Search

Background: Signet ring cell carcinoma (sig) and non-solid poorly differentiated adenocarcinoma (por2) are the histological forms of gastric cancer called diffuse type. They are considered to be a tissue type with a poor prognosis. Adjuvant chemotherapy using S-1 is standard therapy for stage II/III gastric cancer in Japan, however, clinical relevance of histological type to outcome of adjuvant therapy remains unclear. Purpose: The purpose of the present study was to examine the impact of the coexistence of diffuse type on the prognosis of stage II/III gastric cancer. Patients and Methods: We retrospectively analyzed the clinicopathologic data of 935 gastric carcinoma patients who underwent gastrectomy between 2007 and 2015 at our department. Results: We observed that there were 62 cases (17%) with sig mixed (dominant 12 cases, inferiority 50 cases) and 104 cases (30%) with por 2 mixed (dominant 19 cases, inferiority 85 cases). The patients with por2 or sig had more peritoneum dissemination compared with intestinal types. In Stage III, the recurrence rate was high in the case with sig mixed, the 3-year relapse-free survival rate was 36% in the mixed case and 55% in the non-mixed case. However, we found no correlation of sig mixture to prognosis of patients with Stage II. Among the patient who received the S-1 adjuvant chemotherapy, the prognosis of sig mixture was relatively poor. Conclusion: In the case of stage III gastric cancer in which there was mixed signet ring cell carcinoma in the tissue, the recurrence rate was high and the prognosis was poor. Our findings suggested that it should be needed to treat sig mixed cases as a high risk group in the future postoperative adjuvant chemotherapy for gastric cancer. Citation Format: Hiroaki Tanaka, Kazuya Muguruma, Tatsuro Tamura, Takahiro Toyokawa, Masatsune Shibutani, Tatsunari Fukuoka, HIsashi Nagahara, Masaichi Ohira. Clinical significance of diffuse-type histological type coexistence in Stage II/III gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4876.

Background: Human scirrhous gastric carcinoma (SGC) is also known as diffusely infiltrating carcinoma, type 4 on Borrmann’s criteria, and linitis plastica-type carcinoma. SGC is characterized by frequent peritoneal metastasis, high proliferation and infiltration activity with extensive fibrosis in the tumor stroma. We previously reported that a soluble factor(s) from SGC cells changed the peritoneum to pre-metastatic niche such as round shape of mesothelial cells and peritoneal fibrosis, which is a favorable environment for cancer cells to metastasize. Extracellular vesicles (EVs; Exosomes) might be one of soluble factor(s) which might change the peritoneal component to pre-metastatic niche. In this study, we investigated the effect of EVs from SGC cells on the pre-metastatic niche formation of the peritoneum. Methods: Four SGC cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, 2 non-SGC cell lines, MKN74, MKN45, and peritoneal mesothelial cells (PM cells) were used. The effect of EVs from gastric cancer cells on the peritoneum was examined in vitro and in vivo, as follows. PKH26-labeled EVs from OCUM-2MD3 cells were intravenously injected into nude mice for 3 weeks, then we examined the distribution of PKH26-labeled EVs by a fluorescence microscope. Next, we injected EVs intraperitoneally into nude mice, and investigated the morphology of peritoneum. Effect of EVs on the gene expression of PM cells was examined by RT-PCR. Clinical significance of EVs markers, CD9 and CD63, was evaluated by immunohistochemistry using 63 human gastric cancer specimens. Results: PKH26-labeled EVs frequently distributed to peritoneum and the liver. The morphology of PM cells changed from round shape to spindle shape by EVs addiction in vitro and in vivo. mRNA expression level of ZEB and N-cadherin of PM cells was significantly increased following the addiction of EVs. The high expression of EVs markers, CD9 and CD63, was significantly correlated with frequent peritoneal metastasis. Conclusion: EVs from SGC cells might frequently distribute to mesothelial cells of peritoneum. EVs from SGC cells might play an important role for the formation of a pre-metastatic niche on peritoneum by the morphologic change of peritoneal mesothelial cells. Citation Format: Tomohisa Okuno, Masakazu Yashiro, Shuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Kenji Kuroda, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Extracellular vesicles from scirrhous gastric cancer cells induce premetastatic niche formation for peritoneal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5160.

This report describes the successful use of portal venous stent placement for a patient with recurrent melena secondary to jejunal varices that developed after subtotal stomach preserved pancreatoduodenectomy (SSPPD). A 67-year-old man was admitted to our hospital with tarry stool and severe anemia at 2 years after SSPPD for carcinoma of the head of the pancreas. Abdominal computed tomography examination showed severe stenosis of the extrahepatic portal vein caused by local recurrence and showed an intensely enhanced jejunal wall at the choledochojejunostomy. Gastrointestinal bleeding scintigraphy also revealed active bleeding near the choledochojejunostomy. Based on these findings, jejunal varices resulting from portal vein stenosis were suspected as the cause of the melena. Portal vein stenting and balloon dilation was performed via the ileocecal vein after laparotomy. Coiling of the jejunal varices and sclerotherapy of the dilate postgastric vein with 5% ethanolamine oleate with iopamidol was performed. After portal stent placement, the patient was able to lead a normal life without gastrointestinal hemorrhage. However, he died 7 months later due to liver metastasis.

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.

Peritumoral lymphangiogenesis is significantly correlated with lymph node metastasis and poor prognosis in various cancers. However, there are few reports concerning the role of intranodal lymphangiogenesis in lymphatic metastasis. The aim of this study was to examine the association of lymphangiogenesis in regional lymph nodes with the progression of gastric cancer. Lymphatic vessel density (LVD) was immunohistochemically estimated in 1,596 lymph nodes from 52 patients who underwent gastrectomy. Intranodal LVD was significantly correlated with the size of metastasis and the progression of cancer. Patients in the high LVD group had significantly poorer prognosis relative to patients in the low LVD group. Furthermore, expression of VEGF-C mRNA was significantly up-regulated in lymph nodes of pathological node positive patients compared to node negative patients. Thus, intranodal lymphangiogenesis was correlated with nodal metastasis and poor prognosis of patients with gastric cancer. Lymphangiogenesis in regional lymph nodes plays an early role in spreading of tumor cells through the lymphatic system to distant organs in gastric cancer.

Background and Objectives Any gastrointestinal stromal tumors (GISTs) larger than 10 cm are classified as “high risk” according to the modified National Institutes of Health consensus criteria. We conducted a multicenter study to identify a subgroup with moderate prognosis even within the “high-risk” group. Methods We retrospectively collected data on 107 patients with tumors ≥10 cm from a multicenter database of GIST patients. Patients with macroscopic residual lesions or tumor rupture were excluded. The relationship between recurrence-free survival (RFS) and clinicopathological factors was analyzed. Results The median tumor size and mitotic count were 12.5 cm and 8/50 HPF. The RFS rate was 58.5% at 3 years, 52.1% at 5 years. Only mitotic count was an independent prognostic factor of RFS in the multivariate analysis (P = 0.001). The hazard ratio for recurrence in the subgroup with mitotic count >5/50 HPF was 2.91 (95% confidence interval, 1.53 to 5.56). The subgroup with mitotic count ≤5/50 HPF showed significantly better RFS than the mitotic count >5/50 HPF subgroup (P

A 66-year-old woman underwent sigmoidectomy for colon cancer. The final diagnosis was early cancer of pT2 pN0 and M0 (fStage I ). A chest CT revealed lung metastasis and lymph node metastasis 6 years after surgery. The patient was treated sequentially with FOLFOX, FOLFIRI, and XELOX regimens. Since these regimens resulted in progressive disease, regorafenib was started as the fourth regimen. After 8 courses, she was evaluated as having a partial response. Her partial response has continued for 18 months of regorafenib treatment.

Background The purpose of this study was to investigate the impact of the Controlling Nutritional Status (CONUT) score on survival compared with the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) in patients with resectable thoracic esophageal squamous cell carcinoma (ESCC). Methods One hundred eighty-five consecutive patients who underwent subtotal esophagectomy with curative intent for resectable thoracic ESCC were retrospectively reviewed. Time-dependent receiver operating characteristic curve analyses for 3-year overall survival (OS) as the endpoint were performed, and the maximal Youden indices were calculated to assess discrimination ability and to determine the appropriate cut-off values of CONUT, PLR, and NLR. The patients were then classified into high and low groups based on these cut-off values. Correlations between CONUT and other clinicopathological characteristics were analyzed. Prognostic factors predicting overall survival (OS) and relapse-free survival (RFS) were analyzed using Cox proportional hazards models. Results The areas under the curve predicting 3-year OS were 0.603 for CONUT, 0.561 for PLR, 0.564 for NLR, and 0.563 for GPS. The optimal cut-off values were two for the CONUT score, 193 for PLR, and 3.612 for NLR. The high-CONUT group was significantly associated with lower BMI, high-PLR, high-NLR, and GPS1/2 groups. On univariate analysis, high-CONUT, high-PLR, high-NLR, and GPS 1/2 groups were significantly associated with poorer OS and RFS. Of these factors, multivariate analysis revealed that only the CONUT score was an independent prognostic factor for OS (HR 2.303, 95 % CI 1.191–4.455; p = 0.013) and RFS (HR 2.163, 95 % CI 1.139–4.109; p = 0.018). Conclusions The CONUT score was an independent predictor of OS and RFS before treatment and was superior to PLR, NLR, and GPS in terms of predictive ability for prognosis in patients with resectable thoracic ESCC.

We evaluated the prognostic significance of the peripheral lymphocyte count and lymphocyte percentage, which reflect the preoperative immune status, in patients with colorectal cancer (CRC) and then compared their accuracy as predictors of the survival. We retrospectively reviewed a database of 362 patients. We classified the patients into high lymphocyte count and low lymphocyte count groups. We also classified the patients into high lymphocyte percentage and low lymphocyte percentage groups. The 5-year relapse-free survival (RFS) rate in the high lymphocyte count group tended to be higher than that in the low lymphocyte count group. The 5-year overall survival (OS) rate in the high lymphocyte count group was significantly higher than that in the low lymphocyte count group. In contrast, the 5-year RFS and OS rates in the high lymphocyte percentage group were both significantly higher than those in the low lymphocyte percentage group. A multivariate analysis showed that the lymphocyte percentage was independently associated with the OS. These findings suggest that the lymphocyte percentage is a good predictor of the OS and may be a stronger predictor of survival than the lymphocyte count in CRC patients.

All patients with peritoneal-free cancer cells (CY1) do not always develop a peritoneal recurrence (P1). The goal of this study was to identify characteristic features of peritoneal-free cancer cells that could develop into peritoneal recurrence. Of 1,474 patients, 91 were identified with CY1P0, and the remaining 1,383 with CY0P0. Immunohistochemical staining with anti-phosphorylated Smad 2 (p-Smad2) was performed on paraffin-embedded specimens from the 91 CY1P0 patients. CY1 was significantly correlated with Borrmann’s type-4 cancer, clinical T stage, and lymph node metastasis. CY1P0 patients with Borrmann’s type-4 cancer more frequently develop peritoneal recurrence than do those with other types of tumors. The 5-year survival rate of patients with Borrmann’s type-4 tumors was significantly (p = 0.023) low (6.3%) compared with that of patients with other types of tumors (27.7%). The prognosis for p-Smad2-positive patients was significantly poorer than that of p-Smad2-negative patients. In CY1 and/or P1 patients with Borrmann’s type-4 tumors, no significant difference in prognosis was identified between those who had surgery and those who did not. Activated Smad signaling might be associated with a high potential for peritoneal recurrence in CY1P0 patients. Borrmann’s macroscopic criteria and p-Smad2 expression are useful markers for surgeons selecting advanced gastric cancer patients with CY1P0 for gastrectomy.

症例は68歳，男性．不消化性の下痢，曖気の精査加療目的で入院となった．腹部CTで下行結腸～脾彎曲にかけて13cm大の腫瘤性病変を認めた．下部消化管内視鏡検査では下行結腸に隆起を主体とする5型病変を認め，ファイバーは潰瘍底より容易に胃内へと挿入された．腫瘍からの生検で高分化型腺癌と診断された．胃結腸瘻を形成した進行下行結腸癌と診断し，左半結腸切除術，D3リンパ節郭清，胃全摘，膵尾部・脾臓合併切除術を施行した．最終診断はmuc，si，n0，ly0，v0，ow(－)，aw(－)，stageIIで，手術根治度Aであった．われわれは内視鏡が通過することで診断できた胃結腸瘻を形成した下行結腸癌の1例を経験したので，自験例を加えた本邦報告25例の集計および文献的考察を行った．

症例は62歳，男性．37年前に十二指腸潰瘍に対して胃切除術の既往がある．1カ月前から嘔気・嘔吐を認めるようになり近医受診した．腹部CTで吻合部に腫瘤影と輸入脚の著明な拡張を認めた．同日の上部消化管内視鏡検査では吻合部に全周性の3型腫瘍を認め，残胃癌による輸入脚閉塞症と診断し緊急手術を施行した．前回手術はBillroth-II法の結腸後経路で再建されており，Treitz靱帯から吻合部の空腸は暗赤色を呈し著明に拡張していた．残胃全摘術，膵尾部・脾臓合併切除術を施行した．治癒切除であったが，術後3カ月で胃癌死された．残胃癌による輸入脚閉塞症の本邦論文報告7例について，集計および文献的考察を行った．

Background Anastomotic leakage is a major complication after esophagectomy. Recent studies reported that anastomotic leakage is associated with poor prognosis. We aimed to identify the risk factors of anastomotic leakage after esophagectomy for thoracic esophageal cancer. Methods We analyzed retrospectively consecutive patients who underwent esophagectomy with reconstruction using gastric tube by cervical anastomosis for thoracic esophageal cancer between January 2009 and December 2017. In the reconstruction, end-to side mechanical anastomosis with circular stapler through the posterior mediastinal route was preferred until 2014, and end-to end hand-sewn anastomosis through the retrosternal route was preferred from 2015. As inflammation-based and/or nutritional markers, prognostic nutritional index (PNI), modified Glasgow Prognostic Score (mGPS), Controlling Nutritional Status (CONUT) score, and neutrophil lymphocyte ratio (NLR) were investigated. Receiver operator characteristic curve analyses were performed to set the cut-off value of continuous variables. Risk factors predicting anastomotic leakage were analyzed using logistic regression model. Results A total of 170 patients (144 males and 26 females) were evaluated. Median age was 65 years (59 − 70). Anastomotic leakage was observed in 21 patients (12.3%). A mechanical anastomosis with circular stapler (P = 0.047) and longer operative time (≧560 minutes) (P = 0.015) were identified as risk factors of anastomotic leakage in univariate analysis. Multivariate analysis including variables with P Conclusion Our findings suggested that preoperative lower PNI and mechanical anastomosis were independent risk factors of anastomotic leakage after esophagectomy. Further studies aimed at preoperative nutritional intervention and anastomotic technique are warranted. Disclosure All authors have declared no conflicts of interest.

Background Background Advanced esophageal cancer patients often develop tumor recurrence even after curative resection. Inexpensive and easily available prognostic factors are expected in daily clinical practice. The aim of this study was to identify the prognostic factors in patients with resectable cStage II-IV thoracic esophageal squamous cell carcinoma. Methods Patients and Methods The study included 118 patients who underwent esophagectomy with curative intent for resectable cStage II-IV thoracic ESCC between January 2000 and December 2014. Time-dependent receiver operating characteristic curve analyses for 3-year overall survival (OS) as the endpoint were calculated, and the maximal Youden index was estimated to set the cut-off value for continuous variables. Survival rates were calculated by Kaplan-Meier method, and survival curves were compared using log-rank test. Univariate analysis and multivariate analysis for OS were conducted with Cox proportional hazards models. Results Results The median follow-up period was 33 months (1–160 months). The 5-year OS rate for the entire study population was 52.2%. In univariate analysis, age (70 Conclusion Our findings showed that pretreatment total cholesterol level and ASA are independent prognostic factors of overall survival in patients with resectable cStage II-IV thoracic esophageal squamous cell carcinoma. Disclosure All authors have declared no conflicts of interest.

Background: The density of tumor-infiltrating lymphocytes (TILs) have been reported to reflect antitumor immune response and correlate with prognosis in malignancy. However, the methodology for evaluating the density of TILs by an immunohistochemical analysis differs among reports. The aim of this study was to verify the methodology for evaluating the density of TILs by immunohistochemical analysis and thereby identify the optimum methodology in clinical setting. Methods: Three-hundred-thirteen patients who underwent curative operation for stage II/III colorectal cancer were enrolled. We retrospectively examined the density of TILs using immunohistochemical staining according to each method as follows: 1) subset of lymphocytes (i.e. CD4+/CD8+), 2) selected fields (i.e. at random or focusing on hot spots), 3) location in low-power field (i.e. the invasive margin [TILsIM] or the center of the tumor [TILsCT] or the surface of the tumor [TILsST]), and 4) location in high-power field (i.e. in tumor stroma [sTILs] or intra-tumor cells [iTILs] or total TILs [tTILs: sTILs+iTILs]). We then assessed the prognostic value of the density of TILsIM evaluated as described above. We also evaluated the correlation between the density of TILsIM and that of TILsCT/TILsST. Results: In randomly selected fields, the densities of CD8+sTILsIM and CD8+tTILsIM were significantly associated with the survival. However, the densities of TILs evaluated via other methods were not associated with the survival. Furthermore, the density of CD8+TILsIM was significantly associated with that of CD8+TILsCT and CD8+TILsST. Conclusions: We concluded that best and easiest way to evaluate the density of TILs in the clinical setting may be to assess the density of total CD8+TILs at the invasive margin in randomly selected fields. Citation Format: Shinji Matsutani, Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Tatsuro Tamura, Go Ohira, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Verification of the methodology for evaluating tumor-infiltrating lymphocytes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5701.

[Background] Neutrophils are essential effector cells in the host's defence against invasive pathogens, On the other hand, neutrophils in the tumor-microenvironment are known to have potential to induce angiogenesis, lymphangiogenesis, and be an important factor in tumor progression. We have reported that neutrophils infiltrating in gastric cancer tissue (Tumor-Associated Neutrophil: TAN) correlated with lymph node metastasis, systemic inflammatory response and be a poor prognostic factor. So we hypothesized that neutrophils in gastric cancer tissue suppressed anti-tumor immune response, but their details are still unclear. [Aim] The aim of this study was to investigate the immunosuppressive ability of neutrophils in gastric cancer tissue and to explore the influence of neutrophils on the proliferation of CD4 (+) T cells. [Materials and Methods] We isolated neutrophils from blood samples taken from healthy donors and added tumor tissue culture supernatants (TTCS) purified from human scirrhous gastric cancer cell line (OCUM12) or purified supernatants from patients who underwent gastrectomy at our department. Then, we examined the expression of apoptotic cells, PDL-1, and HLA-DR on neutrophils with TTCS. We also observed the expression of PD-1, CD25 on T cells co-cultured with neutrophils added TTCS. Furthermore, CD4 T cell labeled Carboxyfluorescein diacetate succinimidyl ester (CFSE) were co-cultured with allogenic dendritic cells and neutrophils with TTCS, and the proliferation of CD4 (+) T cells were examined by flow cytometry. We also performed immunohistochemistry (IHC) staining using anti CD15 and anti PD-1 antibodies for 117 patients who underwent gastrectomy in our department from 2007 to 2013 to explore the positional relationship. [Results] Neutrophils with TTCS were upregulated the expression of PDL-1 than those without TTCS. We also found that the apoptotic cell ratio and the expression of HLA-DR on neutrophils with TTCS was decreasing. CD4 (+) T cells co-cultured with neutrophils added TTCS were suppressed their proliferation, and upregulated the expression of PD-1 and downregulated the expression of CD25. IHC showed that PD-1 positive cells formed clusters and TAN was infiltrating around the clusters. And a positive correlation was found between the number of TAN and PD-1 positive cells in the scatter plot. [Conclusion] Our findings suggested that neutrophils in gastric cancer tissue inhibited the proliferation of CD4 T cells and formed a local immunosuppressive environment through the PD1-PDL1 pathway. Citation Format: Soichiro Hiramatsu, Hiroaki Tanaka, Yoshihito Yamakoshi, Junya Nishimura, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Masaichi Ohira. Neutrophils in gastric cancer tissue inhibit the proliferation of CD4+T cells and contribute to immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4747.

[Background]Fibroblast Growth Factor Receptor 2(FGFR2) amplification occuers flequently in undifferentiated gastric cancer(GC), and accounts for 3-10% of primay GC. FGFR2 shows two isoforms, IIIb-type expressed in epithelial cells, and IIIc-type expressed in mesenchymal cells. The aim of this study is evaluating clinicopathological significance of FGFR2-IIIb and IIIc expression on GC cells. [Method]562 patients who had undergone GC surgery were retrospectively examined. Immunohistochemistry of resected specimen was used to investigate the expression of FGFR2-IIIb and IIIc. [Result]FGFR2-IIIb and FGFR2-IIIc were positive in 28 cases (4.9%) and 4 cases (0.7%) of 562 gastric cancers. All of FGFR2-IIIc positive tumors were also positive for FGFR2-IIIb in a same tumor, but both were not positive in same cells. 5-year overall survival rate of FGFR2 positive group is significantly poorer (p=0.0011, log-lank) than that of FGFR2 negative. Moreover, the prognosis of FGFR2-IIIc positive group was significantly poorer (p=0.003, log-lank) than that of FGFR2-IIIb positive group. In univariate analysis, the overall survival was significantly correlated to FGFR2-IIIb positive, FGFR2-IIIc positive, invasion depth, macroscopic type, histological type, lymph node metastasis, peritoneal dissemination, lymphatic invasion, and cytology. In multivariate analysis, FGFR2IIIc was significantly correlated to overall survival (p=0.045) [Conclusion] The expression of FGFR2IIIc and/or FGFR2IIIb was observed in 5% of gastric cancer. FGFR2 amplification is associated with poor overall survival. As a result, treatment targeting FGFR2 amplification has the potential to provide clinical benefit for FGFR2 positive GC. Citation Format: Kenji Kuroda, Masakazu Yashiro, Go Masuda, Yuichiro Miki, Tomohisa Okuno, Shingo Togano, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Clinicopathologic significance of fibroblast growth factor 2 type IIIb and type IIIc in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2510.

Background: Tumor-infiltrating CD8+T cells have been found to be associated with favorable outcome of patients in many cancers including esophageal squamous cell carcinoma (ESCC). Dendritic cells (DCs) are the most potent antigen-presenting cells to induce CD8+T cells. Several investigators have shown that tumor infiltrating mature DCs (mDCs) were associated with favorable prognosis of cancer patients. We showed that mDCs were associated with favorable prognosis of ESCC patients who had not received preoperative treatment. Neoadjuvant chemotherapy (NAC) is the standard treatment for Stage II/ III thoracic esophageal carcinoma in Japan. The effect of chemotherapy on tumor infiltrating DCs remains unclear. Purpose: The aim of this study was to examine the correlation of efficacy of NAC and locally infiltrating DCs in ESCC patients. Object and Methods: Formalin-fixed, paraffin-embedded blocks of primary lesions were collected from 50 patients with ESCC who underwent surgical treatment after NAC at Osaka City University Hospital. Immunohistochemical analysis using anti-LAMP-3 antibody and CD8 antibody was used to evaluate tumor infiltrating DCs and CD8+T cells. The number of LAMP-3+DCs and CD8+T cells were counted at ×400 magnification. We divided the 50 cases into two groups according to the median number of tumor infiltrating DCs and CD8+T cells to examine the correlation of efficacy of NAC and locally infiltrating DCs. Results: LAMP-3+DCs were predominantly observed in peritumoral area and sparsely found in intratumoral area, whereas CD8+T cells distributed between both peritumoral and intratumoral areas. LAMP-3+DCs infiltrated the peritumoral space from 0 to 19.0 (median 6.0) and the intratumoral space from 0 to 3.8 (median 0.0). Patients with histological effect (≧Grade 1a) had higher infiltration of mDCs than Grade 0. Patients with high infiltration of mDCs had better prognosis than those with low. The number of mDCs had positive correlation with the number of tumor infiltrating CD8+T cells. Conclusions: Our results suggested that increase of tumor infiltrating mDCs was associated with histological effect of NAC and favorable prognosis in ESCC. Citation Format: Junya Nishimura, Hiroaki Tanaka, Yoshihito Yamakoshi, Soichiro Hiramatsu, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Impact of tumor-infiltrating dendritic cells in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 65.

Tumor lymphangiogenesis is a major prognostic indicator of gastric cancer. Tumor-induced inflammation has been shown to attract tumor-associated macrophages that affect lymphangiogenesis. However, detailed mechanisms of macrophage-induced lymphangiogenesis have not been elucidated. Here, we evaluated the interaction between tumor-associated macrophages and lymphatic endothelial cells (LECs) derived from lymph nodes (LNs) of human gastric cancer. Lymphatic endothelial cells were directly or indirectly cocultured with macrophages from healthy human blood, with or without the supernatant of the gastric cancer cell line, OCUM-12. We analyzed the effect of cancer pretreated macrophages and of macrophages from metastatic LNs of gastric cancer on LECs. We observed morphological changes of LECs in coculture and assessed the gene expression of possible lymphangiogenic molecules of macrophages and LECs after contact coculture, and of cancer pretreated macrophages, by quantitative RT-PCR. Specimens of metastatic LN of gastric cancer were immunofluorescently stained. We found that tubulogenesis of LECs was observed only in the contact coculture model. OCUM-12 cells promoted macrophage-induced tubulogenesis of LECs. Relative gene expression of MMP and adhesion molecules was significantly upregulated in both capillary-forming LECs and cocultured macrophages. Cancer pretreated macrophages upregulated lymphangiogenic factors including inflammatory cytokines, MMPs, adhesion molecules, and vascular endothelial growth factor-C. Blocking of intercellular adhesion molecule-1 and macrophage activation suppressed tubulogenesis of LECs. Immunohistochemistry showed macrophages localized around lymphatic vessels. Our results suggested that interaction between LECs and macrophages may be an important initial step of tumor lymphangiogenesis developing LN metastasis. Understanding of its mechanisms could be useful for future therapeutics of gastric cancer.

A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors.

A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

It is important in the clinical setting to integrate all of the findings when diagnosing and making treatment decisions. We report a case of particular interest for managing cancer patients. A 69-year-old man underwent endoscopic resection for an Rb rectal tumor. The tumor showed a positive vertical margin and required laparoscopy-assisted super low anterior resection with ileostomy for histopathological stage Ⅰrectal cancer. His postoperative course was uneventful. The follow-up computed tomography (CT) scan revealed a tumor locating close to the left common iliac artery. Although positron emission tomography (PET) showed 18F-fluorodeoxyglucose (FDG) accumulation in the tumor, none of the other clinical findings indicated a recurrence of rectal cancer. FDG is not specific to malignant neoplasias, but the location of the tumor and the FDG uptake suggested the possibility of malignancy. No other tests found any evidence of a recurrence. Tumor resection was performed concurrently with ileostomy closure. Histopathology demonstrated it was an asymptomatic abscess in a lymph node. Tumor recurrence and metastases have to be kept in mind even if the primary lesion is in an early stage. This case shows the difficulty in deciding how to manage patients when clinical results are not consistent, especially in cases needing surgical procedures.

This study evaluated the clinicopathological significance of autophagy, an intracellular degradation system, in gastric cancer.The expression levels of three autophagy-related proteins, namely light chain 3 (LC3), Beclin 1 and p62, were analyzed by immunohistochemistry using samples from 510 patients with primary gastric cancer.LC3, Beclin 1, and p62 expression was positive in 79 (15.5%), 126 (24.7%) and 251 (49.2%) out of 510 carcinomas, respectively. Autophagy was defined when samples were positive for at least two out of the three proteins. Autophagy-positive cases were 113 (22.1%) out of the 510. Autophagy determined by LC3, Beclin 1, and p62 significantly correlated with lymph node metastasis, vessel invasion, and hepatic metastasis. A Kaplan-Meier survival curve showed that autophagy was significantly associated with poor survival of patients with gastric cancer, especially for those with disease at stage I. Multivariate analysis indicated that autophagy was an independent prognostic factor.Autophagy promotes the progression of gastric cancer at an early clinical stage.

The cell surface receptor programmed death-1 (PD1) and its ligand (PDL1) have been detected in various cancer types. It has been reported that expression of PDL1 and PD1 in a tumor is associated with poor prognosis of the patient. In the present study, we retrospectively examined tumor expression of PDL1 and intratumoral PD1(+) cell infiltration, and assessed their relationship with patient prognosis according to the pathological stage of gastric cancer.PDL1 and PD1 expression in primary tumors from 431 patients was evaluated using immunohistochemistry. The association between the expression of PDL1/PD1 and clinicopathological features was assessed.High expression of PDL1 was observed in 128 (29.6%) patients. PDL1 expression was correlated with tumor infiltration of PD1(+) cells. In multivariate analysis, PDL1 expression was associated with worse overall survival. In subset analysis, PDL1 expression was significantly associated with survival in patients with stage II/III gastric cancer. In conclusion, PDL1 was an independent prognostic factor for patients with stage II/III gastric cancer. Our results suggested that patients with stage II/III gastric cancer might be appropriate for PD1/PDL1-targeted therapy.

We report a case of long-term survival with complete remission after hepatic arterial infusion chemotherapy (HAIC) for liver metastasis from gastric cancer. A 62-year-old man underwent radical distal gastrectomy with D2 lymphadenectomy for an advanced gastric cancer. Solitary liver metastasis in the S2/3 segment was detected 26 months after initial surgery. The patient underwent HAIC with systemic chemotherapy. Serum CEA levels rapidly decreased, and CT scan showed disappearance of the tumor with complete clinical response 8 months after HAIC. HAIC was performed 83 times in total, until the hepatic artery proper was adequately obstructed. No severe adverse effects were observed during HAIC treatment. The patient is still disease-free without further chemotherapy more than 12 years after HAIC. Our experience suggests that HAIC should be considered as a treatment option in patients with resectable liver metastasis from gastric cancer. However, further studies are needed to verify the validity of HAIC for resectable liver metastasis from gastric cancer.

Markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP) level and Glasgow prognostic score (GPS), have been reported to be useful prognostic indicators for various types of cancers. However, most of the existing reports investigated the preoperative status, and the significance of markers of systemic inflammation remains unclear in patients with unresectable metastatic colorectal cancer. The aim of the present retrospective study was to evaluate the significance of markers of systemic inflammation for predicting the prognosis and chemotherapeutic outcomes and monitoring the progression of the tumor in patients with unresectable metastatic colorectal cancer receiving palliative chemotherapy.A total of 110 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled in the study. We evaluated the relationships between the survival/chemotherapeutic response and pre-/post-treatment markers of systemic inflammation. The pre-treatment markers of systemic inflammation were measured within one week before the initiation of chemotherapy and the post-treatment markers of systemic inflammation were measured eight weeks after initiation of chemotherapy.The overall survival rates were significantly worse in the group with high pre-treatment NLR/CRP/GPS, and that with high post-treatment CRP/GPS; the progression-free survival rate was significantly worse in the high post-treatment CRP group. As for chemotherapeutic response, patients with a low post-treatment CRP level had a significantly higher disease control rate than those with a high post-treatment CRP level. Moreover, the patients with a high pre-treatment CRP level and normalization after treatment exhibited better overall and progression-free survival rates and had a significantly higher disease control rate than those with high pre- and post-treatment CRP levels.Pre-treatment markers of systemic inflammation are useful for predicting prognosis in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. Moreover, the CRP level can be used as a marker for predicting chemotherapeutic outcome and monitoring the progression of the tumor.

Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented.This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP10 mg/l or albumin35 g/l, or CRP10 mg/l and albumin35 g/l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses.Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p0.01). On multivariate analysis, good response to CRT [hazard ratio (HR) =0.449, p0.01], GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, p0.01) were significant prognostic factors, whereas PNI was not.The GPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy.

The prognosis of patients with locally advanced esophageal squamous cell carcinoma (LAESC) is extremely poor. The impact of adverse effects of chemoradiotherapy (CRT), particularly myelosuppression, on postoperative long-term results has remained unclear.A total of 44 patients with LAESC who underwent CRT followed by esophagectomy were enrolled. We compared long-term survival by various clinical variables, including myelosuppression (Grade 3 and 4 leukopenia) due to CRT, response to CRT, performance status, postoperative complications, and pathological nodal status. Finally, multivariate analysis of prognostic factors was assessed by the Cox proportional hazards model.The mean age of patients was 62.8 years and the male/female ratio was 32/9. The response rate to CRT was 75% (33/44), which included five cases with complete response and 28 cases with partial response. Grade 3 and 4 leukopenia was 43% (19/44). Mortality and postoperative pneumonia occurred in 3 (7.3%) and 14 cases (31.8%), respectively. Multivariate analysis demonstrated that myelosuppression was a significant negative prognostic factor in overall survival (OS) [hazard ratio (HR)=4.758, p=0.005]. The 5-year OS rate was significantly poorer in the group with myelosuppression than in the group without (15.4% vs. 69.0%, p=0.003). Discontinuation of the preoperative CRT schedule and dose reduction of chemotherapeutic agents was significantly more frequent in the group with myelosuppression than in the group without (p=0.003), and peripheral lymphocyte counts after surgery was significantly lower, which may explain poor prognosis in the group with myelosuppression.Pre-operative CRT-induced myelosuppression has a negative impact on the prognosis of patients with LAESC. Our findings indicate that a careful postoperative follow-up is required for patients who develop myelosuppression after neoadjuvant CRT followed by curative resection for locally advanced esophageal cancer.

The present study aimed to examine the survival benefit of adjuvant chemotherapy for the patients with stage IB gastric cancer according to the second English edition of the Japanese Classification of Gastric Carcinoma (2nd JCGC).In total, 201 consecutive patients who underwent curative surgery for stage IB gastric cancer according to the 2nd JCGC were retrospectively analyzed.Seventy-four (36.8%) received adjuvant chemotherapy, and 72 (35.8%) had stage II diseases as defined by the 3rd JCGC. The 5-year overall survival (OS) was 86.9%. Multivariate analysis showed that adjuvant chemotherapy was an independent prognostic factor. In the sub-group analysis by stage according to the 3rd JCGC, those with stage II disease had better OS in the adjuvant-chemotherapy group than in the group treated with surgery alone (5-year OS 94.5% vs. 73.9%, p=0.002).Among patients with stage IB gastric cancer by 2nd JCGC, and especially patients with stage II defined by the 3rd JCGC, should be considered for adjuvant-chemotherapy.

Studies of tumor-infiltrating immune cells have revealed that immune escape plays an important role in tumor growth. The aim of the present study was to investigate the impact of metastasis affecting CD4+ T cell subsets in human clinical samples. Single-cell suspensions derived from tumor-draining lymph node (TDLN) and primary cancer specimens were assessed by flow cytometry, qRT-PCR and immunohistochemistry. In the CD4+ T cell subsets detected in TDLN, effector T cells (TE) in metastatic TDLN (mTDLN) was significantly lower than that in metastatic-free TDLN (mfTDLN). TE in mfTDLN were increased compared with normal controls. Similarly, effector memory T cells (TEM) in mTDLN was significantly lower than in control and mfTDLN. There was a significantly positive correlation between the proportion of TEM in TDLN and number of tumor-infiltrating CD4+ and CD8+ T cells. Th1 to Th2 ratio was lower in mTDLN, and Treg in mTDLN was significantly higher than in mfTDLN. CD4+ T cell and TE subsets in TDLN were significantly affected by metastasis. Immunosuppressive cells exhibit increased migration to TDLN, in which a subset of CD4+ TE is skewed towards immune tolerance in the tumor microenvironment.

症例は26歳の男性. 18歳時より高血圧を指摘され, 2年前より降圧剤を内服していた.近医で両側の副腎腫瘤を指摘され,精査加療目的で当院を紹介され入院となった.両側副腎に約4cm大の腫瘤を認め,血中ノルアドレナリン,尿中ノルアドレナリン,ノルメタネフリン, VMAが高値を示し, 113I-MIBGシンチで両側副腎に一致した集積が認められたことから,両側副腎褐色細胞腫と診断した.機能温存を目的として腹腔鏡下両側副腎部分切除術を施行した.術後7日目に軽快退院し,副腎皮質ステロイド剤の内服を漸減している.近年,副腎褐色細胞腫に対しても腹腔鏡下手術が安全に施行できるようになってきた.しかし,両側副腎褐色細胞腫に対して一期的に施行された報告は少ない.副腎機能を温存すべく,鏡視下手術の利点を生かした両側副腎の部分切除術を施行し,良好な経過を得たので,若干の文献的考察を加えて報告する.

症例は71歳の女性.めまいを主訴に当院受診.貧血があり,上腹部中心に圧痛・反跳痛を認めた.腹部CTにて胃壁に連続して約10cm大の充実性腫瘤および腹腔内出血を認めたため緊急開腹術施行.開腹時約1,200mlの腹腔内出血を認め,胃体上部後壁に亜有茎性の腫瘤が存在した.胃壁部分切除を含めて腫瘍摘出術を行った.腫瘍は被膜に覆われて内部に凝血が認められ,被膜の一部が破綻して腹腔内出血したと考えられた.病理組織所見では密集した紡錘型細胞からなり核分裂像はほとんど認めず,免疫組織染色ではc-kit(+), α-SMAは一部のみ(+)でごく一部筋組織への分化を示すgastrointestinal stromal tumor (GIST)であった. GISTに関する報告は近年多くみられるが腹腔内出血で発症したGIST症例は少なく自験例を含めて7例であった.今後とも症例蓄積が重要と考え報告する.

症例は59歳,男性.既往歴に右鼠径ヘルニアがあるが放置されていた. 2002年8月23日右下腹部痛を主訴に当院を受診した.右下腹部に強い圧痛,腹膜刺激症状を認め,腹部CT検査において右側腹部～下腹部に網状・スポンジケーキ様の腫瘤影を認めた.急性虫垂炎の術前診断で,同日手術を施行した.腹腔内に淡血性の腹水と捻転によりうっ血,腫大し,暗赤色を呈した大網を認めたので,捻転した大網を切除した.術後経過は良好で術後14日目に退院した.大網捻転症は比較的稀な疾患で,器質性疾患の有無で特発性と続発性に分類され,自験例は右鼠径ヘルニアに続発した大網捻転症と診断される.近年,大網捻転症の報告が増えているが,続発性について詳細に検討された報告はほとんどない.続発性大網捻転症の本邦報告58例につき集計・検討し,考察を加えた.

症例は50歳の女性. 心窩部痛を主訴に来院し, 腹部単純X線写真上, 仰臥位では右上腹部に胆嚢およびその左側で総胆管の走行に一致した淡い石灰化様陰影を認め, 立位ではこの胆嚢様の石灰化様陰影は下に凸の半月様に変形を示した. CT, DICなどにより総胆管結石, 胆嚢結石, 石灰乳胆汁と診断し手術を施行した. 胆嚢の病理所見は慢性胆嚢炎で, 総胆管結石はコレステロール79%, 炭酸カルシウム21%で胆嚢内の石灰乳胆汁は98%以上が炭酸カルシウムであった.石灰乳胆汁は炭酸カルシウムを主成分とし, 腹部単純X線写真上, 特徴的な石灰化像を示すことで知られる. その生成には胆嚢管または頸部の閉塞が必要で, 通常は胆嚢内にしかみられないが, ごくまれに総胆管内にもみられる. 自験例は嵌頓結石とともに総胆管へ石灰乳胆汁が流出したと思われる症例で, 本邦報告21例を検討し報告する.

62 Background: Conversion surgery after chemotherapy responds to unresectable gastric cancer has long-term prognosis, however, chemotherapy after surgery should also be considered to improve treatment outcome. The effectiveness of immune checkpoint inhibitors for gastric cancer has been proved. In this study, we investigated the association between PDL-1 expression and CD8+ T cell infiltration in the primary tumor and prognosis of patients who underwent conversion surgery after S-1-based multidrug chemotherapy in unresectable gastric cancer. Methods: We evaluated PDL-1 expression and CD8 T cell infiltration by immunohistochemical staining and examined the relationship with prognosis in 90 patients with Stage IV gastric cancer who underwent gastrectomy in our department from 2007 to 2015. Results: 90 cases included 47 cases of palliative resection, 26 cases of CY1P 0cases and 17 cases of conversion surgery. Among Conversion Surgery cases, 11 (65%) patients underwent R0 surgery, and the 5-year survival rate was 66%. The 5-year survival rate of non-curative resected cases was 16%. In immunohistochemical examination, PDL-1 high expression was a poor prognostic factor in palliative surgery and CY1P0 cases. Meanwhile, in the case of Conversion Surgery, the 5-year survival rate was 58%, 32%, 61%, and 30% in the order of PDL-1 high expression group, low expression group, CD8 T cell high infiltration, and low infiltration group, respectively. Prognosis of PDL-1 high expression group and CD8 T cell infiltration group was good. There was no association between curative resection and neither of CD8 T cell infiltration or PDL-1 expression. Conclusions: We found that the prognosis was relatively good in patients where local immune response was enhanced, regardless of R0 excision. Our results suggested that infiltration of CD8 T cells in the primary tumor may be a prognostic predictor, and it is expected to use an immune check point inhibitor after conversion surgery for unresectable gastric cancer.

We report on a 30-year-old man with familial adenomatous polyposis (FAP ) who developed advanced sigmoid colon cancer with desmoid tumors. The patient initially presented with melena. FAP advanced sigmoid colon cancer was diagnosed following a laparoscopy-assisted proctocolectomy in 2007. A computed tomography (CT) scan, conducted 7 months later, revealed a tumor around the branch of the common iliac artery. We diagnosed sigmoid colon cancer recurrence and attempted treatment by surgical removal. However, there were many smooth tumors within the patient's abdomen, which were diagnosed as desmoid tumors using rapid intraoperative pathological diagnosis. Although the patient was administered a COX-2 inhibitor and tamoxifen after surgery, the tumor grew. Dacarbazine (DTIC) and doxorubicin (DOX) were subsequently administered to the patient, and after 4 courses, the tumor was reduced by 60% and stable disease (SD) was achieved. In 2009, a CT scan indicated sigmoid colon cancer recurrence in the liver. The patient underwent a left hepatic lobectomy by laparoscopy-assisted surgery. To date, 4 years and 6 months after surgery, we have been unable to find new disease or desmoid tumor growth.

There are only a few reports in the literature about the effect of recombinant human soluble thrombomodulin (rTM) in patients with solid carcinoma with disseminated intravascular coagulation (DIC). A retrospective study of 40 patients with solid carcinoma with DIC was performed between February 2009 and April 2013. The withdrawal rate was 32.5% (13/40 patients), and the 28-day survival rate was 40.0% (16/40 patients). Patients with successful withdrawal of DIC had significantly better outcomes (p.001). Therapy with rTM is one of the treatment options for patients with solid carcinoma with DIC.

Small cell carcinoma of the esophagus is reported to be both rare and aggressive, and is commonly associated with a short post-diagnosis survival period. We report a case of Stage IV small cell carcinoma of the esophagus involving a relatively long survival period of 2 years. The patient was a 70-year-old man with a chief complaint of epigastric discomfort. Upper gastrointestinal endoscopy by a local physician showed a protruding tumor at the mid-thoracic esophagus. Tumor biopsy revealed small cell carcinoma. Chest-abdominal computed tomography revealed multiple liver metastases, and swelling of a number of regional lymph nodes. The diagnosis was cT3N4M1, cStage IVb esophageal small cell carcinoma. According to the regimen used for lung small cell carcinoma, we administered CDDP/CPT-11. After administration of four courses, the primary lesion, liver metastases, and lymph node metastases significantly reduced, indicating a partial response. However, after completion of eight courses, liver metastasis and lymph node swelling recurred. The patient subsequently received other therapeutic regimens such as CBDCA/VP-16, AMR, NGT, and CDGP/5-FU. However, the tumor gradually progressed, and the patient died approximately 2 years after the first treatment.

A 64-year-old man underwent sigmoidectomy for sigmoid colon cancer 9 years ago. We attempted to discontinue surveillance, as the postoperative course was event free for 5 years; however, we continued the follow-up on the patient's request. Nine years after the operation, elevation of the serum carcinoembryonic antigen (CEA) level was detected, and positron emission tomography-computed tomography (PET-CT) showed a 35-mm mass with an abnormal signal (SUVmax 18.6 Bq/ mL). We performed an abdominal CT and magnetic resonance imaging and found the mass invading the sigmoid colon. We suspected lymph node recurrence of the sigmoid colon cancer and considered curative surgery to be appropriate as there were no other signs of recurrence. We therefore excised the tumor by sigmoidectomy. A histopathological examination revealed metastatic adenocarcinoma in the lymph node. One year after the second operation, there was no evidence of recurrence on imaging and the levels of tumor markers were within the normal limits. Few reports have documented recurrence over 5 years after surgery. We herein describe our case and report the characteristics of a recurrent lesion and also suggest a protocol for surveillance, taking into consideration the previous literature.

To present a series of seven cases of gastric small cell carcinoma (GSCC) treated surgically and to illustrate the clinicopathological features and clinical course.Among 1,832 patients with gastric cancer who underwent gastric resection between 1997 and 2012, we reviewed the clinical records of 7 patients with histopathological diagnoses of GSCC.No patients had preoperative confirmation of GSCC from endoscopic biopsy. Curative resection (R0) was achieved in 5 patients (71.4%). Two out of the 5 patients with curative resection survived more than four years. Two out of 3 patients who received weekly paclitaxel had progression-free survival of more than 10 months. The median survival time for the whole patient group was 14 months and the 3-year survival rate was 25.0%.Curative surgery with adjuvant chemotherapy may be essential to improve the prognosis of GSCC, and weekly paclitaxel chemotherapy may represent a promising chemotherapy for GSCC.

Study Background: In the International Consensus Guidelines 2012 for intraductal papillary mucinous neoplasm (IPMN), 'high-risk stigmata' (HRS) were described as indications for resection. The purpose of this study was to evaluate the prognostic meaning of HRS in the 2012 guidelines. Method: Clinical and pathological data from 98 patients who underwent pancreatic resection for IPMN at our institution between 1994 and 2014 were retrospectively analyzed. Results: The 98 resected IPMNs were categorized as demonstrating no criteria (NC) (n=18), worrisome features (WF) (n=39), or HRS (n=46) according to the guidelines. By multivariate analysis, positive lymph node metastasis and HRS were significantly identified as independent prognostic factors. Five-year disease-specific survival rates for NC and WF were both 100%, whereas that for HRS was significantly poorer at 49.5% (p

Objectives: Diaphragmatic herniation (DH) after transthoracic esophagectomy for esophageal cancer is a rare postoperative complication. This complication sometimes occurs suddenly and leads to a severe post-operative course. However, the incidence of and risk factors for DH are not fully documented. Methods: In our institute, 340 patients with resectable esophageal cancer underwent right-sided transthoracic esophagectomy accompanied by laparoscopic or open gastric mobilization between April 2000 and January 2014. We retrospectively investigated the incidence of DH after surgery and risk factors for DH. Results: During this period, a total of 10 cases (2.9%, 10/340) of DH occurred. In all cases, DH originated from the hiatus and extended to the left thorax. Time interval from initial surgery to surgery for DH widely varied (1 day- 57 months). Eight patients presented with sudden abdominal pain, while two patients had asymptomatic. DH was diagnosed using chest X-ray and/or CT scan in all cases. The hernial contents consisted of transverse colon in 4 cases, both transverse colon and small intestine in 4 cases. An incision of the left pleura around the esophageal hiatus and the direct route between left thorax and abdominal cavity were observed in all cases. Univariate analysis revealed that the laparoscopic approach of the abdominal cavity at the initial surgery were significant risk factors for DH. Conclusion: DH after transthoracic esophagectomy is relatively a rare but certain incidence of complication. Intraoperative prevention and careful postoperative attention might be required for DH after laparoscopic esophageal surgery.