BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal t...BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.展开更多
AIM To provide evidence regarding the postoperative treatment of patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer, for which guidelines have not been established. METHODS Patients who had undergone curative resect...AIM To provide evidence regarding the postoperative treatment of patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer, for which guidelines have not been established. METHODS Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4 b N1-3 M0/Tx N3 b M0 for gastric cancer were retrospectively analyzed; staging was based on the 7 th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis.RESULTS The 5-year overall survival(OS) of the whole group(n = 176) was 16.8%, and the median OS was 25.7 mo(95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate(NPR) ≥ 0.8 were associated with a poor prognosis(P = 0.01 and P = 0.048, respectively). One hundred forty-seven(83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve(6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164(93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS(17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS(18.5% vs 17.4%, P = 0.661). Thirty-nine(22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo(95%CI: 30.6-48.2), significantly longer than the 21.6 mo(95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months(P = 0.001).CONCLUSION Patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them.展开更多
文摘BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.
文摘AIM To provide evidence regarding the postoperative treatment of patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer, for which guidelines have not been established. METHODS Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4 b N1-3 M0/Tx N3 b M0 for gastric cancer were retrospectively analyzed; staging was based on the 7 th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis.RESULTS The 5-year overall survival(OS) of the whole group(n = 176) was 16.8%, and the median OS was 25.7 mo(95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate(NPR) ≥ 0.8 were associated with a poor prognosis(P = 0.01 and P = 0.048, respectively). One hundred forty-seven(83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve(6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164(93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS(17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS(18.5% vs 17.4%, P = 0.661). Thirty-nine(22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo(95%CI: 30.6-48.2), significantly longer than the 21.6 mo(95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months(P = 0.001).CONCLUSION Patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them.
