Hye-Kyung Jung, Seung Joo Kang, Yong Chan Lee, Hyo-Joon Yang, Seon-Young Park, Cheol Min Shin, Sung Eun Kim, Hyun Chul Lim, Jie-Hyun Kim, Su Youn Nam, Woon Geon Shin, Jae Myung Park, Il Ju Choi, Jae Gyu Kim, and Miyoung Choi, Korean College of Helicobacter and Upper Gastrointesinal Research. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl20288

The aim of this study was to analyze the clinicopathologic characteristics and prognosis of signet ring cell carcinoma (SRC) according to disease status (early vs advanced gastric cancer) in gastric cancer patients. The prognostic implication of gastric SRC remains a subject of debate. A retrospective analysis was performed using the clinical records of 7667 patients including 1646 SRC patients who underwent radical gastrectomy between 2001 and 2010. A further analysis was also performed after dividing patients into three groups according to histologic subtype: SRC, well-to-moderately differentiated (WMD), and poorly differentiated adenocarcinoma. SRC patients have younger age distribution and female predominance compared with other histologic subtypes. Notably, the distribution of T stage of SRC patients was distinct, located in extremes (T1: 66.2% and T4: 20%). Moreover, the prognosis of SRC in early gastric cancer and advanced gastric cancer was contrasting. In early gastric cancer, SRC demonstrated more favorable prognosis than WMD after adjusting for age, sex, and stage. In contrast, SRC in advanced gastric cancer displayed worse prognosis than WMD. As stage increased, survival outcomes of SRC continued to worsen compared with WMD. Although conferring favorable prognosis in early stage, SRC has worse prognostic impact as disease progresses. The longstanding controversy of SRC on prognosis may result from disease status at presentation, which leads to differing prognosis compared with tubular adenocarinoma.

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.

In early gastric cancer (EGC), tumor invasion depth is an important factor for determining the treatment method. However, as endoscopic ultrasonography has limitations when measuring the exact depth in a clinical setting as endoscopists often depend on gross findings and personal experience. The present study aimed to develop a model optimized for EGC detection and depth prediction, and we investigated factors affecting artificial intelligence (AI) diagnosis. We employed a visual geometry group(VGG)-16 model for the classification of endoscopic images as EGC (T1a or T1b) or non-EGC. To induce the model to activate EGC regions during training, we proposed a novel loss function that simultaneously measured classification and localization errors. We experimented with 11,539 endoscopic images (896 T1a-EGC, 809 T1b-EGC, and 9834 non-EGC). The areas under the curves of receiver operating characteristic curves for EGC detection and depth prediction were 0.981 and 0.851, respectively. Among the factors affecting AI prediction of tumor depth, only histologic differentiation was significantly associated, where undifferentiated-type histology exhibited a lower AI accuracy. Thus, the lesion-based model is an appropriate training method for AI in EGC. However, further improvements and validation are required, especially for undifferentiated-type histology.

The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.