AIM To provide more information and therapeutic methods about gastric neuroendocrine carcinomas(G-NECs) which occur rarely but are highly malignant and clinically challenging.METHODS We retrospectively analyzed the cl...AIM To provide more information and therapeutic methods about gastric neuroendocrine carcinomas(G-NECs) which occur rarely but are highly malignant and clinically challenging.METHODS We retrospectively analyzed the clinicopathological characteristics, treatments, and prognosis of 43 G-NEC patients at our hospital between January 2007 and December 2014. The diagnosis was based on the 2010 World Health Organization criteria.RESULTS Forty-three G-NECs containing 39 small cell carcinomas and 4 large cell NECs with Ki67 > 60% were included in this study, accounting for only 0.95% of all gastric carcinomas. The median patient age was 62 years (range, 33-82) and the male-to-female ratio was 4.4:1. All patients underwent surgery, including 38 curative resections and 5 palliative resections. Among these 43 patients, nearly half(48.84%) of these tumors were located in the cardiac region of the stomach, regional lymph node metastasis was found in 31 cases(72.09%), and liver metastasis was found in 6 cases(13.95%). Follow-up information was got for 40 patients. Twentythree die of this disease with a median survival of 31 mo(range 1-90). The 1-year, 2-year, 3-year, and 5-year survival rate was 77.50%, 57.04%, 44.51%, and 35.05%, respectively. Survival was better in patients with tumor located in the cardiac region of the stomach, less than 7 lymph nodes metastasis and no liver metastasis. Five patients did not undergo postoperative chemotherapy, and the median survival time for these patients was 15 mo. For the remaining 34 patients who received postoperative chemotherapy, the median survival time was 44 mo and those received etoposide, cisplatin, and Paclitaxel survived the best. One patient with resected liver metastasis who received postoperative Capecitabine plus Oxaliplatin and Paclitaxel systemic chemotherapy plus octreotide LAR(30 mg intramuscularly, every 4 wk, for 2 years) has survived for 74 mo with no recurrence.CONCLUSION G-NECs are mostly nonfunctioning, which lead to a delay in detection. Local and/or distant me展开更多
BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, t...BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.展开更多
背景与目的:胃神经内分泌肿瘤(neuroendocrine neoplasm,NEN)是胃恶性肿瘤中一种较为罕见的类别,根据2019年世界卫生组织(World Health Organization,WHO)消化系统NEN的分类标准,分为分化好的神经内分泌瘤(neuroendocrine tumor,NET)和...背景与目的:胃神经内分泌肿瘤(neuroendocrine neoplasm,NEN)是胃恶性肿瘤中一种较为罕见的类别,根据2019年世界卫生组织(World Health Organization,WHO)消化系统NEN的分类标准,分为分化好的神经内分泌瘤(neuroendocrine tumor,NET)和分化差的神经内分泌癌(neuroendocrine carcinoma,NEC)。目前,关于胃NEC(gastric NEC,GNEC)辅助化疗预后的研究匮乏,本研究旨在探讨辅助化疗能否使GNEC患者获益,以期为临床决策提供参考依据。方法:回顾性分析中山大学肿瘤防治中心、中山大学附属第一医院和复旦大学附属肿瘤医院2008年7月—2019年6月收治的184例GNEC患者的临床病理学资料,随访截至2022年5月31日。利用Kaplan-Meier法绘制生存曲线,根据单因素COX回归分析和多因素COX回归分析筛选出影响GNEC患者生存的独立预后因素,并进一步分析化疗、手术等因素对患者预后的影响。检验水准为α=0.05,所有统计学分析均使用SPSS 25.0软件。结果:单因素分析显示,手术(P<0.001)、化疗(P<0.001)、综合治疗模式(P<0.001)、N分期(P=0.029)、M分期(P<0.001)及TNM综合分期(P<0.001)是影响GNEC患者预后的变量。多因素COX回归分析显示,手术(P<0.001)、化疗(P<0.001)及M分期(P<0.001)是影响GNEC患者生存的独立预后因素。在所有患者中,TNMⅠ、Ⅱ、Ⅲ和Ⅳ期的3年累积生存率分别为51.9%、55.8%、40.7%和23.6%。在行根治性切除的患者中,辅助化疗可以改善GNEC患者的预后,辅助化疗和非辅助化疗的3年累积生存率分别为58.8%和33.3%(P=0.008)。分层分析结果显示,辅助化疗能够改善TNMⅡ(P=0.018)和Ⅲ期(P=0.023)患者的预后。此外,NEC化疗方案[依托泊苷+顺铂(etoposide plus cisplatin,EP)、伊立替康+顺铂(irinotecan plus cisplatin,IP)]与胃腺癌方案[奥沙利铂+卡培他滨(oxaliplatin plus capecitabine,XELOX)、奥沙利铂+替吉奥(oxaliplatin plus tegafur,SOX)、奥沙利铂+5-氟尿嘧啶(oxaliplatin plus 5-fluorouracil,F展开更多
A gastric biopsy specimen from a 14-year-old Yorkshire terrier was analysed using light microscopy, immunohistochemistry and transmission electron microscopy. The biopsies were obtained from a 3 × 3 × 4 cm m...A gastric biopsy specimen from a 14-year-old Yorkshire terrier was analysed using light microscopy, immunohistochemistry and transmission electron microscopy. The biopsies were obtained from a 3 × 3 × 4 cm mass located at the gastric cardia. Light microscopy revealed solid nests and sheets of tumour cells separated by abundant fibrovascular stroma in all gastric layers. The tumour cells were monomorphic, with eosinophilic cytoplasm and demonstrated palisading at the periphery. Nuclei were round to oval with densely packed chromatin and inconspicuous nucleoli. The tumour cells immunohistochemically stained strongly positive for chromogranin A, synaptophysin, and pan-cytokeratin. Electron microscopy revealed electron dense neurosecretory granules of 100 - 150 nm in diameter. Metastases were found in regional lymph nodes. Gastric neuroendocrine carcinoma was diagnosed, according to the histological, immunohistochemical and electron microscopic features.展开更多
基金Supported by Chinese Society of Clinical Oncology,No.Y-N2013-014
文摘AIM To provide more information and therapeutic methods about gastric neuroendocrine carcinomas(G-NECs) which occur rarely but are highly malignant and clinically challenging.METHODS We retrospectively analyzed the clinicopathological characteristics, treatments, and prognosis of 43 G-NEC patients at our hospital between January 2007 and December 2014. The diagnosis was based on the 2010 World Health Organization criteria.RESULTS Forty-three G-NECs containing 39 small cell carcinomas and 4 large cell NECs with Ki67 > 60% were included in this study, accounting for only 0.95% of all gastric carcinomas. The median patient age was 62 years (range, 33-82) and the male-to-female ratio was 4.4:1. All patients underwent surgery, including 38 curative resections and 5 palliative resections. Among these 43 patients, nearly half(48.84%) of these tumors were located in the cardiac region of the stomach, regional lymph node metastasis was found in 31 cases(72.09%), and liver metastasis was found in 6 cases(13.95%). Follow-up information was got for 40 patients. Twentythree die of this disease with a median survival of 31 mo(range 1-90). The 1-year, 2-year, 3-year, and 5-year survival rate was 77.50%, 57.04%, 44.51%, and 35.05%, respectively. Survival was better in patients with tumor located in the cardiac region of the stomach, less than 7 lymph nodes metastasis and no liver metastasis. Five patients did not undergo postoperative chemotherapy, and the median survival time for these patients was 15 mo. For the remaining 34 patients who received postoperative chemotherapy, the median survival time was 44 mo and those received etoposide, cisplatin, and Paclitaxel survived the best. One patient with resected liver metastasis who received postoperative Capecitabine plus Oxaliplatin and Paclitaxel systemic chemotherapy plus octreotide LAR(30 mg intramuscularly, every 4 wk, for 2 years) has survived for 74 mo with no recurrence.CONCLUSION G-NECs are mostly nonfunctioning, which lead to a delay in detection. Local and/or distant me
基金Supported by Municipal Commission of Health and Family Planning of Shanghai,China(No.20174Y0243 to Liu DJ,No.20154Y0163 to Chen XJ)Cultivating Funds of Renji Hospital,School of Medicine,Shanghai Jiao Tong University,China(No.PYXJS 16-002 to Liu W)
文摘BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.
文摘背景与目的:胃神经内分泌肿瘤(neuroendocrine neoplasm,NEN)是胃恶性肿瘤中一种较为罕见的类别,根据2019年世界卫生组织(World Health Organization,WHO)消化系统NEN的分类标准,分为分化好的神经内分泌瘤(neuroendocrine tumor,NET)和分化差的神经内分泌癌(neuroendocrine carcinoma,NEC)。目前,关于胃NEC(gastric NEC,GNEC)辅助化疗预后的研究匮乏,本研究旨在探讨辅助化疗能否使GNEC患者获益,以期为临床决策提供参考依据。方法:回顾性分析中山大学肿瘤防治中心、中山大学附属第一医院和复旦大学附属肿瘤医院2008年7月—2019年6月收治的184例GNEC患者的临床病理学资料,随访截至2022年5月31日。利用Kaplan-Meier法绘制生存曲线,根据单因素COX回归分析和多因素COX回归分析筛选出影响GNEC患者生存的独立预后因素,并进一步分析化疗、手术等因素对患者预后的影响。检验水准为α=0.05,所有统计学分析均使用SPSS 25.0软件。结果:单因素分析显示,手术(P<0.001)、化疗(P<0.001)、综合治疗模式(P<0.001)、N分期(P=0.029)、M分期(P<0.001)及TNM综合分期(P<0.001)是影响GNEC患者预后的变量。多因素COX回归分析显示,手术(P<0.001)、化疗(P<0.001)及M分期(P<0.001)是影响GNEC患者生存的独立预后因素。在所有患者中,TNMⅠ、Ⅱ、Ⅲ和Ⅳ期的3年累积生存率分别为51.9%、55.8%、40.7%和23.6%。在行根治性切除的患者中,辅助化疗可以改善GNEC患者的预后,辅助化疗和非辅助化疗的3年累积生存率分别为58.8%和33.3%(P=0.008)。分层分析结果显示,辅助化疗能够改善TNMⅡ(P=0.018)和Ⅲ期(P=0.023)患者的预后。此外,NEC化疗方案[依托泊苷+顺铂(etoposide plus cisplatin,EP)、伊立替康+顺铂(irinotecan plus cisplatin,IP)]与胃腺癌方案[奥沙利铂+卡培他滨(oxaliplatin plus capecitabine,XELOX)、奥沙利铂+替吉奥(oxaliplatin plus tegafur,SOX)、奥沙利铂+5-氟尿嘧啶(oxaliplatin plus 5-fluorouracil,F
文摘A gastric biopsy specimen from a 14-year-old Yorkshire terrier was analysed using light microscopy, immunohistochemistry and transmission electron microscopy. The biopsies were obtained from a 3 × 3 × 4 cm mass located at the gastric cardia. Light microscopy revealed solid nests and sheets of tumour cells separated by abundant fibrovascular stroma in all gastric layers. The tumour cells were monomorphic, with eosinophilic cytoplasm and demonstrated palisading at the periphery. Nuclei were round to oval with densely packed chromatin and inconspicuous nucleoli. The tumour cells immunohistochemically stained strongly positive for chromogranin A, synaptophysin, and pan-cytokeratin. Electron microscopy revealed electron dense neurosecretory granules of 100 - 150 nm in diameter. Metastases were found in regional lymph nodes. Gastric neuroendocrine carcinoma was diagnosed, according to the histological, immunohistochemical and electron microscopic features.
