who underwent Roux-en-Y. The patients had a double primary cancer in the cardia and esophagus. There were no events of colon necrosis. However, a pneumothorax occurred in one patient (10%) and a proximal anastomotic stricture occurred in one patient. There were no reports of heartburn, regurgitation, thoracic or epigastric fullness, and one patient even gained weight, 16 kg. CONCLUSION: Colon interposition after esophagogastrectomy was safe and effective and should be considered as an additional surgical option for locally advanced type II cardia cancer patients with esophageal invasion.

Clinicopathologic Characteristics of Adenocarcinoma in Cardia according to Siewert Classification / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to evaluate clinicopathologic differences between Type II and Type III groups that were classified by Siewert in cardia cancer. METHODS: A hundred forty-one patients who were diagnosed as gastric cardia cancer and underwent surgery between January 1990 and December 2006 by single surgeon at Department of Surgery, Yonsei University College of Medicine were included in this study. The Kaplan-Meier method and log rank test were used for survival analysis. RESULTS: Barrett's adenocarcinoma was recognized in two patients so called type I. There were significant differences between type II and III in aspect of depth of invasion, Lauren's classification, and the number of retrieved lymph nodes in which cancer infiltrated. In type III, prognostic factors affecting survival were depth of invasion and nodal status in contrast to the no demonstrable prognostic factors existing in type II. However, there were no differences in recurrence and survival between two groups. CONCULSIONS: Several clinicopathologic differences exist between type II and III cardia cancer. In the future, further evaluation is needed regarding the classification and entities of the cardia cancer.

Adenocarcinoma of the Gastro-esophageal Junction: Application of Siewert's Classification to the Eastern Experience

PURPOSE: Since the approval of Siewert's classification during the 2nd International Gastric Cancer Congress in 1997, there has been no report on gastro-esophageal junction (GEJ) cancer using this new classification in Korea. The aim of this study was to assess the clinical usefulness of the new classification by applying it to the Eastern experience. MATERIALS AND METHODS: One hundred forty-six patients with an adenocarcinoma of the GEJ who underwent surgery from January 1990 to December 1998 were retrospectively classified according to the Siewert's classification. RESULTS: There were 2 patients (1.4%) with type I, 37 patients (25.3%) with type II, and 107 patients (73.3%) with type III. The proportion of the GEJ cancer among all gastric cancer patients who underwent operation was found to be 6.6%. The average age was 46 years in type I, 53 years in type II, and 55 years in type III. All types of GEJ cancers predominantly affected men. No significant differences in the pathologic variables including gross appearance, tumor size, and histologic findings were found between type II and type III. A curative resection (R0) was achieved in 118 cases (80.8%) without difference among tumor types. Type I tumors were treated with a gastrectomy with distal esophagectomy. Most of the type II tumors were treated with a total gastrectomy, and in some patients, a transhiatal partial esophagectomy was added. Type III tumors were treated with a total gastrectomy. Among resected cases with curative intent, microscopic tumor involvement of the proximal resection margin was noted in two patients (6.3%) with type II tumors. Lymph node metastasis was found in 2 patients (100%) with type I, 24 patients (64.9%) with type II, and 66 patients (61.7%) with type III. Lymph nodes along the lesser curvature were the most common site of metastasis, followed by pericardial nodes. The main lymphatic drainage directed the lymph nodes along the left gastric artery among the group 2 nodes. There was no difference in patterns of lymph node metastasis between type II and type III. Postoperative complications occurred in 29 patients, and operative mortality was 2.7%. Five-year survival rates were 0% for type I, 54.3% for type II, and 51.8% for type III. CONCLUSION: The distribution of subtypes of adenocarcinomas of GEJ was markedly different in this study compared with reported Western data. Therefore, Siewert's classification is useful for discussing GEJ cancer in an international setting as it clearly specifies the subtype of GEJ cancer. However, discrimination of type II and type III may have little clinical benefit since there were no significant differences in clinicopathologic characteristics or in the recommended types of surgery.

Analysis of Clinocopathologic Difference between Type II and Type III Cancers in Siewert Classification for Adenocarcinomas of the Cardia

PURPOSE: To determine the clinical value of the Siewert classification for gastic-cancer patients in Korea, we evaluated and compared the clinicopathologic factors of type II and type III cancer. MATERIALS AND METHODS: The medical records of 89 consecutive patients who had undergone surgery for an adenocarcinoma of the gastroesophageal junction (GEJ) at the Department of Surgery, Hanyang University Hospital, between Jun. 1992 and Dec. 2003 were reviewed retrospectively. RESULTS: There were one patient with type I, 12 pateints with type II and 77 patients with type III. During the same period, 1,341 patients underwent surgery for a gastric carcinoma, so proportion of GEJ cancer being 6.6%. The median follow- up duration was 31 months (range: 2~135 months), and the follow-up rate was 100%. Between type II and type III cancers, there were no significant differences in the clinicopathologic variables including age, sex, gross appearance, histologic type, depth of invasion, and pathologic stage. The longest diameter of the tumor was larger in type III (6.1+/-2.1 cm) than in type II (3.9+/-1.1 cm)(P=0.001). A total gastrectomy with Roux-en-Y esophagojejunostomy was done most frequently, while jejunal interposition was done in 3 cases of type II and 2 cases of type III. More than a D2 lymphadenectomy was done all cases. The numbers of dissected lymph nodes and metastatic lymph nodes in type II were 43.8 and 5.8 respectively, while they were 49.8 and 8.1 in type III, but the difference between the two groups were not statistically significant. The mean length of the proximal resection margin was 15+/-5 mm in type II and 21+/-13 mm in type III, but this difference was not statistically significanct. The time to recurrence after operation was 19.3 months in type II and 16.9 months in type III. The five-year survival rates of type II and III were 68.8% and 52.7% respectively, but difference was not significant. CONCLUSION: There were no significant differences in the clinicopathologic variables, including survival rate, between type II and type III cancers in Korean patients. According to these findings, it appears to be reasonable to classify type III cancer as a cardia cancer in a broad sense.