• Journal of Gastric Cancer
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• v.17 no.3
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• pp.228-236
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• 2017

Purpose: Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC). Materials and Methods: To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells. Results: In terms of histology as per the World Health Organization criteria (P=0.34), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P<0.01), lymph node metastasis (P=0.01), advanced stage group (P<0.01), cancer-related death (P<0.01), and cancer recurrence (P<0.01). Additionally, a Kaplan-Meier survival analysis revealed that the NSE-OE group had longer cumulative survival times than the NSE-UE group (log-rank test, P<0.01). However, there were no significant differences in the serum levels of NSE expression in patients with GC and healthy volunteers (P=0.28). Conclusions: Patients with NSE overexpressing GC tissues showed better prognostic results, implying that NSE could be a candidate biomarker of GC.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.120-131
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• 2017

Purpose: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. Materials and Methods: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). Results: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. Conclusions: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.295-305
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• 2017

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.374-383
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• 2017

Purpose: Bleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC. Materials and Methods: This study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated. Results: Successful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ${\geq}5$ units of RBCs was a significant risk factor for rebleeding. Conclusions: Despite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (${\geq}5$ units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.283-294
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• 2017

Purpose: This study primarily aimed to investigate the short- and long-term remission rates of type 2 diabetes (T2D) in patients who underwent surgical treatment for gastric cancer, especially patients who were non-obese, and secondarily to determine the potential factors associated with remission. Materials and Methods: We retrospectively reviewed the clinical records of patients with T2D who underwent radical gastrectomy for gastric cancer, from January 2008 to December 2012. Results: T2D improved in 39 out of 70 (55.7%) patients at the postoperative 2-year follow-up and 21 of 42 (50.0%) at the 5-year follow-up. In the 2-year data analysis, preoperative body mass index (BMI) (P=0.043), glycated hemoglobin (A1C) level (P=0.039), number of anti-diabetic medications at baseline (P=0.040), reconstruction method (statistical difference was noted between Roux-en-Y reconstruction and Billroth I; P=0.035) were significantly related to the improvement in glycemic control. Unlike the results at 2 years, the 5-year data analysis revealed that only preoperative BMI (P=0.043) and A1C level (P=0.039) were statistically significant for the improvement in glycemic control; however, the reconstruction method was not. Conclusions: All types of gastric cancer surgery can be effective in short- and long-term T2D control in non-obese patients. In addition, unless long-limb bypass is considered in gastric cancer surgery, the long-term glycemic control is not expected to be different between the reconstruction methods.

• Sleep Medicine and Psychophysiology
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• v.12 no.1
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• pp.64-67
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• 2005

Obstructive sleep apnea syndrome(OSAS) is a common disease in the field of otorhinolaryngology and is characterized by repeated upper airway occlusions occurring during sleep. OSAS can occur due to various etiologies of the nasal, oral, pharyngeal and laryngeal airway in adults. Nasal obstruction can be caused by septal deviation, nasal polyps, concha bullosa, choanal atresia, neoplasms, foreign body, postoperative/post-traumatic synechiae, various rhinitis and so on. There are various kinds of surgical treatment of OSAS including nasal surgery, LAUP, UPPP, surgery of tongue base, tracheostomy and so on, but the effect of nasal surgery on snoring and OSAS is controversial. The authors report the case of a patient who had experienced nasal obstruction, moderate snoring and OSAS and who improved after septoplasty and turbinoplasty.

• Archives of Craniofacial Surgery
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• v.17 no.2
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• pp.56-62
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• 2016

Background: The two most common skin cancers are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The purpose of this study was to describe the detailed clinical behavior of BCC and SCC in the head and neck region over 19 years at a single institution. Methods: A retrospective analysis was performed for all patients with non-melanoma skin cancer who had undergone surgical resection over an 18-year period. Patient charts were reviewed for demographic information, tumor size, onset-to-diagnosis, anatomic location, clinical subtype, histologic differentiation, method of surgical treatment, and recurrence. Results: The review identified 265 cases of either BCC or SCC in 226 patients. Of the 226 patients, 80 (35.4%) were men and 146 (64.6%) were women. BCC (n=138, 55.9%) was more frequent than SCC (109, 44.1%). The most frequent age group was 70-to-79 year olds (45 patients, 35.2%) for BCC and 80-to-89 year olds (41 patients, 41.8%) for SCC. By aesthetic units of the face, the most common location was the nasal unit (44 cases, 31.9%) for BCC and the buccal unit (23 cases, 21.1%) for SCC. The most common clinical subtype of BCC was the nodular type (80 cases, 58.0%). Local flaps were most commonly used to cover surgical defects (136 cases, 55.1%). Recurrent rates were 2.2% for BCC and 5.5% for SCC. Conclusion: In our study, many characteristics of BCC and SCC were compared to previously published reports were generally similar, except the ratio of BCC to SCC. Further study can help to establish the characteristics of BCC and SCC.

• Tuberculosis and Respiratory Diseases
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• v.71 no.1
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• pp.8-14
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• 2011

Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.221-225
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• 2009

Background: Pain is one of the most troublesome problems caused by malignancy. We evaluated the change in pain status according to observance of NCCN guidelines in lung cancer patients. Methods: Lung cancer patients complaining of pain at admission were examined. The pain was assessed with visual analogue scale (VAS) for 20 days and moderate-to-severe pain was defined as more than VAS level 3. The guideline observance was classified as high (more than 80%), medium (50~79%) and low (less than 50%). Results: Among the total 91 lung cancer patients with pain, 34 patients (37%) had moderate-to-severe pain. Their average VAS score at admission was 5.6. It decreased to 2.9 after a 20-day period of pain management. The time to reach a VAS less than 3 was 3 days in a high guideline observance group, while it took 6 days in a low observance group. In addition, the pain in the high observance group was controlled to less than 3 VAS level in 86% of patients, whereas only 25% of patients in the low observance group succeeded. Conclusion: Pain was more effectively controlled when the dose of drugs was modified according to NCCN guidelines in lung cancer patients indicating the importance of guideline observance in pain management.