Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea.

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Reliability of endoscopic ultrasonography and endoscopy in measurement of gastric subepithelial tumor size.

BACKGROUND: Subepithelial tumor (SET) size is important in determining the treatment plan; however, size estimation for gastric SETs has not been well investigated. We aimed to investigate which method predicts SET size most accurately by retrospectively analyzing surgically removed SETs. METHODS: From January 2015 through June 2020, patients who underwent surgical gastric SET removal at Asan Medical Center, Seoul, Korea, were enrolled. SET sizes measured by pathologists and endoscopists were retrospectively reviewed. The reliability of SET size measurement by endoscopic ultrasonography (EUS) and endoscopy was calculated using intraclass correlation coefficient (ICC), with pathologic size as the gold standard. RESULTS: Overall, EUS was highly reliable (ICC 0.86, P < 0.001), and endoscopy was moderately reliable (ICC 0.75, P < 0.001). When analyzed according to SET location, endoscopy was highly reliable in the lesser curvature's lower third (ICC 0.86, P = 0.014), middle third (ICC 0.88, P < 0.001), and upper third (ICC 0.90, P < 0.001); as well as the anterior wall's middle third (0.84, P < 0.001) and the posterior wall's upper third (ICC 0.80, P < 0.001). EUS (ICC 0.96, P = 0.005) and endoscopy (ICC 0.95, P = 0.008) both were most reliable for lower-third posterior wall lesions, whereas endoscopy was unreliable for middle-third greater curvature lesions (ICC 0.41, P = 0.05). CONCLUSIONS: Both EUS and endoscopy were reliable methods for measuring gastric SET size, and overall, EUS was more reliable than endoscopy. In terms of SET location, EUS was consistently reliable, whereas endoscopy showed variable reliability. When measuring SET size by endoscopy, additional size measurements with EUS should be considered in certain locations.

Sarcopenia is associated with severe erectile dysfunction in older adults: a population-based cohort study.

BACKGROUND/AIMS: Sarcopenia and erectile dysfunction (ED) are associated with poor health and quality of life in older men. We investigate the association between sarcopenia and severe ED in community-dwelling older men. METHODS: We prospectively assessed sarcopenia and ED in 519, community-dwelling, older men (mean age, 74.0) in Pyeongchang, Korea, in 2016 to 2017. Sarcopenia was based on muscle mass, grip strength, and gait speed according to the Asian Working Group consensus algorithm. Severe ED was defined as 5-item International Index of Erectile Function questionnaire score under 8. Logistic regressions were used to study associations between incident severe ED and sarcopenia, after adjusting age, cardiovascular risk factors, depression, and polypharmacy. RESULTS: The prevalence of severe ED was 52.4% and that of sarcopenia was 31.6%. At baseline, the prevalence of severe ED was higher in men with sarcopenia than in those without (73.2% vs. 42.8%; adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.18 to 3.03; p = 0.008). Slow gait speed (aOR, 2.80; 95% CI, 1.18 to 6.62; p = 0.019) and decreased muscle mass (aOR, 2.54; 95% CI, 1.11 to 5.81; p = 0.027) were associated with the incidence of severe ED, while decreased grip strength (aOR, 0.76; 95% CI, 0.30 to 1.91; p = 0.564) was not. CONCLUSION: Sarcopenia was associated with severe ED. Slow gait speed, and decreased muscle mass was independently associated with incident severe ED at 1 year. Further research is warranted to examine whether an intervention targeting these components can prevent severe ED.

Relationship between iliac screw loosening and proximal junctional kyphosis after long thoracolumbar instrumented fusion for adult spinal deformity.

PURPOSE: Authors assumed that the stability of iliac screw (IS) fixation could affect the development of proximal junctional kyphosis (PJK). The purpose of this study was to analyze the relationship between IS loosening and PJK after long fusion surgery for adult spinal deformity (ASD). METHODS: Sixty-eight ASD patients (6 males, 62 females; mean age, 68.1 years) who underwent long fusion surgery with IS fixation were reviewed. The incidence and risk factors of IS loosening were investigated. The relationship between IS loosening and PJK was also analyzed. RESULTS: IS loosening and PJK appeared in 33 and 19 patients, respectively. The median time for IS loosening and PJK to develop was 6.0 months (range 1.3-59.2) and 9.1 months (range 1.3-73.2), respectively. PJK developed in patients without IS loosening more frequently than in patients with IS loosening. PJK did not develop in 28 patients who presented with IS loosening first. IS loosening developed 5 months postoperatively in those 28 patients, whereas IS loosening was present 11 months postoperatively in 4 patients who presented with PJK first. Preoperative PT (OR = 1.091) and IS loosening (OR = 0.343) were significantly related with the development of PJK. IS loosening was significantly associated with postoperative PI-LL > 10° (OR = 0.957), postoperative SVA (OR = 1.023), and postoperative PT (OR = 1.072). CONCLUSION: Postoperative sagittal malalignment should be avoided to prevent IS loosening and PJK. IS loosening occurred earlier than PJK and seemed to affect the development of PJK. This relationship supports the hypothesis that distal stability of long constructs may increase proximal junctional stress. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.

Characteristics of sarcopenia by European consensuses and a phenotype score.

BACKGROUND: We aimed to assess the clinical characteristics of sarcopenia by the original and revised European Working Group on Sarcopenia in Older People (EWGSOP 1 and 2), and to propose a new sarcopenia phenotype score (SPS) to improve relevance of clinical outcomes. METHODS: Analyses were performed in 1408 older adults of the Aging Study of PyeongChang Rural Area, a community-based cohort in Korea. For sarcopenia definitions, we used EWGSOP 1, EWGSOP 2, and SPS, a new index counting number of abnormal domains among components of grip strength, gait speed, or muscle mass. Frailty status by the frailty index and the Cardiovascular Health Study frailty score was compared with sarcopenia measures. Prediction ability for composite outcome combining death and institutionalization due to functional decline was assessed among sarcopenia measures. RESULTS: Generally, sarcopenia spectrum by both EWGSOP 1 and 2 was associated with worse functional status in parameters of geriatric assessments. However, population who were considered as sarcopenic by EWGSOP 1, but not by EWGSOP 2, showed increased risk of composite outcome and worse frailty status, compared with people who were classified as not sarcopenic by both EWGSOP 1 and 2. With SPS, dose-response relationship was observed with both frailty status and outcome prediction. Prediction for composite outcome was better in SPS than in EWGSOP 2 classification. CONCLUSIONS: A new SPS might be used to classify sarcopenic burden in older adults to resolve possible inconsistencies in phenotype correlation and outcome prediction of EWGSOP 2 criteria.

Validation of a novel endoscopic program for measuring the size of gastrointestinal lesions.

BACKGROUND: Valid and reliable methods for measurement of lesion sizes during endoscopy have not been established. METHODS: We developed a novel software program (ENDOVER; Poinbionics, Seoul, Republic of Korea) to measure lesions sizes and assessed its validity and reliability. To validate the program, we measured standard coin sizes and estimated measurement errors. To assess program reliability, 32 pictures of endoscopically resected specimens were used to measure tissue sizes six times in a 24-h interval by two examiners. Intraclass correlation coefficients (ICCs) were used to assess intraobserver and interobserver agreements. Agreement between the program and pathological measurements was assessed by absolute differences. RESULTS: The nominal standard sizes of 10-won, 100-won, and 500-won coins were 18.0, 24.0, and 26.5 mm, and the calculated sizes were 18.09, 24.48, and 26.31 mm, respectively. ICCs of the long and short diameters were, respectively, 0.92 [95% confidence interval (CI) 0.87-0.95] and 0.93 (CI 0.89-0.96) for examiner 1 and 0.88 (CI 0.81-0.93) and 0.92 (CI 0.87-0.95) for examiner 2. Interobserver ICCs of the long and short diameters were 0.97 (CI 0.94-0.99) and 0.97 (CI 0.94-0.99), respectively. The mean absolute differences between the program and pathological measurements were 4.4 and 4.7 mm for the long and short diameters, respectively. CONCLUSIONS: Our findings indicate that the novel measurement program is a valid and reliable method for estimation of lesion sizes from endoscopic findings during and after examination.

Can Endoscopic Bleeding Control Improve the Prognosis of Advanced Gastric Cancer Patients?: A Retrospective Case-Control Study.

BACKGROUND: Gastric bleeding is not rare and difficult to treat in gastric cancer patients. We investigated whether this affects survival and if successful bleeding control improves the prognosis. PATIENTS/MATERIAL AND METHODS: We retrospectively reviewed medical records for 64 subjects who underwent endoscopic therapy for gastric cancer bleeding at Asan Medical Center from January 2012 to December 2014 (bleeding group). Each subject was matched 1:2 by age, sex, and American Joint Committee on Cancer staging with 128 randomly selected patients treated for stomach cancer during the same period (control group). Median survival, bleeding treatment methods, successful bleeding control, and rebleeding rate were investigated. RESULTS: The median age was 58.5 years, the male to female ratio 4.3:1. The initial hemostasis rate was 73.4%. Most patients were treated with a single method (37 patients, 57.8%); the coagrasper (32/95 cases, 33.7%) was the most frequently used treatment. Among the 47 patients in which successful bleeding control was achieved, 17 (36.2%) experienced rebleeding after 3 days. The median survival was longer in the control than in the bleeding group (18.5 vs. 6.5 mo), and in the successful bleeding control than in the failed bleeding control group (8.5 vs. 1.8 mo). However, the successful bleeding control group had lower survival than the control group (18.5 vs. 8.5 mo). Multivariate analysis showed that the risk of bleeding was lower in Borrmann type II, IV cancer, but was higher in the patients using antiplatelet or anticoagulant. CONCLUSIONS: Successful bleeding control is essential for improving survival in bleeding gastric cancer patients.

Helicobacter pylori Eradication Therapy Is Effective as the Initial Treatment for Patients with H. pylori-Negative and Disseminated Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

BACKGROUND/AIMS: We investigated the effectiveness of Helicobacter pylori eradication therapy for gastric mucosaassociated lymphoid tissue (MALT) lymphoma regardless of the H. pylori infection status or disease stage. METHODS: From November 1995 to September 2014, 345 subjects who were diagnosed with gastric MALT lymphoma and had received eradication therapy as their first-line treatment were eligible for inclusion in this study. A retrospective review was performed using the medical records. RESULTS: Of the 345 patients, H. pylori infection was detected in 317 patients (91.9%). The complete remission (CR) rate after eradication therapy was 82.3%, which was higher in H. pylori -positive patients than in H. pylori-negative patients (84.5% vs 57.1%, p=0.001). CR rates after eradication did not present significant differences between stages, and the CR rate was 83.3% for stage IE1 and 74.4% for stage IE2 or above (p=0.167). The overall CR rate was 87.2% after additional treatment, and neither H. pylori infection status nor stage showed differences according to the treatment response. CONCLUSIONS: Eradication therapy led to CR in 57.1% of H. pylori-negative patients and in 74.4% of patients with stage IE2 or above. Eradication therapy is worthwhile as an initial treatment for gastric MALT lymphoma regardless of the H. pylori infection status and stage.

Myeloid cell leukemia-1 promotes epithelial-mesenchymal transition of human gastric cancer cells.

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during cancer progression, and cancer stem cells have been shown to acquire the EMT phenotype. Myeloid cell leukemia-1 (Mcl-1) has been implicated in cancer progression and is overexpressed in a variety of human cancers. However, the interaction between Mcl-1 and EMT in human gastric cancer (GC) is unclear. We investigated the impact of Mcl-1 expression levels on EMT and the underlying signaling pathways in human GC cells. We used the human GC cell lines, AGS and SNU638, and small interfering RNAs (siRNAs) to evaluate the effects of Mcl-1 knockdown on cell adhesion, migration and invasion. Expression of Mcl-1 and other target genes was determined using reverse transcription-polymerase chain reaction assays and western blotting. The results revealed that expression levels of Mcl-1 mRNA and protein in the AGS and SNU638 cells were reduced following transfection with Mcl-1 siRNAs. Knockdown of Mcl-1 led to increased cellular adhesion to fibronectin and collagen. Expression levels of vimentin, MMP-2, MMP-9 and Snail protein were decreased following knockdown of Mcl-1. However, expression of E-cadherin was increased in the AGS cells following knockdown of Mcl-1. The expression of cancer stemness markers, such as CD44 and CD133, was not altered by knockdown of Mcl-1. Knockdown of Mcl-1 suppressed tumor cell migration and invasion in both human GC cell lines. Signaling cascades, including the ß-catenin, MEK1/2, ERK1/2 and p38 pathways, were significantly blocked by knockdown of Mcl-1. Our results indicate that Mcl-1 expression induces EMT via ß-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.

Clinical impact of prophylactic antibiotic treatment for self-expandable metallic stent insertion in patients with malignant colorectal obstruction.

Purpose. The aim of this study was to determine the efficacy of prophylactic antibiotics (PA) for reducing the infectious complications and the potential risk factors responsible for the infectious complications after stent insertion for malignant colorectal obstruction. Methods. We performed a retrospective review of 224 patients who underwent self-expandable metallic stent (SEMS) insertion for malignant colorectal obstruction from May 2004 to December 2012. Results. There were 145 patients in the PA group and 79 in non-PA group. The CRP level in PA group was significantly higher than that in non-PA. Abdominal tenderness and mechanical ileus were significantly more frequent in PA group than those in non-PA. The frequency of post-SEMS insertion fever, systemic inflammatory response syndrome (SIRS), and bacteremia was not significantly different between PA and non-PA groups. In multivariate analysis, the CRP level was risk factor related to post-SEMS insertion SIRS. However, in propensity score matching analysis, there was no independent risk factor related to post-SEMS insertion fever, SIRS, and bacteremia. Conclusion. The use of PA in patients with malignant colorectal obstruction may be not effective to prevent the development of infectious complications after SEMS insertion.

Bronchiolitis obliterans associated with Stevens-Johnson syndrome: a case report.

We report a case of bronchiolitis obliterans associated with Stevens-Johnson syndrome. A 59-year-old man presented with respiratory distress that gradually worsened over 3 months. He had been diagnosed with Stevens-Johnson syndrome 3 months before admission. He had no history of previous airway disease. On physical examination, expiratory breathing sounds were not audible, and a chest X-ray revealed a hyperinflated lung. A pulmonary function test indicated a severe obstructive pattern. Computed tomography scans of inspiratory and expiratory phases of respiration showed oligemia and air trapping, and both were more prominent on expiration view than on inspiration view. The pathogenesis of bronchiolitis obliterans associated with Stevens-Johnson syndrome is largely unknown.

Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer.

The expression of myeloid cell leukemia-1 (Mcl­1), a member of the anti-apoptotic Bcl-2 protein family, has been associated with tumor progression and adverse patient outcome. The aims of current study were to evaluate whether Mcl-1 affects the survival or death of gastric cancer cells, and to investigate the prognostic value of its expression in gastric cancer. PcDNA3.1-Mcl-1 expression and Mcl-1 siRNA vectors were used to overexpress and silence Mcl-1 expression in gastric cancer cell lines including SNU638 and TMK1, respectively. Immunohistochemistry was used to determine the expression of Mcl-1 in gastric cancer tissues. Apoptosis was determined by the TUNEL assay, and cell proliferation was determined by immunostaining with a Ki-67 antibody. Mcl-1 knockdown induced apoptosis through the upregulation of caspase-3, and -7, and PARP activity, and the release of Smac/DIABLO and Omi/HtrA2 into the cytoplasm. Additionally, cell cycle arrest occurred due to decrease of cyclin D1, cell division cycle gene 2 (cdc2), and cyclin-dependent kinase 4 and 6. In contrast, overexpression of Mcl-1 inhibited apoptosis and cell cycle arrest. Mcl-1 knockdown did not suppress tumor cell proliferation in gastric cancer cells, whereas overexpression of Mcl-1 enhanced tumor cell proliferation. The JAK2 and STAT3 signaling cascades were significantly blocked by Mcl-1 knockdown. The mean Ki-67 labeling index (KI) value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. However, there was no significant difference between Mcl-1 expression and the apoptotic index (AI). Mcl-1 expression was significantly increased in gastric cancer tissues compared to normal gastric mucosa tissues, and was associated with age, tumor size, stage, depth of invasion, lymph node metastasis and poor survival. Our study showed that Mcl-1 regulates the cell growth and might be a potential prognostic marker for gastric cancer.

Myeloid cell leukemia-1 is associated with tumor progression by inhibiting apoptosis and enhancing angiogenesis in colorectal cancer.

Myeloid cell leukemia-1 (Mcl-1) is a highly expressed anti-apoptotic Bcl-2 protein in cancer. Therefore, inhibition of its expression induces apoptosis in cancer cells and enhances sensitivity to cancer treatment. The aims of this study were to evaluate whether Mcl-1 affects the oncogenic behaviors of colorectal cancer cells, and to document the relationship of its expression with various clinicopathological parameters in colorectal cancer. Mcl-1 knockdown induced apoptosis by activating cleaved caspase-3 and -9, and increasing the expression of the pro-apoptotic protein, PUMA. Mcl-1 knockdown induced cell cycle arrest by decreasing cyclin D1, CDK4 and 6, and by increasing p27 expression. Mcl-1 knockdown decreased both endothelial cell invasion and tube formation, and decreased the expression of VEGF. The phosphorylation level of STAT3 was decreased by Mcl-1 knockdown. The mean apoptotic index value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. The mean microvessel density value of Mcl-1 positive tumors was significantly higher than that of negative tumors. Mcl-1 expression was significantly increased in colorectal cancer, also associated with tumor stage, lymph node metastasis, and poor survival. These results indicate Mcl-1 is associated with tumor progression through its inhibition of apoptosis and enhancement of angiogenesis in colorectal cancer.

Endoscopic ultrasonographic characteristics of gastric schwannoma distinguished from gastrointestinal stromal tumor.

BACKGROUND/AIMS: Gastric schwannoma (GS), a rare neurogenic mesenchymal tumor, is usually benign, slow-growing, and asymptomatic. However, GS is often misdiagnosed as gastrointestinal stromal tumors (GIST) on endoscopic and radiological examinations. The purpose of this study was to evaluate EUS characteristics of GS distinguished from GIST. METHODS: A total of 119 gastric subepithelial lesions, including 31 GSs and 88 GISTs, who were histologically identified and underwent EUS, were enrolled in this study. We evaluated the EUS characteristics, including location, size, gross morphology, mucosal lesion, layer of origin, border, echogenic pattern, marginal halo, and presence of an internal echoic lesion by retrospective review of the medical records. RESULTS: GS patients comprised nine males and 22 females, indicating female predominance. In the gross morphology according to Yamada's classification, type I was predominant in GS and type III was predominant in GIST. In location, GSs were predominantly located in the gastric body and GISTs were predominantly located in the cardia or fundus. The frequency of 4th layer origin and isoechogenicity as compared to the echogenicity of proper muscle layer was significantly more common in GS than GIST. Although not statistically significant, marginal halo was more frequent in GS than GIST. The presence of an internal echoic lesion was significantly more common in GIST than GS. CONCLUSIONS: The EUS characteristics, including tumor location, gross morphology, layer of origin, echogenicity in comparison with the normal muscle layer, and presence of an internal echoic lesion may be useful in distinguishing between GS and GIST.

Livin is associated with the invasive and oncogenic phenotypes of human hepatocellular carcinoma cells.

AIM: Livin, a member of the inhibitors of apoptosis proteins, is expressed in variable cancers, and its expression is considered a poor prognostic marker. The aims of this study were to observe the effect of Livin on the behaviors of hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC tissues and its relation to prognosis. METHODS: The biological effects of Livin on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells. Migration, invasion and proliferation assays were performed. Flow cytometric analyses and western blotting were used to evaluate the impact of Livin on apoptosis and the cell cycle. In addition, western blotting and immunohistochemistry were used to investigate Livin expression in HCC tissues. RESULTS: Livin knockdown suppressed tumor cell migration, invasion and proliferation in HCC cells, and increased the proportion of apoptotic cells as compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown resulted in the activation of caspases and increased apoptosis. In addition, Livin knockdown modulated cell cycle regulatory protein levels such as decrease of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor (CDKI) level in HCC cells. The Livin protein level was significantly elevated in HCC tissues as compared with normal hepatic tissues. However, Livin expression was not found to be associated with clinicopathological parameters, which included patient survival. CONCLUSION: These results suggest that Livin is associated with invasive and oncogenic phenotypes of human HCC cells.

Expression of early growth response-1 in colorectal cancer and its relation to tumor cell proliferation and apoptosis.

Early growth response-1 (Egr-1) is implicated in the regulation of cell growth, proliferation, differentiation and apoptosis. Egr-1 is considered tobe either a tumor-suppressor or tumor-promoter, depending on the cell type and environment. The aim of the present study was to evaluate the expression of Egr-1 in colorectal cancer and its correlation with tumor cell proliferation, apoptosis and clinicopathological features. The expression of Egr-1 in colorectal cancer tissues was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and cellular proliferative activity was evaluated by immunohistochemical staining with the Ki-67 antibody. Egr-1 expression was significantly elevated in colorectal cancer tissues, when compared to that in the paired normal mucosa at the mRNA and protein levels. In addition, Egr-1 expression was significantly increased in the metastatic lymph node tissues, when compared to that in the non­metastatic lymph node tissues at the protein level. The mean Ki-67 labeling index (KI) and apoptotic index (AI) values for 158 tumors were 53.6±15.4 and 9.0±1.0, respectively. Higher KI values were significantly associated with distant metastasis. Lower AI values were significantly associated with lymph node metastasis. However, KI or AI values were not associated with patient survival. The mean KI value of Egr-1-positive tumors was significantly higher than that of Egr-1-negative tumors. However, there was no significant difference between Egr-1 expression and AI value. Positive expression of Egr-1 was significantly associated with age, lymphovascular invasion, lymph node and distant metastasis, tumor stage and poor survival. These results indicate that Egr-1 may be associated with colorectal cancer progression via tumor cell proliferation.

Expression of early growth response-1 in human gastric cancer and its relationship with tumor cell behaviors and prognosis.

The early growth response-1 (Egr-1) is crucial in many cell regulatory processes related to the progression of human cancers. Its overexpression has been demonstrated in variable human cancers and may have prognostic significance. The aims of this current study were to evaluate whether Egr-1 affects invasive and oncogenic phenotypes of human gastric cancer cells, and to examine the relationships between its expression and various clinicopathological parameters, including survival in human gastric cancer patients. We investigated the biologic role of Egr-1 in tumor cell behavior by using a small interfering RNA in human gastric cancer cell lines, AGS and TMK1. The expression of Egr-1 by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry was investigated in human gastric cancer tissues. The knockdown of Egr-1 suppressed tumor cell migration and invasion in AGS and TMK1 cells. Egr-1 expression was significantly increased in human gastric cancer and metastatic lymph node tissues compared to the normal gastric mucosa and non-metastatic lymph node tissues. Positive expression of Egr-1 was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that Egr-1 is associated with human gastric cancer progression through the alteration of tumor cell behavior, such as migration and invasion. Egr-1 expression may help in predicting the clinical outcomes of human gastric cancer patients.

Expression and prognostic significance of Livin in gastric cancer.

Livin is one of the most important members of the inhibitor of apoptosis protein family. It is overexpressed in several types of tumors and may have prognostic significance. The present study investigated the biological role of Livin in the oncogenic behavior of gastric cancer cells, the expression of Livin in gastric cancer tissue and the relationship of its expression with various clinicopathological parameters and patient survival. Small interfering RNA blocked Livin gene expression in AGS and SNU638 human gastric cancer cell lines. The expression of Livin was investigated in gastric cancer tissues by RT-PCR, western blotting and immunohistochemistry. The associations with various clinicopathological parameters and survival were analyzed. Livin knockdown inhibited tumor cell migration, invasion and proliferation in AGS and SNU638 cells. Livin knockdown induced apoptosis by activating caspase-3, caspase-7 and PARP. Livin knockdown induced cell cycle arrest by a decrease in cyclin D1, cyclin-dependent kinase 4 and 6 and an increase in expression of p21 and p27. The ERK1/2 and JNK signaling pathways were inhibited by Livin knockdown. Livin expression was upregulated in gastric cancer tissues at the mRNA and protein levels. However, no significant correlation was found between Livin expression and various clinicopathological parameters including survival. In conclusion, Livin expression may be important in the alteration of invasive and oncogenic phenotypes of gastric cancer cells. The prognostic relevance of Livin remains unclear.

Expression of Livin in colorectal cancer and its relationship to tumor cell behavior and prognosis.

BACKGROUNDS: Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer. METHODS: We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining. RESULTS: Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival. CONCLUSIONS: These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.

Synchronous quadruple primary tumors of thyroid, breast, pancreas, and stomach: a case report.

We herein present the first case to be reported of synchronous quadruple primary cancer of the thyroid, breast, pancreas and stomach in a 70-year-old female. Fluorine-18-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) revealed increased FDG activity in the thyroid, left breast, pancreatic body and antrum of the stomach. To make a definitive diagnosis of synchronous quadruple primary tumors, ultrasound-guided fine-needle aspiration (FNA) cytology and biopsy of the thyroid, breast, pancreas and stomach were performed. FNA cytology and biopsy findings showed papillary carcinoma of the thyroid, invasive ductal adenocarcinoma of the breast, adenocarcinoma of the pancreas and gastrointestinal stromal tumor. To the best of our knowledge, this combination of synchronous multiple primary tumors has not been reported.