AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetu...AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.展开更多
BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal neoplasm that can arise in many different organs with a broad spectrum of biological behavior,from indolent to aggressive progression.Only te...BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal neoplasm that can arise in many different organs with a broad spectrum of biological behavior,from indolent to aggressive progression.Only ten cases of gastric PEComas have been reported in the English literature,which were treated with endoscopic,laparoscopic,or open resections.Due to its rarity,the optimal surgical management and prognosis of this tumor are still uncertain.CASE SUMMARY We present a case of robotic wedge resection of a 6.5 cm bleeding lesion of the gastric fundus located 3 cm below the esophago-gastric junction in a 55-year-old man.Biopsy revealed a malignant tumor with epithelioid cells focally positive for muscle markers desmin and smooth muscle actin.In addition,histology revealed that the tumor was positive for HMB-45,melan-A(MART-1),microphthalmia transcription factor and negative for pan-cytokeratin AE1/AE3,CD34,p40,DOG-1,CD117(c-kit),S100,CD3,CD79a,caldesmon and myogenin.These markers suggested the possibility of a PEComa.The patient underwent a diagnostic laparoscopy via the da Vinci■Si^TM system and robotic wedge resection.Final pathology confirmed a malignant gastric PEComa with negative margins.At his 11-mo follow-up visit,the patient remained disease-free.CONCLUSION Gastric PEComa can be treated with a robotic R0 resection with acceptable postoperative and short-term oncological outcomes.展开更多
基金the Fondazione Veronesi that granted Daniela Vivenza and Martino Monteverde with PostDoctoral Fellowship Veronesithe Fondazione Cassa Risparmio of Cuneo for partially supporting the study
文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.
文摘BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal neoplasm that can arise in many different organs with a broad spectrum of biological behavior,from indolent to aggressive progression.Only ten cases of gastric PEComas have been reported in the English literature,which were treated with endoscopic,laparoscopic,or open resections.Due to its rarity,the optimal surgical management and prognosis of this tumor are still uncertain.CASE SUMMARY We present a case of robotic wedge resection of a 6.5 cm bleeding lesion of the gastric fundus located 3 cm below the esophago-gastric junction in a 55-year-old man.Biopsy revealed a malignant tumor with epithelioid cells focally positive for muscle markers desmin and smooth muscle actin.In addition,histology revealed that the tumor was positive for HMB-45,melan-A(MART-1),microphthalmia transcription factor and negative for pan-cytokeratin AE1/AE3,CD34,p40,DOG-1,CD117(c-kit),S100,CD3,CD79a,caldesmon and myogenin.These markers suggested the possibility of a PEComa.The patient underwent a diagnostic laparoscopy via the da Vinci■Si^TM system and robotic wedge resection.Final pathology confirmed a malignant gastric PEComa with negative margins.At his 11-mo follow-up visit,the patient remained disease-free.CONCLUSION Gastric PEComa can be treated with a robotic R0 resection with acceptable postoperative and short-term oncological outcomes.