1.Efficacy analysis of single-agent versus multi-agent adjuvant chemotherapy after radical gastrec-tomy for elderly patients with stage Ⅲ gastric cancer
Zichen WANG ; Yangyang WANG ; Shuchang WANG ; Chaojie WANG ; Enhao ZHAO ; Hui CAO
Chinese Journal of Digestive Surgery 2023;22(10):1212-1218
Objective:To compare the efficacy of single-agent versus multi-agent adjuvant chemotherapy after radical gastrectomy for elderly patients with stage Ⅲ gastric cancer.Methods:The propensity score matching and retrospective cohort study were conducted. The clinicopatholo-gical data of 456 elderly patients with stage Ⅲ gastric cancer who underwent D 2 radical resection in the Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine from January 2016 to December 2020 were collected. There were 343 males and 113 females, aged 71(range, 65?89)years. Of the 456 patients, 274 cases undergoing single-agent adjuvant chemotherapy after surgery were divided into single-agent chemotherapy group, 182 cases undergoing double-agent or triple-agent adjuvant chemotherapy after surgery were divided into multi-agent chemotherapy group. Observa-tion indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) adverse events during chemotherapy; (3) follow-up. Propensity score matching was done by the 1∶1 ratio, with the caliper value of 0.05. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parameter rank sum test. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 456 patients, 306 cases were successfully matched, including 153 cases in the single-agent chemotherapy group and 153 cases in the multi-agent chemotherapy group. The elimination of age, age-adjusted Charlson comorbidity index, pathological TNM staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Adverse events during chemotherapy. In terms of hematological adverse events, 6 cases in the single-agent chemotherapy group and 16 cases in the multi-agent chemotherapy group had neutropenia, showing a significant difference in the neutropenia ( χ2=4.90, P<0.05). In terms of non-hematological adverse events, cases with anorexia and nausea were 77 and 50 for the single-agent chemotherapy group, versus 96 and 69 for the multi-agent chemotherapy group, showing significant differences between the two groups ( χ2=4.80, 4.96, P<0.05). (3)Follow-up. All the 306 patients were followed up for 48(range, 8?61)months. The 5-year overall survival rates of the single-agent chemotherapy group and the multi-agent chemotherapy group were 36.08% and 38.31%, respectively, showing no significant difference between the two groups ( hazard ratio=0.93, 95% confidence interval as 0.70?1.20, P>0.05). Results of further analysis showed that the 5-year overall survival rates were 32.41% and 39.40% for 97 patients of the single-agent chemotherapy group and 97 patients with double-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=1.20, 95% confidence interval as 0.82?1.70, P>0.05). The 5-year overall survival rates were 43.15% and 37.11% for 56 patients of the single-agent chemotherapy group and 56 patients with triple-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=0.81, 95% confidence interval as 0.65?1.00, P>0.05). Conclusions:For adjuvant chemotherapy in elderly patients with stage Ⅲ gastric cancer, there is no significant survival advantage of double-agent or triple-agent chemotherapy over single-agent oral chemotherapy. However, there is a higher incidence of neutropenia, anorexia, ausea.
2.Clinicopathologic features and differential diagnosis of multilocular cystic renal cell carcinoma.
Wei ZHANG ; Yujun LI ; Qing LU ; Jie ZHUANG ; Qiang WANG ; Hui ZHAO ; Wenjuan YU ; Enhao KANG ; Zengwen FENG
Chinese Journal of Pathology 2014;43(11):723-727
OBJECTIVETo investigate the clinicopathological characteristics and the diagnosis of multilocular cystic renal cell carcinoma (MCRCC).
METHODSThe clinicopathological data of 19 MCRCC cases were collected and immunohistochemical staining assays were carried out. Forty-six cases of other cystic kidney lesions within the same period were collected as controls, including extensively cystic clear cell RCC (12 cases), clear cell tubulopapillary renal cell carcinoma (6 cases), tubulocystic carcinoma (2 cases), simple cortical cysts (22 cases), multilocular cystic nephroma (1 cases) and multicystic kidney (3 cases).
RESULTSThe patients included 14 males and 5 females. The ages ranged from 31 to 66 years (median age = 50 years). Most of the MCRCC cases were detected incidentally in physical examination, occasionally accompanied with hematuria, back pain or other symptoms. The follow-up period of 17 patients ranged from 6 to 170 months. All patients were alive without evidence of tumor recurrence or metastasis. Pathological findings showed that macroscopically, tumor size ranges from 1.5 to 7.0 cm in the maximum diameter, generally a entirely of various sized. The cysts contain serous, hemorrhagic or turbid fluid. Solid areas or substantially discernible mural nodules were absent; histologicallly, single layer of cuboidal and flattened epithelial tumor cells were lined in the cysts, described as clear cytoplasm, small nuclear, no nucleoli and low Fuhrman nuclear grade (I or II). Multilayer tumor cells could be observed in a few cysts, with granular cytoplasm and small intracystic papillae formed. The clear tumor cell clusters, similar as cystic lined tumor cells, were seen within pathological fibrous in almost all cases, and significant myofibroblastic proliferation was found in 14 cases. Immunohistochemically, the cysts lined epithelial cells and the clear tumor cell clusters were positive for epithelium markers, including CKpan(19/19), EMA(16/19) and CK7 (15/19); higher percentage of CAIX (17/19) and PAX8(15/19) than control groups, but lower percentage of CD10 (7/19), RCC (6/19) and AMACR(2/19); and all were negative for 34βE12, CD117 and CD68.
CONCLUSIONSMultilocular cysts, clear cells clusters of low Fuhrman grade within fibrous septa and capillary vessel proliferation under epithelium are important features of MCRCC. The united using of CAIX, CK7, CD10 and RCC is helpful for differentiating variable cystic renal tumor. MCRCC usually has an excellent prognosis, nephron sparing surgery is first recommended as a therapeutic strategy.
Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Biomarkers ; Carcinoma, Renal Cell ; metabolism ; pathology ; Cysts ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Kidney Diseases, Cystic ; metabolism ; pathology ; Kidney Neoplasms ; metabolism ; pathology ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Racemases and Epimerases ; metabolism
3.2-hydroxybenzylamine(2-HOBA)curbs the pathogenesis of aging-associated atherosclerosis
Enhao WANG ; Pengcheng LUO ; Yu LIU ; Cuntai ZHANG
Chinese Journal of Geriatrics 2023;42(6):720-725
Objective:To explore the effects of different concentrations of 2-hydroxybenzylamine(2-HOBA)on atherosclerosis and vascular smooth muscle cell senescence and the underlying mechanisms.Methods:Fourteen apolipoprotein E-deficient(ApoE-/-)mice were used to establish an atherosclerosis model and were divided into two groups(n=7)using the random number method: a high-fat diet(HD)group and a high-fat diet plus 2-HOBA(1 mg/ml)(HD+ HOBA)group.Pulse wave velocity was used to assess vascular stiffness and a treadmill was used to assess exercise endurance.Oil Red O staining was used to detect the size and number of atherosclerotic plaques.Masson staining was used to detect the morphology of collagen fibers and elastic fibers in the plaque, the size of the necrotic core area of the plaque, and the thickness of the fibrous cap.Mouse smooth muscle cells were treated with different concentrations of 2-HOBA(100 μmol/L, 250 μmol/L and 500 μmol/L)to establish an H 2O 2-induced senescence model.Senescence-associated β-galactosidase staining was used to detect cell senescence.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of senescence-related secretory phenotype factors, and Western blot was used to detect the expression levels of senescence-related signaling proteins. Results:Compared with the HD group, the HD+ HOBA group showed that the area and number of aortic atherosclerotic plaques were decreased, and the atherosclerotic plaques were stabilized.In addition, compared with the HD group, vascular stiffness in the HD+ 2-HOBA group decreased by 26%(2.59±0.32 mm/ms vs.3.50±0.28 mm/ms), with a statistically significant difference( P<0.01), and exercise endurance increased by 62%[(143.74±24.25)m vs.(233.50±30.21)m, P<0.01], suggesting that 2-HOBA was able to improve aortic vascular stiffness and exercise endurance in mice.2-HOBA ameliorated H 2O 2-induced vascular smooth muscle cell senescence and decreased the mRNA levels of H 2O 2-induced senescence-associated secretory phenotype factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1.Meanwhile, 2-HOBA also inhibited the expression of p53 and p21, the key signaling factors of senescence. Conclusions:2-HOBA suppresses the development and progression of atherosclerosis through inhibiting oxidative stress-related p53/p21 signaling activation and ameliorating vascular smooth muscle cell senescence and the aging-related inflammatory phenotype.