Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Impact of Intra-Abdominal Adhesion on Living Donor Right Hepatectomy.

The impact of intra-abdominal adhesion (IAA) on living donor right hepatectomy (LDRH) remains to be clarified. The purpose of this study was to compare both the donor and recipient outcomes of right lobe living donor liver transplantation according to IAA detected intraoperatively. LDRH donors were identified through a prospectively maintained database at the authors' institution between March 2008 and February 2014. IAA was graded according to Beck et al (Dis Colon Rectum 2000; 43: 1749-1753). LDRH donors with IAA (group A) were matched 1:3 to those without IAA (group B) based on age, gender, and BMI. Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow-up were compared. Thirty-two (7.6%) of a total of 420 LDRH donors had IAA around the liver. Nineteen donors had previous abdominal surgery. LDRH was successfully completed under upper midline laparotomy in all donors. Compared with group B, group A had a longer operative time (270 vs. 172 min; p < 0.001), a higher wound complication rate (28.1% vs. 4.2%; p = 0.009), and a longer postoperative stay (10 vs. 7 days; p = 0.009). All donors recovered completely to their previous activities. The 1-year graft and recipient survivals of recipients were comparable between two groups. These findings support the feasibility and safety of LDRH in patients with IAA.

Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease.

BACKGROUND: Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments. AIMS: To conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease. METHODS: Patients with a Crohn's Disease Activity Index (CDAI) of 220-450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12. RESULTS: Six hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI -6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI -6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively. CONCLUSIONS: We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed.

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.

BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).

Asthma and COPD overlap syndrome is associated with increased risk of hospitalisation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis and a high health care burden. The incidence of asthma and COPD overlap syndrome is increasing, and contributes to a high financial burden and poor prognosis. OBJECTIVE: To investigate clinical features of the overlap syndrome among Asian patients and to analyse its impact on hospitalisation due to respiratory problems or death compared to COPD alone. DESIGN: We performed a retrospective cohort analysis of 2933 COPD patients presenting at the Asan Medical Center from 1 January 2000 to 31 December 2009. Kaplan-Meier and Cox proportional hazard models were used to analyse the significance of clinical parameters, including age, sex, smoking history, body mass index (BMI), severity of airflow limitation, airway obstruction reversibility and overlap syndrome with hospitalisation due to respiratory problems or death. RESULTS: Overlap syndrome patients were older, included smaller proportions of males and of smokers and had lower forced expiratory volume in 1 s (FEV1) (% predicted). Shorter hospitalisation-free and survival periods were noted among overlap syndrome patients. Overlap syndrome was significantly associated with risk of hospitalisation due to respiratory problems after adjusting for age, smoking history, BMI, FEV1 (% predicted) and changes in FEV1 (P < 0.001). CONCLUSION: Asthma and COPD overlap syndrome is associated with a higher risk of hospitalisation due to respiratory problems than COPD alone.

Vertebral compression fractures may increase mortality in male patients with chronic obstructive pulmonary disease.

BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic obstructive pulmonary disease (COPD) patients. However, little is known about whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether VCFs might increase death in COPD patients. METHODS: In this retrospective cohort study, we enrolled 254 COPD patients with a recent history of hospitalisation due to respiratory problems. Patients were assessed for VCF using quantitative morphometric analyses of lateral chest radiographs; 211 patients received follow-up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60 (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox proportional hazard analysis revealed that VCF is an independent risk factor for death after adjusting for age, sex, body mass index, smoking, dyspnoea scale, forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk factor for death in male COPD patients.

Pretransplant serum levels of C-reactive protein predict prognoses in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Preoperative absolute C-reactive protein (CRP) has been shown to correlate with prognoses in various malignancies, including hepatocellular carcinoma (HCC). METHODS: The aim of this study was to investigate whether pretransplant CRP levels predict prognoses in patients undergoing liver transplantation (LT) for HCC. We retrospectively analyzed clinicopathological factors in 211 patients with available pretransplant serum CRP levels who underwent LT for HCC between January 2005 and April 2012. RESULTS: By means of receiver operating characteristic curve analysis, a CRP level of >0.3 mg/dL was considered to be elevated. By multivariate analysis, the high CRP level, the maximal tumor size >5 cm, the presence of intrahepatic metastasis, and positive findings in pretransplant (18)fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) were related to tumor recurrence, whereas the high CRP level, the presence of intrahepatic metastasis, and positive findings in pretransplant (18)F-FDG PET/CT were related to poor overall survival. When subgroup analysis was conducted according to the Milan criteria, the high CRP level was an independent factor for predicting poor outcomes in patients with HCC beyond the Milan criteria (P = .001 for recurrence-free survival and P = .010 for overall survival), and not for patients within the criteria. CONCLUSIONS: Pretransplant serum CRP levels can predict prognoses in patients undergoing LT for HCC, especially in patients with HCC exceeding the Milan criteria.

Successful living donor liver transplantation between septuagenarians.

We report a case of a 76-year-old female who underwent living donor right hepatectomy for her 75-year-old husband with recurrent hepatocellular carcinoma. With her voluntary decision, full medical and psychiatric assessment was performed. The operative time was 130 min in the donor and 399 min in the recipient. Both the donor and recipient had an uneventful recovery and were discharged on days 7 and 10, respectively with normal liver function. The couple has had no complication so far and is currently doing well in good health 26 months after living donor liver transplantation.

Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-year results from the PRECiSE 3 study.

BACKGROUND: The efficacy and safety of certolizumab pegol (CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies (PRECiSE 1 & 2). AIM: To report the safety and efficacy outcomes of long-term, CZP therapy from PRECiSE 3, in which patients received treatment up to 7 years treatment. METHODS: Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400 mg, open-label, every 4 weeks (without additional induction therapy) for up to 7 years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation. RESULTS: A total of 595 patients entered the study; 117 (20%) completed 7 years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were ≥68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively. CONCLUSION: Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7 years. ClinicalTrials.gov identifier NCT00552058.

The 'either test positive' strategy for latent tuberculous infection before anti-tumour necrosis factor treatment.

SETTING: A ttertiary referral centre in South Korea. OBJECTIVES: The 'either test positive' strategy, incorporating both the tuberculin skin test (TST) and the T-SPOT(®).TB(T-SPOT) assay, was evaluated as a novel method for diagnosing latent tuberculous infection (LTBI) before treatment with anti-tumour necrosis factor (TNF) in patients with immune-mediated inflammatory diseases. DESIGN: From June 2008 to April 2012, 430 patients received anti-TNF treatment at our institution. TST and T-SPOT were performed simultaneously at baseline. LTBI was defined as a positive TST or a positive T-SPOT result. RESULTS: The positivity rates for the TST and T-SPOT assays were respectively 19.1% (82/430) and 44.2% (190/430), yielding an LTBI-positive rate of 48.6% (209/430). LTBI treatment was initiated in 46.0% (198/430) of patients and was completed by 89.4% (177/198). During follow-up (median 884 days), 0.9% (4/430) of the patients developed active tuberculosis (TB). All four TB patients were TST-negative at baseline, although two received LTBI treatment based on the baseline positive T-SPOT assay results. CONCLUSIONS: The either test positive strategy is a valid method for diagnosing LTBI before anti-TNF treatment, although it is not clear whether it is superior to other strategies.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

Clinical outcomes and risk factors of hepatitis B virus recurrence in patients who received prophylaxis with entecavir and hepatitis B immunoglobulin following liver transplantation.

INTRODUCTION: Although entecavir (ETV) and hepatitis B immunoglobulin (HBIG) have widely been used for prophylaxis of hepatitis B virus (HBV) recurrence following liver transplantation (OLT), there have been few studies about clinical outcomes and risk factors of HBV recurrence. MATERIALS AND METHODS: This study retrospectively assessed clinical outcomes and identified risk factors of post-transplant HBV recurrence in 154 patients who received prophylaxis with both ETV and HBIG after OLT. RESULTS: The median follow-up duration was 28.0 months (range, 1.0-57.8). Post-transplant HBV recurrence occurred in 5 patients (3.2%) without any ETV-resistant mutants. The overall rates of HBV recurrence at 1, 2, and 4 years were 0.6%, 1.6%, and 6.2%, respectively. We found that recurrent hepatocellular carcinoma (HCC) was an independent risk factor of HBV recurrence (hazard ratio = 13.5, 95% confidence interval, 2.4-74.4; P = .006). CONCLUSIONS: Prophylaxis with a combination of ETV and HBIG resulted in a low HBV recurrence rate following OLT without any emergence of ETV-resistant mutants. Recurrent HCC was an independent risk factor of HBV recurrence in patients who received prophylaxis with both ETV and HBIG for prophylaxis following OLT.

A survival benefit of major hepatectomy for hepatocellular carcinoma identified by preoperative [18F] fluorodeoxyglucose positron emission tomography in patients with well-preserved hepatic function.

AIMS: Hepatic resection can cure hepatocellular carcinoma (HCC). However, the optimal extent of resection remains controversial. Major hepatectomy could minimize a tumor recurrence, but it is harmful due to decreased hepatic functional reserve. [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) scans are known as their reflection tumor differentiation and biological activity in HCC. To evaluate a benefit of major hepatectomy for HCC, we performed this retrospective analysis in patients with well-preserved hepatic function, and further analyzed in the subset identified by preoperative FDG-PET. METHODS: We reviewed the medical records of 189 patients with HCC who underwent curative resection between August 2004 and December 2010 at two institutes. All patients underwent anatomical resection, either by major or minor hepatectomy. RESULTS: Median overall survival did not differ significantly between the major and minor hepatectomy groups (29.4 versus 26.3 months, p = 0.269). However, the major hepatectomy group had a better recurrence-free survival (24.5 versus 19.9 months, p = 0.004). On multivariate analysis, the presence of intrahepatic metastasis independently predicted overall survival (p = 0.009), but other examined variables did not. Overall survival and recurrence-free survival were significantly better following major hepatectomy rather than minor hepatectomy in patients whose preoperative FDG-PET indicated that the maximum standardized uptake value of the tumor (SUVtumor) was ≥4 and the tumor-to-nontumor SUV ratio (TNR) was ≥1.5. CONCLUSIONS: Our findings suggest that preoperative FDG-PET may be useful in identifying patients with favorable hepatic reserve who are most likely to benefit from major rather than minor hepatectomy.

Effects of exercise training on cardiac apoptosis in obese rats.

BACKGROUND AND AIM: The purpose of this study was to evaluate the effects of exercise training on cardiac apoptotic pathways in obesity. METHODS AND RESULTS: Sixteen lean Zucker rats (LZR) and sixteen obese Zucker rats (OZR) of 5-6 months of age as well as the other sixteen obese rats were subjected to treadmill running exercise for 1 h everyday for 3 months (OZR-EX). After exercise training or sedentary status of the rats, the excised hearts from the three groups were measured by heart weight index, H&E staining, TUNEL assays and Western blotting. Cardiac TUNEL-positive apoptotic cells, the protein levels of TNF alpha, Fas ligand, Fas receptors, Fas-associated death domain (FADD), Bad, Bax, activated caspase 8, activated caspase 9, and activated caspase 3 were higher in OZR than those in LZR. The protein levels of TNF alpha, Fas ligand, Fas receptors, FADD, activated caspase 8, and activated caspase 3 (Fas pathway) and the protein levels of Bad, Bax, Bax-to-Bcl2 ratio, activated caspase 9, and activated caspase 3 (mitochondria pathway) were lower in OZR-EX than those in OZR. CONCLUSION: Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways become more activated in obesity. Exercise training can prevent obesity-activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways. Our findings demonstrate a new therapeutic effect of exercise training to prevent delirious cardiac Fas-mediated and mitochondria-mediated apoptosis in obesity.

Combined use of a TST and the T-SPOT®.TB assay for latent tuberculosis infection diagnosis before anti-TNF-α treatment.

BACKGROUND: Diagnosis of latent tuberculosis infection (LTBI) before anti-tumour-necrosis factor (anti-TNF) treatment is important. However, the tuberculin skin test (TST) has limitations, and the role of interferon-gamma release assays has not yet been determined. OBJECTIVE: To evaluate the combined use of TST and the T-SPOT(®).TB (T-SPOT) assay prior to anti-TNF treatment. METHODS: From July 2004 to March 2008, 281 patients were treated with anti-TNF agents. TST and T-SPOT were performed simultaneously at baseline. LTBI was defined as a positive TST of ≥10 mm induration or as a positive T-SPOT if TST was ≥5 mm but <10 mm. LTBI treatment was initiated, and patients were followed until August 2010. RESULTS: Positivity rates for TST and T-SPOT were respectively 33.6% (94/280) and 69.1% (186/269). LTBI treatment was initiated in 35.9% (101/281) of the patients, and active TB developed in 2.1% (6/281). Among the six TB patients, three were TST-negative at baseline and received no LTBI treatment, whereas all four who underwent T-SPOT showed positive results at baseline. CONCLUSION: In a TB-prevalent country, TST-defined LTBI diagnosis and treatment seem to be limited in preventing the development of TB before anti-TNF treatment. Further studies for T-SPOT alone or the combined use of TST and T-SPOT (either test positive strategy) for detecting LTBI are necessary.

Cancer risk in patients with pyogenic liver abscess: a nationwide cohort study.

BACKGROUND: There has been no large-scale population-based study on the relationship between pyogenic liver abscesses (PLA) and subsequent cancer risk. AIM: To estimate all cancer risk following a diagnosis of PLA. METHODS: Based on Taiwan's National Health Insurance Research Database, 1257 patients with PLA without prior cancers in the period 1996-2008 were identified and followed-up. The standard incidence ratio (SIR) of each cancer was calculated as the number of observed cancer cases arising among the PLA patients divided by the expected case number of cancer cases according to the national cancer rates. RESULTS: Of the 1257 PLA patients identified, 598 (47.6%) had diabetes mellitus. After a median (±s.d.) follow-up of 3.33 ± 3.45 years, 186 were diagnosed with cancers, including 56 liver cancer, 22 biliary tract cancer and 40 colorectal cancer patients. Patients with PLA had a higher risk of all cancers (SIR, 3.83; 95% CI, 3.30-4.42), liver cancer (SIR, 7.87; 95% CI, 5.94-10.21), biliary tract cancer (SIR, 34.58; 95% CI, 21.67-52.36) and colorectal cancer (SIR, 5.27; 95% CI, 3.76-7.18). The highest SIRs of all cancers, liver cancer, biliary tract cancer and colorectal cancer occurred within 90 days of follow-up (360.82; 95% CI, 278.46-459.91, 257.28; 95% CI, 186.17-346.56, 1153.38; 95% CI 694.08-1801.24, and 52.63; 95% CI 25.2-96.8 respectively). CONCLUSIONS: Pyogenic liver abscesses may herald the onset of cancer, especially hepato-biliary and colon cancer. Further surveys should be conducted for the detection of occult cancers in such patients.

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection.

PURPOSE: To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT). METHODS: Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤ 0.15 [n=80], 0.16-0.3 [n=44], >0.3 [n=30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). RESULTS: LNR (≤ 0.15, 0.16-0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p<0.001) and DFS (66.7%, 55.8%, and 21.9%; p<0.001) rates. In a multivariate analysis, LNR (≤ 0.15, 0.16-0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p<0.001) and DFS (HRs, 1, 1.699, and 3.960; p<0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥ 12 harvested LNs (p<0.05). CONCLUSION: LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.

Relative bioavailability of two 5-mg montelukast sodium chewable tablets: a single dose, randomized, open-label, 2-period crossover comparison in healthy korean adult male volunteers.

Montelukast sodium, cysteinyl leukotriene receptor 1 specific antagonist, has been marketed in Korea for the treatment of bronchial asthma and allergic rhinitis. The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of montelukast 5-mg chewable tablets in healthy Korean male volunteers to meet KFDA regulatory criteria for marketing of the new generic formulation. This study was designed as a single-dose, 2-treatment, and 2-period crossover trial with 32 healthy volunteers. Each subject was randomly assigned to receive the test (Dong-Kook Montelukast Sodium Chewable Tablet 5 mg®) or reference (Singulair Chewable Tablet 5 mg®) formulation. The tablet was chewed 20 times, and then swallowed with 240 mL of water. Plasma concentrations of montelukast up to 24 h after the dose were determined using a validated UPLC-MS/MS method, and the bioequivalence between the 2 formulations was assessed by statistical analysis of mean ratios of log-transformed AUC0-24 h and Cmax. No period or sequence effects were detected. The AUC0-24 h was 1 835 ng·h/mL for the test formulation, and 1 930 ng·h/mL for the reference formulation. The respective values of AUC0-∞ were 1 917 and 2 015 ng·h/mL. The Cmax of the test and reference products (247 and 283 ng/mL, respectively) reached at 2.25 and 2.72 h, respectively. Then, they gradually decreased with the mean terminal t1/2 of 5.25 and 5.30 h for the test and reference products, respectively. The 90% CIs for the ratio of log-transformed AUC0-24 h and Cmax for the test and reference formulations were 0.92-0.99 and 0.83-0.91, respectively. No adverse events were reported in this study. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these fasting healthy Korean male volunteers.

Clinical features of subjects with an isolated FEV1 reduction.

BACKGROUND: The clinical significance of an isolated reduction in forced expiratory volume in 1 second (FEV(1); i.e., low FEV(1), but normal forced vital capacity [FVC] and FEV(1)/FVC) has not been established. OBJECTIVE: To examine the clinical features of subjects with an isolated FEV(1) reduction. METHODS: Clinical, spirometry and radiological data were retrospectively collected from 15,192 subjects attending a medical check-up at the Health Promotion Center of the Asan Medical Center, Korea. Predicted spirometry values were calculated from the Korean reference equations, and the lower limit of normal was set at the 5th percentile. Subjects were divided into four groups: isolated FEV(1) reduction, normal (normal FVC, FEV(1) and FEV(1)/FVC), obstructive (low FEV(1)/FVC) and restrictive (low FVC and normal FEV(1)/FVC). The groups were compared in terms of clinical characteristics. RESULTS: Of the 15,192 subjects, 323 (2.1%) had an isolated FEV(1) reduction, 10,591 (69.7%) were normal, 951 obstructive (6.3%) and 3327 (22.0%) restrictive. The isolated FEV(1) reduction group had a higher proportion of subjects with smoking history (63.2% vs. 45.7%), radiology abnormalities (15.5% vs. 4.3%) and history of respiratory disease (8.4% vs. 3.0%) than the normal group (all P < 0.001). CONCLUSION: An isolated FEV(1) reduction suggests abnormal spirometry, and further study is needed to evaluate whether these cases belong to the obstructive or restrictive group.

Prognostic significance of peritoneal washing cytology in patients with gastric cancer.

BACKGROUND: Positive peritoneal washing cytology is a poor prognostic factor in patients with gastric cancer. The right therapeutic approach for this condition has not been well documented. METHODS: Patients who underwent surgery for gastric cancer with suspected serosal invasion and peritoneal washing cytology at the Korean National Cancer Centre between May 2001 and December 2009 were included in this retrospective study. Clinicopathological factors and overall survival were analysed with respect to the cytological results and presence of peritoneal metastases. Prognostic factors were analysed in patients with positive cytology but without overt peritoneal metastases. RESULTS: A total of 1072 patients were included in the analysis, of whom 900 had negative cytology (C0 group) and 172 had positive cytology (C1 group). No peritoneal metastases (P0) were found in 830 patients (92·2 per cent) in the C0 group. Peritoneal metastases (P1) were found in 76 patients (44·2 per cent) in the C1 group. Median overall survival times in the P0 C1, P1 C0 and P1 C1 subgroups were 20·0, 14·0 and 10·0 months respectively. Multivariable analysis of the P0 C1 subgroup revealed that clinical N0-2 category and gastric resection were significantly associated with better prognosis (median survival 24·0 versus 13·0 months for N0-2 versus N3, and 21·0 versus 4·0 months for resected versus non-resected). CONCLUSION: Positive washing cytology in patients with gastric cancer is a negative prognostic factor for patients with, as well as those without, overt peritoneal metastases. Resection is an option in patients with clinical stage N0-2 disease without peritoneal metastases but with a positive washing cytology finding.