Objective:The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study.Background:Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized.Methods:Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%.Results:Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1.Conclusion:The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.

The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. Of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. The epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P less than 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes.

E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (alpha-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and alpha-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which alpha-cat expression was preserved, and 42 (70%) reduced cases. The reduction of alpha-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of alpha-cat and E-cad. Seventeen (28%) tumours preserved both molecules [alpha-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [alpha-cat(-)/E-cad(-)], whereas 9 (15%) tumours exhibited alpha-cat(-)/E-cad(+). The frequency of lymph node metastasis in alpha-cat(-)/E-cad(+) tumour (67%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (24%) and was close to that in alpha-cat(-)/E-cad(-) tumours (82%). The frequency of haematogenous liver metastasis in alpha-cat(-)/E-cad(+) tumours (44%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (6%) or alpha-cat(-)/E-cad(-) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in alpha-cat(-) tumours than in alpha-cat(+) tumours. alpha-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.

Three surgical procedures for U-EGC did not result in differences in weight loss, but PG-EG and PG-JI were better than TG-RY according to some nutritional markers. In U-EGC, where patients are expected to have long survival times, PG-EG and PG-JI should be used rather than TG-RY.