OBJECTIVE: To investigate the clinical effects of the combined modality therapy for the patients with difficult-to-treat rhinosinusitis (DTRS). METHOD: The clinical data involving 42 patients with DTRS were analyzed retrospectively. All patients received revision endoscopic sinus surgery (ESS) and combined modality therapy systematically and individually. The clinical effects of all patients were observed 6- and 12-month following revision ESS. RESULT: Forty-two patients were followed up for 6 months, whereas 35 patients were followed for 12 months post operation. VAS scores of the patients significantly improved (P < 0.01) 6- and 12-month after revision ESS, but there was no statistic difference (P > 0.05) between 6- and 12-month post operation. Moreover, Lund-Kennedy scores by endoscopy significantly improved (P < 0.01) 6- and 12-month following ESS. Similarly, there was no statistic difference (P > 0.05) between 6- and 12-month postoperatively. Additionally, within 6 months follow-up, 16 of 42 patients (38.1%) were cured, 19 of 42 patients (45.2%) were improved, and 7 of 42 patients (16.7%) were ineffective. The total effective rate in all patients was 83.3% 6 months postoperatively. While within 12 months follow-up, 11 of 35 patients (31.4%) were cured, 15 of 35 patients (42.9%) were improved, and 9 of 35 patients (25.7%) were ineffective. Hence, the total effective rate in 35 patients was 74.3% after 12-month follow-up. There was no statistic difference (χ² = 1.019, P > 0.05) between 6- and 12-month postoperatively. CONCLUSION Appropriate revision ESS plus the combined modality therapy has been proven to be an effective method for the treatment of DTRS. The clinical effects in this study are significant and stable, and thus it is worthy of further clinical applications.
Combined Modality Therapy ; Endoscopy ; Humans ; Nasal Surgical Procedures ; Paranasal Sinuses ; surgery ; Postoperative Period ; Reoperation ; Retrospective Studies ; Rhinitis ; surgery ; therapy ; Sinusitis ; surgery ; therapy ; Treatment Outcome

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.

BACKGROUNDSunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma (mRCC). Analysis of clinical data of 22 patients, who were exposed to sunitinib for at least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC.

METHODSA total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events (AEs), or death. Among them, 22 patients continued treatment for at least 1 year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors.

RESULTSMedian progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome (95%) and hypertension (91%). Other common AEs were thyroid-stimulating hormone elevation (82%), platelet decrease (77%), and loss of appetite (77%). Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions.

CONCLUSIONLong-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Renal Cell ; drug therapy ; pathology ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Indoles ; administration & dosage ; Kidney Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Pyrroles ; administration & dosage ; Young Adult

BACKGROUNDThe tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.

METHODSA total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.

RESULTSThe median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting ≥ 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively).

CONCLUSIONSThe results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; mortality ; Drug Administration Schedule ; Female ; Humans ; Indoles ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.

Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan-Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10

The aim of this study was to investigate the role of S100 calcium binding protein A16 (S100A16) in lipid metabolism in hepatocytes and its possible biological mechanism. HepG2 cells (human hepatoma cell line) were cultured with fatty acid to establish fatty acid culture model. The control model was cultured without fatty acid. Each model was divided into three groups and transfected with S100a16 over-expression, shRNA and vector plasmids, respectively. The concentration of triglyceride (TG) in the cells was measured by kit, and the lipid droplets was observed by oil red O staining. Immunoprecipitation and mass spectrometry were used to find the interesting proteins interacting with S100A16, and the interaction was verified by immunoprecipitation. The further mechanism was studied by Western blot and qRT-PCR. The results showed that the intracellular lipid droplet and TG concentrations in the fatty acid culture model were significantly higher than those in the control model. The accumulation of intracellular fat in the S100a16 over-expression group was significantly higher than that in the vector plasmid transfection group. There was an interaction between heat shock protein A5 (HSPA5) and S100A16. Over-expression of S100A16 up-regulated protein expression levels of HSPA5, inositol-requiring enzyme 1α (IRE1α) and pIREα1, which belong to endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway. Meanwhile, over-expression of S100A16 up-regulated the mRNA expression levels of adipose synthesis-related gene Srebp1c, Acc and Fas. In the S100a16 shRNA plasmid transfection group, the above-mentioned protein and mRNA levels were lower than those of vector plasmid transfection group. These results suggest that S100A16 may promote lipid synthesis in HepG2 cells through endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway.
Endoplasmic Reticulum Stress ; Endoribonucleases ; physiology ; Heat-Shock Proteins ; physiology ; Hep G2 Cells ; Humans ; Lipid Metabolism ; Protein-Serine-Threonine Kinases ; physiology ; S100 Proteins ; physiology ; Triglycerides ; biosynthesis ; X-Box Binding Protein 1 ; physiology