Objective:To investigate the neuroprotective effect of ibuprofen, and influence of ibuprofen in hippocampal nod-like receptor protein 3 (NLRP3) inflammatome and its related products in chronic epilepsy rats models.Methods:Thirty male SD rats were randomly divided into 3 groups: control group, pentylenetetrazol (PTZ) group and PTZ+ibuprofen group ( n=10). Rats in the PTZ group were intraperitoneally injected with PTZ (35 mg/kg) once every one d, and rats in the PTZ+ibuprofen group were intraperitoneally injected with ibuprofen (30 mg/kg) once every one d 30 min before PTZ injection; rats in the control group were intraperitoneally injected with the same amount of normal saline every one d. Injection for 15 times was performed. After the last injection, the rats were observed for 10 min, and the latency, seizure level and complete ignition of the rats in each group were recorded. Electroencephalogram (EEG) was used to detect the abnormal brain discharge in rats. Four h after last injection, HE staining and Nissl staining were used to detect the proportion of damaged hippocampal neurons in each group. Immunohistochemical staining was used to detect the absorbance values of NLRP3 inflammasome, caspase-1 and interleukin (IL)-18 positive cells in the hippocampus of rats in each group; Western blotting was used to detect the protein expressions of NLRP3 inflammatome, caspase-1 and interleukin (IL)-18 in the hippocampus of each group. Results:(1) As compared with the PTZ group, rats in the PTZ+ibuprofen group had statistically lower incidence of complete ignition, significantly longer latency and significantly lower seizure level ( P<0.05). EEG showed spikes and high amplitude epileptic wave discharge in rats of the PTZ group; EEG showed low amplitude small spiny wave and slow spiny wave in rats of the PTZ+ibuprofen group. (2) As compared with the control group, the proportion of injured hippocampal neurons significantly increased in the PTZ group and PTZ+ibuprofen group ( P<0.05); and the proportion of injured hippocampal neurons in the PTZ+ibuprofen group signficantly decreased as compared with that in the PTZ group ( P<0.05). (3) As compared with those in the control group, the absorbance values of NLRP3 inflammatome, caspase-1 and IL-18 positive cells, and the protein expressions of NLRP3 inflammatome, caspase-1 and IL-18 in the hippocampus of the PTZ group and PTZ+ibuprofen group were all significantly increased ( P<0.05); as compared with the PTZ group, the the absorbance values of NLRP3 inflammatome, caspase-1 and IL-18 positive cells, and the protein expressions of NLRP3 inflammatome, caspase-1 and IL-18 in the hippocampus in the PTZ+ibuprofen group were all significantly decreased ( P<0.05). Conclusion:Ibuprofen can inhibit the expressions of NLRP3 inflammatome, caspase-1 and IL-18, reduce the intensity of seizures, and play a neuroprotective role.

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001). Conclusion The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

Objective To investigate the clinical efficacy and prognostic factors of breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) receiving neoadjuvant chemotherapy,surgery combined with radiotherapy at diagnosis.Methods Therapeutic outcomes of 65 breast cancer patients with ISLNM treated in our hospital between 1999 and 2013 were retrospectively analyzed.All patients were pathologically diagnosed with breast cancer.They were complicated with ISLNM,without distant metastasis confirmed by pathological or imaging examinations.All patients received multi-modality therapy consisting of neoadjuvant chemotherapy,surgery and postoperative radiotherapy.KaplanMeier method was adopted to calculate the overall survival (OS),progression-free survival (PFS) and supraclavicular lymph node recurrence (SCFR).The differences between two groups were statistically analyzed by the log-rank test.Results The median follow-up time was 66 months (range:6-137 months).Five patients had SCFR after corresponding treatment.The overall 5-year SCFR,OS and PFS rates were 9.2％,71.5％ and 49.5％,respectively.Following preoperative chemotherapy,the complete response (CR) of supraclavicular lymph node was a prognostic factor affecting OS.The 5-year OS rates in patients with and without CR were 81.4％ and 53.9％ (P=O.035).The size of supraclavicular lymph node (≤ 1 cm vs.＞ 1 cm at diagnosis was a risk factor of the SCFR (0％ vs.21.0％,P=0.037) and OS rates (≤1 cm vs.＞1 cm:86.1％ vs.55.6％,P =0.001).Conclusions Breast cancer patients with ISLM at diagnosis can obtain high OS rate and excellent tumor control after undergoing multi-modality therapy consisting of preoperative chemotherapy,surgery and postoperative radiotherapy.

Objective To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1?2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods a total of 1 823 female patients with T1?2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log?rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic ( ROC ) analyses and the concordance index ( C?index ). Results 5?year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5?year distant metastasis (DM) rate was 11.5%, 5?year disease?free survival (DFS) was 85.0%, and 5?year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P＜0.05). Compared with stage by 7th edition, 1 278 (70.1%) were assigned to a different prognostic stage group: 1 088 ( 85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stageⅠA,ⅠB,ⅡA,ⅡB and ⅢA according to 8th edition of the AJCC staging system(P＜0.001). Prognostic stage had significantly higher C?indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system ( P＜0.001). Conclusion The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1?2N1M0 breast cancer, and has better clinical therapeutic guidance value.

Objective To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1?2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods a total of 1 823 female patients with T1?2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log?rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic ( ROC ) analyses and the concordance index ( C?index ). Results 5?year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5?year distant metastasis (DM) rate was 11.5%, 5?year disease?free survival (DFS) was 85.0%, and 5?year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P＜0.05). Compared with stage by 7th edition, 1 278 (70.1%) were assigned to a different prognostic stage group: 1 088 ( 85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stageⅠA,ⅠB,ⅡA,ⅡB and ⅢA according to 8th edition of the AJCC staging system(P＜0.001). Prognostic stage had significantly higher C?indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system ( P＜0.001). Conclusion The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1?2N1M0 breast cancer, and has better clinical therapeutic guidance value.

OBJECTIVETo evaluate the outcome of radical surgery combined with adjuvant radiotherapy for patients aged over 75 years with stage II( or III( rectal cancer.

METHODSFrom 2000 to 2010, 178 patients aged over 75 years at diagnosis who underwent radical surgery in National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were selected from 3995 patients with stage II( or III( rectal cancer in the database of the above center and enrolled into this retrospective cohort study, which was approved by ethics committee of the above hospital (ClinicalTrials.gov number, NCT02312284).

RESULTSMedian age of patients was 77 years (range 75-87). There were 37 (20.8%), 69 (38.8%), and 72 (40.4%) patients with tumors locating in the high, middle and low rectum respectively; 89(50%) patients of pathological stages II( and III( respectively; 21(11.8%), 137(77%), 19(10.7%), and 1(0.6%) patients with poorly, moderately, well differentiated adenocarcinoma, and mucinous adenocarcinoma respectively. The Charlson/Deyo comorbidity index (CCI) score was 0 in the majority (73.6%) of patients. Fifty-three patients underwent abdominoperineal resection, 116 underwent low anterior resection and 9 underwent Hartmann resection. All the patients received computed tomography-based simulation and treatment planning using an anal marker in a prone or supine position. Patients were treated with linear accelerator by megavoltage photons (6MV), with 2D technique in early years and 3D conformal or simplified intensity-modulated radiotherapy technique later, at a dose of 50 Gy in 25 fractions to the pelvis within an overall treatment time of 35 days. Sixty-one patients (34.3%) received surgery combined with radiation (ART group), in whom 16 received radiation alone 117 patients did not receive radiation(NORT group). The baseline data between ART and NORT group were not significantly different(all P>0.05). There was no significant difference in 5-year overall survival between ART and NORT groups (61.0% vs. 63.0%, P=0.586). The cumulative local relapse was 10.9% and 25.4% in ART and NORT group respectively (P=0.032). Cox multivariate analysis revealed that surgery combined with radiation improved local control significantly(HR=0.27, 95%CI:0.11-0.68, P=0.005).

CONCLUSIONSFor elderly patients aged over 75 years with stage II( or III( rectal cancer, radical surgery combined with radiation does not increase the overall survival, but can improve local control rate. It is reasonable to selectively apply adjuvant radiotherapy to the elderly patients in the setting of radical surgery.

Adenocarcinoma ; radiotherapy ; surgery ; Aged ; Aged, 80 and over ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; radiotherapy ; surgery ; Retrospective Studies

Objective: To analyze the clinical features and prognosis of the ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery. Methods: From 1999 to 2013, 63 women with IBTR after breast conserving surgery were retrospectively reviewed. All patients had adequate information on tumor location both at first presentation and at recurrence, with or without regional recurrence or distant metastasis. The histologic changes between true local recurrence and elsewhere recurrence groups were compared. The local recurrence, the overall survival after IBTR (IBTR-OS), the disease-free survival after IBTR (IBTR-DFS) were also compared. Results: All patients had undergone lumpectomy, including 38 cases with additional axillary lymph node dissection and 13 cases with sentinel lymph node biopsy. There were 11.3% (7/63) cases received neoadjuvant systemic therapy, 68.3% (43/63) had adjuvant radiotherapy, 60.3% (38/63) underwent adjuvant chemotherapy and 47.6% (30/63) received hormonal therapy. Forty-five cases (71.4%) had recurrence in the same quadrant, and 18 cases (28.6%) had elsewhere recurrence. Compared with histology at presentation, 10.3% of the patients (6/58) had different ones at recurrence and 28.9% of patients (13/45) had different molecular subtypes. The conversion rate of estrogen receptor status (33.3% vs 9.5%, P=0.012) and progesterone receptor status (56.3% vs 19.0%, P=0.005) in patients with elsewhere recurrence was significantly higher than that in patients with same quadrant recurrence. Fifty-nine cases had undergone surgery after IBTR, with 48 cases of secondary breast-conserving surgery and 11 cases of salvage mastectomy. The median time to IBTR of same quadrant recurrence and elsewhere recurrence groups were 26 months and 62 months (P=0.012), respectively. There were 84.4% and 44.4% cases who had local recurrence within 5 years after breast conserving surgery, respectively. Of all cases, the overall 5-year IBTR-OS and 5-year IBTR-DFS rates were 79.4% and 60.4%, respectively. There were no significant differences in 5-year IBTR-OS (77.4% vs. 83.6%, P=0.303) or 5-year IBTR-DFS (60.0% vs. 62.8%, P=0.780) between same quadrant recurrence and elsewhere recurrence groups. Univariate analysis showed that pN0-1 (P<0.001), luminal subtype (P=0.026), adjuvant endocrine therapy (P=0.007) at first presentation, recurrent tumor < 3 cm (P=0.036) and having surgery after IBTR(P=0.002) were favorable factors of IBTR-OS. pN0-1 (P<0.001) at first presentation, recurrent tumor stage Ⅰ-Ⅱ (P<0.001) and having surgery after IBTR(P=0.001) were favorable factors of IBTR-DFS. There was no significant difference between second breast-conserving surgery and salvage mastectomy in IBTR-OS and IBTR-DFS (P>0.05). Conclusions The IBTR after breast conserving surgery mainly occurred at the original quadrant. Second breast-conserving surgery did not affect patient′s prognosis. There were significant differences in biological features between the same quadrant recurrence and elsewhere recurrence, requiring different therapeutic strategies in the future.

Objective: To investigate the overall efficacy of early breast cancer after breast-conserving treatment. To analyze risk factors affecting local regional recurrence (LRR), distant metastasis (DM) and survival. Methods: 1 791 breast cancer patients treated with breast-conserving surgery were retrospectively analyzed. The inclusion criteria were pathologic diagnosis of invasive breast cancer without supraclavicular and internal mammary node metastasis, T1-2N0-3M0, and no neoadjuvant therapy. Univariate analysis of survival was performed by Kaplan-Meier method and log rank test. Cox regression model was used for multivariate analysis. Results: The median follow-up time was 4.2 years. For all patients, the 5-year LRR, DM, disease-free survival(DFS) and overall survival(OS) rates were 3.6%, 4.6%, 93.0% and 97.4%, respectively. The LRR rates of patients with Luminal A, Luminal B1, Luminal B2, HER-2 over-expressed and triple-negative breast cancer were 2.0%, 6.1%, 5.9%, 0 and 10.0%, while the DM rates were 3.2%, 6.7%, 8.3%, 4.8% and 7.3%, respectively. Among the N0 patients, axillary dissection was performed in 689 cases and sentinel lymph node biopsy in 652 cases. The 5-year LRR rates were 3.3% and 3.2% (P=0.859), and the OS rates were 98.2% and 98.3% (P=0.311) respectively, which showed no statistically significant. There were 1 576 patients that underwent postoperative radiotherapy. Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone (2.5% vs 12.9%). The 5-year LRR rates of patients who received conventional fractionated radiotherapy and hypo-fractionated radiotherapy were 2.7% and 3.1%, respectively. But the difference was not statistically significant (P=0.870). Multivariate analysis showed that age, lymphovascular invasion, pathological T staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors of LRR in breast cancer patients (all P<0.05). Histological grade and pathological N staging were independent factors of DM (all P<0.05). The age, lymphovascular invasion, pathological T and N staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors for DFS (all P<0.05). Histological grade, pathological N staging, ER/PR status and endocrine therapy were factors for OS (all P<0.05). Conclusions With contemporary standard treatment, the recurrence rate of early breast cancer after breast conserving treatment is less than 10%. Node-negative patients after sentinel lymph node biopsy did not need axillary dissection. The overall utilization of radiotherapy after breast conserving surgery is satisfactory. Hypofractionated radiotherapy is as effective as conventional fractionated radiotherapy. Local regional recurrence and distant metastasis have different risk factors.

Objective To evaluate the value of postmastectomy radiotherapy (PMRT) in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (neoCT) and modified radical mastectomy, and to investigate the possibility of individualized radiotherapy according to the response to neoCT.Methods We analyzed 523 patients with stage ⅢA and ⅢB breast cancer who received neoCT and modified radical mastectomy in our hospital from 1999 to 2013.Of all patients, 404 received PMRT, and 119 did not.The locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method, survival difference analysis and univariate prognostic analysis were performed using the log-rank test, and multivariate prognostic analysis was performed using the Cox regression model.Results Compared with those not treated with PMRT, the patients treated with PMRT had a significantly lower 5-year LRR rate (13.9% vs.24.8%, P=0.013), a significantly higher DFS rate (64.1% vs.53.9%, P=0.048), and an insignificantly higher OS rate (83.2% vs.78.2%, P=0.389).In the patients with ypT3-T4, ypN2-N3, or pathologic stage Ⅲ disease, those treated with PMRT had a significantly reduced 5-year LRR rate (P<0.05) and a significantly increased 5-year OS rate (P<0.05), as compared with those not treated with PMRT.Among the 158 patients with ypN0 disease, the 5-year LRR rate was significantly lower in those treated with PMRT than in those not treated with PMRT (P=0.004).Of 41 patients who achieved a pathologic complete response, 2 patients, who did not receive PMRT, developed LRR.The multivariate prognostic analysis indicated that PMRT was an independent prognostic factor associated with reduced LRR in all patients and ypN0 patients.Conclusions In patients with stage ⅢA and ⅢB breast cancer treated with neoCT and modified radical mastectomy, PMRT can significantly reduce LRR for all patients and can reduce both recurrence and mortality for those with ypT3-T4, ypN2-N3, or pathologic stage Ⅲ disease.There is no sufficient evidence that PMRT can be omitted safely for ypN0 or pCR patients according to their response to neoCT.

Objective: To analyze the outcomes of clinical T1-3N1M0 breast cancer patients with pathological negative axillary lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) and mastectomy, and investigate the role of postmastectomy radiotherapy (PMRT). Methods: A total of 185 patients with clinical T1-3N1M0 breast cancer treated between 1999 and 2013 were retrospectively reviewed. All patients were treated with NAC and mastectomy, and achieved ypN0. Of them, 89 patients received additional PMRT and 96 patients did not. 101 patients had clinical stage Ⅱ disease. 84 patients had clinical stage Ⅲ disease. The rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. Univariate analysis was used to interpret the impact of clinical features and treatment on patients′ outcome. Results: The 5-year rates of LRR, DM, DFS, and OS for all patients were 4.5%, 10.4%, 86.6%, and 97.1%, respectively. For patients with and without PMRT, the 5-year LRR rates were 1.1% and 7.5% (P=0.071), the 5-year DM rates were 5.1% and 15.0% (P=0.023), the 5-year DFS rates were 95.0% and 79.0% (P=0.008), and the 5-year OS rates were 100.0% and 94.5% (P=0.089) respectively. In univariate analysis, lymph-vascular space invasion (LVSI) was poor prognostic factor of LRR (P=0.001), < 40 years old and lack of PMRT was a poor prognostic factor for DM (P<0.05), lack of PMRT was a poor prognostic factor for DFS (P=0.008), primary lesion residual and mild-moderate pathological response to NAC were poor prognostic factors for OS (P<0.05). In the subgroup of Stage Ⅲ disease, for patients with and without PMRT, the 5-year LRR rates were 1.9% and 14.4% (P=0.041), the 5-year DFS rates were 91.9% and 67.4% (P=0.022), respectively. In the subgroup of Stage Ⅱ disease, for patients with and without PMRT, the 5-year DM rates were 0 and 11.5% (P=0.044), the 5-year DFS rates were 100.0% and 84.9% (P=0.023), respectively. Conclusions The LRR rate of clinical T1-3N1M0 breast cancer patients who achieved ypN0 after NAC and mastectomy was low. PMRT decreased the DM rate and increased DFS rate in all patients, and significantly decreased the LRR rate in Stage Ⅲ disease. PMRT should be considered for patients with Stage Ⅲ disease, and further research is warranted to investigate the benefit of PMRT for Stage Ⅱ disease.