Robotic gastrectomy (RG) is increasingly performed, particularly in East Asia. With articulated devices, surgeons are able to perform every procedure more comfortably and meticulously, which makes RG ideal from the surgeon’s standpoint. However, it is still unclear whether it is a suitable treatment strategy from the patient’s viewpoint, due to the lack of solid evidence obtained from randomized controlled trials. The feasibility of RG has been demonstrated in many retrospective comparative studies, which showed similar trends, including relatively less estimated blood loss and longer operation time with RG than laparoscopic gastrectomy (LG), equivalent number of harvested lymph nodes and similar length of postoperative hospital stay between RG and LG. However, considering the higher medical expenses associated with RG, its superiority in terms of long-term survival outcomes will need to be confirmed for it to be accepted more widely.

Peritoneal dissemination (PD) is the most common cause of metastasis in gastric cancer (GC). Because there are no standard treatments for PD, it is associated with a poor prognosis. Although clinicians have performed intraperitoneal chemotherapy for GC with PD, the outcome remains unsatisfactory. Therefore, the development of novel treatments and diagnostic tools for PD is expected to improve the prognosis of GC patients with PD. Notably, it is essential to elucidate the molecular mechanisms involved in the development of PD in GC. In this review, the molecular mechanisms of PD (three steps: detachment from the primary tumor, adaptation to the microenvironment of the peritoneal cavity, and attachment to peritoneal mesothelial cells) and new topics in GC are highlighted.

Laparoscopic gastrectomy is considered as an indispensable option between endoscopic resection and standard gastrectomy with open laparotomy for patients with early-stage gastric cancer. However, the extent of gastrectomy and remnant gastric function may affect patients’ quality of life (QOL) after surgery. Therefore, function-preserving gastrectomy in addition to laparoscopic surgery could be considered in patients with early-stage gastric cancer. A prospective multicenter trial and meta-analyses of sentinel node (SN) mapping and biopsy for early-stage gastric cancer have demonstrated favorable SN detection rates and accuracy of nodal metastatic status. Although a combination of radioactive colloids with blue dyes as tracers is currently considered as the promising procedure of SN mapping in early-stage gastric cancer, several new technologies, such as indocyanine green fluorescence imaging, may markedly improve its accuracy. For early-stage gastric cancer, the development of laparoscopic personalized minimized gastrectomy with SN mapping may help retain patents’ QOL after surgery. A recently developed full-thickness partial gastrectomy with SN mapping and basin dissection would become a reliable minimally invasive gastrectomy for treating patients with cN0 early-stage gastric cancer.

Accumulating evidence has suggested the potential clinical utility of novel body fluid biomarkers, or “liquid biopsy”, using circulating tumor cells and cell-free nucleic acids from cancer patients. Noninvasive and reproducible, liquid biopsy could provide the basis for individualized therapeutic strategies by identifying genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. MicroRNAs (miRNAs) are short noncoding RNAs that post-transcriptionally regulate gene expression. They also play important roles in various physiological and developmental processes as oncogenic or tumor-suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Circulating miRNAs have been detected in plasma and serum, and this in blood has attracted the attention of researchers for their potential as noninvasive biomarkers. Circulating miRNAs have emerged as tumor-associated biomarkers that reflect not only the existence of cancer, but also the dynamics, malignant potential, and drug resistance of tumors. Herein, we review the recent biological and clinical research on the circulating miRNAs of gastric cancer and discuss future perspectives for their clinical applications as a liquid biopsy.

Aim: To analyze clinical features and survival outcomes of patients with surgically-treated stage IV gastric cancer, in order to evaluate the suitability of surgery in these patients.

Methods: We performed a systematic literature search using PubMed, MEDLINE, and Embase on October 9th, 2017. Survival outcomes data were collected.

Results: The original search returned 2434 papers. Thirty-nine studies were included in the final review, of which 26 evaluated liver metastasis resection, four pulmonary metastasis resections and nine palliative gastrectomies. In total 933 patients underwent hepatectomy for liver metastasis from gastric cancer and median survival rates were 73%, 37% and 27% at 1-, 3- and 5-year respectively, with a median overall survival of 22 months (9-52 months). Data regarding resection of lung metastases were scarce and extremely heterogeneous. In total 1115 patients underwent palliative gastrectomy and median overall survival of patients was 12 months (8-53 months). In the only randomized controlled trial, no survival benefit of additional gastrectomy over chemotherapy alone was found, in contrast with the retrospective studies.

Conclusion: Survival benefit of surgery in advanced gastric cancer is still unclear. Surgery may play an important role in highly selected patients. However, further randomized controlled trials are necessary to clarify the actual impact of surgery in these patients.

Gastric cancer is one of the major causes of cancer-related deaths, despite the gradual decrease of its incidence in the West. Minimally invasive procedures, such as endoscopic resection and laparoscopic gastrectomy, have been successfully introduced in European high-volume centres, in the treatment of early gastric cancer. Regarding advanced, localized gastric cancer a number of prospective trials have been completed in search of better therapeutic options, aiming to optimize the efficacy vs. adverse effect ratio. From the results of these prospective randomized trials, the therapeutic strategy has in the last decades shifted emphasis from adjuvant therapy to neoadjuvant or perioperative chemotherapy, in curatively intended treatment. Moreover, recent studies have shown promising results in the use of molecular targeted agents, both in perioperative and palliative settings. The introduction of molecularly targeted therapy will enable a personalized approach based on each patient’s and tumor’s characteristics, maximizing the benefits from chemotherapy. The present review article focuses on recent therapeutic trends, as well as future perspectives, of surgical and oncological gastric cancer treatment in the Western setting, mainly based on landmark clinical trials.


Circulating tumor cells (CTCs) have received a lot of attention as a novel biomarker for cancer research in past decades. CTCs infiltrate the bloodstream derived from the primary tumor, and are significantly involved in cancer metastasis and recurrence. Although clinical applications have been challenging owing to the difficulties of CTC identification, recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment. Furthermore, CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis. A number of clinical studies have already been carried out on the basis of CTC technology. Nevertheless, the clinical utility of CTCs is still unknown in gastric cancer. In this review, we elaborate on the latest advances of CTC research in gastric cancer.

Gastric cancer (GC) remains one of the most common cancers and serious health problems worldwide. For unresectable or metastatic advanced gastric cancer, chemotherapy treatment is first selected. Although chemotherapy has improved survival in patients with advanced gastric cancer (AGC), the prognosis of these patients remains poor. In recent years, some therapies targeting biological molecules have been reported to prolong the survival of patients with AGC. Since trastuzumab, a monoclonal antibody that targets HER2, was established as standard therapy for unresectable GC in a HER2-positive patient, many other targets have been reported as new therapy targets. Many molecular targeted therapies, such as HER2, VEGFR or EGFR, have been verified as established standard treatments with or without chemotherapy in clinical trials. Furthermore, immunotherapy is expected to be an effective treatment with promising clinical trial data. Especially, immune checkpoint inhibiters, such as PD-1/PD-L1 or CTLA-4, have demonstrated innovative progression in GC therapy. Moreover, ongoing clinical trials including targeted therapy and immunotherapy have shown promising results in improving clinical outcomes, safety, and tolerability. In this article, we review targeting therapies and immunotherapies for GC and summarize future prospective treatments.

Pancreaticoduodenectomy (PD) is performed to achieve an R0 resection for gastric cancer with pancreatic and/or duodenal invasion. Several retrospective case series have been published, but the sample cohorts in each study were heterogeneous and small. Moreover, the absence of prospective studies results in a lack of solid evidence that will help determine who can benefit from this procedure. Although the morbidity and mortality of PD have been reported by most studies to be acceptable and that the procedure is feasible, these remained to be much higher than those of standard gastrectomy. Therefore, careful selection of patients should be considered. Based on a review of previous case series and our own experience, PD appears to be beneficial to patients with gastric cancer with pancreatic invasion when R0 resection is possible. In addition, multidisciplinary treatment such as neoadjuvant chemotherapy, is anticipated to improve survival. Nevertheless, considering that prospective randomized studies are difficult to perform, a large-scale multicenter retrospective cohort study is required to evaluate this highly invasive procedure.

The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor, despite using a variety of regimens using cytotoxic agents. Recent understanding of molecular characteristic and tumor microenvironment of this cancer is currently instigating new therapeutic options. In this review, we summarized previous evidences of cytotoxic agents widely used worldwide, and updated recent developments of molecular targeted drugs, and immune checkpoint inhibitors.

Gastric cancer with distant metastases, such as para-aortic lymph node metastases, hepatic metastases, and peritoneal dissemination, is classified as stage IV. In this situation, cancer cells have formed micrometastases throughout the body; therefore, according to the algorithm of the Japanese guidelines, stage IV cancer is outside the indication for curative resection. Recent advances in some chemical agents have been remarkable, and some patients have survived for long periods even with stage IV gastric cancer. Thus, even in patients with stage IV gastric cancer, there is a possibility that gastrectomy as conversion surgery could play an important role in the treatment strategy. Gastrectomy as conversion therapy can be safely conducted without perioperative mortality and is considered a sufficiently acceptable treatment strategy. However, the significance of conversion surgery for stage IV gastric cancer remains controversial. In this review, we summarize the treatment strategies and outcomes of conversion surgery for stage IV gastric cancer.

Despite recent progress in diagnostic imaging, gastric cancer (GC) is occasionally found at an advanced stage with distant metastasis. As metastatic GC is difficult to cure, the treatment strategy should be considered individually based on the physical and socioeconomic status of patients as well as on the GC symptoms. The first choice of treatment for metastatic GC is chemotherapy, and several chemotherapeutic regimens for metastatic or recurrent GC have been developed through randomized controlled trials. Ongoing clinical trials will provide novel therapeutic options for patients with metastatic GC in the near future, while individualization of treatment based on detailed molecular information, so-called precision medicine, is eagerly anticipated. In this article, we review recent publications and guidelines focusing on recent progress in the treatment of metastatic GC in Japan.

Gastric adenocarcinoma (GAC) is estimated as the fifteenth most common cancer in the USA. Incidence rate has been gradually decreasing, but prognosis remains dismal. For patients with locally advanced GAC (stage > T1B and < T4B), multimodality therapies, such as surgery, chemotherapy, and radiation therapy, are needed. Perioperative chemotherapy or postoperative chemoradiation/chemotherapy is recommended. For metastatic GAC patients, combination of two cytotoxics (platinum compound and fluoropyrimidine) has become a common place in the USA, and when HER2 is positive, trastuzumab is added. When GAC progresses after the first line therapy, additional biomarkers (microsatellite instability and programmed death ligand 1) should be tested so that checkpoint inhibitors can be used. Overall, the options for advanced GAC patients are limited and more research is needed.

Tumor tissues contain cancer cells, other cellular and non-cellular components. Tumor microenvironments consist of cancer cells and various types of stromal cells, cancer associated fibroblasts, bone marrow-derived cells, endothelial cells, and hematopoietic cells, mainly tumor-associated macrophages and tumor-infiltrating lymphocytes. Increasing recent evidence has demonstrated that alteration of tumor microenvironments is deeply implicated in tumor progression and metastasis in gastric cancer (GC) patients. Recent investigations have provided insights into the molecular mechanisms of the interaction between tumor cells and tumor microenvironments. Interactions between cancer cells and their microenvironment with cytokines and microRNA in extracellular vesicles, such as the exosome, can have a substantial impact on tumor characteristics. Alterations in the tumor microenvironment may play a crucial role in facilitating the progression of tumor cells and metastasis, as well as the activation of cell signaling pathways, which are associated with GC cell proliferation and invasion by genetic or epigenetic alterations. In this review, significant molecular insights into the tumor microenvironment, which consist of cancer associated fibroblasts, bone marrow-derived cells, tumor-associated macrophages and tumor-infiltrating lymphocytes; the interactions between cancer cells and their microenvironment; and the clinical impacts of alterations of GC microenvironments will be discussed.

Gastric cancer (GC) is a major cause of cancer-related deaths worldwide. The existence of cancer stem cells (CSCs) is known to be the main reason for resistance to anticancer agents as well as for the development of distant metastases. Although CSCs themselves harbor self-renewal and differentiation abilities, the tumor microenvironment that surrounds CSCs provides secreted factors and supports angiogenesis and is thus responsible for the maintenance of their CSC properties. The current review provides information regarding the impact of the tumor microenvironment on gastric CSCs, which will support the development of novel therapeutic strategies for targeting gastric CSCs.

Gastric cancer is an aggressive malignancy that may metastasize through the bloodstream to the liver, through lymphatics to regional lymph nodes, or by penetration of the peritoneal lining of the stomach to result in seeding of the abdominal and pelvis surfaces. Peritoneal metastases are the most common mode of cancer dissemination. Technologies to prevent or treat peritoneal metastases from advanced gastric cancer are presented in this manuscript. The world’s literature, both recent and over the past three decades, was reviewed in order to identify publications that present information regarding gastric cancer peritoneal metastases. Over one dozen randomized controlled trials to test perioperative chemotherapy for prevention of peritoneal metastases were reviewed. All of the trials performed with regional chemotherapy during or shortly after gastrectomy were positive. The clinical data regarding the treatment of peritoneal metastases diagnosed at the time of primary cancer resection or in follow-up were reviewed. Neoadjuvant intraperitoneal and systemic chemotherapy shows that some long-term survivors occur after these treatments were combined with cytoreductive surgery and gastrectomy. Similar treatments are advocated for primary gastric cancer with cytology positive for gastric cancer but no visible implants. Surgery for gastric cancer should be combined with perioperative systemic and regional chemotherapy in order to maximally benefit patients with this disease by reducing the negative impact of peritoneal metastases on survival.

Peritoneal metastasis is the most common pattern of recurrence and the most frequent cause of death after surgery in patients with gastric cancer. Peritoneal free cancer cells disseminated from the primary lesion site have been considered the main cause of peritoneal metastasis. Peritoneal lavage cytological examination (PLC) has been shown to be an independent predictor of gastric cancer relapse after curative resection and poor overall survival. However, the conventional cytological examinations have high rates of false-positive and false-negative findings. To improve the sensitivity, molecular-based methods using reverse transcriptase polymerase chain reaction have been developed for detecting cancer cells in peritoneal wash fluids of patients with gastric cancer. We performed a PubMed search for articles describing PLC in gastric cancer. Relevant articles were reviewed and data on available outcomes elaborated. The clinical roles and attributes of PLC in gastric cancer were reviewed, and its future application to this disease is discussed.

Aim: Gastric cancer is the cancer with the highest rate of peritoneal metastization and this type of spread is associated with a higher death rate compared to distant organ metastasis. The systemic chemotherapy has a minimal effect in peritoneal metastasis so new types of treatment have emerged. The authors revised the main studies done in pressurized intraperitoneal aerosol chemotherapy (PIPAC) and presented the main conclusions.

Methods: A PubMed search was conducted focusing on PIPAC in gastric cancer. The MeSH database was searched with the terms: “Gastric cancer [MeSH] and intraperitoneal aerosol chemotherapy”.

Results: Seven studies were analyzed. All the studies performed the technique with aerosol of doxorubicin and cisplatin. All cases were well tolerated, with minor adverse effects. Patients presented resolution of their abdominal symptoms and regression of macroscopic carcinomatosis. Cytoreductive surgery or hypertermic intraperitoneal chemotherapy could be performed in some patients with good response to PIPAC. The peritonitis caused by the chemotherapy was well tolerated.

Conclusion: PIPAC can induce remission in end-stage and resistant disease with acceptable side effects, good safety levels for patients and health professionals, and quality of life improvement.