Recent Advances in Management of Gastric Cancer

Abstract

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates: at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called “intestinal metaplasia”; phenotypic antralization of fundic units, which is called “spasmolytic polypeptide-expressing metaplasia”; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Gastric carcinogenesis arises as a consequence of a complex interaction between host and environmental factors. H. pylori infection is the major risk factor associated with non-cardia gastric cancer, and data has emerged with regard to the role of H. pylori eradication for primary prevention of gastric cancer. Smoking has also been implicated as a risk factor for non-cardia cancer. Furthermore, host genetic polymorphisms have an impact on host responses to gastric inflammation and acid secretion, thereby interacting with H. pylori infection and other environmental factors in gastric carcinogenesis. In contrast to non-cardia cancer, H. pylori infection does not play an important role in cardia cancer, with obesity and smoking identified as the main risk factors. Although dietary, lifestyle and metabolic risk factors have been identified, and addressing these lifestyle and metabolic risk factors may contribute to health, the actual impact in terms of cancer prevention is unclear. In the overall scheme of management, H. pylori infection represents a target for primary prevention, but once irreversible histological changes have occurred, endoscopic surveillance would be required, all in the hope of detection of early gastric cancer that is amenable to curative endoscopic resection, or earlier stage disease that is surgically curable. For more advanced cancer requiring chemotherapy, a robust molecular classification system represents hope for molecularly tailored personalised therapies, which may improve prognosis. Available imaging techniques include endoscopic ultrasound (EUS), computerized tomography (CT), magnetic resonance imaging (MRI) and fluorodeoxyglucose F-18 positron emission tomography (FDG-PET). A systematic review of the T staging evaluation by EUS, CT and MRI showed a similar accuracy between these techniques (65%–92.1%, 77.1%–88.9%, and 71.4%–82.6%, respectively). Serosal involvement assessment also showed similar sensitivity and specificity across trials, although it is specified that greater experience is available with EUS Laparoscopic gastrectomy is a promising minimally invasive surgery for gastric cancer that has become popular and standardized. LADG shows better or comparable outcomes compared to ODG in terms of short-term results. The long-term outcome after LADG may be comparable to ODG in EGC, and ongoing Korean and Japanese muticenter RCTs will provide more clear evidence. Data on LATG are still limited, and the stable laparoscopic anastomosis technique is still under debate. LAPPG seems to be optimistic for EGC located in the middle third of the stomach in terms of preservation of function and comparable oncologic outcome. The clinical body of evidence concerning LADG for AGC is still insufficient, and the lack of generalization still remains an issue even after ongoing Korean multicenter RCTs have provided clinical evidence. Laparoscopic SN navigation surgery seems to be experimental and the surgical procedure has yet to be standardized. Robotic gastrectomy is