[Show abstract][Hide abstract] ABSTRACT: Purpose:
Treatment of patients with para-aortic lymph node metastasis from colorectal cancer is controversial. The goal of this study was to investigate the technical feasibility of laparoscopic intrarenal para-aortic lymph node dissection in patients with colorectal cancer and clinically suspected para-aortic lymph node dissection.
The inclusion criteria for the laparoscopic approach were patients with infrarenal para-aortic lymph node metastasis from colorectal cancer. Patients who had any other distant metastatic lesion or metachronous para-aortic lymph node metastasis were excluded from this study. Perioperative outcomes and survival outcomes were analyzed.
Between November 2004 and October 2013, 40 patients underwent laparoscopic para-aortic lymph node dissection. The mean operating time was 192.3 ± 68.8 minutes (range, 100-400 minutes) and the mean estimated blood loss was 65.6 ± 52.6 mL (range, 20-210 mL). No patient required open conversion. The postoperative complication rate was 15.0%. Sixteen patients (40.0%) had pathologically positive lymph nodes. In patients with metastatic para-aortic lymph nodes, the 3-year overall survival rate and disease-free survival rate were 65.7% and 40.2%, respectively.
The results of our study suggest that a laparoscopic approach for patients with colorectal cancer with metastatic para-aortic lymph nodes can be a reasonable option for selected patients.
Preview · Article · Jan 2016 · Annals of Surgical Treatment and Research
[Show abstract][Hide abstract] ABSTRACT: Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB) are the leading causes of nosocomial infections. A rapid and sensitive test to detect CRPA and CRAB is required for appropriate antibiotic treatment. We optimized a loop-mediated isothermal amplification (LAMP) assay to detect the presence of bla(VIM-2), bla(IMP-1), and bla(oxA-23), which are critical components for carbapenem resistance. Methods: Two sets of primers, inner and outer primers, were manually designed as previously described. The LAMP buffer was optimized (at 2mM MgSO4) by testing different concentrations of MgSO4. The optimal reaction temperature and incubation time were determined by using a gradient thermocycler. Then, the optimized bla(VIM-2), bla(IMP-1), and bla(oxA-23) LAMP reactions were evaluated by using 120 P aeruginosa and 99 A. baumannii clinical isolates. Results: Only one strain of the 100 CRPA isolates harbored bla(IMP-1), whereas none of them harbored bla(VIM-2). These results indicate that the acquisition of bla(VIM-2) or bla(IMP-1) may not play a major role in carbapenem resistance in Korea. Fifty two strains of the 75 CRAB isolates contained bla(oxA-23), but none contained bla(VIM-2) and bla(IMP-1) alleles. Conclusions: Our results demonstrate the usefulness of LAMP for the diagnosis of CRPA and CRAB.
Preview · Article · Jan 2016 · Annals of Laboratory Medicine
[Show abstract][Hide abstract] ABSTRACT: The causative agent of pandemic cholera, Vibrio cholerae, infects the anaerobic environment of the human intestine. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly induced during anaerobic respiration with trimethylamine N-oxide (TMAO) as an alternative electron acceptor. However, the molecular mechanism of TMAO-stimulated CT production is not fully understood. Herein, we reveal that CT production during anaerobic TMAO respiration is affected by glucose fermentation. When the seventh pandemic V. cholerae O1 strain N16961 was grown with TMAO and additional glucose, CT production was markedly reduced. Furthermore, an N16961 Δcrp mutant, devoid of cyclic AMP receptor protein (CRP), was defective in CT production during growth by anaerobic TMAO respiration, further suggesting a role of glucose metabolism in regulating TMAO-mediated CT production. TMAO reductase activity was noticeably decreased when grown together with glucose or by mutation of the crp gene. A CRP binding region was identified in the promoter region of the torD gene, which encodes a structural subunit of the TMAO reductase. Gel shift assays further confirmed the binding of purified CRP to the torD promoter sequence. Together, our results suggest that the bacterial ability to respire using TMAO is controlled by CRP, whose activity is dependent on glucose availability. Our results reveal a novel mechanism for the regulation of major virulence factor production by V. cholerae under anaerobic growth conditions.
No preview · Article · Dec 2015 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: Background:
Neoadjuvant concurrent chemoradiotherapy combined with total mesorectal excision is the main treatment for patients with locally advanced rectal cancer (LARC). However, because distant metastasis remains the major challenge in the management of LARC, we proposed an additional one cycle of chemotherapy before surgery to improve systemic control.
One hundred sixty-eight patients with clinical stage II and III rectal cancer were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between January 2011 and December 2013 and were considered the study group. In addition, 160 patients were retrospectively reviewed as the historical control group. All the patients underwent total mesorectal excision at 8 weeks after completing the radiotherapy and receiving a total of six cycles of 5-fluorouracil plus leucovorin.
Overall, 155 (96.9 %) of the 168 patients completed their planned six cycles of study treatment. Dose modification at any cycle was observed in 18 patients (10.7 %). The grade 3 to 4 treatment-related toxicity rate was 27.3 %, and the most common grade 3 to 4 hematologic adverse event was neutropenia. With a median follow-up duration of 38 months, the estimated 3-year disease-free survival and OS rates were 79.5 and 86.9 %, respectively.
Adding one cycle of chemotherapy during the resting period between chemoradiotherapy and surgery was found to be feasible in patients with LARC in terms of the chemotherapy-related adverse events and postoperative complications. These results warrant further investigation in future prospective randomized trials.
No preview · Article · Dec 2015 · Annals of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: This study investigated effects of a flavonoid-rich ethanol extract of persimmon leaf (PL), an ethanol extract of Citrus junos Sieb (CJS), and a PL-CJS mixture (MPC) on mice fed a high-fat diet (HFD). We sought to elucidate the mechanisms of biological activity of these substances using measurements of blood coagulation indices and lipid metabolism parameters. C57BL/6J mice were fed a HFD with PL (0.5% w/w), CJS (0.1% w/w), or MPC (PL 0.5%, CJS 0.1% w/w) for 10 weeks. In comparison with data obtained for mice in the untreated HFD group, consumption of MPC remarkably prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas exposure to PL prolonged aPTT only. Lower levels of plasma total cholesterol (Total-C), hepatic cholesterol, and erythrocyte thiobarbituric acid-reactive substances (TBARS), hepatic HMG-CoA reductase, and decreased SREBP-1c gene expression were observed in mice that received PL and MPC supplements compared to the respective values detected in the untreated HFD animals. Our results indicate that PL and MPC may have a beneficial effect on blood circulation and lipid metabolism in obese mice.
No preview · Article · Dec 2015 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: The detection of biomarkers in the liquid phase using mechanical sensors is difficult because of noise caused by the liquid. To reduce and verify the side effects of liquid loading, we performed calculations and experiments to determine the shift in resonant frequency according to the loading conditions. A 2-μm-thick piezoelectric rectangular micro-diaphragm with a 500 × 500 μm membrane was used. These dimensions were determined such that there would be an analogous resonant frequency shift ratio in both (1, 1) and (2, 2) modes. By calculating and measuring the resonant frequency, we verified that the resonant frequency of the sensor would change only through contact with the liquid, even the resonant frequency change by only liquid much higher than the changes caused by the nanoparticles. The real signal constituted only 0.017% of the initial resonant frequency. To enhance the sensitivity by reducing the unexpected surface stress in the liquid, the liquid was dropped onto the surface of the micro-diaphragm. This resulted in an improvement of more than 10 times the sensitivity in both modes. In addition, by controlling the position in the micro-diaphragm resonating sensor, more sensitive positions with large displacements were determined according to each mode.
[Show abstract][Hide abstract] ABSTRACT: We developed a multichannel all-in-one phantom dosimeter system composed of nine sensing probes, a chest phantom, an image intensifier, and a complementary metal-oxide semiconductor (CMOS) image sensor to measure the dose distribution of an X-ray beam used in radiation diagnosis. Nine sensing probes of the phantom dosimeter were fabricated identically by connecting a plastic scintillating fiber (PSF) to a plastic optical fiber (POF). To measure the planar dose distribution on a chest phantom according to exposure parameters used in clinical practice, we divided the top of the chest phantom into nine equal parts virtually and then installed the nine sensing probes at each center of the nine equal parts on the top of the chest phantom as measuring points. Each scintillation signal generated in the nine sensing probes was transmitted through the POFs and then intensified by the image intensifier because the scintillation signal normally has a very low light intensity. Real-time scintillation images (RSIs) containing the intensified scintillation signals were taken by the CMOS image sensor with a single lens optical system and displayed through a software program. Under variation of the exposure parameters, we measured RSIs containing dose information using the multichannel all-in-one phantom dosimeter and compared the results with the absorbed doses obtained by using a semiconductor dosimeter (SCD). From the experimental results of this study, the light intensities of nine regions of interest (ROI) in the RSI measured by the phantom dosimeter were similar to the dose distribution obtained using the SCD. In conclusion, we demonstrated that the planar dose distribution including the entrance surface dose (ESD) can be easily measured by using the proposed phantom dosimeter system.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Distal myopathy is a heterogeneous group of muscle diseases characterized by predominant distal muscle weakness. A study was done to identify the underlying cause of autosomal recessive adolescent-onset distal myopathy.
Four patients from two unrelated Korean families were evaluated. To isolate the genetic cause, exome sequencing was performed. In vitro and in vivo assays using myoblast cells and zebrafish models were performed to examine the ADSSL1 mutation causing myopathy pathogenesis.
Patients had an adolescent-onset distal myopathy phenotype which included distal dominant weakness, facial muscle weakness, rimmed vacuole, and mild elevation of serum creatine kinase. Exome sequencing identified completely cosegregating compound heterozygous mutations (p.D304N and p.I350fs) in ADSSL1 which encodes a muscle-specific adenylosuccinate synthase in both families. None of the controls had both mutations, and the mutation sites were located in well conserved regions. Both the D304N and I350fs mutations in ADSSL1 led to decreased enzymatic activity. The knock-down of the adssl1 gene significantly inhibited the proliferation of mouse myoblast cells, and the addition of human wild-type ADSSL1 reversed the reduced viability. In an adssl1 knock-downed zebrafish model, muscle fibers were severely disrupted, which was evaluated by myosin expression and birefringence. In these conditions, supplementing wild-type ADSSL1 protein reversed the muscle defect.
We suggest that mutations in ADSSL1 are the novel genetic cause of the autosomal recessive adolescent-onset distal myopathy. This study broadens the genetic and clinical spectrum of distal myopathy and will be useful for exact molecular diagnostics. This article is protected by copyright. All rights reserved.
No preview · Article · Oct 2015 · Annals of Neurology
[Show abstract][Hide abstract] ABSTRACT: Objective:
The goal of this study was to ascertain optimal assisted hatching (AH) method in frozen embryo transfer. We compared the effect of depending on whether mechanical or laser-AH was performed before or after the vitrification of embryo development rate and blastocyst cell numbers.
In order to induce superovulation, pregnant mare's serum gonadotropin followed by human chorionic gonadotropin were injected into 4- to 5-week-old female mice. 2-cell embryos were then collected by flushing out the oviducts. The Expanded blastocysts were recovered after the collected embryos were incubated for 48 hours, and were then subjected to artificial shrinkage (AS) and cross-mechanical AH (cMAH) or quarter-laser zona thinning-AH (qLZT-AH) were carried out using the expanded blastocysts before or after vitrification. After 48 hours of incubation, followed by vitrification and thawing (V-T), and blastocysts were fluorescence stained and observed.
The rate of formation of hatched blastocysts after 24 and 72 hours of incubation was significantly higher in the AS/qLZT-AH/V-T group than in the other groups (p<0.05). The cell number of the inner cell mass was higher in AS/V-T/non-AH and AS/V-T/cMAH groups than those of others (p<0.05). In the control group, the number of trophectoderm and the total cell number were higher than in the AS-AH group (p<0.05).
The above results suggest that AS and AH in vitrification of expanded blastocysts lead to the more efficient formation of hatched blastocysts in mice.
Preview · Article · Oct 2015 · Clinical and Experimental Reproductive Medicine
[Show abstract][Hide abstract] ABSTRACT: We evaluated the clinical influence of cancer stem cells (CSCs) on residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were assessed. To identify CSCs, immunohistochemistry was performed using their surrogate makers (CD44 and aldehyde dehydrogenase 1 [ALDH1]) in full section tissues. Of the 145 cases, ALDH1 and CD44 positivity was found in 80.0 % (n = 116) and 47.6 % (n = 69), respectively; ALDH1 positivity showed weakly positive correlation with CD44 (r
= 0.269, P = 0.002). ALDH1 and CD44 positivity was related to lower tumor regression grade (TRG) (P = 0.009 and 0.003, respectively). Additionally, ALDH1 positivity was associated with positive circumferential resection margin (P = 0.019). However, ALDH1 and CD44 positivity showed no relationship with KRAS or BRAF mutation. In univariate analysis, ALDH1 positivity was associated with short recurrence-free survival (RFS) (P = 0.005) and rectal cancer-specific survival (RCSS) (P = 0.043), but not CD44 positivity (RFS, P = 0.725; RCSS, P = 0.280). In multivariate analysis, ALDH1 positivity was an independent prognostic factor for poor RFS (P = 0.039; hazard ratio = 2.997; 95 % confidence interval = 1.059–8.478), but not RCSS (P = 0.571). The expression of ALDH1 assessment independently predicts RFS in patients with residual disease after CRT. These results suggest that targeting CSCs could be an effective therapeutic approach to rectal cancer patients receiving preoperative CRT.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications.
From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive.
During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis.
In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.
[Show abstract][Hide abstract] ABSTRACT: A microarray study has been employed to understand changes of gene expression in E. coli KD43162 resistant to ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, cefazolin, cefepime, aztreonam, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, fosfomycin, and trimethoprim-sulfamethoxazole except for amikacin using disk diffusion assay. Using Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and MALDI-TOF MS analyses, 36 kDa of outer membrane proteins (OMPs) was found to be deleted in the multidrug resistant E. coli KD 43162. Microarray analysis was used to determine up- and down-regulated genes in relation to multidrug resistant E. coli KD43162. Among the up-regulated genes, these genes were corresponded to express the proteins as penicillin-binding proteins (PBPs), tartronate semialdehyde reductase, ethanolamine utilization protein, shikimate kinase I, allantoinase, predicted SAM-dependent methyltransferase, Lglutamine: D-fructose-6-phosphate aminotransferase (GFAT), phosphoglucosamine mutase, predicted N-acetylmannosamine kinase, and predicted N-acetylmannosamine-6-P epimerase. Up-regulation of PBPs, one of primary target sites of antibiotics, might be responsible for the multidrug resistance in E. coli with increasing amount of target sites. Up-regulation of GFAT enzyme may be related to the up-regulation of PBPs because GFAT produces N-acetylglucosamine, a precursor of peptidoglycans. One of GFAT inhibitors, azaserine, showed a potent inhibition on the growth of E. coli KD43162. In conclusion, up-regulation of PBPs and GFATs with the loss of 36 kDa OMP refers the multidrug resistance in E. coli KD 43162.
No preview · Article · Sep 2015 · Journal of Applied Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: The autofluorescence of the retina that originates primarily from lipofuscin fluorophores in retinal pigment epithelial cells, is observed to undergo photobleaching during the acquisition of fundus autofluorescence images. Bisretinoid fluorophores isolated from retinal pigment epithelial cells have the spectral characteristics consistent with their being the source of fundus autofluorescence. Clinically relevant experiments were designed to better understand conditions in the micromilieu of bisretinoid fluorophores that can influence fluorescence efficiencies, photobleaching, and subsequent fluorescence recovery of this fluorophore. The consumption of the bisretinoid A2E due to photooxidation-induced degradation was quantified in solvent systems of variable relative permittivity (formerly called dielectric constant), in micelles, and in phospholipid vesicles of varying composition. Reorganization within biphasic systems was also examined. A2E content was measured by high performance liquid chromatography (HPLC) and fluorescence intensity was quantified spectroscopically. As solvent polarity was increased, A2E fluorescent spectra exhibited red-shifted maxima and reduced intensity. A2E was depleted by light irradiation and the loss was more pronounced in less polar solvents, lower concentrations of anionic surfactant, and in gel- versus fluid-ordered phospholipid liposomes. Conditions that permit A2E aggregation promoted photooxidation/photodegradation, while movement of A2E between bisphasic systems was associated with fluorescence recovery after photobleaching. The fluorescence characteristics of A2E are subject to environmental modulation. Photooxidation and photodegradation of bisretinoid can account for fundus autofluorescence photobleaching. Return of fluorescence intensity after photobleaching likely occurs due to redistribution of A2E fractions amongst co-existing heterogeneous microdomains of the lysosomal compartment.
[Show abstract][Hide abstract] ABSTRACT: The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) and its Portsmouth modification (P-POSSUM) are comprehensive assessment methods for evaluating patient and surgical factors widely used to predict 30-day mortality rates. In this retrospective study, we evaluated the usefulness of POSSUM and P-POSSUM in predicting 30-day mortality after intraoperative cardiac arrests in adult patients undergoing non-cardiac surgery.
Among 190486 patients who underwent anesthesia, 51 experienced intraoperative cardiac arrest as defined in our study protocol. Predicted mortality rates were calculated using POSSUM and P-POSSUM equations and were compared with actual outcomes using exponential and linear analyses. In addition, a receiver operating characteristic curve analysis was undertaken, and area-under-the-curve (AUC) values with confidence intervals (CIs) were calculated for POSSUM and P-POSSUM.
Among the 51 patients with intraoperative cardiac arrest, 32 (62.7%) died within 30 days postoperatively. The overall predicted 30-day mortality rates using POSSUM and P-POSSUM were 65.5% and 57.5%, respectively. The observed-to-predicted (O:E) ratio for the POSSUM 30-day mortality was 1.07, with no significant difference between the observed and predicted values (χ²=4.794; p=0.779). P-POSSUM predicted mortality equally well, with an O:E ratio of 1.10 (χ²=8.905; p=0.350). AUC values (95% CI) were 0.771 (0.634-0.908) and 0.785 (0.651-0.918) for POSSUM and P-POSSUM, respectively.
Both POSSUM and P-POSSUM performed well to predict overall 30-day mortality following intraoperative cardiac arrest in adults undergoing non-cardiac surgery at a university teaching hospital in Korea.
Preview · Article · Sep 2015 · Yonsei medical journal