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1.  High morbidity in myocardial infarction and heart failure patients after gastric cancer surgery 
AIM: To evaluate to morbidity and mortality differences between 4 underlying heart diseases, myocardial infarction (MI), angina pectoris (Angina), heart failure (HF), and atrial fibrillation (AF), after radical surgery for gastric cancer.
METHODS: We retrospectively collected data from 221 patients of a total of 15167 patients who underwent radical gastrectomy and were preoperatively diagnosed with a history of Angina, MI, HF, or AF in 8 hospitals.
RESULTS: We find that the total morbidity rate is significantly higher in the MI group (44%) than the Angina (15.7%), AF (18.8%), and HF (23.1%) groups (P < 0.01). Moreover, we note that the risk for postoperative cardiac problems is higher in patients with a history of HF (23.1%) than patients with a history of Angina (2.2%), AF (4.3%), or MI (6%; P = 0.01). The HF and MI groups each have 1 case of cardiogenic mortality.
CONCLUSION: We conclude that MI patients have a higher risk of morbidity, and HF patients have a higher risk of postoperative cardiac problems than Angina or AF.
PMCID: PMC4458773  PMID: 26074701
Stomach neoplasm; Comorbidity; Morbidity; Heart disease; Heart failure
2.  Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001) 
Journal of Gastric Cancer  2013;13(3):164-171.
Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer.
Materials and Methods
Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation.
Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).
PMCID: PMC3804675  PMID: 24156036
Gastrectomy; Stomach neoplasms; Lymph node excision
3.  Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients 
AIM: To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.
METHODS: We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008. We investigated patients who had shown acute renal failure (ARF), and examined their clinical characteristics, laboratory data, use of preventive measures, treatment cycles, the amount of cisplatin administered, recovery period, subsequent treatments, and renal status between the recovered and unrecovered groups.
RESULTS: Forty-one of the 552 patients had serum creatinine (SCR) levels greater than 1.5 mg/dL. We found that pre-ARF SCR, ARF SCR, and ARF glomerular filtration rates were significantly associated with renal status post-ARF between the two groups (P = 0.008, 0.026, 0.026, respectively). On the receiver operating characteristic curve of these values, a 1.75 mg/dL ARF SCR value had 87.5% sensitivity and 84.8% specificity (P = 0.011).
CONCLUSION: Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.
PMCID: PMC3163249  PMID: 21941418
Acute renal failure; Cisplatin; Drug toxicities; Nephrotoxicity
4.  Solid fusion after lumbosacral arthroplasty 
World Journal of Orthopedics  2013;4(3):157-160.
A 55-year-old female was diagnosed with L5-S1 degenerative disc disease (DDD). Initial scores by the visual analogue scale (VAS) were 5 (back) and 9 (leg) and the Oswestry disability index (ODI) was 32. Arthroplasty was performed. Clinical and radiographic monitoring took place thereafter at one month, three months, six months and annually. At one month, VAS scores were 2 (back) and 3 (leg), ODI was 12 and ROM was 2.1° by radiographs. At two years, VAS scores were 1 (back) and 2 (leg), ODI was 6 and ROM was approaching 0. Five years after surgery, the entire operated segment (L5-S1) was solidly fused. A malpositioned disc implant may impair normal spinal movement, culminating in heterotopic ossification or complete fusion of the operated segment.
PMCID: PMC3717251  PMID: 23878786
Total disc replacement; Lumbar spine; Heterotopic ossification; Fusion, Arthroplasty; Solid fusion
5.  Successful Treatment of Duodenal Variceal Bleeding by Endoscopic Clipping 
Clinical Endoscopy  2013;46(4):403-406.
Duodenal varix bleeding is an uncommon cause of gastrointestinal bleeding in patients with portal hypertension but can cause severe and potentially fatal bleeding. However, the incidence is low and a good treatment method has not been well established yet. Duodenal variceal bleeding can be treated surgically or nonsurgically. We have successfully treated a patient with duodenal variceal bleeding secondary to liver cirrhosis using hemoclips to control the bleeding.
PMCID: PMC3746148  PMID: 23964340
Gastrointestinal bleeding; Duodenal varix; Endoscopic clipping
7.  A New Technical Approach to Monitor the Cellular Physiology by Atomic Force Microscopy 
Atomic force microscopy (AFM) has become an important medical and biological tool for non-invasive imaging and measuring the mechanical changes of cells since its invention by Binnig et al. AFM can be used to investigate the mechanical properties of cellular events in individual living cells on a nanoscale level. In addition, the dynamic cellular movements induced by biochemical activation of specific materials can be detected in real time with three dimensional resolution. Force measurement with the use of AFM has become the tool of choice to monitor the mechanical changes of variable cellular events. In addition, the AFM approach can be applied to measure cellular adhesion properties. Moreover, the information gathered from AFM is important to understanding the mechanisms related to cellular movement and mechanical regulation. This review will discuss recent contributions of AFM to cellular physiology with a focus on monitoring the effects of antihypertensive agents in kidney cells.
PMCID: PMC3597918  PMID: 23508877
Atomic force microscopy; Mesangial cell; Antihypertensive agents
8.  Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy 
AIM: To investigate the relationship between the function of vagus nerve and peptide YY3-36 and ghrelin levels after subtotal gastrectomy.
METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.
RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].
CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY3-36.
PMCID: PMC3420002  PMID: 22912556
Anal cushion; Anal incontinence; Liquids continence test; Wexner score; Hemorrhoidectomy
9.  Comparison of Percutaneous Endoscopic Lumbar Discectomy and Open Lumbar Microdiscectomy for Recurrent Disc Herniation 
The purpose of this study was to compare clinical and radiological outcomes of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar microdiscectomy (OLM) for recurrent disc herniation.
Fifty-four patients, who underwent surgery, either PELD (25 patients) or repeated OLM (29 patients), due to recurrent disc herniation at L4-5 level, were divided into two groups according to the surgical methods. Excluded were patients with sequestrated disc, calcified disc, severe neurological deficit, or instability. Clinical outcomes were assessed using Visual Analogue Scale (VAS) score and Oswestry Disability Index (ODI). Radiological variables were assessed using plain radiography and/or magnetic resonance imaging.
Mean operating time and hospital stay were significantly shorter in PELD group (45.8 minutes and 0.9 day, respectively) than OLM group (73.8 minutes and 3.8 days, respectively) (p < 0.001). Complications occurred in 4% in PELD group and 10.3% in OLM group in the perioperative period. At a mean follow-up duration of 34.2 months, the mean improvements of back pain, leg pain, and functional improvement were 4.0, 5.5, and 40.9% for PELD group and 2.3, 5.1, and 45.0% for OLM group, respectively. Second recurrence occurred in 4% after PELD and 10.3% after OLM. Disc height did not change after PELD, but significantly decreased after OLM (p = 0.0001). Neither sagittal rotation angle nor volume of multifidus muscle changed significantly in both groups.
Both PELD and repeated OLM showed favorable outcomes for recurrent disc herniation, but PELD had advantages in terms of shorter operating time, hospital stay, and disc height preservation.
PMCID: PMC2803265  PMID: 20062565
Reherniation; Discectomy; Lumbar spine
10.  Microdecompression for Extraforaminal L5-S1 Disc Herniation; The Significance of Concomitant Foraminal Disc Herniation for Postoperative Leg Pain 
To analyze the relationship of concomitant foraminal lumbar disc herniation (FLDH) with postoperative leg pain after microdecompression for extraforaminal lumbar disc herniation (EFLDH) at the L5-S1 level.
Sixty-five patients who underwent microdecompression for symptomatic EFLDH at the L5-S1 level were enrolled. According to the severity of accompanying FLDH, EFLDH was classified into four categories (Class I : no FLDH; Class II : mild to moderate FLDH confined within a lateral foraminal zone; Class III : severe FLDH extending to a medial foraminal zone; Class IV : Class III with intracanalicular disc herniation). The incidence of postoperative leg pain, dysesthesia, analgesic medication, epidural block, and requirement for revision surgery due to leg pain were evaluated and compared at three months after initial surgery.
The incidences of postoperative leg pain and dysesthesia were 36.9% and 26.1%, respectively. Pain medication and epidural block was performed on 40% and 41.5%, respectively. Revision surgery was recommended in six patients (9.2%) due to persistent leg pain. The incidences of leg pain, dysesthesia, and requirement for epidural block were higher in Class III/IV, compared with Class I/II. The incidence of requirement for analgesic medication was significantly higher in Class III/IV, compared with Class I/II (p=0.02, odds ratio=9.82). All patients who required revision surgery due to persistent leg pain were included in Class III/IV.
Concomitant FLDH seems related to postoperative residual leg pain after microdecompression for EFLDH at the L5-S1 level.
PMCID: PMC2588286  PMID: 19096652
Extraforaminal; Intervertebral disc; Lumbosacral spine
11.  The Vibrio cholerae vieSAB Locus Encodes a Pathway Contributing to Cholera Toxin Production 
Journal of Bacteriology  2002;184(15):4104-4113.
The genes encoding cholera toxin (CT), ctxAB, are coregulated with those for other Vibrio cholerae virulence factors by a cascade of transcriptional activators, including ToxR, TcpP, and ToxT. Additional regulators that modulate expression of ctxAB during infection were recently identified in a genetic selection. A transposon insertion in vieS, the sensor kinase of the VieSAB three-component signal transduction system, resulted in failure to induce expression of a ctxA-recombinase fusion during murine infection. To determine which components of the VieSAB system are essential for CT regulation, ctxAB transcript levels were assessed by RNase protection assay in various vieSAB in-frame deletion mutants after growth in vitro under virulence gene inducing conditions. A threefold reduction in ctxAB transcript levels was observed for the ΔvieSAB strain; consistent with this, the ΔvieSAB strain produced twofold less CT protein than the wild type, and this defect was complementable in trans. These results suggest that the VieSAB three-component system is required for full activation of the ctxAB operon during in vitro growth as well as during infection. The VieSAB system may regulate ctxAB expression indirectly by affecting production of ToxT, because decreased toxT transcript levels were observed in the ΔvieSAB strain.
PMCID: PMC135224  PMID: 12107127
12.  Feasibility of Single-Input Tracer Kinetic Modeling with Continuous-Time Formalism in Liver 4-Phase Dynamic Contrast-Enhanced CT  
The modeling of tracer kinetics with use of low-temporal-resolution data is of central importance for patient dose reduction in dynamic contrast-enhanced CT (DCE-CT) study. Tracer kinetic models of the liver vary according to the physiologic assumptions imposed on the model, and they can substantially differ in the ways how the input for blood supply and tissue compartments are modeled. In this study, single-input flow-limited (FL), Tofts-Kety (TK), extended TK (ETK), Hayton-Brady (HB), two compartment exchange (2CX), and adiabatic approximation to the tissue homogeneity (AATH) models were applied to the analysis of liver 4-phase DCE-CT data with fully continuous-time parameter formulation, including the bolus arrival time. The bolus arrival time for the 2CX and AATH models was described by modifying the vascular transport operator theory. Initial results indicate that single-input tracer kinetic modeling is feasible for distinguishing between hepatocellular carcinoma and normal liver parenchyma.
PMCID: PMC4521587
Continuous-time tracer kinetic modeling; Bolus arrival time; Vascular transport operator; Four-phase dynamic contrast-enhanced CT
13.  The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial 
PLoS ONE  2015;10(6):e0128632.
Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.
PMCID: PMC4476682  PMID: 26098847
14.  Changes in the Adjacent Segment 10 Years After Anterior Lumbar Interbody Fusion for Low-Grade Isthmic Spondylolisthesis 
Adjacent segment degeneration is a long-term complication of arthrodesis. However, the incidence of adjacent segment degeneration varies widely depending on the patient’s age and underlying disease and the fusion techniques and diagnostic methods used.
We determined (1) the frequency of adjacent segment degeneration and increased lordosis on imaging tests, (2) the frequency and severity of clinical sequelae of these findings, including revision surgery, and (3) the sequence of degeneration and risk factors for degeneration.
Seventy-three patients underwent anterior lumbar interbody fusion for low-grade isthmic spondylolisthesis at one institution between October 2000 and February 2002. Forty-nine (67%) of the original patients had complete radiographic and clinical followup for 10 years. CT and MRI were performed at 5 years and 10 years in all cases. The disc height, sagittal profiles, and facet and disc degeneration at adjacent levels were examined to identify radiographic and clinical adjacent segment degeneration. Mean followup was 134.2 months (range, 120–148 months).
Cranial segment lordosis increased (from 14.8° to 18.5°; p < 0.001), while caudal segment lordosis changed little (from 16.4° to 17.3°). Radiographic and clinical adjacent segment degeneration occurred in 19 (38.8%) and six (12.2%) patients, respectively, and two patients (4.1%) underwent revision surgery. Patients with adjacent segment degeneration had more advanced preexisting facet degeneration than patients without adjacent segment degeneration (odds ratio: 18.6; 95% CI, 1.97–175.54, p = 0.01). Acceleration of disc and facet degeneration occurred in 4.1% and 10.2%, respectively.
Adjacent segment degeneration requiring surgery is rare, although radiographic adjacent segment degeneration is common after anterior lumbar interbody fusion for isthmic spondylolisthesis. The only risk factor we found was preexisting facet degeneration of the cranial segment.
Level of Evidence
Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence
PMCID: PMC4016462  PMID: 23990447
15.  Correlations of Human Epithelial Growth Factor Receptor 2 Overexpression with MUC2, MUC5AC, MUC6, p53, and Clinicopathological Characteristics in Gastric Cancer Patients with Curative Resection 
Background. The purpose of this study was to evaluate the relationships between HER2 overexpression in the tumor and MUC2, MUC5AC, MUC6, and p53 status and clinicopathological characteristics of gastric cancer patients. Methods. This retrospective study included 282 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between April 2011 and December 2012. All tumor samples were examined for HER2 expression by immunohistochemistry (IHC) and MUC2, MUC5AC, MUC6, and p53 expression by staining. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results. The HER2-positive rate was 18.1%. Although no association was found between HER2 expression and MUC5AC, the expression of MUC2, MUC6, and p53 was significantly correlated with HER2 positivity, respectively (P = 0.004, 0.037, 0.002). Multivariate analysis revealed that HER2 overexpression and nodal status were independent prognostic factors. Conclusions. HER2 overexpression in gastric carcinoma is an independent poor prognostic factor.
PMCID: PMC4427822  PMID: 26060493
16.  Imaging for assessment of treatment response in hepatocellular carcinoma: Current update 
Morphologic methods such as the Response Evaluation Criteria in Solid Tumors (RECIST) are considered as the gold standard for response assessment in the management of cancer. However, with the increasing clinical use of antineoplastic cytostatic agents and locoregional interventional therapies in hepatocellular carcinoma (HCC), conventional morphologic methods are confronting limitations in response assessment. Thus, there is an increasing interest in new imaging methods for response assessment, which can evaluate tumor biology such as vascular physiology, fibrosis, necrosis, and metabolism. In this review, we discuss various novel imaging methods for response assessment and compare them with the conventional ones in HCC.
PMCID: PMC4419421  PMID: 25969635
Computed tomography perfusion; diffusion weighted imaging; dynamic contrast-enhanced magnetic resonance imaging; hepatocellular carcinoma; positron emission tomography
17.  Does pre-existing L5-S1 degeneration affect outcomes after isolated L4-5 fusion for spondylolisthesis? 
Concerns have been raised regarding residual symptoms of caudal segment (L5-S1) degeneration that may affect clinical outcomes or require additional surgery after isolated L4-5 fusion, especially if there is pre-existing L5-S1 degeneration. This study aimed to evaluate the L5-S1 segment after minimally invasive lumbar interbody fusion at the L4-5 segment, as well as the influence of pre-existing L5-S1 degeneration on radiologic and clinical outcomes.
This retrospective study evaluated patients with isthmic spondylolisthesis and degenerative spondylolisthesis who underwent mini-open anterior lumbar interbody fusion with percutaneous pedicle screw fixation (PSF) or minimally invasive transforaminal interbody fusion with PSF at the L4-5 segment. The minimum follow-up period was 7 years, and radiographic evaluations were conducted via magnetic resonance imaging, computed tomography, and plain radiography at the 5-year follow-up. Clinical outcomes were assessed using the Visual Analog Score, Oswestry Disability Index, and surgical satisfaction rate. Patients were divided into two groups, those with and without pre-existing L5-S1 degeneration, and their final outcomes and incidence of radiographic and clinical adjacent segment disease (ASD) were compared.
Among 70 patients who underwent the procedures at our institution, 12 (17.1%) were lost to follow-up. Therefore, this study evaluated 58 patients, with a mean follow-up period of 9.4 ± 2.1 years. Among these patients, 22 patients had pre-existing L5-S1 degeneration, while 36 patients did not have pre-existing L5-S1 segmental degeneration. There were no significant differences in the clinical outcomes at the final follow-up when the two groups were compared. However, radiographic ASD at L5-S1 occurred in seven patients (12.1%), clinical ASD at L5-S1 occurred in three patients (5.2%), and one patient (1.7%) required surgery. In the group with pre-existing degeneration, L5-S1 degeneration was radiographically accelerated in four patients (18.2%) and clinical ASD developed in one patient (4.5%). In the group without pre-existing degeneration, L5-S1 degeneration was radiographically accelerated in three patients (8.3%) and clinical ASD developed in two patients (5.7%). There were no differences in the incidence of ASD when we compared the two groups.
Pre-existing L5-S1 degeneration does not affect clinical and radiographical outcomes after isolated L4-5 fusion.
PMCID: PMC4397729  PMID: 25889310
Pre-existing degeneration; Anterior lumbar interbody fusion; Transforaminal lumbar interbody fusion; Adjacent segment disease; Spondylolisthesis; L5-S1
18.  Postoperative Expansion of Dural Sac Cross-Sectional Area after Unilateral Laminotomy for Bilateral Decompression: Correlation with Clinical Symptoms 
Korean Journal of Spine  2014;11(4):227-231.
Dural sac cross-sectional area (DSCSA) is a way to measure the degree of central spinal canal compression. The objective was to investigate the correlation between the expansion ratio of DSCSA after unilateral laminotomy for bilateral decompression (ULBD) and the clinical results for lumbar spinal stenosis.
We retrospectively reviewed the clinical data and radiographs of 103 patients who underwent ULBD for symptomatic spinal stenosis in one year. We compared preoperative and postoperative clinical data and DSCSA and evaluated the correlation between clinical and radiographic measurements.
There was a significant increase of DSCSA after ULBD (p=0.000) and mean expansion ratio of DSCSA was 203.7±147.2%(range -32.9-826.1%). Clinical outcomes, measured by VAS and ODI were improved significantly not only in early postoperative period, but also in the last follow-up. However, there were no statistically significant correlations between the preoperative DSCSA and clinical symptoms, Perioperative expansion ratio of DSCSA and clinical parameters were also not correlated to the improvement of clinical symptoms significantly in both early postoperative phase and last follow-up.
Our result indicates that the DSCSA itself has a definite limitation to be correlated to the clinical symptoms, and thus meticulous correlation between the clinical presentation and MRI imaging is essential in determination of surgical treatment.
PMCID: PMC4303278  PMID: 25620982
Spinal stenosis; Minimally invasive spinal surgery; Laminotomy; Radiculopathy
19.  Acute Pancreatitis Due to a Duodenal Ulcer 
Clinical Endoscopy  2014;47(6):579-583.
Duodenal ulcers and acute pancreatitis are two of the most commonly encountered gastrointestinal diseases among the general population. However, duodenal ulcer-induced pancreatitis is very rarely reported worldwide. This report elaborates on a distinct medical treatment that contributes to partial or complete treatment of acute pancreatitis induced by a duodenal ulcer scar.
PMCID: PMC4260110  PMID: 25505728
Duodenum; Ulcer; Scar; Pancreatitis; Stent
20.  Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease 
Journal of Korean Medical Science  2014;29(Suppl 2):S123-S130.
It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with ≥200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with ≥200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.
PMCID: PMC4194282  PMID: 25317016
Chronic Renal Insufficiency; Sodium Chloride; Renin; Angiotensinogen
21.  Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection 
Journal of Gastric Cancer  2014;14(3):180-186.
At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab (Herceptin®; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection.
Materials and Methods
A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors.
The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor.
HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.
PMCID: PMC4199885  PMID: 25328763
Stomach neoplasms; Human epidermal growth factor receptor 2; Prognosis
22.  Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles 
PLoS ONE  2014;9(7):e100229.
We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs) is effective for protecting against hemolytic uremic syndrome (HUS) caused by enterohemorrhagic E. coli (EHEC) O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA)-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB). Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs) at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN)/Creatinin (Cr) were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB) subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.
PMCID: PMC4102476  PMID: 25032703
23.  Assessment of mOMV adjuvant efficacy in the pathogenic H1N1 influenza virus vaccine 
Since the pandemic (H1N1) 2009 virus has been a seasonal flu which still poses great human health concerns worldwide, vaccination would be considered as the most effective strategy to control the influenza virus spreading. Here, we assessed adjuvant efficacy of modified outer membrane vesicle (mOMV) towards the pandemic H1N1 split antigen.
Materials and Methods
For this study, mice were vaccinated twice with various amount of antigen (0.05, 0.1, and 0.5 µg/dose hemagglutinin [HA]) that were mixed with mOMV, aluminum hydroxide (alum), and MF59, as well as the combined adjuvant comprising the mOMV plus alum.
We found that all the adjuvanted vaccines of A/California/04/09 (CA04, H1N1) containing HA antigen more than 0.1 µg/dose protected effectively from lethal challenge (maCA04, H1N1) virus, compared to the antigen only group. Furthermore, vaccinated mice received as low as 0.05 µg/dose of the split vaccine containing the combined adjuvant (10 µg of mOMV plus alum) showed a full protection against lethal challenge with H1N1 virus. Taken together, these results suggest that mOMV can exert not only the self-adjuvanticity but also a synergy effect for the vaccine efficacy when combined with alum.
Our results indicate that mOMV could be a promising vaccine adjuvant by itself and it could be used as a vaccine platform for development of various vaccine formulations to prepare future influenza pandemic.
PMCID: PMC4083072  PMID: 25003093
Influenza A virus; A/California/04/09 (CA04, H1N1); Adjuvant; mOMV
24.  A Case of Midazolam Anaphylaxis 
Clinical Endoscopy  2014;47(3):262-265.
Midazolam is a type of anesthetic agent frequently used for conscious sedation during a variety of medical procedures. Anaphylactic reactions to midazolam are rarely reported. However, we observed a case of midazolam hypersensitivity in which emergency measures were required to ensure patient recovery after administration of midazolam as a sedative. The occurrence of the anaphylactic reaction to midazolam was confirmed by elevated serum tryptase levels. The current case report presents a discussion of our findings.
PMCID: PMC4058546  PMID: 24944992
Midazolam; Anaphylaxis; Tryptases
25.  Oblique paraspinal approach for thoracic disc herniations using tubular retractor with robotic holder: a technical note 
European Spine Journal  2012;21(12):2620-2625.
Symptomatic thoracic disc herniations (TDHs) are uncommon and can be surgically treated. Although transthoracic decompression is considered the gold standard, it is associated with significant comorbidities. In particular, approach via a posterior laminectomy has been associated with poor results. Several strategies have been developed for the resection of TDHs without manipulating the spinal cord. We describe a minimally invasive technique by using 3-D navigation and tubular retractors with the aid of a robotic holder via an oblique paraspinal approach.
Materials and Methods
The 20-mm working tube via an oblique trajectory through the fascia provides a good surgical field for thoracic discectomy through a microscope. We present our first five patients with TDHs operated using this minimally invasive approach.
Neurological symptoms were improved postoperatively, and there were no surgical complications. There was no instability or recurrence during the follow-up period.
The oblique paraspinal approach may offer an alternative surgical option for treating TDHs.
PMCID: PMC3508237  PMID: 22825631
Oblique paraspinal approach; O-arm; Robotic arm; Thoracic disc herniation; Tubular retractor

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