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Altered Recepteur d'Origine nantais (RON) expression transduces signals inducting invasive growth phenotype that includes cell proliferation, migration, matrix invasion, and protection of apoptosis in human cancer cells. The aims of the current study were to evaluate whether RON affects tumor cell behavior and cellular signaling pathways including activator protein-1 (AP-1) and Akt/forkhead box O (FoxO) in human colorectal cancer cells.To study the biological role of RON on tumor cell behavior and cellular signaling pathways in human colorectal cancer, we used small interfering RNA (siRNA) to knockdown RON gene expression in human colorectal cancer cell line, DKO-1.Knockdown of RON diminished migration, invasion, and proliferation of human colorectal cancer cells. Knockdown of RON decreased AP-1 transcriptional activity and expression of AP-1 target genes. Knockdown of RON activated cleaved caspase-3, -7, -9, and PARP, and down-regulated the expression of Mcl-1, survivin and XIAP, leading to induction of apoptosis. Knockdown of RON induced cell cycle arrest in the G2/M phase of cancer cells by an increase of p27 and a decrease of cyclin D3. Knockdown of RON inhibited the phosphorylation of Akt/FoxO signaling proteins such as Ser473 and Thr308 of Akt and FoxO1/3a.These results indicate that knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells.

KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of current study was to evaluate whether KITENIN affects tumor cell invasion and prognosis in human colorectal cancers. We investigated the biologic role of KITENIN on tumor cell invasion by using small interfering RNA in Caco2, DLD1, and SW480. We evaluated the expression of KITENIN and activator protein-1 (AP-1) target genes in human colorectal cancer tissues. The tumor cell invasion was decreased by knockdown of KITENIN in three tested cell lines. The mRNA expression of cyclin D1 and COX-2 was decreased in KITENIN knockdown Caco2 and the mRNA expression of MMP-3 and COX-2 was decreased in KITENIN knockdown DLD1 and SW480. The extracellular-signal protein kinase 1/2 (ERK1/2) phosphorylation was decreased in KITENIN knockdown in three tested cell lines. Expression of KITENIN and AP-1 target genes was significantly increased in human colorectal cancer tissues. The ERK1/2, c-Jun N-terminal kinase (JNK) and p38 phosphorylations were increased in human colorectal cancer tissues. Expression of KITENIN was significantly associated with lymphovascular invasion, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN is associated with human colorectal cancer progression including invasion and metastasis.

KITENIN promotes cancer cell migration and invasion in vitro and cancer metastasis in mouse cancer models, including colon and head and neck cancers. The purposes of this study were to observe the effect of KITENIN on tumor cell behaviors of human hepatocellular carcinoma (HCC) cells and to evaluate its expression in human HCC tissues. To functionally characterize KITENIN in human HCC, we depleted its expression in human HCC cell lines, HepG2 and Huh7, by using small interfering RNA (siRNA). Invasion and proliferation assays were performed. The activator protein-1 (AP-1) transcriptional activity and expression of AP-1 target genes were evaluated by AP-1 luciferase reporter assay and RT-PCR. The contribution of mitogen-activated protein kinase (MAPK) cascade signaling involved in AP-1 activation was assessed by Western blotting. We evaluated the expression of KITENIN and AP-1 target genes at mRNA levels by RT-PCR in human HCC tissues and paired normal hepatic mucosa of the same patients taken by surgery. Knockdown of KITENIN in HepG2 and Huh7 cells resulted in a significant reduction of tumor cell invasion. The tumor cell proliferation was significantly decreased in the KITENIN knocked down Huh7 cells compared to the negative control. The mRNA expressions of MMP-3 and COX-2 were decreased in KITENIN knocked down Huh7 cells. The mRNA expression of MMP-1 was decreased in KITENIN knocked down HepG2 cells. The AP-1 transcriptional activity in Huh7 cells was significantly decreased by knockdown of KITENIN. The JNK and ERK1/2 phosphorylations were decreased in KITENIN knocked down HepG2 and the p38 phosphorylation was decreased in KITENIN knocked down Huh7 cells. The mRNA expressions of KITENIN, MMP-1, and MMP-3 were significantly upregulated in human HCC tissues compared to paired normal mucosa. These results indicate that KITENIN is associated with activation of AP-1 target genes via MAPK cascades signaling in human HCC progression.

Overexpression of recepteur d'Origine nantais (RON) and urokinase plasminogen activator receptor (uPAR) have been observed in human gastric cancers. However, the interaction between RON and uPAR in gastric cancer is unclear. The present study investigated the effect of macrophage-stimulating protein (MSP, the RON ligand) on uPAR expression and the underlying signal pathways in human gastric cancer AGS cells. uPAR messenger RNA expression was induced by MSP in a time- and concentration-dependent manner. MSP also induced uPAR promoter activity. The introduction of RON-specific small interfering RNA (siRNA) significantly affected the MSP-induced uPAR transcription. Deleted and site-directed mutagenesis studies demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the MSP-induced uPAR expression. Studies with expression vectors encoding mutated-type NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the MSP-induced uPAR expression. In addition, MSP induced the activation of extracellular signal-regulated kinase-1/2 (Erk-1/2), c-Jun amino terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Dominant-negative mutants (K97M and TAM67) and specific inhibitors of Erk-1/2 and JNK were able to suppress the MSP-induced uPAR expression. AGS cells pretreated with MSP showed a remarkably enhanced invasiveness, which was partially abrogated by siRNA-targeted RON and uPAR-neutralizing antibodies. The above results suggest that MSP induces uPAR expression via MAPK, AP-1 and NF-κB signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells.

Dysphagia aortica is a rare etiology of dysphagia resulting from extrinsic compression of esophagus by thoracic aortic aneurysm or tortuosity and elongation of thoracic aorta. The clinical findings resemble those of esophageal malignancy or esophageal motility disorders. Therefore, primary diagnosis of dysphagia aortica is very difficult. We, herein, report a case of dysphagia aortica aggravated by wearing the abdominal binder in a 70-year-old woman and review the literature pertaining to this condition. Dysphagia aortica should be considered in the differential diagnosis of dysphagia.

Background and aims 90K, a tumour-associated glycoprotein, interacts with galectins and has roles in host defence by augmenting the immune response, but the serum 90K level was suggested to indicate poor prognosis in several cancers. The cellular mechanisms of 90K action on colorectal cancer (CRC) cell motility and its effect on CRC progression were investigated. Methods The impact of 90K was analysed by combining cell cultures, in vitro assays, and immunohistochemistry. Results Secreted 90K suppresses CRC cell invasion, but this action of 90K is masked through binding with extracellular galectins. A novel pathway is identified comprising a secretory 90K and a CD9/CD82 tetraspanin web; in this pathway, 90K interacts with CD9/CD82, suppresses the Wnt/β-catenin signal via a novel proteasomal-ubiquitination mechanism of β-catenin that is dependent on ISG15 (interferon-stimulated gene-15) modification (ISGylation) but not on glycogen synthase kinase 3β (GSK-3β) and Siah/Adenomatous polyposis coli (APC). In a syngeneic mouse colon tumour model, tumour growth and lung metastasis were increased with 90K knockdown. In colon tissues from stage IV human CRC and invading cancer cells of corresponding metastatic liver tissues, in which β-catenin and galectin expression was higher, immunostained 90K and CD9/CD82 were lower than in adjacent hepatic tissues or colon tissues from stage I. Conclusions 90K itself has antitumour activity in CRC cells via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin when it interacts with CD9/CD82, but is downregulated in advanced CRC tissues. The data suggest a strategy of strengthening this novel pathway with concomitant knockdown of galectins as a potential therapeutic approach to CRC progression.

Rationale Liver abscesses caused by Clostridium species infection are extremely rare. Patient concerns The authors report the first case of a liver abscess due to Clostridium haemolyticum, which occurred after transarterial chemoembolization (TACE) for hepatocellular carcinoma, in a 76-year-old woman who presented with right upper quadrant pain and fever. Diagnoses Computed tomography of the abdomen after the second TACE showed an air-filled abscess around a compact, lipiodolized lesion in the right hepatic lobe. Pus culture showed the growth of C haemolyticum. Interventions Broad-spectrum antibiotics, including piperacillin/tazobactam and metronidazole, were administered, and a percutaneous 10-French pigtail catheter for pus drainage and culture was inserted in the liver abscess. Outcomes Despite administering intensive treatments, she presented with rapid deterioration in mental status, liver function, and infection markers. She was transferred to the local hospital for palliative conservative treatment. Lessons Clostridia infections, including those involving C haemolyticum, are extremely rare, but should be considered as one of the causative organisms of liver abscess formation after TACE because of its rapid and fatal clinical course.

Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation-specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty-five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.

697 Background: The association of DNA mismatch repair (MMR) and KRAS mutation on clinical outcome of patients with colorectal cancer are frequently documented. However, development of more accurate prediction on clinical outcome using combination of both biomarkers remains a worthy area of investigation. The aim of this study was to evaluate the clinical relevance of KRAS mutation and MMR status in Korean patients with colorectal cancer (CRC). Methods: Clinical and pathological information for 1174 patients, who underwent surgery for colorectal cancer in 3 teaching hospitals from 2011 to 2013, were reviewed and recorded. Mutation analysis for exon 2 of KRAS gene was performed by Sanger sequencing. Expression of MMR proteins including MLH1 and MSH2 was evaluated by immunohistochemistry. Results: The overall frequencies of KRAS mutation was 34.9%. Mutations in KRAS codon 12 and codon 13 were detected in 26.7% and 8.2% of patients, respectively. Overall, 90 s (7.7%) tumors that had at least loss of expression for at least one MMR protein were defined as MMR protein deficient (MMR-D), and the remaining tumors were classified as MMR protein intact (MMR-I). According to KRAS mutation and MMR status, CRC was classified to 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group 4 had the best prognosis, and patients in Group 2 had the worst overall survival. KRAS mutation was independently associated with shorter time to recurrence and poorer overall survival. Conclusions: Combination status of KRAS mutation and MMR provide fundamental genetic signatures affecting tumor behavior, and may be used as a prognostic biomarker for CRC patient. These findings should be validated by further larger prospective study. [Table: see text]

Purpose The endoscopic management of a fully covered self-expandable metal stent (SEMS) has been suggested for the primary treatment of patients with anastomotic leaks after total gastrectomy. Embedded stents due to tissue ingrowth and migration are the main obstacles in endoscopic stent management. Materials and methods The effectiveness and safety of endoscopic management were evaluated for anastomotic leaks when using a benign fully covered SEMS with an anchoring thread and thick silicone covering the membrane to prevent stent embedding and migration. We retrospectively reviewed the data of 14 consecutive patients with gastric cancer and anastomotic leaks after total gastrectomy treated from January 2009 to December 2016. Results The technical success rate of endoscopic stent replacement was 100%, and the rate of complete leaks closure was 85.7% (n=12). The mean size of leaks was 13.1 mm (range, 3-30 mm). The time interval from operation to stent replacement was 10.7 days (range, 3-35 days) and the interval from stent replacement to extraction was 32.3 days (range, 18-49 days). The complication rate was 14.1%, and included a single jejunal ulcer and delayed stricture at the site of leakage. No embedded stent or migration occurred. Two patients died due to progression of pneumonia and septic shock 2 weeks after stent replacement. Conclusions A benign fully covered SEMS with an anchoring thread and thick membrane is an effective and safe stent in patients with anastomotic leaks after total gastrectomy. The novelty of this stent is that it provides complete prevention of stent migration and embedding, compared with conventional fully covered SEMS.

Introduction Cholecystokinin (CCK) belongs to a group of endogenous molecules known as brain-gut neuropeptides and functions as a neuropeptide as well as a gut hormone. It remains unclear whether genetic variation of the CCK receptor plays a role in irritable bowel syndrome (IBS). The aim of this study was to determine and compare the allele and genotype frequencies of the CCK1 receptor polymorphisms between healthy controls and patients with IBS.

Background and Aim: Selective bile duct cannulation is a prerequisite for performing therapeutic endoscopic biliary intervention. This study aimed to evaluate if using a soft-tipped guidewire to cannulate the bile duct would increase the success rate of needle-knife fistulotomy for difficult bile duct access. Methods: We reviewed sixty 60 patients with difficult bile duct access who underwent conventional cannulation with radiocontrast dye (29) or guidewire cannulation (31) after needle-knife fistulotomy. Results: There were no significant differences in the demographic data between the two groups. The initial success rate of selective bile duct cannulation was significantly higher in the guidewire cannulation group compared with the conventional cannulation group: 100% versus 79.3%, P = 0.009. The success rate of selective biliary cannulation in the patients with non-dilated common bile duct (

Background/Aims: Food residue is frequently observed in the gastric remnant after distal gastrectomy, despite adequate preparation. We devised a water-intake method to reduce food residue in the gastric remnant by drinking large quantities of water in a short time. The aims of this study were to identify the risk factors for food residue and to study the effectiveness of this new method for endoscopy preparation. Methods: A cohort of 708 patients who underwent distal gastrectomy for gastric cancer was reviewed prospectively. Sixty patients with large amounts of food residue were randomly divided into two groups: a water-intake group (n=40) and a prolonged fasting group (n=20). Results: The incidences of a large amount of food residue were 15.7%, 5.8%, 7.5%, and 2.8% at 3, 12, 24, and 36 months, respectively, after distal gastrectomy. Independent risk factors for food residue were endoscopy at 3 months, diabetes mellitus, a body mass index of ＜19.5, and laparoscopic surgery. The proportion of successful preparations at follow-up endoscopy was higher for the water-intake group (70%) than for the prolonged fasting group (40%, p=0.025). Conclusions: The water- intake method can be recommended as a preparation for endoscopy in patients who have had repetitive food residue or risk factors after distal gastrectomy. (Gut and Liver 2009;3:186-191)

Background ERCP is difficult in patients with a Billroth II gastrectomy because of anatomical changes. Objective Cap-assisted ERCP can improve the cannulation rate and the success rate of stone removal. Design Case series. Setting A tertiary referral center. Patients and Interventions Ten consecutive patients with bile-duct stones (9) or a distal common bile duct stricture (1), who had previously undergone Billroth II gastrectomy and were referred for ERCP, were analyzed for the outcome of their ERCP. All procedures were carried out with a cap-fitted regular forward-viewing endoscope. Main Outcome Measurements Ability to perform afferent loop intubation and bile-duct cannulation. Results Of 10 patients in whom ERCP was attempted, afferent loop intubation and selective bile-duct cannulation were achieved in all patients (100%). Endoscopic sphincterotomy (EST) was successful in all 10 patients (100%). All stones were removed by EST alone in 7 patients and by both EST and endoscopic papillary balloon dilation in 2 patients. There were no serious complications in the patients. Limitations Small sample size, single-center experience. Conclusions Diagnostic and therapeutic ERCP with a cap-fitted regular forward-viewing endoscope was successful in all patients with a prior Billroth II gastrectomy. The high rate of successful ERCP was achieved by improving afferent loop intubation and bile-duct cannulation with a cap-fitted endoscope.

Angiogenesis and lymphangiogenesis are involved in the dissemination of tumor cells from solid tumors to regional lymph nodes and various distant sites. KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor progression and poor clinical outcomes in various cancers including colorectal cancer. The aim of the present study was to evaluate whether KITENIN affects tumor angiogenesis and lymphangiogenesis in colorectal cancer. A KITENIN small interfering RNA vector was used to silence KITENIN expression in colorectal cancer cell lines including DLD1 and SW480 cells. To evaluate the ability of KITENIN to induce angiogenesis and lymphangiogenesis in human umbilical vein endothelial cells (HUVECs) and lymphatic endothelial cells (HLECs), we performed Matrigel invasion and tube formation assays. Immunohistochemistry was used to determine the expression of KITENIN in colorectal cancer tissues. Angiogenesis and lymphangiogenesis were evaluated by immunostaining with CD34 and D2-40 antibodies. KITENIN silencing inhibited both HUVEC invasion and tube formation in the DLD1 and SW480 cells. KITENIN silencing led to decreased expression of the angiogenic inducers vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α and increased expression of the angiogenic inhibitor angiostatin. KITENIN silencing did not inhibit either HLEC invasion or tube formation in all tested cells, but it resulted in decreased expression of the lymphangiogenic inducer VEGF-C. KITENIN expression was significantly associated with tumor stage, depth of invasion, lymph node and distant metastases and poor survival. The mean microvessel density was significantly higher in the KITENIN-positive tumors than that in the KITENIN-negative tumors. However, the mean lymphatic vessel density of KITENIN-positive tumors was not significantly higher than that of the KITENIN-negative tumors. These results suggest that KITENIN promotes tumor progression by enhancing angiogenesis in colorectal cancer.

Interleukin-18 (IL-18) is a pleiotropic, pro-inflammatory cytokine that is capable of promoting the Th1 response. A predominant Th1 response induces chronic and persistent inflammatory changes in the gastric mucosa in response to Helicobacter pylori (H. pylori) infection. The aim of this study was to investigate the potential association between IL-18 gene polymorphisms and susceptibility to H. pylori infection in the Korean population. A total of 678 subjects who underwent a routine health check-up were enrolled. The IL-18 gene polymorphisms at positions −656, −607, −137, +113, and +127 were genotyped. H. pylori positivity was demonstrated in 456 subjects (67.3%). The allele frequencies of IL-18 gene polymorphisms at position −137 (rs187238) were different based on the status of H. pylori infection (G vs. C, adjusted OR 0.64 CI: 0.47–0.87, P = 0.005). The results indicate that the genetic variants in the IL-18 gene may be associated with susceptibility to H. pylori infection in the Korean population, suggesting that IL-18 plays a role in the pathogenesis of H. pylori-associated diseases. However, this finding requires further replication and validation.

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 β-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 β-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.

The incidence of paranasal sinus (PNS) osteoma was 6.4%. The most common site of PNS osteoma was the ethmoid sinus. All surgically treated patients underwent endoscopic surgery, and there was no recurrence in any patient. Technical improvements, including an image guidance system, extended the indications for endoscopic surgery for PNS osteomas, especially in the frontal sinus region.The purpose of this study was to investigate the incidence and location of PNS osteomas detected by computed tomography (CT) scan at our hospital, and to describe our experience in the surgical treatment of PNS osteomas.This study was performed on 1724 patients undergoing CT scans because of suspected sinus disease between 2004 and 2013. Endoscopic surgery was performed in 34 symptomatic patients. Medical records of the patients were reviewed, and clinical findings and treatment outcomes were investigated.PNS osteomas were detected in 110 patients (6.4%). Triple osteomas were detected in two patients. Double osteomas were detected in seven patients. In total, 121 lesions were identified as PNS osteomas. The ethmoid sinus was the most commonly affected site (57.0%), followed by the frontal sinus (25.6%), frontal recess (9.1%), maxillary sinus (5.0%), olfactory fissure (1.7%), and sphenoid sinus (1.7%) in descending order of frequency. Thirty-three patients were surgically treated for PNS osteomas through a purely endoscopic approach, and one patient with a frontal sinus osteoma underwent combined endoscopic surgery and frontal trephination. Image-guided surgery was performed in nine patients with involvement of the orbit and skull base, including the frontal sinus/recess. There were no major surgical complications and there was no tumor recurrence.

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.

Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metallo-proteinase-9 (MMP-9) is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA)-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.

Small-caliber upper endoscopes can be used safely and effectively for sedation-free colonoscopy. The objective of the study is to assess the efficacy of a small-caliber upper endoscope (9.2 mm) comparing with a standard colonoscope (12.2 mm).In a prospective trial, patients undergoing sedation-free colonoscopy were randomly assigned to the upper endoscope (E) or the standard colonoscope (C). Outcome measures included patient self-assessed pain score (4-point scale), endoscopist-assessed pain score (4-point scale), cecal intubation rate, difficult cecal intubation rate (900 s), number of polyps detected, and complication rates.A total of 244 patients were entered. Clinical characteristics were not different between the two groups. Cecal intubation was achieved in 91.0% of the patients in each group. The mean patient self-assessed pain score (SD) was significantly lower in the E group compared with the C group: 1.44 (0.81) versus 2.08 (1.10), p0.001. The mean endoscopist assessment of patient pain score (SD) was significantly lower in the E group compared with the C group as well: 1.27 (0.67) versus 1.58 (0.90), p= 0.003. In patients with low body mass index (BMI22 kg/m(2)), the cecal intubation rate was significantly higher in the E group (97.7%vs 79.4%, p= 0.026) and the difficult cecal intubation rate was significantly lower in the E group (9.3%vs 32.4%, p= 0.011). There were no significant differences in the number of polyps detected and complication rates between the two groups.A small-caliber upper endoscope is tolerable and effective for sedation-free colonoscopy, especially in patients with low BMI.

To evaluate the risk factors and clinical outcomes in patients with spontaneous rupture of pyogenic liver abscess (PLA).A total of 602 patients diagnosed with PLA between January 2004 and July 2013 were retrospectively analyzed. Among them, 23 patients experienced a spontaneous rupture of liver abscess (SRLA).The prevalence of SRLA was 3.8%. Using multivariate analysis, liver cirrhosis (OR 4.651, P = 0.009), gas-forming abscesses (OR 3.649, P = 0.026), abscess ≥6 cm in diameter (OR 10.989, P = 0.002) and other septic metastases (OR 1.710, P = 0.047) were risk factors for SRLA. Regarding the site of rupture, 20 (87.0%) patients had a localized rupture, specifically, subphrenic abscess in 3 (13.0%), peri-hepatic abscess in 10 (43.5%), localized peritoneal abscess in 3 (13.0%) and empyema in 4 (17.5%); and the other 3 (13%) had peritonitis. Ruptures resulting in peritonitis require urgent surgery, whereas localized ruptures were managed with surgical or percutaneous drainage in addition to appropriate antibiotics. The in-hospital mortality rate of SRLA was 4.3%.Patients with cirrhosis, having abscess ≥6 cm in diameter, gas-forming abscesses and other septic metastases in those with PLA should be monitored closely and may need early intervention for SRLA.

Summary We investigated the impact of rice prolamin extract (RPE) on lipopolysaccharide (LPS)-induced nuclear factor (NF)-κB signalling in intestinal epithelial cells and macrophages, and determined the therapeutic efficacy of RPE in acute murine colitis. The effect of RPE on LPS-induced NF-κB signalling and proinflammatory gene expression was evaluated by reverse transcription–polymerase chain reaction (RT–PCR), Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in-vivo efficacy of RPE was assessed in mice with 3% dextran sulphate sodium (DSS)-induced colitis. Apoptotic and cellular proliferative activities were evaluated by immunostaining with cleaved caspase-3 and proliferating cell nuclear antigen (PCNA) antibodies. RPE inhibited LPS-induced expression of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha and LPS-induced NF-κB signalling in intestinal epithelial cells and macrophages. RPE-fed, DSS-exposed mice showed less weight loss, longer colon length and lower histological score compared to control diet-fed, DSS-exposed mice. Immunostaining analysis revealed a significant decrease of cleaved caspase-3 positive cells in RPE-fed, DSS-exposed mice compared to DSS-exposed mice. Also, the number of PCNA-positive cells within intact colonic crypts decreased significantly in RPE-fed, DSS-exposed mice compared to control diet-fed, DSS-exposed mice. DSS-induced NF-κB signalling was inhibited by RPE. RPE ameliorates intestinal inflammation by inhibiting NF-κB activation and modulating intestinal apoptosis and cell proliferation in an acute murine colitis.

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.

// Kyung-Hwa Lee 1,* , Eun-Jung Ahn 2,* , Se-Jeong Oh 1 , Ok Kim 1 , Young-Eun Joo 3 , Jeong-A Bae 4 , Somy Yoon 4 , Hyang-Hwa Ryu 2 , Shin Jung 2 , Kyung-Keun Kim 4 , Jae-Hyuk Lee 1 and Kyung-Sub Moon 2 1 Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea 2 Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea 3 Department of Internal Medicine, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea 4 Medical Research Center of Gene Regulation and Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, South Korea * These authors contributed equally to this work Correspondence: Kyung-Sub Moon, email: // Keywords : Neoplastic stem cell, Epithelial-mesenchymal transition, Glioma, Neoplasm invasiveness, Human VANGL1 protein Received : October 21, 2014 Accepted : December 18, 2014 Published : December 26, 2014 Abstract KITENIN (KAI1 COOH-terminal interacting tetraspanin) promotes tumor invasion and metastasis in various cancers. This study assessed the association between KITENIN expression and advanced glioma grade in patients. In vitro assays revealed that KITENIN knockdown inhibited the invasion and migration of glioma cells, whereas KITENIN overexpression promoted their invasion and migration. In orthotopic mouse tumor models, mice transplanted with KITENIN-transfected glioma cells had significantly shorter survival than mice transplanted with mock-transfected cells. Patients with low KITENIN expression showed a significantly longer progression-free survival than patients with high KITENIN expression. KITENIN induced the expression of the epithelial-mesenchymal transition (EMT) markers (N-cadherin, ZEB1, ZEB2, SNAIL and SLUG) as well as the glioma stemness markers (CD133, ALDH1 and EPH-B1). Taken together, these findings showed that high levels of KITENIN increased glioma invasiveness and progression, associated with the up-regulation of EMT and stemness markers.

The transcription factor, early growth response 1 (EGR1) belongs to the early growth response family. EGR1 regulates the transactivation of genes involved in growth inhibition and apoptosis by ionizing radiation. The aims of the present study were to evaluate the expression of EGR1, and its relationship to prognosis, in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) receiving chemoradiation therapy, and to observe the effect of EGR1 on the apoptosis of head and neck squamous cell carcinoma (HNSCC) cells treated with ionizing radiation. Expression of the EGR1 protein in tissue samples from patients with LHSCC was detected by immunohistochemistry. A high expression of the EGR1 protein was observed in 37 (67.3%) of the 55 LHSCC tissue samples examined. A high EGR1 protein expression in patients with LHSCC who were treated with chemoradiation was significantly associated with improved larynx-preservation survival (p=0.04). The 5-year disease-specific survival rate with larynx preservation was 59% in patients with a high EGR1 protein expression vs. 30% in those with a low EGR1 protein expression. In the human HNSCC cell line, PCI50, EGR1 mRNA expression was induced at 30-60 min, and EGR1 protein expression was induced at 60-120 min, after exposure to a 5 Gy dose of ionizing radiation. To evaluate the impact of EGR1 on radiation-induced apoptosis, we used small‑interfering RNA to knock down endogenous EGR1 gene expression. Cleaved caspase 3, cleaved caspase 7, and cleaved PARP were decreased, while XIAP was increased, in EGR1-knockdown PCI50 cells compared to negative control PCI50 cells, at all observed post-irradiation time points. These findings suggested that EGR1 knockdown inhibits radiation-induced apoptosis. In conclusion, EGR1 may be associated with larynx-preservation survival, through the regulation of radiation-induced apoptosis in patients with LHSCC treated with chemoradiation. Although further investigations are required to support the present study, EGR1 serves as a favorable biomarker of radiosensitivity in the treatment of LHSCC.

Accessory middle turbinate is one of the rare anatomical variations of the nasal turbinate. To date, the accessory middle turbinate with an isolated pathological lesion has not been reported in the literature. A 62-year-old woman presented with the left-sided nasal obstruction. An endoscopic examination showed a polypoid mass above the inferior turbinate. On magnetic resonance imaging, T2-weighted imaging showed the cystic lesions of the left accessory middle turbinate and infratemporal fossa with isosignal intensity, compatible with accessory middle turbinate accompanying a mucocele. The patient underwent endoscopic sinus surgery, and the postoperative course was uneventful. In the present study, we report the first case of accessory middle turbinate accompanying a mucocele in a 62-year-old woman, and review the literature pertaining to this condition.

Patients with irritable bowel syndrome (IBS) commonly present with abdominal pain associated with altered bowel habit. Abdominal pain is the symptom most likely to result in medical consultation in IBS patients.1,2 Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, is produced in the central nervous system microglia in response to noxious stimuli and associated with pain modulation and central sensitization. There are large evidences that BDNF may play an important role in visceral pain and hypersensitivity states.3-6 Recently, Yu et al7 investigated the impact of BDNF expression on altered gut sensation in patients with IBS. First, this study was performed in colonic biopsies from 40 patients with IBS and 21 healthy controls. A significant increase in the expression of BDNF and nerve fibers was found in colonic biopsies from patients with IBS, compared with healthy controls. No significant difference was observed in the expression of BDNF and nerve fibers between the IBS subgroups. Transmission electron microscopy showed the ultrastructural damage of nerve axons in the colonic mucosa of patients with IBS. Also, increased expression of BDNF correlated significantly with the severity and frequency of abdominal pain/discomfort in patients with IBS. Next, animal studies using BDNF+/- and BDNF+/+ mice were performed to evaluate the role of BDNF in visceral hypersensitivity. The visceral response to colorectal distention (CRD) was evaluated by abdominal withdrawal reflex (AWR) scores. The AWR scores were significantly lowered in BDNF+/- mice at 45 and 60 mmHg CRD pressures applied. The mucosal protein gene product 9.5 was significantly lowered in BDNF+/- mice. Intraperitoneal injection of BDNF induced a significant dose-dependent decrease in threshold pressure and an increased expression of the post-synaptic tyrosine protein kinase B (TrkB) receptor in the dorsal root ganglia of BDNF+/+ mice. Transmission electron microscopy showed the degenerative changes of nerve axons and Schwann cells in BDNF+/- mice. The authors concluded that the increased expression of BDNF with ultrastructural alterations of nerve innervation in the colonic mucosa may contribute to the visceral hyperalgesia in patients with IBS.

Although the initial rate of hemostasis achieved by endoscopic epinephrine injection for peptic ulcer bleeding is high, bleeding recurs in 14.6% to 35.5% of patients. The aim of this study was to compare rates of recurrent bleeding after endoscopic injection of two different volumes of epinephrine in patients with peptic ulcer bleeding.A total of 72 patients with peptic ulcer with active bleeding or a non-bleeding visible vessel were randomly assigned to 15 to 25 mL or 35 to 45 mL injections of a 1:10,000 solution of epinephrine.The two groups were similar with respect to all background variables. The mean volume of epinephrine injected was 19.4 mL: 95% CI [18.7, 20.1] in the 15 to 25 mL group and 41.1 mL: 95% CI [40.0, 42.2] in the 35 to 45 mL group. Initial hemostasis was achieved in 35 of 36 patients (97.2%) in the 15 to 25 mL group and in all 36 patients in the 35 to 45 mL group. The 35 to 45 mL volume was significantly more effective in preventing recurrent bleeding than the 15 to 25 mL volume (0% vs. 17.1%; p0.05). For ulcers in the gastric body, the 35 to 45 mL volume was significantly more effective in preventing recurrent bleeding than the 15 to 25 mL volume (0% vs. 31.6%; p = 0.003). For ulcers in other locations, including the gastric antrum and the duodenum, there were no significant differences in the rate of recurrent bleeding between the two groups.Injection of 35 to 45 mL of a 1:10,000 solution of epinephrine is more effective than injection of 15 to 25 mL of the same solution for prevention of recurrent bleeding from ulcers in the body of the stomach.

The hemostatic efficacy of mechanical methods of hemostasis, together with epinephrine injection, was compared with that of epinephrine injection alone in bleeding peptic ulcer.Ninety patients with a peptic ulcer with active bleeding or a non-bleeding visible vessel were randomly assigned to undergo a mechanical method of hemostasis (23 hemoclip application, 22 band ligation) plus epinephrine injection, or epinephrine injection alone.The two groups were similar with respect to all background variables. Initial hemostasis was achieved in 44/45 (97.8%) patients in both groups. The mean number of hemoclips and elastic bands applied were 2.8: 95% CI[2.5, 3.1] and 1.1: 95% CI[1.0, 1.2], respectively, and the mean volume of epinephrine injected was 19.9 mL: 95% CI[19.3 mL, 20.5 mL]. The rate of recurrent bleeding in the combination group (2/44, 4.5%) was significantly lower in comparison with the injection group (9/44, 20.5%, p0.05). The mean number of therapeutic endoscopic sessions needed to achieve permanent hemostasis in the combination group (1.04: 95% CI[1.01, 1.07]) was significantly lower vs. the injection group (1.22: 95% CI[1.15, 1.30]).The combination of an endoscopic mechanical method of hemostasis plus epinephrine injection is more effective than epinephrine injection alone for the treatment of bleeding peptic ulcer.

Histologically, the majority of gallbladder cancers are adenocarcinomas. Among the adenocarcinomas, the mucinous adenocarcinoma is relatively uncommon. Porcelain gallbladder is a rare finding and the risk of gallbladder cancer is significantly increased in porcelain gallbladder. We describe a rare case of mucinous adenocarcinoma with porcelain gallbladder. A 46-year-old man was admitted to Chonnam National University Hospital with a 2-week history of right upper quadrant pain. Three and 2 years previously, he had two episodes of cholecystitis with gallstones. An abdominal computed tomography revealed a contracted gallbladder with circumferential mural calcification, and the possibility of gallbladder cancer and porcelain gallbladder were considered. At laparotomy, cholecystectomy, liver wedge resection, and radical lymph node dissection were performed. The resected gallbladder showed thickened wall, luminal narrowing and mucosal irregularity. A histological examination of the resected gallbladder showed a mucinous adenocarcinoma composed of poorly differentiated glandular cells with mucin lakes. Porcelain gallbladder may be an end result of a chronic inflammatory reaction, and this change is associated with the development of gallbladder cancer.

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.

Background Cyclin-dependent kinase inhibitors (CDKI), including p21, p27 and p57 of the KIP family, are negative regulators of cell cycle progression and potentially act as tumor suppressors. The expression of p21 is induced by tumor suppressor gene p53. Mutations of p53 are common and found in various human cancers. Thus, the function of p21 as a tumor suppressor may be not retained after p53 mutation in human cancers. The aim of our study was to evaluate the tumor suppressive activity of p21 and p53 in human gastric cancer. Methods One hundred and two patients who underwent surgery for gastric cancer at Chonnam National University Hospital were selected retrospectively for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of p21 and p53 in human gastric cancer tissue by immunohistochemistry and the correlation between their expression and clinicopathological variables. Results p21 and p53 immunoreactivities were localized in the nuclei of carcinoma cells. Positive nuclear expression of p21 and p53 was demonstrated in 63.7 and 33.3% of cancer tissues, respectively. No apparent correlation was noted between p21 and p53 expression. Negative expression of p21 correlated with advanced stage and lymph node metastasis (p = 0.028 and 0.017, respectively). Moreover, negative expression of p21 correlated with poor survival (p = 0.037). Positive expression of p53 correlated with depth of tumor invasion (p = 0.029). However, no significant correlation could be observed between the status of p53 expression and survival. Combined analysis of p21 and p53 status showed that p21 negative and p53 positive tumors had a poorer survival than other group tumors (p = 0.026). Conclusion These results suggest that the status of p21 and p53 expression may help in predicting the aggressive behavior of gastric cancer. However, further studies are warranted to clarify the impact of p53 on the function of p21 as a tumor suppressor.

An accessory bile duct is found in up to 4% of necropsies and is usually a single thin-walled channel that drains a segment of the right lobe of the liver into the common bile duct or, rarely, into the gallbladder. However, accessory bile ducts draining into the gastrointestinal tract are extremely rare. We report a patient with an accessory bile duct draining into the stomach and review the literature pertaining to this condition.

Background Angiogenesis has been shown to be a critical aspect of tumor growth and progression. Vascular endothelial growth factor (VEGF) has potent angiogenic activity and has been identified in a wide variety of malignancies, including pancreatic carcinoma. The tumor-suppressor gene p53 has been thought to regulate VEGF in angiogenesis. The aim of the current study was conducted to investigate the association between p53 mutation and VEGF expression and the prognostic value of these factors in pancreatic carcinoma. Methods Formalin-fixed, paraffin-embedded tissue specimens were obtained from 30 patients who underwent surgery for pancreatic carcinoma. We used an immunohistochemical technique to localize VEGF and p53 in pancreatic carcinoma tissues. Results Positive expression of VEGF was detected in 17 out of 30 (56.7%) tumors. Positive expression of VEGF correlated with the depth of tumor invasion (p = 0.002). There was a trend towards an association between positive expression of VEGF and distant metastasis, although these associations were not statistically significant (p = 0.070). p53 mutations were identified in 18 out of 30 (60.0%) tumors. However, no significant correlation was found between p53 expression and various clinicopathological parameters. The correlation between p53 mutation and VEGF expression was statistically significant (p = 0.004). Conclusion VEGF, a key factor for the induction of tumor-associated angiogenesis, may be involved in tumor characteristics, including tumor invasion and metastasis. And p53 mutation may be implicated in the regulation of angiogenesis through a VEGF up-regulation.

E-Cadherin and its associated cytoplasmic proteins, catenins, are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor invasion suppressor role for E-cadherin and catenins and loss of expression, as well as mutations, has been described in a number of epithelial cancers. The aim of this study was to evaluate the expression of E-cadherin and catenins in pancreatic adenocarcinoma tissue, and to examine the relationship between these expression and various clinicopathological parameters.In this study, we conducted an immunohistochemical investigation of expression of E-cadherin, alpha- and beta-catenins in 30 tissue samples obtained from pancreatic ductal adenocarcinoma patients undergoing surgical treatment.In the pancreatic mucosa of noncancerous areas, epithelial cells showed equally strong membranous expression of E-cadherin, alpha- and beta-catenin proteins at the cell-cell boundaries. Reduced expression of E-cadherin, alpha- and beta-catenins was demonstrated in 60.0, 40.0, and 56.7% of cancer tissues, respectively. Reduced expression of E-cadherin, alpha- and beta-catenins correlated with tumor dedifferentiation (p = 0.012, 0.013, and 0.033, respectively). Reduced expression of E-cadherin correlated with stage and lymph node involvement (p = 0.031, 0.009, respectively). alpha-Catenin and beta-catenin expression did not correlate with the patient's age and sex, with the tumor size, location, stage and depth of invasion, or lymph node involvement and distant metastasis.These results suggest that the E-cadherin and catenins may be a useful marker of differentiation and prognosis in pancreatic adenocarcinoma, although the mechanisms underlying changes in E-cadherin and catenin expression are not fully known.

Background/Aims: Cyclooxygenase-2 (COX-2) expression appears to be increased in several different types of human cancers, suggesting that the presence of COX-2 is associated with carcinogenesis. Recently, increased expression of COX-2 has been frequently detected in gastric cancer, and this may have prognostic significance. In the present study, we aimed to analyze the expression of COX-2 in a much larger sample to determine whether COX-2 expression is related to the clinicopathological features and survival rates of patients with gastric cancer. Methods: We investigated 140 patients with gastric cancer who underwent surgery between January 1992 and December 1993 and examined the expression of COX-2 in human gastric cancer tissue by immunohistochemistry. Results: COX-2 expression was present in the cytoplasm of tumor cells but not in normal gastric epithelia. Positive expression of COX-2 was detected in 86 of 140 gastric cancers analyzed (61.4%). Positive expression of COX-2 correlated with the depth of tumor invasion (p = 0.015). However, there was no association between COX-2 expression and tumor stage or status of lymph node or distant metastasis. Furthermore, COX-2 expression was not associated with patient survival (p = 0.816). Positive expression of COX-2 occurred more frequently in intestinal than in diffuse or mixed types of cancer and correlated with tumor differentiation (p < 0.001, p = 0.001, respectively). Conclusion: These results suggest that COX-2 may play an important role in the evolution of gastric carcinogenesis and be associated with well-differentiated and intestinal type pathways in gastric carcinogenesis. However, COX-2 expression seems to be less useful for establishing prognosis for gastric cancer.

Background : Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer. Methods : In this study, we conducted an immunohistochemicai investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. Results : High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor. Conclusion : VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.

Most colonic lipomas are asymptomatic and need no treatment, whereas lesions larger than 2 cm can cause acute abdominal pain, changes in bowel habits, gastrointestinal bleeding, intussusception or bowel obstruction. Autoamputation of polypoid lesions in the gastrointestinal tract is indeed a rare phenomenon, and its precise mechanism remains unknown. It presumably occurs due to ischemic necrosis of the polyp by peristalsis-induced torsion or tension. Here, we report a case of autoamputation of a giant colonic lipoma in a 48-year-old man. In our case, colonoscopic examination showed a huge autoamputated mass in the rectum and a remnant long stalk in the transverse colon. The autoamputated mass in the rectum was completely removed after fragmentation using an electrosurgical snare, and the remnant long stalk located in the transverse colon was also resected safely by endoscopic snare polypectomy. To our knowledge, these endoscopic treatments for removal of an autoamputated mass and a remnant long stalk of colonic lipoma have not been reported previously.

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.

To evaluate the expression of Livin in human laryngohypopharyngeal squamous cell carcinoma (LHSCC) and investigate whether Livin-knockdown using small interfering-RNA (siRNA) affects tumor aggressiveness in LHSCC cells.Immunohistochemistry, reverse transcription-polymerase chain reaction, western blotting, cell invasion assay, cell migration assay, and cell apoptosis assays were performed to assess the impact of Livin on cancer cell behavior in human LHSCC.High immunoreactivity of Livin was observed in 22 (36.7%) of the 60 LHSCC tissues relative to adjacent normal mucosa. In the positive-Livin expression group, distant metastasis tended to occur frequently, but the difference was not statistically significant (p=0.06). Livin-knockdown by siRNA induced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP ribose polymerase in LHSCC cells. Livin-knockdown also resulted in significantly reduced cell invasion and migration in LHSCC cells.siRNA-mediated silencing of Livin may be associated with the reversal of invasive capacity in LHSCC.

Primary squamous cell carcinoma of the colon is an extremely rare malignancy. A 48-year-old male visited our hospital for screening colonoscopy. Colonoscopic examination showed a 1 cm sized sessile polyp in the ascending colon. The patient underwent endoscopic mucosal resection (EMR) without any complication. The pathologic findings were compatible with squamous differentiation of tumor cells in inflammatory colonic mucosa. The tumor was confined to the mucosa and the margins of the excised tissue were found to be free of the tumor. There were no other primary sites and no distant metastases in the extensive evaluation using a whole body CT scan and PET-CT. Additional surgical resection was not done. Follow-up colonoscopy performed eight month later showed a whitish scar without evidence of local recurrence and follow-up PET-CT demonstrated no evidence of recurrence. Herein, we report a case of primary squamous cell carcinoma of the ascending colon presenting as a sessile polyp which was removed by EMR.

Background/Aims: To evaluate the efficacy of proton pump inhibitors (PPIs) in reducing rebleeding and bleeding-related death rates after endoscopic gastric variceal obliteration (GVO) using N-butyl-2-cyanoacrylate (NBC). Methods: This study enrolled 341 patients who were consecutively diagnosed with and treated for bleeding gastric varices. The patients were divided into PPI and non-PPI groups, and their endoscopic findings, initial hemostasis outcomes, rebleeding and bleeding-related death rates, and treatment-related complications were analyzed. Results: The rate of initial hemostasis was 97.1%. rebleeding occurred in 2.2% of patients within 2 weeks, 3.9% of patients within 4 weeks, 18.9% of patients within 6 months, and 27.6% of patients within 12 months of the GVO procedure. A previous history of variceal bleeding (relative risk [RR], 1.955; 95% confidence interval [CI], 1.263 to 3.028; p = 0.003) and use of PPIs (RR, 0.554; 95% CI, 0.352 to 0.873; p = 0.011) were associated with rebleeding. Child-Pugh class C (RR, 10.914; 95% CI, 4.032 to 29.541; p < 0.001), failure of initial hemostasis (RR, 13.329; 95% CI, 2.795 to 63.556; p = 0.001), and the presence of red-colored concomitant esophageal varices (RR, 4.096; 95% CI, 1.320 to 12.713; p = 0.015) were associated with bleeding-related death. Conclusions: The prophylactic use of PPIs reduces rebleeding after GVO using NBC in patients with gastric variceal hemorrhage. However, prophylactic use of PPIs does not reduce bleeding-related death.

Intraductal tumor invasion of hepatocellular carcinoma (HCC) is considered rare. Transarterial chemoembolization (TACE) is effective for tumor thrombus of HCC in the bile duct. However, a few cases of obstructive jaundice caused by migration of a tumor fragment after TACE have recently been reported. The aim of this study was to identify factors that affect tumor migration after TACE. At this writing, a review of the medical literature disclosed seven reported cases of biliary obstruction caused by migration of a necrotic tumor cast after TACE. We, herein, report on an additional case of acute obstructive cholangitis complicated by migration of a necrotic tumor cast after TACE for intrabile duct invasion of HCC, in a 71-year-old man. The tumor cast in the common bile duct was removed successfully using a basket during ERCP and was pathologically confirmed to be a completely necrotic fragment of HCC. The patient's symptoms showed dramatic improvement. In summary, physicians should be aware of acute obstructive cholangitis complicated by tumor migration in a patient undergoing TACE. We suggest that an intrabile duct invasion would be a major predisposing factor of tumor migration after TACE and drainage procedures such as ERCP or percutaneous transbiliary drainage could be effective treatment modalities in these patients.

Leptin, which is encoded by the obese gene, is a multifunctional neuroendocrine peptide that regulates appetite, bone formation, reproductive function and angiogenesis. The aims of the present study were to investigate the expression of leptin in 80 patients with colorectal cancer (CRC) and to determine the effects of leptin on the malignant properties of CRC cells. We evaluated the expression of leptin in tissues of 80 patients with CRC. Suspension cultures were used to isolate CRC stem cells following pretreatment with leptin. We analyzed the effects of leptin on the adhesion and invasive capacities of CRC cell lines. The effects of leptin on JAK and ERK activation were examined using western blotting. Leptin expression was associated with CRC progression and increased the number and size of spheroid formation by CRC cell lines. Leptin enhanced cell invasion and adhesion and activated JAK and ERK signaling in the CRC cell lines. The present study demonstrated that leptin influences the growth and survival of CRC stem cells and regulates adhesion and invasion of colorectal carcinoma through activation of the JAK and ERK signaling pathways.