The development of a risk assessment tool for patients with postoperative pneumonia after gastrectomy for gastric cancer.

BACKGROUND: Although frail patients are known to experience increased postoperative complications, this is unclear for postoperative pneumonia (POP). We investigated associations between frailty and POP in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: In this prospective study conducted between August 2016 and December 2022, we preoperatively assessed frailty in 341 patients with GC undergoing gastrectomy using a frailty index (FI). Patients were divided into high FI vs low FI groups to examine frailty and pneumonia rates after gastrectomy for GC. RESULTS: Of 327 patients, 18 (5.5%) experienced POP after gastrectomy. Multivariate analyses showed that a high FI and total or proximal gastrectomy (TG/PG) were independent risk factors for POP (high FI: odds ratio [OR], 5.00; 95% CI, 1.77-15.54; TG/PG: OR, 3.07; 95% CI, 1.09-8.78). The proportion of patients with POP was 2.4% in those with nonhigh FI and non-TG/PG, 5.3% in those with nonhigh FI and TG/PG, 7.1% in those with high FI and non-TG/PG, and 28.0% in those with high FI and TG/PG (P < .001). The area under the receiver operating characteristic curve for this risk assessment for predicting POP was 0.740. CONCLUSION: In patients with GC undergoing gastrectomy, POP was independently associated with preoperatively high FI and TG/PG. Our simple POP risk assessment method, which combines these factors, may effectively predict and prepare patients for POP.

Study of Short-Term and Long-Term Outcomes Between Esophagogastrostomy and Double-Tract Reconstruction After Proximal Gastrectomy.

BACKGROUND: As the opportunities for proximal gastrectomy (PG) for early gastric cancer in the upper third stomach have been increasing, the safety and feasibility of PG have been a great concern in recent years. This study aimed to compare the short-term and long-term outcomes between patients who underwent esophagogastrostomy (EG) and those who underwent double-tract reconstruction (DTR) after PG. METHODS: We retrospectively reviewed the medical records of 34 patients who underwent EG and 39 who underwent DTR at our hospital between 2011 and 2022. We compared the procedure data and postoperative complications including anastomotic complications within 1 year after surgery as short-term outcomes and the rates of change in nutritional status, skeletal muscle mass, and 3-year survival as long-term outcomes. RESULTS: Although operation time of the DTR group was significantly longer than that of the EG group, there were no significant differences in postoperative complications between 2 groups. Regarding the endoscopic findings, the incidence of anastomotic stenosis and reflux esophagitis was significantly higher in the EG group than in the DTR group (26.5% vs 0%, p < 0.001; 15.2% vs 0%, p = 0.020). In long-term outcomes, there were no significant differences in body weight, BMI, laboratory data, and skeletal muscle mass index between 2 groups for 3 years. The 3-year overall survival rates of 2 groups were similar. CONCLUSION: DTR after PG could prevent the occurrence of anastomotic complications in comparison to EG. The long-term outcomes were similar between these 2 types of reconstruction.

The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. RESULTS: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. CONCLUSION: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.

The importance of psychosocial support in youth dilated cardiomyopathy patient who underwent cardiac rehabilitation.

Poor health-related quality of life (HR-QOL) and anxiety status in younger patients living with heart failure and dilated cardiomyopathy (DCM) may be caused by the illness itself or the numerous life events that traditionally occur earlier in life, such as establishing a career, meaningful relationships, family, and financial security. The present case involved a 26-year-old man diagnosed with DCM who participated in an outpatient cardiac rehabilitation (CR) program once a week. No cardiovascular events were observed during CR. At follow-up after 12 months, exercise tolerance improved from 18.4 to 24.9 mL/kg/min. Regarding HR-QOL, the Short-Form Health Survey showed that only general health, social function, and physical component summary were improved during follow-up. However, other components showed no significant increasing trend. The State-Trait Anxiety Inventory showed a better improvement in trait anxiety (from 59 to 54 points) than state anxiety (from 46 to 45 points). For young patients with DCM, it is crucial to consider not only physical status but also psychosocial status even with improved exercise tolerance. Learning objective: Younger adults with dilated cardiomyopathy (DCM) had strikingly worse health-related quality of life with both the emotional and physical components of the scale. Beyond physical symptoms alone, living with heart failure and DCM at a younger age negatively impacts role fulfillment, autonomy, perception, and psychological well-being. Cardiac rehabilitation (CR) comprised medical evaluation of patients, exercise therapy, education for secondary prevention, and support for psychosocial factors including counseling and cognitive-behavioral therapy. Therefore, early detection of the psychosocial problem and providing further support by participating in CR is important.

Nutritional Status in Patients Undergoing Phase II Cardiac Rehabilitation by Mini Nutritional Assessment.

Background: Malnutrition impairs quality of life and prognosis of patients with cardiovascular disease. The Mini Nutritional Assessment (MNA) is a screening tool developed for the nutritional assessment of older adults. However, usefulness of MNA for patients undergoing cardiac rehabilitation (CR) has not been fully investigated. Methods: From March 2017 to September 2019, the MNA-short form (MNA-SF) and the MNA total score in patients undergoing phase II CR at the Juntendo University Hospital were evaluated. Results: A total of 336 patients (mean age 70.1 ± 11.4 years; males: 209) were analyzed. In the MNA-SF, 157 patients (47%) were found to be malnourished or at risk of malnutrition. In MNA total score, 168 patients (50%) were found to be malnourished or at risk of malnutrition. The MNA-SF < 12 group had significantly lower body mass index (BMI), hemoglobin level, low MNA scores for protein/water intake, self-evaluation of nutrition and health, and upper arm and calf circumferences compared to the MNA-SF ≥ 12 group. Assuming BMI < 18.5 as malnutrition, the sensitivity and specificity for malnutrition were 100% and 58.9% for MNA-SF, and 96.9% and 54.9% for MNA total score, respectively. Conclusions: MNA is useful in screening for malnutrition in patients undergoing CR. Approximately 50% of them were determined to be malnourished or at risk of malnutrition, suggesting the need for detailed evaluation regarding their food intake and dietary intervention.

GATA6 regulates expression of annexin A10 (ANXA10) associated with epithelial-mesenchymal transition of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) can disturb oral function and quality of life and is associated with poor survival, likely due to the development of cervical lymph node metastases. Epithelial-mesenchymal transition (EMT) is a process in which cells acquire molecular alterations that facilitate cell motility and invasion, and has been associated with tumor metastasis. EMT changes also play important roles in the induction of lymph node metastasis in OSCC. GATA6 is known as the earliest marker of the primitive endoderm lineages. GATA6 inhibits de-differentiation and EMT in human pancreatic ductal adenocarcinoma cells and promotes EMT. However, in OSCC, the expression and function of GATA6 in EMT and lymph node metastasis remains unclear. Therefore, this study aimed to clarify the targets of GATA6 in OSCC cells and whether the change in GATA6 expression affects EMT in OSCC cells, as well as the association between GATA6 and lymph node metastasis. The results showed that GATA6 knockdown OSCC cells promoted EMT and increased lymph node metastasis compared with control cells, whereas the overexpression of GATA6 inhibited the induction of EMT and reduced lymph node metastasis. In addition, annexin A10 (ANXA10) which is the largest type of Ca2+-regulated phospholipid-binding protein in eukaryotic cells was detected as a target gene for GATA6 and ANXA10 suppressed Vimentin expression in EMT in OSCC. Therefore, the GATA6/ANXA10 cascade may be a potential therapeutic approach for the treatment of lymph node metastases in OSCC patients.

[A Case of Double Colorectal Cancer Diagnosed by Preoperative CT Colonography].

A 66‒year‒old man was admitted to our hospital because of anemia and a positive fecal occult blood test in the medical examination. Colonoscopy revealed a type 2 advanced sigmoid colon cancer with circular stenosis. Computed tomography (CT)colonography was performed to examine the oral colon. The apple core signs were found both in the sigmoid and transverse colon. We diagnosed a double colon cancer and performed a laparoscopic left hemicolectomy and sigmoidectomy. The tumor was histopathologically diagnosed as a multiple cancer including a transverse and a sigmoid colon cancer. Although evaluations of the intestine for colon cancer with stenosis are performed by enema examination or endoscopic examination after colon stent placement, both examinations are invasive. CT colonography is considered to be a minimally invasive and an effective preoperative examination for colorectal cancer with stenosis.

Induction of Immunogenic Cell Death of Esophageal Squamous Cell Carcinoma by 5-Fluorouracil and Cisplatin.

BACKGROUND/AIM: Neoadjuvant chemotherapy (NAC) using 5-FU (5-fluorouracil)/CDDP (cisplatin) is a standard therapy for stage II/III thoracic esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to investigate whether 5-FU/CDDP could induce immunogenic cell death in ESCC cell lines. MATERIALS AND METHODS: Tumor samples for immunohistochemistry were obtained from 50 patients (mean age=63.1 years) with pathological stage 0-IVa ESCC who underwent NAC followed by surgery. Cell lines T.T and KYSE30 were used for the in vitro experiments. RESULTS: The concentrations of HMGB1 were elevated in the cell line supernatants treated with 5-FU/CDDP. 5-FU/CDDP treated dendritic cells (DCs) showed a mature phenotype, and enhanced T cell proliferation capacity. In addition, mature DCs were observed in surgical specimens with a histological response after treatment with 5-FU/CDDP chemotherapy. CONCLUSION: 5-FU/CDDP could induce immunogenic cell death in the tumor microenvironment of ESCC.

[A Case of Advanced Gastric Cancer-Recurrence of Skin Metastasis Nine Years after Surgery and Rectal Stenosis Due to Peritoneal Dissemination Ten Years Later].

A 70-year-old man previously underwent laparoscopic total gastrectomy for gastric cancer in 2010 and pathological diagnoses were pT4a, pN3, M0, pStage ⅢC. The postoperative adjuvant chemotherapy was interrupted due to nausea, but the patient had no apparent recurrence within 5 years after gastrectomy. In 2019, a swelling appeared from the left inguinal region to the scrotum, and MRI scan showed subcutaneous edematous changes in the same region. Biopsy showed adenocarcinoma and we diagnosed a recurrence of gastric cancer with skin metastasis. In November 2020, the patient complained of defecation disorder, and CT scan showed a circumferential wall thickening with contrast effect in the rectum. Although colonoscopy revealed rectal stenosis, biopsy specimen showed no malignant findings. We suspected rectal stenosis due to peritoneal dissemination of gastric cancer and performed a colostomy. Intraoperative findings showed that the rectal wall was remarkably thickened with serosal erythema. Adenocarcinoma cells were found from the cytology of ascites. The patient was treated with nab-paclitaxel plus ramucirumab, then treated with nivolumab after failure of first-line therapy.

[Short- and Long-Term Surgical Outcomes for Patients with Colorectal Cancer Aged 80 Years or Older].

This study aimed to assess short-term and long-term outcomes and to identify the factors that affect outcomes for patients with colorectal cancer aged 80 years or older. Two hundred patients with colorectal cancer who were underwent resection of the primary tumor between January 2013 and December 2018 were enrolled. Short-term outcomes of elderly patients with poor PS and of those who take antithrombotic agents and of those who were underwent open surgery were poor. Long-term outcomes of elderly patients with high GNRI and of those who were underwent D3 lymph nodes dissection were better. Laparoscopic surgery with D3 lymph nodes dissection for elderly patients who were more than 80 years old should be useful to improve short- and long-term outcomes. GNRI might be a prognostic predictive factor for patients with colorectal cancer aged 80 years or older.

[Prognostic Analysis of Colorectal Cancer Patients by the Controlling Nutritional Status(CONUT)Score].

We examined the controlling nutritional status(CONUT)score and the long-term prognosis of colorectal cancer surgery cases. We retrospectively examined the prognosis of colorectal cancer patients who underwent surgery between January 2013 and December 2015. We targeted 449 patients who were able to calculate the CONUT score. A total of 266 patients (59.2%)had normal nutritional status(1 or less)and 183 patients(40.8%)had mildly poor or worse nutritional status (2 or more). The CONUT score was calculated through preoperative blood tests. The relationship between the CONUT score and overall survival was examined in the low and high groups. Overall survival was significantly shorter in the high group but relapse-free survival did not differ significantly between the 2 groups. There was no difference in cancer-specific survival between the 2 groups, but the survival time due to death from other diseases was significantly shorter in the high group. The CONUT score obtained from preoperative blood sampling suggested that the overall survival time was short in the malnourished group, and that it could be used as an index of prognosis due to death from other diseases.

[Short-Term Clinical Outcome of Robotic Surgery for Advanced Rectal Cancer after Neoadjuvant Therapy].

We examined 14 cases who underwent robotic rectal resection with neoadjuvant chemotherapy(NAC)or neoadjuvant chemoradiation therapy(NACRT)for local advanced rectal cancer in our hospital from 2018 June to 2020 December. Two patients underwent NACRT, 12 patients underwent NAC. Sex was 10 males and 4 females. The median age was 66. The surgical procedure was ISR 2 cases, LAR 8 cases, APR 4 cases. The median operation time was 397 minutes and the median blood loss was 73 mL. The histological response grade were Grade 3: 1 case, 2: 7 cases, 1b: 3 cases, and 1a: 3 cases. Surgical margin was negative in all cases. Postoperative complications(≥Clavien-Dindo Grade Ⅲ)required reoperation due to intestinal obstruction in 1 case. Urinary dysfunction was nothing in all cases. Although long-term results such as prognosis and function preservation need to be examined, short-term results of robot-assisted rectal resection after NAC or NACRT were generally good.

[A Case of Robot Assisted Low Anterior Resection for a Patient with Persistent Descending Mesocolon].

Persistent descending mesocolon(PDM)is caused by absence of fusion of the descending colon to the retroperitoneum. A 67-year-old man with bloody stools was diagnosed with rectal cancer on colonoscopy. A computed tomography showed a medial displacement of his descending colon. The preoperative clinical diagnosis was rectal cancer with PDM, and robot assisted low anterior resection was performed. We found that the left-sided colon was shifted to the midline and adhered the cecum and the mesentery of small intestine. Robot assisted surgery enables surgery with the precise adhesiotomy in a stable field. PDM is a relatively rare anatomic abnormality. Character of PDM is adhesion between the left-sided colon and other organs and radially branch from the inferior mesenteric artery. It is important to understand the anatomical characteristics of PDM and to improve on existing surgical procedures to ensure safe robot assisted surgery these patients.

Percutaneous transesophageal gastro-tubing for the management of anastomotic leakage after upper GI surgery: a report of two clinical cases.

BACKGROUND: Anastomotic leakage is a serious, sometimes critical complication of upper gastrointestinal (GI) surgery. The cavity and target drainage tubes are difficult to reach; therefore, a nasogastric tube (NGT) and fasting are required for an extended period. We successfully treated and managed two patients with anastomotic leakage using percutaneous transesophageal gastro-tubing (PTEG). CASE PRESENTATION: In case 1, a 79-year-old man with gastric cancer underwent total gastrectomy; 1 week later, he underwent emergent open laparotomy due to panperitonitis attributed to anastomotic leakage-related jejunojejunostomy. We resected the portion between esophagojejunostomy and jejunojejunostomy and reconstructed it using the Roux-en-Y technique. On postoperative day (POD) 9, anastomotic leakage was diagnosed at the esophagojejunostomy site and jejunotomy staple line. After using a circular stapler for jejunojejunostomy, a stapled jejunal closure was added. We inserted an NGT and performed aspiration for bowel decompression. As he did not improve within 2 weeks, we decided to perform PTEG to free him of the NGT. We kept performing intermittent aspiration; leakage stopped shortly after, due to effective inner drainage. The PTEG catheter was removed after oral intake was restarted. In case 2, an 81-year-old man with esophagogastric junction cancer underwent resection of the distal esophagus and proximal stomach. After shaping the remnant stomach, esophagogastrostomy was performed under the right thoracotomy. On POD 11, anastomotic leakage was identified, along with a mediastinal abscess. We inserted an NGT into the abscess cavity through the anastomotic leakage site. On POD 25, we performed PTEG and inserted a drainage tube, instead of an NGT. Although the abscess cavity disappeared, anastomotic leakage persisted as a fistula. We exchanged the PTEG with a double elementary diet (W-ED) tube with jejunal extension, with the side hole located near the anastomosis. The anastomotic fistula disappeared after treatment. Dysphagia persisted due to disuse atrophy of swallowing musculature; PTEG was useful for enteral feeding, even after the leakage occurred. CONCLUSION: Patients are sometimes forced to endure pain for a long time for transnasal inner drainage. Using PTEG, patients will be free of sinus pain and discomfort; PTEG should be helpful for patients withstanding NGT.

[Clinical Significance of Preoperative Chemotherapy for Advanced Colorectal Cancer].

We examined 22 cases who underwent preoperative chemotherapy in our hospital from 2013 April to 2018 December. Seven patients were treated as neoadjuvant chemotherapy(NAC). Out of 15 patients with unresectable diseases before chemotherapy, 6 patients were able to R0 resection after chemotherapy(conversion). Although only one patients was underwent RM1 resection, the other patients were underwent RM0 resection. The median overall survival was 42 months in NAC group, 28 months in conversion group, and 17 months in palliative resection group, respectively. Recurrence was observed in 1 patient in NAC group, however, all patients had recurrent disease in conversion group. In this study, although further examination should be done according to the clinical significance of preoperative chemotherapy, preoperative chemotherapy may be carried out without severe adverse event and severe postoperative complication.

[A Case Report with R0 Resection for Locally Advanced Appendiceal Cancer Invading to the Right External Iliac Vessels].

A 46-year-old man presented with right lower quadrant pain. Enhanced CT revealed a 30 mm sized irregular shaped mass originating from the appendix and invading the abdominal wall. We performed the laparoscopic appendectomy. Finally, the pathologic finding revealed a local advanced appendiceal carcinoma. From the intraoperative findings, the residual tumor was existed around the right external iliac vessels and abdominal wall. The patient was treated with chemotherapy for 13 months. Although the residual tumor encased the right external iliac vessels, the abdominal wall, and psoas major muscle, there were no signs of distant metastasis. We performed ileocecal resection with D3 lymph node dissection. The right external iliac vessels, abdominal wall, and psoas major muscle were resected simultaneously, and reconstructed by femoral- femoral bypass. As a result, R0 resection was achieved pathologically.

Gastric cancer cells alter the immunosuppressive function of neutrophils.

Tumor­associated neutrophils (TANs) have an immunosuppressive function and play an important role in tumor progression. However, the detailed mechanism is largely unknown. The present study investigated the immunosuppressive ability of TANs in gastric cancer. Tumor tissue culture supernatant (TTCS) and non­tumor tissue culture supernatant (NTCS) were purified and added to neutrophils. Expression of programmed cell death ligand­1 (PDL­1), 7­amino­actinomycin D and human leukocyte antigen­DR (HLA­DR), and the levels of hydrogen peroxide (H2O2) were determined. Levels of programmed cell death­1 (PD­1) and CD25 were assessed in T cells co­cultured with neutrophils. Furthermore, CD4+ T cells were co­cultured with dendritic cells and neutrophils to examine their proliferation. CD15 and PD­1 immunohistochemical staining was also performed to explore the positional relationship. The results revealed that the neutrophils incubated with TTCS showed upregulation of PDL­1 expression, as well as a decreases in the ratio of apoptotic cells, expression of HLA­DR, and levels of H2O2. CD4+ T cells co­cultured with neutrophils conditioned with TTCS showed a decrease in proliferation, upregulation of PD­1 expression, and downregulation of CD25 expression. IHC showed that PD­1+ T cells formed clusters and TANs infiltrated around the clusters. In conclusion, neutrophils in gastric cancer tissue inhibit the proliferation of CD4+ T cells and may form a local immunosuppressive environment through the PD­1/PDL­1 pathway.

Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells to induce cytotoxic T lymphocytes in the tumor environment. After acquiring antigens, DCs undergo maturation and their expression of MHC and co-stimulation molecules are enhanced, along with lysosome-associated membrane glycoprotein 3 (LAMP-3), which is a specific marker of mature DCs. In general, mature DCs are usually considered to be immunostimulatory in the cancer microenvironment. In addition, it is known that tumor-infiltrating lymphocytes (TILs) are associated with a good prognosis in esophageal squamous cell carcinoma (ESCC). However, few studies have targeted the interaction between DCs and TILs in the local immunity of ESCC. We investigated the localization of mature DCs within ESCC tissue and their relationship to TILs as well as the clinical outcome. METHODS: We evaluated 80 ESCC patients who underwent surgical treatment without preoperative treatment, using immunohistochemistry with LAMP-3 and CD8. RESULTS: The results showed that LAMP-3 DCs were predominantly observed in the peritumoral area. Intratumoral CD8 T cells were found to be associated with a favorable prognosis, and the number of infiltrating LAMP-3 DCs was correlated with the number of intratumoral CD8 T cells. CONCLUSION: At the local tumor site, mature LAMP-3 DCs might be associated with increasing tumor infiltrating CD8 T cells.

Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response.

BACKGROUND: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15+neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer. RESULTS: Immunohistochemical staining showed that the median number of CD15+TANs was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs, respectively. Patients were divided into high and low infiltration groups based on the median number. A high number of infiltrating CD15+TANs in the primary tumors and in the TDLNs were associated with depth of invasion and lymph node metastasis. Kaplan-Meier analysis revealed that a poor overall survival was associated with high numbers of CD15+TANs, and the multivariate analyses revealed that a high number of CD15+TANs in the TDLNs was an independent prognostic factor. The numbers of CD15+TANs in the primary tumors and TDLNs showed weak positive correlation. The number of CD15+TANs in the primary tumors was positively correlated with the preoperative NLR, (P = 0.001, R = 0.327) and immunohistochemical staining revealed that C-X-C motif chemokine receptor 2 (CXCR2) +neutrophils might be the origin of the CD15+TANs. Flow cytometry analysis indicated that infiltrating neutrophils increased in the tumor and TDLN compared to non-cancerous tissue. Neutrophils treated with cancer supernatant upregulated TWIST and IL-6 genes in vitro. CONCLUSION: Our findings suggested that local infiltration of CD15+TANs may be correlated with inflammation in TDLNs and systemic response to cause metastasis in gastric carcinoma.

[Significance of Immune-Cell Infiltration in Gastric].

There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL). On the other hand, it has been proved that CD8+ T cells react in an antigen-specific manner even in advanced gastric cancer, suggesting the possibility that memory T cells, NK cells andNKT cells in gastric cancer tissues correlate with goodprognosis. Recently, it has been reportedthat the presence of follicular lymphoidstructure calledtertiary lymphoidstructure(TLS)in gastric cancer tissue is associatedwith favorable prognosis. Although immune responses are suppressedin gastric cancer tissues, the effectiveness of an immune checkpoint inhibitor(anti-PD-1 antibody)has been provedin 2017. The tumor-infiltrating immune cells is known as a predictive effect biomarker. As cancer genome research progresses, which type of immune response is induced is gradually being elucidated in near future. Thus, assessing the invasive morphology and function of various tumorinfiltrating immune cells is considered to be extremely important in Precision Medicine for gastric cancer.