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Background: With the increasing number of elderly people in Japan, there are more and more opportunities for physicians to treat elderly patients. In general, elderly patients are considered to be at increased risk for treatment due to a decreased organ reserve. In recent years, the concept of frailty has been attracting attention as a comprehensive indicator of the various effects of aging, but no conclusion has been reached on how to evaluate it. The present study investigated the adverse effect of preoperative frailty on short- and long-term outcomes in patients with gastric cancer using a questionnaire about frailty. Methods: Of the 149 patients who underwent curative gastrectomy for gastric cancer in our department between April 2015 and December 2016 and had pathological stage (p Stage) I/II/III, 125 were enrolled in this study, excluding 24 patients who failed to respond to the preoperative questionnaire on frailty.The frailty index (FI) was calculated by dividing the total score of 50 questions, consisting of 1 point per question, by 50. The study used a multiple logistic regression analysis with the 5-year overall survival (OS) as the endpoint to create a receiver operating characteristic (ROC) curve to determine the cut-off point for the FI. Based on the results, patients were classified into frail and non-frail groups. The short- and long-term outcomes of the frail and non-frail groups were then compared, and prognostic factors for the OS were examined. Postoperative complications were defined as those of Clavien-Dindo grade ≥3a. Results: Regarding the short-term outcomes, the postoperative complication rates did not differ significantly between the frail and non-frail groups. Regarding the5-year OS rates of the patients with p Stages II/III, the outcomes in the frail group were significantly poorer than those in the non-frail group. In the multivariate analysis of the OS, frailty was independently associated with unfavorable outcomes in patients with gastric cancer. Conclusion: Frailty in the present study encompasses not only patients' physical factors but also their psychological and social factors, which may be useful for predicting the long-term prognosis of patients undergoing surgical treatment for advanced gastric cancer.

Several studies have reported that tissue‐resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103+ T cells and to assess the association between CD103+ T cells and TLSs. CD103+ T cells were observed in the tumor epithelium accompanied by CD8+ T cells and were associated with a better prognosis in GC. Furthermore, CD103+ T cells were located around TLSs, and patients with CD103high had more rich TLSs. Patients who had both CD103high cells and who were TLS‐rich had a better prognosis than patients with CD103low cells and who were TLS‐poor. Moreover, for patients who received PD‐1 blockade therapy, CD103high and TLS‐rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103+CD8+ T cells and showed that CD103+CD8+ T cells in GC expressed higher levels of PD‐1, granzyme B, and interferon‐γ than CD103−CD8+ T cells. Our results suggested that CD103+CD8+ cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC., Many CD103+ T cells were observed in the tumor epithelium accompanied by CD8+ T cells and were located around tertiary lymphoid structures (TLSs). Patients with a combination of CD103high and TLS‐rich had a good prognosis.

Esophageal cancer has high frequency of lymph node (LN) metastasis and poor prognosis, and often relapse early even after radical esophagectomy. Extensive LN dissection has made it possible to grasp the detailed metastatic status and the relationship between LN metastasis and prognosis. It is necessary to study more about metastatic style and prognostic factors for minimalization of surgical invasion and individualization of treatment. We analyzed about metastatic location, prognosis and recurrence for esophageal cancer cases with a few LN metastasis. We study 168 stageII, III esophageal cancer cases that underwent radical esophageal resection with regional LN dissection (D2 or more) from January 2015 to December 2017. Those cases included 37 or 29 cases with one or two LN metastasis. The number of cases on each tumor location (Ce/Ut/Mt/Lt/Ae) were 4/19/80/55/10 cases. On LN dissection, D2 were 68 cases and D3 were 100 cases. In a comparison of survival rate, age ( Esophageal cancer with a few metastatic lymph nodes had relatively good prognosis, and metastasis was likely to stay nearby the primary lesion. However, it is difficult to detect metastasis precisely prior to surgery, so developing the further technique of diagnosis and individualized treatment are expected in the future.

Background/Aim: Recently, several studies have reported that CD103+ T cells are associated with antitumor immunity in gastric cancer (GC). However, the significance of CD103+ T cells in Borrmann type 4 GC remains unclear. The aim of this study is to assess the association of CD103+ T cells with type 4 GC. Materials and Methods: Tissue samples obtained from surgically resected specimens of patients with type 4 GC were collected, and immunohistochemical staining was performed to detect the presence of CD103+ T cells. Results: A total of 46 patients were analyzed. In some patients, high CD103 expression was observed, and patients with high CD103 expression tended to have a better prognosis than those with low CD103 expression. In particular, for patients who receive doublet chemotherapy after surgery, high CD103 expression was associated with a good prognosis. Conclusion: CD103+ T cells may be a prognostic marker in type 4 GC.

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.

Currently, the immunotherapy approved for gastric cancer is immune checkpoint blockade( ICB) therapy. The effects of ICB depend on the T cell-mediated immune response elicited at the cancer site. Based on the results of previous clinical trials, it is clear that an enhanced immune response to cancer improves prognosis. Thus, the development of biomarkers to predict local immune responses may increase the significance of future immunotherapy for gastric cancer. Biomarker research has clearly progressed with the rapid development of genetic analysis technologies, enabling the analysis of data from clinical trials. Not only the molecular biomarkers known to date for ICB biomarkers, but immune cells that influence ICB therapy are also reviewed in this article.

We report a case of advanced gastric cancer with stenosis under severe malnutrition, in which nutritional treatment along with chemotherapy using an elemental diet(ED)tube led to complete resection of the tumor. A 66-year-old man who presented with difficulty in dietary intake came to our hospital. He was emaciated with a body mass index(BMI)score of 13.5 and a prognostic nutritional index(PNI)score of 33.8 and was admitted to the hospital for an emergency. He was diagnosed with advanced gastric cardia cancer invading the distal pancreas, spleen, and left diaphragm(U, type 3, tub2, cT4bN3M0, cStage ⅢC, HER2 score 0). There was obstruction of the passage of food due to the tumor, we performed nutrition therapy and chemotherapy consisting of 3 courses of S-1 and oxaliplatin using an ED tube. After chemotherapy, the primary tumor and lymph nodes were reduced, and we performed total gastrectomy with D2 lymph node, distal pancreas, spleen, and left partial diaphragm dissection. Histopathological diagnosis was ypT4aN1M0, ypStage ⅢA, indicating a pathological partial response(Grade 1). Adjuvant chemotherapy was performed for 6 months, and there has been no relapse for 3 years since the operation.

A 66-year-old man had an elevated CEA level. Further examinations showed a pancreatic head tumor. A pancreaticoduodenectomy was then performed. The histopathological examination showed a mixed tumor of papillary adenocarcinoma and neuroendocrine cancer. In addition, a tumor in the upper lobe of the right lung was found 18 months after the initial pancreatic resection, and the bronchoscope indicated lung metastasis. The patient underwent partial pneumonectomy. After the pneumonectomy, he received S-1 chemotherapy. Thirty -nine months after the pneumonectomy, CEA was slightly elevated. We changed the chemotherapy to gemcitabine and nab-paclitaxel without further examinations to confirm the recurrence. The patient discontinued chemotherapy after CEA fell within the normal range. He has been alive without tumor relapse for 64 months since the second operation for the lung metastasis. We report a successful case of lung resection for lung metasta- sis from pancreatic cancer.

Tertiary lymphoid structures (TLSs), which consist of B cells, T cells, follicular dendritic cells and high endothelial venules, have recently been found to be associated with effective antitumor immune responses in patients with cancer. Tumor-infiltrating T cells and B cells have each been demonstrated to be associated with survival in patients with cancer. We hypothesized that TLSs, an assembly of immune cells, may be important for the initiation and/or maintenance of T cell and B cell responses against tumors. The aim of the present study was to examine the cellular mechanism of B cells in TLSs within gastric cancer and to understand the antitumor immune response of TLSs. Each B cell subset in a tumor was examined using flow cytometry to evaluate B cell differentiation and the functional status of B cells. In addition, B cell clonality was investigated by analyzing the B cell antigen receptor gene using PCR, and the function and formation/maintenance of TLSs were evaluated using reverse transcription-quantitative PCR. Tumor-infiltrating B cells were more differentiated compared with that in distant non-tumor tissues and tumor-draining lymph nodes. The PCR results revealed specific BCR gene expression in tumor-infiltrating B cells. The expression of co-stimulatory factors, CD80 and CD86, was observed, in addition to the constantly expressed major histocompatibility complex molecules (HLA-ABC and HLA-DR). CD70 was expressed in addition to CD27 in both CD20+ B cells and CD8+ T cells, indicating that these factors are activated together through their interaction. The mRNA expression levels of CCL21, CXCL13, PD-L1, perforin and granzyme B in TLSs was significantly higher compared with that in non-TLSs. The majority of tumor-infiltrating B cells in gastric cancer exist in the form of TLSs around the tumor and have been antigen-sensitized and differentiated, and proliferated in TLSs but not in the lymph nodes. In addition, B cells in TLSs might primarily function as antigen-presenting cells and be associated with the induction of cytotoxic T cells.

We report a case of gastrointestinal stromal tumor(GIST)with long-term survival treated by multidisciplinary therapy, including surgery and imatinib to prevent repeated recurrence. A 76-year-old woman visited our hospital with difficulty in defecation and bloody bowel discharge. She was diagnosed with rectal GIST and underwent transanal partial resection of the rectum. Local recurrence occurred 1 year after the operation, and the tumor was resected transanally. Hepatic metastasis occurred 8 months after the second operation. The patient was administered imatinib for 2 months, which caused the tumor to shrink, and extended left lobectomy was performed. Imatinib was administered for 2 years after hepatectomy. After another 2 years, metastasis to the liver and thoracic and lumbar vertebrae occurred. The recurrent tumors reverted to cystic lesions after 6 months of imatinib treatment. She has been alive without tumor progression during re-treatment with imatinib for 7 years(13 years after the first surgery).

The prognosis of HCC with vascular invasion is dismal, but surgery is elected when the hepatic reserve is adequate. The case involved a 68-year-old male HCV carrier. A 10 cm diameter tumor occupying the central 2 segments of the liver and liver metastasis in the left lobe were detected. The patient was diagnosed with multiple HCC with severe vascular invasion of Vp2 and Vv3. The tumor shrunk dramatically after starting HAIC therapy with cisplatin and oral administration of sorafenib. A laparoscopic partial hepatectomy was performed for the viable lesion. The tumor showed almost complete coagulative necrosis. Multiple hepatic metastases were found 4 months after surgery, but the tumor was under control at 25 months after the first HAIC due to HAIC, oral administration of sorafenib, and RFA. An improved prognosis for multiple HCC with severe vascular invasion can be expected by performing multidisciplinary treatments including surgery.

Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease.

A 69-year-old man underwent surgery for pancreatic head cancer. During surgery, a few tubercles were found in the bursa omentalis, which were diagnosed pathologically as peritoneal dissemination. Curative resection was impossible, and exploratory laparotomy was completed. After surgery, 17 cycles of S-1/gemcitabine combination chemotherapy were administered for 1 year. Significant changes were not observed in the primary tumor on computed tomography (CT) scan, but the uptake of fluorodeoxyglucose (FDG) in the tumor decreased on positron emission tomography combined with CT(PET/CT), suggesting a decrease in tumor activity. Although imaging modalities could not identify distant or peritoneal metastases, levels of serological tumor markers increased at this time. Therefore, a second exploratory laparotomy was performed 13 months after the initial surgery. The nodules in the bursa omentalis had disappeared, and the patient underwent a pancreatoduodenectomy with common hepatic artery resection. Histopathological findings revealed mucinous carcinoma of the pancreas. The postoperative diagnosis was pT3, pN2, M0, Stage IVa.

The stenting strategy for portal vein stenosis in cases with unresectable hilar malignancies reduces portal hypertension and maintains portal vein blood flow. This not only improves quality of life, but also leads to aggressive therapy with anticancer agents. A 65-year-old woman presented with painless jaundice 8 months after left hemihepatectomy with lymph node dissection for intrahepatic cholangiocellular carcinoma. Seven months after biliary stenting for bile duct stenosis, progressing pancytopenia and ascites were noted. Imaging studies revealed portal vein stenosis by the tumor at the hepatic hilum. Percutaneous transhepatic portal vein stent placement was performed, and pancytopenia and ascites improved immediately thereafter. Chemotherapy for recurrence of intrahepatic cholangiocellular carcinoma at the hepatic hilum has been initiated, and the patient has been alive 15 months since.