A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Gastric Cancer - We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association...     

Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray-drying technique

A poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray-drying technique. To develop a novel ibuprofen-loaded gelatin microcapsule with bioavailability enhancement, the effect of spray-drying conditions, gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol encapsulated in gelatin microcapsule were investigated. The ibuprofen solubility and amount of encapsulated ethanol increased as inlet temperature and amount of sodium lauryl sulfate increased, reached maximum at 105 degrees C and 0.6%, respectively and after that followed a rapid decrease. Furthermore, they abruptly increased as the amount of gelatin increased, reaching maximum at 4% then remaining almost stable, but the encapsulated ethanol content decreased noticeably. Likewise, the ibuprofen solubility increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility. However, the encapsulated ethanol content hardly changed irrespective of the amount of ibuprofen. Furthermore, the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 showed ibuprofen solubility of about 290microg/ml and ethanol content of about 160microg/mg. This gelatin microcapsule dramatically increased the initial dissolution rate of ibuprofen compared to ibuprofen powder in pH 1.2 simulated gastric fluid. Moreover, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen in rats than did ibuprofen powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. Our results suggested that the enhanced oral bioavailability of ibuprofen in the gelatin microcapsule was contributed by the marked increase in the absorption rate of ibuprofen due to the crystallinity change to amorphous form and increase in dissolution rate of ibuprofen in the gelatin microcapsule in rats. Thus, the ibuprofen-loaded gelatin microcapsule developed using spray-drying technique with gelatin would be useful to deliver ibuprofen in a pattern that allows fast absorption in the initial phase, leading to better absorption.     

Pretreatment Lymphopenia,Poor Performance Status,and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10⁹/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.     

Efficacy and Safety of Rebamipide versus Its New Formulation,AD-203, in Patients with Erosive Gastritis: A Randomized,Double-Blind,Active Control,Noninferiority, Multicenter,Phase 3 Study

Background/AimsThe mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta^Ⓡ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis.MethodsThis double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups AD-203 twice daily or Mucosta^Ⓡ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta^Ⓡ, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta^Ⓡ, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated.ResultsAccording to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta^Ⓡ-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta^Ⓡ-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta^Ⓡ-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates.ConclusionsThe new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta^Ⓡ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.     

Current status and challenges in sentinel node navigation surgery for early gastric cancer

Although a number of feasibility studies for sentinel node (SN) concepts in gastric cancer have been conducted since 2000,there remains a debate regarding detailed detection techniques and oncological safety.Two important multicenter phase Ⅱ clinical trials were performed in Japan that used different methods and reached different conclusions;one confirmed acceptable results with a false-negative rate of 7％,and the other showed an unacceptably high false-negative rate of 46.4％.The Sentinel Node Oriented Tailored Approach (SENORITA) trial is a multicenter randomized controlled phase Ⅲ trial being performed in Korea.Patient enrollment is now complete and the long-term results are currently awaited.Recently,an image-guided SN mapping technique using infrared ray/fluorescence was introduced.This method might be a promising technology because it allows the clear visualization of SNs.With regard to the primary tumor,the non-exposed endoscopic wall-inversion surgery technique and non-exposure endolaparoscopic full-thickness resection with simple suturing technique have been reported.These methods prevent abdominal infection and tumor seeding and can be good alternatives to conventional laparoscopic gastric wedge resection.For indications,SN navigation surgery can be extended to patients who underwent non-curative endoscopic resection.Although a few studies have been performed on these patients,sentinel concepts may be beneficial to patients as they omit the need for additional gastrectomy.SN navigation surgery can lead to actual organ-preserving surgery and plays a key role in improving the quality of life of patients with early gastric cancer in the future.     

Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores

After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0–1) in 68.2% and high (2–3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2–3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P < 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P < 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥?3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.     

Improvement of diabetes and hypertension after gastrectomy: A nationwide cohort study

AIM: To evaluate the effect of gastrectomy on diabetes mellitus(DM) and hypertension(HTN) in non-obese gastric cancer patients. METHODS: A total of 100000 patients, diagnosed with either type 2 DM or HTN, were randomly selected from the 2004 Korean National Health Insurance System claims. Among them, 360 diabetes and 351 hypertensive patients with gastric cancer who had been regularly treated without chemotherapy from January 2005 to December 2010 were selected. They were divided into three groups according to their treatment methods: total gastrectomy(TG), subtotal gastrectomy(STG) and endoscopic resection(ER). RESULTS: The drug discontinuation rate of antidiabetic and anti-hypertensive agents after gastric cancer treatment was 9.7% and 11.1% respectively. DM appeared to be improved more frequently(22.8%) and earlier(mean ± SE 28.6 ± 1.8 mo) in TG group than in the two other groups [improved in 9.5% of ER group(37.4 ± 1.1 mo) and 6.4% of STG group(47.0 ± 0.8 mo)]. The proportion of patients treated with multiple drugs decreased more notably in TG group compared to others(P = 0.001 in DM, and P = 0.035 in HTN). In TG group, adjusted hazard ratio for theimprovement of DM was 2.87(95%CI: 1.15-7.17) in a multi-variate analysis and better control of DM was observed with survival analysis(P 0.001).CONCLUSION: TG was found to decrease the need for anti-diabetic medications which can be reflective of improved glycemic control, to a greater extent than either ER or STG in non-obese diabetic patients.