Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients. Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial. Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 & 60, patients achieving target BP (<140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported. Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58?mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm?Hg. The upper boundary of the 95% CI was below the margin of 10?mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days. Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the prognostic significance of liver kinase b1 (LKB1) loss in patients with operable colon cancer (CC). MATERIALS AND METHODS: Two hundred sixty-two specimens from consecutive patients with stage III or high-risk stage II CC, who underwent surgical resection with curative intent and received adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, were analyzed for LKB1 protein expression loss, by immunohistochemistry as well as for KRAS exon 2 and BRAF(V600E) mutations by Sanger sequencing and TS, ERCC1, MYC, and NEDD9 mRNA expression by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: LKB1 expression loss was observed in 117 patients (44.7%) patients and correlated with right-sided located primaries (p=0.032), and pericolic lymph nodes involvement (p=0.003), BRAF(V600E) mutations (p=0.024), and TS mRNA expression (p=0.041). Patients with LKB1 expression loss experienced significantly lower disease-free survival (DFS) (hazard ratio [HR], 1.287; 95% confidence interval [CI], 1.093 to 1.654; p=0.021) and overall survival (OS) (HR, 1.541; 95% CI, 1.197 to 1.932; p=0.002), compared to patients with LKB1 expressing expressing tumors. Multivariate analysis revealed LKB1 expression loss as independent prognostic factor for both decreased DFS (HR, 1.217; 95% CI, 1.074 to 1.812; p=0.034) and decreased OS (HR, 1.467; 95% CI, 1.226 to 2.122; p=0.019). CONCLUSION: Loss of tumoral LKB1 protein expression, constitutes an adverse prognostic factor in patients with operable CC.

Aberrant expression of miRNAs predicts recurrence and survival in stage-II colorectal cancer patients from Egypt

Background: Patients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify prognostic biomarkers that can define more aggressive forms of the disease. We assessed the expression levels of five miRNAs that have been previously addressed in relation to the development and progression of solid and hematological tumors. Methods: We measured the expression levels of miR-21, miR-137, miR-145, miR-320 and miR-498in stage II CRC patients from Egypt (124 tissues and 41 blood samples) by quantitative real time PCR (qPCR). The results were correlated with relevant clinicopathological factors, response to treatment and survival rates of the patients. Results: miR-137, miR-145 and miR-320 were significantly reduced in 39.5%, 48.4% and 52.4%; respectively whereas miR-21 and miR-498 were significantly overexpressed in 48.4% and 40.3% of the CRC tissues compared to the control group. In patients' blood, miR-137, miR-145 and miR-320 were significantly reduced in 46.3%, 46.3% and 51. 2%; respectively whereas mir-21 and miR-498 were significantly overexpressed in 46.3% and 43.9% of the cases, respectively. The concordance between tissue and blood was weak for miR-320 and miR-145 (kappa 40-65%), intermediate for miR-498 and miR-137 (kappa 65-75%) and strong for miR-21 (kappa 75-85%). In univariate analysis performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS. However, in multivariate analysis, miR-498 and miR-320 were independent prognostic factors for DFS whereas miR-21 was independent prognostic factors for OS. Conclusions: miRNAs play an important role in the development and progression of stage II CRC. A five markers panel (miR-21, miR-498, miR-137, miR-145 and miR-320) can predict recurrence and survival in stage II CRC patients from Egypt (AU)

Preservation of Scaphoid in Scaphoid Nonunion Advanced Collapse Stage II and III / 대한정형외과학회잡지

PURPOSE: The purpose of this study is to investigate the outcome of open reduction and internal fixation with a headless screw and auto iliac bone graft for patients of scaphoid nonunion advanced collapse (SNAC) stage II and III. MATERIALS AND METHODS: A retrospective analysis was conducted for 10 patients diagnosed with stage II or III SNAC, and consequently treated with open reduction and internal fixation with a headless screw and auto iliac bone graft with or without radial styloidectomy between 2010 and 2013. Radiographic results were evaluated by bone union, the scapholunate angle and lateral intrascaphoid angle. Clinical results were evaluated by range of motion, pain, grip strength, Mayo wrist score, and assessment of Maudsley. RESULTS: All patients showed union after the operation. Final follow-up X-rays show smoothening of the articular surface with improvement of sclerotic lesions of the articular surface, cystic lesions and osteopenic lesions. Pain decreased after the operation compared with preoperative status, grip strength and Mayo wrist score showed significant improvement. Scapholunate angle and lateral intrascaphoid angle decreased after the operation, but it was not significant. According to assessment of Maudsley, among 10 cases, there were 4 excellent cases, 4 good cases and 2 fair cases. CONCLUSION: Restoration of stability of scaphoid is important to SNAC stage II and III, open reduction and internal fixation with a headless screw and auto iliac bone graft shows satisfactory clinical and radiologic outcomes. Thus it is considered a recommendable operation.

Assessment of prognosis in patients with stage II colon cancer / Avaliação o prognóstico de pacientes com cancer de colon no estadio II

Pathologic staging is currently the most important prognostic factor in colon cancer, although individually this procedure does not provide a complete clinical outcome. This study aimed to determine the disease-specific survival of patients with colon cancer treated in the Braga Hospital from January 2005 to December 2013, according to the American Joint Committee on Cancer, 6th edition, and the disease-free survival and disease- specific survival of high- and low-risk stage II patients, whether in use, or not, of adjuvant chemotherapy. We obtained a total sample of 578 patients, with 145 and 65 high- and low-risk stage II patients, respectively. We observed a 5-year disease-specific survival rate of 93%, 27.4% and 75% for stage IIA, IIB and IIIA patients, respectively, where IIIA and IIB present statistically significant differences (p = 0.001). In high-risk stage II patients, disease-free survival (p = 0.107) and disease-specific survival (p = 0.037) were higher in the group submitted to chemotherapy. In low- risk patients, disease-free survival was higher in the group submitted to chemotherapy (p = 0.494), while disease-specific survival was lower (p = 0.426). The differences observed between stage IIB and IIIA survival can be explained by the consensual use of adjuvant chemotherapy in stage IIIA, and by its controversial use in stage IIB. Adjuvant chemotherapy showed to be effective only in high-risk stage II patients in terms of disease-specific survival. In the future, other markers, namely molecular ones, may be used to stratify the risk of stage II patients and determine who will benefit from adjuvant chemotherapy. (AU)

O estadiamento patológico é, atualmente, o fator de prognóstico mais importante do câncer de cólon, embora individualmente não preveja totalmente o resultado clínico. Neste estudo, pretendeu-se determinar a sobrevivência para uma doença específica (SDE) dos pacientes com câncer de cólon tratados no Hospital de Braga entre janeiro de 2005 e dezembro de 2013, de acordo com a 6a edição da American Joint Committee on Cancer e a Sobrevivência Livre de Doença (SLD) e SDE dos doentes em estadio II, classificados em alto e baixo risco, de acordo com a realização ou não de quimioterapia adjuvante. Obtivemos uma amostra total de 578 pacientes, dos quais uma parcela pertencia ao estadio II de alto ou de baixo risco (145 e 65 pacientes, respetivamente). Observamos SDE a 5 anos de: 93%, 27,4% e 75% para os estadios IIA, IIB e IIIA, respetivamente; IIIA e IIB apresentaram diferenças significativas (p = 0,001). SLD (p = 0,107) e SDE (p = 0,037) para o estadio II de alto risco foram superiores no grupo tratado com quimioterapia. Nos doentes de baixo risco, SLD foi superior no grupo tratado com quimioterapia (p = 0,494), enquanto que SDE foi inferior (p = 0,426). As diferenças de sobrevivência observadas para os estadios IIB e IIIA podem se dever ao uso controverso da quimioterapia em IIB e ao uso consensual em IIIA. O uso da quimioterapia adjuvante demonstrou ser efetivo nos doentes em estadio II de alto risco em termos de SDE. Futuramente, outros marcadores, nomeadamente moleculares, poderão vir a ser uti- lizados para estratificar o risco do estadio II e definir quem se beneficiará com o tratamento adjuvante. (AU)

Analysis on Medication Rules of Using Chinese Medicine in Reducing Recurrence and Metastasis of Stage II and III Colorectal Cancer among Postoperative Patients / 世界科学技术-中医药现代化

This study was aimed to analyze the living status and medication rules of traditional Chinese medicine (TCM) treatment of postoperative patients with stage II and III colorectal cancer by Prof. Y ang Y ufei. A total of 70 postoperative patients with stage II and III colorectal cancer were enrolled in the cohort study at the Xiyuan Hospital from September 2007 to August 2009. The out-patient records were reviewed and follow-ups were given for the analysis. The results showed that until July 2013, the loss to follow-up rate was 8.6%, which was less than 15%. The four-year postoperative recurrence and metastasis rates of the high and low exposure group were 7.1% and 25.0%, respectively. The Fisher exact probability test showed that the high exposure and long period therapy of TCM treatment can significantly reduce the recurrence and metastasis rate of patients (P < 0.05). The analysis of Prof. Y ang Y ufei's medication rules in TCM treatment of postoperative colorectal cancer showed that the syndrome differ-entiation pattern with the highest frequency was spleen-stomach deficiency pattern; and the liver-kidney yin defi-ciency pattern was in the second place. The prescriptions used with the highest frequency were Si-Jun-Zi Decoction and Liu-Wei-Di-Huang Decoction. It was concluded that the comprehensive TCM treatment can improve the prog-nosis of stage II and III colorectal cancer. The treatment also has certain meaning in the reducing of the recurrence and metastasis rate of patients, and prolonging the time of the recurrence and metastasis.

Comparison of Open Fixation and Closed Percutaneous Pinning in Jakob Stage II Lateral Condylar Fractures of Children

PURPOSE: To compare the results of open fixation and closed percutaneous pinning in managing Jakob stage II lateral condylar fractures of children's elbow. MATERIALS AND METHODS: Since Febuary 2000, We operated 21 children with Jakob stage II lateral condylar fractures of elbow. Eleven of the 21 were treated with closed percutaneous pinning, open fixation was done to the other 10 children. Each patient was evaluated about range of motion, carrying angle, scar satisfaction and radiologic findings for comparison between closed pinning and open fixation groups. RESULTS: Open fixation group showed 3.8 degrees decrease of elbow motion while closed pinning group showed no significant decrease. Carrying angle and radiologic findings were not different between the two groups. Open fixation group expressed dissatisfaction to their scars (average 5.2 cm) whereas all the patients of closed pinning group were satisfied with their functional and cosmetic outcomes. CONCLUSION: In managing Jakob stage II lateral condyle fractures of children's elbow, closed percutaneous pinning was thought to be superior to open fixation because of the same functional outcome and much better cosmetic results.

Impact of Adjuvant Chemoradiation Therapy on the Postoperative 5-year Survival Rates for Stage-II Gastric Cancer

PURPOSE: This study was conducted to evaluate the effectiveness and the role of post-operative adjuvant chemoradiation therapy in a stage-II (UICC,1997) primary gastric cancer. MATERIALS AND METHODS: From September 1994 to December 2004, 954 stage-II gastric-cancer patients were seen, and all of them underwent a curative resection with extensive (D2) lymph-node dissection. The chemotherapy consisted of fluorouracil (400 mg/m2) plus leucovorin (20 mg/m2) for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two five-day cycles of chemotherapy were given four weeks after the completion of radiotherapy. The Kaplan-Meier method was used to estimate the survival rates. To assess the importance of potential prognostic factors, we performed univariate and multivariate analyses using a log-rank test and Cox's proportional hazards regression model. A P value <0.05 was considered significant. RESULTS: Univariate analysis revealed that age, tumor size, gross type, surgical method, and postoperative adjuvant therapy had statistical significance. Among these factors, age, surgical method, tumor size, surgical method, and postoperative adjuvant therapy were found to be independent prognostic factors by using a multivariate analysis. The postoperative adjuvant chemotherapy group and the chemoradiation therapy group had survival benefit compared to the surgery-only group. However, the chemoradiation therapy group had no significant survival benefit compared to the chemotherapy group. CONCLUSION: The postoperative adjuvant therapy in stage-II gastric-cancer patients had significant benefit. Therefore, postoperative adjuvant chemoradiation therapy has an acceptable effect. A large-scale, randomized study is needed to evaluate the effectiveness and the role of postoperative radiation therapy.

Impact of Adjuvant Chemoradiation Therapy on the Postoperative 5-year Survival Rates for Stage-II Gastric Cancer

PURPOSE: This study was conducted to evaluate the effectiveness and the role of post-operative adjuvant chemoradiation therapy in a stage-II (UICC,1997) primary gastric cancer. MATERIALS AND METHODS: From September 1994 to December 2004, 954 stage-II gastric-cancer patients were seen, and all of them underwent a curative resection with extensive (D2) lymph-node dissection. The chemotherapy consisted of fluorouracil (400 mg/m2) plus leucovorin (20 mg/m2) for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two five-day cycles of chemotherapy were given four weeks after the completion of radiotherapy. The Kaplan-Meier method was used to estimate the survival rates. To assess the importance of potential prognostic factors, we performed univariate and multivariate analyses using a log-rank test and Cox's proportional hazards regression model. A P value <0.05 was considered significant. RESULTS: Univariate analysis revealed that age, tumor size, gross type, surgical method, and postoperative adjuvant therapy had statistical significance. Among these factors, age, surgical method, tumor size, surgical method, and postoperative adjuvant therapy were found to be independent prognostic factors by using a multivariate analysis. The postoperative adjuvant chemotherapy group and the chemoradiation therapy group had survival benefit compared to the surgery-only group. However, the chemoradiation therapy group had no significant survival benefit compared to the chemotherapy group. CONCLUSION: The postoperative adjuvant therapy in stage-II gastric-cancer patients had significant benefit. Therefore, postoperative adjuvant chemoradiation therapy has an acceptable effect. A large-scale, randomized study is needed to evaluate the effectiveness and the role of postoperative radiation therapy.

Expression of E-cadherin and beta-catenin in Stage II Colorectal Cancer Patients with Metachronous Distant Metastasis

PURPOSE: Decreased expressions of E-cadherin and beta-catenin are known to be associated with tumor metastases. but the clinical relationship between the degree of expression and the prognosis in colorectal cancer remains unclear. In this study, the expressions of E-cadherin and beta-catenin in stage II colorectal cancer patients were evaluated and their relation with metachronous distant metastasis analyzed. METHODS: From the patients who underwent a curative resection for stage II colorectal cancer, 25 who had a recurrence after surgery due to distant metastasis (group with recurrence) were selected, and matched with 25 patients who did not have a recurrence (group without recurrence). Paraffin embedded blocks from these patients and samples from normal colon, primary colon cancer were prepared in tissue microarrays and were stained by immunohistochemistry. The expressions were classified as grades 0, 1, 2, or 3 compared to those of normal tissue. RESULTS: The mena age of the patients was 55.7 years, with a median follow up period of 73.7 months. There are no significant differences in the clinicopathological data between the groups with recurrence and without recurrence. There were no significant differences in the degrees of E-cadherin and beta-catenin expression between the two groups (P=0.16, 0.10), or in the 5-year survival and disease free survival rates between the high and low expression groups (degree > or =2.5 and < or =2, respectively) of E-cadherin and beta-catenin. CONCLUSION: The expressions of E-cadherin and beta-catenin may not play a prognostic role in the prediction of metachronous distant metastasis in stage II colorectal cancers patients.

Comparative Analysis of Three Subgroups in Stage II Stomach Cancer

PURPOSE: Three subgroups of stage II stomach cancer (T1N2M0, T2N1M0, T3N0M0) by UICC-TNM staging system show obvious survival difference to each other, which becomes the pitfall of the current staging system. We analyzed the survival and relapse pattern of stage II stomach cancer patients in three subgroups retrospectively to prove the need for change in staging system. MATENRIALS AND METHODS: From July 1989 to December 1995, curative gastric resection was performed in 1,037 patients with gastric adenocarcinoma, and among them 268 patients (26%) were in stage II. The number in each of subgroups (T1N2M0, T2N1M0, and T3N0M0) were 17, 139 and 112 respectively. Survival and relapse pattern were analyzed and median follow up period was 46 months. RESULTS: The 3-year cumulative survival rates of T1N2M0, T2N1M0, and T3N0M0 were 50%, 80%, and 76% respectively (p=0.001). And the 3-year cumulative survival rates of T1N2M0 was comparable to those of 2 subgroups of stage IIIa (T2N2M0, T3N1M0), 47% and 45% (p>0.05). Peritoneal recurrence was the most frequent in T3N0M0. And hematogenous spread was more frequent in T2N1M0 while nodal spread was more frequent in T1N2M0. Ten out of 17 cases of T1N2M0 died of recurrence. Most of them showed submucosal tumor with depressed lesion and mean tumor size was 3.3 cm. CONCLUSION: Up-staging of T1N2M0 should be considered because it has the lowest survival rate and the worst prognosis among the three subgroups of Stage II stomach cancer patients. In early gastric cancer patients with high-risk factors (large tumor size, invasion into the submucosal layer, and lymphatic vessel involvement), lymph node dissection and postoperative adjuvant therapy is recommended in an attempt to prevent recurrence in the form of lymph node metastasis.

Comparative Study by Primary Tumor (T) and Nodal Involvement (N) in Stage II Gastric Cancer

PURPOSE: This study was done to evaluate the differences in clinical parameters and survival rates between the primary tumor (T) and nodal involvement (N) in stage II cancers. METHODS: This report is a retrospective clinical analysis of 100 patients of stage II gastric cancer who were treated surgically at the Department of Surgery, Chonbuk National University Hospital from Jan. 1990 to Dec. 1999. Among the 100 patients, the pT3N0 group included 48 patients, and the pT2N1 group 52 patients. In this study, we used the UICC TNM staging system (the fourth edition). RESULTS: There were no significant differences except for age and tumor sizes between the pT3N0 and the pT2N1 groups with regard to the mode of presentation, sex, location of tumor, type of resection, lymph node dissection, Borrmann and Lauren classification, cell cytology, recurrence, number of resected lymph nodes, and the 5-year survival rate. Based on the number of lymph nodal metastases, no significant difference was observed in the 5-year survival rate, but based on the ratio of lymph nodal metastases, the 5-year survival rate for those with up to 20% frequency of metastases was 85.2% and the 5-year survival rate for those with greater than 20% was 40.0%, which is significant difference in the 5-year survival rate. CONCLUSION: In stage II gastric cancer, there was no difference between the pT3N0 and the pT2N1 group, except that in the pT2N1 group, a subdivision of the pN stage according to the ratio of lymph nodal metastases could be successfully applied to the clinical evaluation of stage II gastric cancer.