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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.

Esophageal cancer (EC) is associated with malnutrition in the vast majority of patients, and this often leads to sarcopenia, which is characterised by loss of skeletal muscle mass (SMM). Although sarcopenia could be one of the risk factors for postoperative pneumonia (PP), the optimal definition of sarcopenia using skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) remains unknown for predicting PP after esophagectomy in patients with EC. Therefore, this study aimed to identify high-risk patients for PP after esophagectomy through evaluating SMI by BIA and set an appropriate cut-off value for this purpose. A total of 73 patients with EC who underwent subtotal esophagectomy with lymph node dissection at Osaka City University Hospital between 2017 and 2019 were reviewed retrospectively. The association between PP and perioperative factors including SMI by BIA were analysed. When SMI was lower than the cut-off values proposed by two study groups (Asian Working Group for Sarcopenia (AWGS) and original European Working Group on Sarcopenia in Older People (EWGSOP)) or SMM was less than 90% of standard, the patient was diagnosed with sarcopenia. Receiver operating characteristic analysis was performed to set the appropriate cut-off value of SMI, and a new criterion (modified EWGSOP) was formulated by using the value. Clinicopathological factors and postoperative complications between sarcopenia and non-sarcopenia groups were compared, which were classified by four different criteria: (1) AWGS, (2) original EWGSOP, (3)

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.

Chemotherapy for elderly patients requires ingenuity in treatment to mitigate its high risk. Therefore, we investigated an upfront dose reduction in the first cycle of chemotherapy for unresectable/recurrent gastric cancers in patients over 80 years old. We examined 6 patients over 80 years old, who underwent S-1 plus L-OHP therapy(SOX)for unresectable/recurrent gastric cancer in our department between January 2020 and January 2021. There were no adverse events over Grade 3 in the upfront dose reduction group(U group), while 1 case(50.0%)in the normal dose group(N group)experienced an adverse event over Grade 3. Moreover, only the U group continued treatment for 4 or more courses, whereas none from the N group did. Partial response(PR)was achieved as a therapeutic effect in 3 patients of the U group. Only 2 cases of the U group advanced to the second-line regimen and both were able to transition to the third-line regimen. However, none were able to even transition to the second-line regimen in the N group. Therefore, it was suggested that by reducing the dose of chemotherapy from the first cycle for elderly patients over 80 years old, the incidence of adverse events can be kept low, which makes it possible to continue long-term chemotherapy.

An 80-year-old man underwent laparoscopic rectal high anterior resection with perineal dissemination for the management of RS rectal cancer. Following the diagnosis of RS rectal cancer with muc, pT4a, N3(14/15), M1c, P1, pStage Ⅳc, RAS/BRAF: wild type, treatment was initiated with mFOLFOX6 plus panitumumab(Pmab). Laboratory examination on admission revealed mild renal dysfunction(Cr 1.45 mg/dL). The patient became confused on day 3 of chemotherapy(JCS Ⅲ-200). Furthermore, laboratory findings revealed a serum ammonia level of 338μg/dL. He was diagnosed with 5-FU- induced hyperammonemic encephalopathy. Discontinuation of high-dose 5-FU and branched-chain amino acid solutions improved his mental status and decreased serum ammonia levels. We switched his chemotherapy regime to CPT-11 plus Pmab, but it was discontinued after 1 course on his request.

BACKGROUND/AIM We have previously reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling was associated with the malignant progression of gastric cancer (GC). We thus examined the clinicopathological significance of CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8, in GC. PATIENTS AND METHODS The expression of CXCR2 ligands in 590 GC cases was investigated by immunohistochemistry. RESULTS The expression was as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis and peritoneal cytology positivity were correlated with high expression of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p

Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two main types: intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type that are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1-based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathological mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy. The clinicopathological data of 968 patients with gastric carcinoma who underwent gastrectomy between 2007 and 2016 at Osaka City University Hospital were retrospectively analyzed. In the present study, tumors containing Sig or Por2 were classified as diffuse type, and those not containing them were classified as intestinal type. There were 307 cases of diffuse type and 661 cases of intestinal type. Diffuse type included 189 cases with Sig. A pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III gastric cancer. Patients with diffuse type had a worse overall survival rate than those with intestinal type at stage III gastric cancer. Among the patients who received S-1 adjuvant chemotherapy, the prognosis of patients with stage III gastric cancer with Sig but not Por2 was significantly worse compared with that of patients with intestinal type. Therefore, the present study revealed that the coexistence of Sig in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. The current findings suggested that, since mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy was performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in patients with stage III gastric cancer.

A 50s old woman admitted to our hospital with anal pain, who was diagnosed as rectal gastrointestinal stromal tumor (GIST). After neoadjuvant therapy with imatinib mesylate for 6 months, the tumor reduced by 75% from its original size and anus preserving operation(low anterior resection)was performed. After operation adjuvant therapy with imatinib mesylate was performed for 2 years and 6 months. The patient is alive without recurrence 5 years after surgery. It is suggested that neoadjuvant therapy with imatinib mesylate is useful and safety for large rectal GIST, from the standpoint of anal preservation.

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.

A 69-year-old woman, who complained of appetite loss, was diagnosed with Type 3 gastric cancer, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2-por), Group 5. Abdominal computed tomography (CT) revealed bulky metastatic lymph nodes around the stomach and the aorta. The diagnosis was cT4a, cN2, cM1(LYM), cStage ⅣB, and SP therapy(a combination of S-1 and cisplatin) was immediately administered. On the completion of 3 courses of SP therapy, both the primary tumor and lymph nodes markedly decreased in size. Based on this finding, D2 total gastrectomy, No. 16 lymph node dissection, splenectomy, and right adrenal tumor resection were performed. Histopathology showed no residual tumor cells in the stomach or lymph nodes. Postoperatively, she received S-1 therapy, which was discontinued on completion of the first course due to its side effects. She survived for over 7 years postoperatively without receiving chemotherapy and showed no recurrence.

Background Gastric cancer (GC) patients frequently develop peritoneal metastasis. Recently, it has been reported that peritoneal mesothelial cells (PMCs) activated by GC cells acquire a migratory capacity and promote GC cell invasion. The invasiveness of PMCs reportedly depends on the activity of Tks5, an adaptor protein required for invadopodia formation. However, the relationship between clinicopathologic features and Tks5 expression in PMCs has been poorly documented. In this study, we evaluated the clinicopathologic significance of the Tks5 expression of PMCs in GC patients. Materials and methods A total of 110 GC patients who underwent gastrectomy were enrolled in this study. Tks5 expressions in PMCs from the greater omentum, lesser omentum and retroperitoneum were evaluated by immunohistochemistry. We analyzed the correlation between Tks5 expressions in PMCs and the patients’ clinicopathologic features. Results Tks5 expression was found in 71 (64.5%) of the 110 patients, while 39 (35.5%) were Tks5-negative. Tks5 positivity was significantly (p = 0.038) associated with a greater tumor depth (i.e., T3/4 compared with T1/T2). Peritoneal recurrence was found in 12 of 98 cases within 3 years of surgery. The 3-year peritoneal recurrence-free survival (PRFS) rate in Tks5-positive cases was significantly poorer than that in Tks5-negative cases (80.1% vs 97.4%, p = 0.024). Multivariate analysis revealed that Tks5 positivity and lymph node metastasis were independent factors for PRFS. Conclusion Tks5 is frequently expressed in PMCs in advanced-stage gastric cancer. Tks5 might be a useful predictor for peritoneal recurrence in GC patients.

A 63-year-old asymptomatic woman was diagnosed with multiple liver tumors and a left pulmonary tumor by CT. Colonoscopy( CS)showed a Type 2, quarter circular tumor on Rb. The diagnosis was cT3N1aM1b(H3, PUL1), cStage Ⅳb rectal cancer. She was administered 8 courses of induction-adjuvant chemotherapy with CAPOX and bevacizumab(BEV). After the chemotherapy, CT and CS revealed shrinkage(up to 50%)of the metastatic liver tumor and primary tumor, and decreasing tumor marker levels. Laparoscopic abdominoperineal resection and partial hepatectomy(S5/6, S8)were performed. After the operation, she was administered 2 courses of chemotherapy with UFT and LV, after which thoracoscopy-assisted upper lobectomy of the left lung was performed. Currently, at 1 and a half years after treatment, no recurrence has been observed, and she is being followed up as an outpatient.

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.

Background Although many studies have identified several inflammation-based and/or nutritional markers with prognostic value for patients with various types of cancer, the optimal markers and cut-off values for these markers remain obscure. Therefore, this retrospective study aimed to identify optimal markers and their cutoffs. Methods We compared prognostic values among established preoperative inflammation-based and/or nutritional markers in 225 patients who underwent R0 resection for stage III gastric cancer. Inflammation-based and/or nutritional markers comprised C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic nutritional index (PNI), Glasgow prognostic score (GPS), and prognostic index (PI). Time-dependent receiver operating characteristic curves were analyzed to assess predictive ability and to determine the optimal cut-off values. Prognostic factors predicting overall survival (OS) and cancer specific survival (CSS) were analyzed using Cox proportional hazards models. Results Multivariate analyses revealed that CAR and PLR cut-off values of 0.47 and 172, respectively, were independent prognostic factors for overall survival (OS) (HR, 2.257; 95% CI, 1.180–4.319; p = 0.014 and HR, 1.478; 95% CI, 1.025–2.133; p = 0.037, respectively) and cancer-specific survival (CSS) (HR, 2.771; 95% CI, 1.398–5.493; p = 0.004 and HR, 1.552; 95% CI, 1.029–2.341; p = 0.036, respectively). These results were different from those we previously reported in patients with stage II. Conclusions Among inflammation-based and/or nutritional markers, CAR and PLR were independent prognostic factors of OS and CSS in patients with stage III gastric cancer. The optimal markers and their cut-off values should be determined in specific populations.

Background: Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two types, intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type and are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1 based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathologic mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy.Methods: The clinicopathological data of 968 gastric carcinoma patients who underwent gastrectomy between 2007 and 2016 at our department were retrospectively analyzed. In this study, tumors containing Sig or Por2 were classified as Diffuse type, and those not containing them were classified as Intestinal type.Results: There were 307 cases of Diffuse type and 661 of Intestinal type. Diffuse type included 189 cases with Sig. Pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III. Patients with Diffuse type had worse overall survival than those with Intestinal type in Stage III. Of the patients who received S-1 adjuvant chemotherapy, the prognosis of Stage III patients with Sig but not Por2 was Significantly worse compared to patients with Intestinal type.Conclusions: The coexistence of Signet ring cell carcinoma in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. These findings suggest that, because mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy were performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in stage III gastric cancer.

Background Neoadjuvant treatment with imatinib mesylate (IM) has not been established for gastrointestinal stromal tumor (GIST). A case of a giant gastric GIST that was radically resected following neoadjuvant therapy with IM is reported. Case report A 71-year-old woman with abdominal distension was referred to our hospital for treatment. Contrast-enhanced computed tomography showed a large (>30 cm), heterogeneous mass, with dilated vessels around the tumor. The diagnosis was a gastric GIST by endoscopic ultrasound-fine needle aspiration, and neoadjuvant therapy with 400 mg IM daily was started. Radical surgery was performed after 13 months. Since the tumor was not invasive, complete resection by partial gastrectomy was achieved without the need for combined resection of other organs. The patient remains alive without recurrence 12 months after surgery. Conclusion A giant GIST, larger than 30 cm in size, is quite rare. Neoadjuvant IM treatment should be considered in the management of large GISTs.

Introduction: In recent years, certain single-nucleotide polymorphisms (SNPs) have been reported to be associated with increased risk of cancer and prognosis. A Fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism (rs351855) which caused the substitution of arginine for glycine in the transmembrane domain of the receptor, was reported to increase cancer risk or not. The meta-analysis results showed that FGFR4 Gly388Arg polymorphism (rs351855) might be a cancer risk factor for majority Asians, especially in breast cancer and prostate cancer. There is also a report that FGFR4 Gly388Arg polymorphism (rs351855) may be a prognostic biomarker for lung squamous-cell carcinoma patients with lymph node metastasis and uterine cervical cancer. But few studies have been conducted in gastric cancer. And the Isocitrate Dehydrogenase 1 (IDH1) mutations in patients with acute myelogenous leukemia (AML) who have a normal karyotype are associated with a poor prognosis. IDH1 rs11554137:C>T, which is located in codon 105 in the same exon as the IDH1 codon 132 arginine (IDH1R132) mutation, has been described in patients with AML and has been identified as an adverse prognostic factor. It has also been reported that IDH1 rs11554137:C>T has a negative effect on glioblastoma patients in terms of both progression free survival and overall survival (OS). We investigated the association of the gastric cancer with two SNPs. Methods: This study included 30 cases and the tumor samples obtained from gastric cancer patients by surgery between October 2010 and December 2018. We evaluated all 30 samples by a panel testing (OncoGuide NCC Oncopanel system). And we searched for the expression of FGFR4 Gly388Arg polymorphism (rs351855) and the IDH1 rs11554137. Univariate analysis and Kaplan-Meier analysis was performed based on the OS. Comparison between two groups was evaluated using chi-squared test and Fisher's exact test. The stage evaluation of the cancer adopted Japanese Gastric Cancer Association the 15th Edition. Results: Median age is 70 (34-86) years, gender is Male/Female=18/12 cases, histology is Intestinal/diffuse/Scirrhous=8/13/9 cases. There were 21 cases of FGFR4 Gly388Arg polymorphism (rs351855) expression and 2 cases of the IDH1 rs11554137 expression in 30 cases of gastric cancer. The expression of FGFR4 Gly388Arg polymorphism (rs351855) and the IDH1 rs11554137 was compared with various clinic-pathologic factors, however, no significant correlation was found between clinic-pathologic factors and FGFR4 Gly388Arg polymorphism (rs351855) and the IDH1 rs11554137 expression. Conclusion: Our results suggest that neither FGFR4 Gly388Arg polymorphism (rs351855) nor IDH1 rs11554137 is not associated with the progression of gastric cancer. Citation Format: Tomohiro Sera, Masakazu Yashiro, Yurie Yamamoto, Yukako Kushitani, Atsushi Sugimoto, Syuhei Kushiyama, Kenji Kuroda, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira. Association between FGFR4 Gly388Arg polymorphism rs351855 or the IDH1 rs11554137 and Japanese gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5856.

Background: Cancer progression has been recognized as not only the proliferation of tumor cells but also an interaction between cancer cells and the surrounding stroma in the tumor microenvironment. Among the tumor stromal cells, fibroblasts (especially cancer-associated fibroblasts) have been reported to be closely associated with tumor development in various solid carcinomas. We reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling might play an important role in the pathogenic construction of tumor fibroblasts in the gastric tumor microenvironment, suggesting that gastric cancer cells might alter their adjacent stroma to form a permissive environment for tumor progression. Following those findings, we reported that chemokine (C-X-C motif) ligand 1 (CXCL1) from cells stimulated the recruitment of bone marrow cells into the gastric cancer (GC) microenvironment via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling, resulting in the malignant progression of GC. The reported CXCR2 ligands are not only CXCL1 but also CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8. However, there has been only a single in vitro study of significance of these CXCR2 ligands in GC. We thus examined the clinicopathological significance of these members of the CXCL family in GC. Method: We retrospectively analyzed the cases of 590 GC patients. The expressions of CXCR2 ligands were investigated by immunohistochemistry, and we then analyzed the correlation between the clinicopathological features of the patients and the expressions of CXCR2 ligands. Result: The expressions were as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis was correlated with high expressions of CXCL1 and CXCL7. Lymphatic invasion and venous invasion were correlated with CXCL1 and CXCL7 expression. Peritoneal cytology positivity was correlated with high expressions of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p Conclusion: Among the CXCR2 ligands, CXCL1 and CXCL7 were frequently expressed in GC cells. CXCL1 was closely associated with malignant potential of GC and was an independent prognostic factor. CXCL1 might play an important role in the malignant progression of GC via CXCL1/CXCR2 signaling. Citation Format: Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Syuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Masakazu Yashiro. The clinicopathologic significance of the CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6193.

A 46-year-old man underwent a medical check-up and gastrointestinal endoscopy, which revealed a brown lesion at the greater curvature of the gastric body. Biopsy was performed, and a gastric neuroendocrine tumor(NET)was diagnosed. The serum levels of gastrin and other tumor markers were not elevated. The preoperative diagnosis was Rindi type Ⅲ gastric NET, and laparoscopic distal gastrectomy with D1 plus lymph node dissection was performed. Histological examination showed that the resected specimen was positive for chromogranin A, CD56, and synaptophysin, which was consistent with the findings of NET. Even though the tumor diameter was only 3 mm, a metastatic #4d lymph node was found. This case suggests that Rindi type Ⅲ gastric NET has high malignant potential, and gastrectomy with lymph node dissection is necessary, regardless of tumor size.

A 40-year-old woman was admitted to our hospital with the chief complaint of miction pain. MRI showed fundal wall thickening of the bladder in contact with the appendix. Under cystoscopy, redness of the mucous membrane was found in the posterior wall of the bladder. Therefore, laparo-appendectomy with partial cystectomy was performed. Microscopically, adenocarcinoma cells were observed in the lumen of the appendix, invading the wall of the urinary bladder at the fundus of the appendix. We performed laparo-ileocecal resection for a regional lymphadenectomy. Thus, the patient was diagnosed with adenocarcinoma of the appendix[V, type 3, 16×7 mm, tub2, pT4b(SI, urinary bladder), int, INF b, ly0, v0, pN0, cM0, pStage Ⅱ]. The patient has been receiving adjuvant chemotherapy using capecitabine for 6 months. There was no evidence of recurrence after 9 months of follow-up.

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.

Objective: Lymph node (LN) metastasis is one of the most important prognostic factors for undifferentiated-type early gastric cancer (EGC). The aim of this study was to examine expansion of micrometastasis in regional LNs to clarify the importance of lymphadenectomy for undifferentiated-type EGC. Methods: Clinicopathological features of 307 patients with undifferentiated-type EGC who underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the Department of Surgical Oncology, Osaka City University, were retrospectively reviewed. Micrometastasis in LNs was detected by immunohistochemistry using anticytokeratin antibody. Results: The incidence of LN metastasis was 1.8% in patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b) tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth were independently related to LN metastasis. Micrometastasis was found in 41 (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the perigastric region. Micrometastasis had spread to the area along the left gastric or common hepatic artery in 12 patients. Patients with an upgraded stage by micrometastasis had significantly worse disease-free survival. Conclusions: LN micrometastasis was observed beyond the perigastric LNs and correlated with poor outcomes in patients with undifferentiated-type EGC. These data underscore the importance of adequate lymphadenectomy for patients with undifferentiated-type EGC.