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Colorectal laterally spreading tumors (LSTs) are large, flat neoplasms that are usually treated using different endoscopic techniques based on their morphology, size, and histology. The aim of this study was to evaluate the clinical outcomes of LSTs with advanced histology treated by endoscopic resection. A total of 246 LSTs with advanced histology [i.e., high-grade dysplasia (HGD) and adenocarcinoma (AC)] treated by endoscopic resection [i.e., endoscopic mucosal resection (EMR), EMR-precutting (EMR-P), and endoscopic submucosal dissection (ESD)] were enrolled. Clinicopathological characteristics were collected by review of patient’s medical records. The en bloc resection and R0 resection rates were 75.6% and 85.0%, respectively. The bleeding and perforation rates were 10.2% and 2.4%, respectively. The frequency of cancerous pit pattern and bleeding was significantly higher in LSTs with AC than in LSTs with HGD. The R0 resection rate in LSTs with HGD was significantly higher than that in LSTs with AC. The frequency of cancerous pit patterns in LST cases with submucosal AC was significantly higher than those with intramucosal AC. The mean size of the LSTs was significantly larger in ESD group than in EMR or EMR-P groups. The frequencies of nodular mixed subtype, cancerous pit patterns, and en bloc resection rates were significantly higher in the ESD group than in the EMR or EMR-P groups. However, the frequency of perforation was significantly higher in EMR-P group than in EMR or ESD groups. These results indicate that ESD is a more acceptable treatment approach for resection of colorectal LSTs of larger size, with nodular mixed subtype, having a cancerous pit pattern or AC, using either en bloc or curative resection methods, compared to EMR or EMR-P procedures.

Background and aims Laterally spreading colorectal tumors (LSTs) are divided into four subtypes, including homogenous (HG), nodular mixed (NM), flat elevated (FE), and pseudo-depressed (PD), based on their different endoscopic morphologies. The aim of this study was to investigate the clinicopathological significance of LST subtypes and their association with advanced histology. Methods We investigated the medical records of consecutive patients with LST who initially underwent endoscopic resection at five university hospitals in Honam province of South Korea between January 2012 and December 2013. A total of 566LST lesions removed via endoscopic procedures were collected retrospectively for data analysis. Results The PD, FE, and NM subtypes were more common in the distal colon and the HG subtype in the proximal colon. The PD subtype had the biggest tumor size, followed by the NM subtype. The frequency of adenomatous pit pattern was significantly higher in the HG, NM, and FE subtypes than in the PD subtype. In contrast, the frequency of cancerous pit pattern was significantly higher in the PD subtype than in the other three subtypes. The rate of advanced histology (high-grade dysplasia or carcinoma) among the LSTs was 36.0%. The risk of advanced histology increased in the distal colon compared with the proximal colon. The PD subtype had the highest incidence of villous component, advanced histology,submucosal invasion, and postprocedure perforation among the four subtypes. The distal colon as tumor site, larger tumor size, PD subtype, and villous component were associated with a statistically significant increased risk of advanced histology. Conclusion Our results indicate that the location, size, endoscopic subtype, and histologic component of the LSTs are associated with an increased risk of advanced histology. Therefore, these clinicopathological parameters may be useful in selecting therapeutic strategies in the clinical setting.

Objective To evaluate the risk factors and clinical outcomes in patients with spontaneous rupture of pyogenic liver abscess (PLA). Methods 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). Results 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%. Conclusion 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.

Metastasis of hepatocellular carcinoma (HCC) to the nasal septum is extremely rare. The proper management of this rare condition has not been established. A 45-year-old male had been treated for HCC for 5 years. He presented with right-sided nasal obstruction. He had lung metastasis, and had been undertaking chemotherapy. On endoscopic examination, a 1.5 cm-sized mass on the anterior nasal septum was observed. Biopsy taken from the septal mass revealed HCC, but he refused further intervention. Six months later, the mass grew and totally obstructed the right nasal cavity. For palliative treatment, radiofrequency ablation to the septal mass was done. At the 4-month postoperative follow up, the septal mass had disappeared and septal perforation was noted on endoscopic examination and computed tomography of the paranasal sinus. One month later, the mass recurred in the upper lip; this lesion had not been previously recognized. His general condition rapidly deteriorated and he eventually died. Metastatic HCC should be considered in the differential diagnosis of nasal septal masses. Radiofrequency ablation might be a feasible palliative treatment option in the treatment of metastatic septal lesions if a target lesion is properly located.

WNT1-inducible-signaling pathway protein-1 (WISP-1) belongs to the family of cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed matricellular proteins, which are involved in various biological processes, including cell adhesion, proliferation, differentiation, angiogenesis and carcinogenesis. In the present study, the expression of WISP-1 was investigated, and its association with clinicopathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC) was evaluated. Additionally, the role of WISP-1 in invasion and apoptosis of human OSCC cells was evaluated. Immunoreactivity of WISP-1 was increased in OSCC tissue compared with adjacent normal tissue samples. High expression of WISP-1 protein was observed in 24/84 (28.57%) OSCC specimens. Additionally, high WISP-1 expression was significantly associated with treatment failure (P=0.042). The 5-year overall survival rate was 33% in patients with high WISP1 expression, and 66% in patients with low WISP-1 expression. WISP-1 expression in the human OSCC SCC-1483 cell line was observed. Furthermore, WISP-1 knockdown using small interfering (si)RNA significantly reduced cell invasion and induced apoptosis compared with control siRNA-transfected cells. These findings suggested that WISP-1 is associated with tumor progression and poor prognosis by increasing tumor cell invasion and inhibiting cell apoptosis in human OSCC.

Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals 50 years old. We compared the risk of metachronous neoplasia between younger (20-49 years) and older (50-54 years) cohorts.This multicenter retrospective cohort study compared the incidence of metachronous neoplasia in younger and older cohorts according to baseline risk stratification. Subjects were eligible if they underwent their first colonoscopy between June 2006 and May 2010 and had at least 1 or more surveillance colonoscopy up to June 2015.Among a total of 10,477 subjects who underwent baseline colonoscopy, 9722 were eligible after excluding 755 subjects. Of those 9722 subjects, 43% underwent surveillance colonoscopy. In the baseline high-risk adenoma group (n = 840), the 3-year risk of metachronous advanced neoplasia was 10.7% in the younger patients on screening colonoscopy and 8.9% in the older patients (P.1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P.1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P.1).Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history.

Piperine, a kind of natural alkaloid found in peppers, has been reported to exhibit anti-oxidative and anti-tumor activities, both in vitro and in vivo. Interleukin-6 (IL-6) is an important cytokine that activates the signal transduction, promotes tumor cell metastasis, and induces malignancy, including in gastric cancer. However, the effects of piperine on IL-6 expression in gastric cancer cells have not yet been well defined. In this study, we investigated the effects of piperine on the IL-6 expression, and examined the underlying signaling pathways via RT-PCR, promoter studies and Western blotting in human gastric cancer TMK-1 cells. Our results showed that piperine inhibited interleukin-1β (IL-1β)-induced IL-6 expression in a dose-dependent manner. In addition, piperine also inhibited IL-6 promoter activity. Experiments with mitogen-activated protein kinase (MAPK) inhibitors and dominant negative mutant p38 MAPK indicated that p38 MAPK was essential for IL-6 expression in the TMK-1 cells. Additionally, signal transducer and activator of transcription 3 (STAT3) was also involved in the IL-1β-induced IL-6 expression in gastric cancer cells. Piperine inhibited IL-1β-induced p38 MAPK and STAT3 activation and, in turn, blocked the IL-1β-induced IL-6 expression. Furthermore, gastric cancer cells pretreated with IL-1β showed markedly enhanced invasiveness, which was partially abrogated by treatment with IL-6 siRNA, piperine, and inhibitors of p38 MAPK and STAT3. These results suggest that piperine may exert at least part of its anti-cancer effect by controlling IL-6 expression through the suppression of p38 MAPK and STAT3.

Background/Aims: Many authors recommend performing a second-look endoscopy (SLE) to reduce the frequency of delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasms, but these recommendations have been made despite a lack of reliable evidence supporting the effectiveness of SLE. Methods: From January 2012 to May 2013, we investigated 441 gastric neoplasms treated by ESD to assess the risk factors for delayed bleeding. Delayed bleeding occurred in four of these lesions within 1 postoperation day. Therefore, we enrolled the patients with the remaining 437 lesions to determine the utility of SLE performed on the morning of postoperative day 2. All lesions were randomly assigned to SLE (220 lesions) groups or non-SLE (217 lesions) groups. Results: Delayed bleeding occurred in 18 lesions (4.1%). A large tumor size (>20 mm) was the only independent risk factor for delayed bleeding (p=0.007). The chance of delayed bleeding was not significantly different between the patients receiving a SLE (eight cases) and those patients not receiving a SLE (six cases, p=0.787). Furthermore, SLE for lesions with a large tumor size did not significantly decrease delayed bleeding (p=0.670). Conclusions: SLE had little or no influence on the prevention of delayed bleeding, irrespective of the risk factors. (Gut Liver 2014;8:480-486)

Cadmium exposure has been linked to human cancers, including stomach cancer. In this study, the effects of cadmium on urokinase-type plasminogen activator receptor (uPAR) expression in human gastric cancer cells and the underlying signal transduction pathways were investigated. Cadmium induced uPAR expression in a time- and concentration-dependent manner. Cadmium also induced uPAR promoter activity. Additionally, cadmium induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and the activation of c-Jun amino terminal kinase (JNK). A specific inhibitor of MEK-1 (PD98059) inhibited cadmium-induced uPAR expression, while JNK and p38 MAPK inhibitors did not. Expression vectors encoding dominant-negative MEK-1 (pMCL-K97M) also prevented cadmium-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift studies showed that sites for the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1) were involved in cadmium-induced uPAR transcription. Suppression of the cadmium-induced uPAR promoter activity by a mutated-type NF-κB-inducing kinase and I-κB and an AP-1 decoy oligonucleotide confirmed that the activation of NF-κB and AP-1 are essential for cadmium-induced uPAR upregulation. Cells pretreated with cadmium showed markedly enhanced invasiveness and this effect was partially abrogated by uPAR-neutralizing antibodies and by inhibitors of ERK-1/2, NF-κB, and AP-1. These results suggest that cadmium induces uPAR expression via ERK-1/2, NF-κB, and AP-1 signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS 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.

BACKGROUND/AIMS To evaluate the long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding gastric varices. METHODS We retrospectively analyzed the records of 455 patients with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC from January 2004 to July 2013, with a mean follow-up period of 582 days. The patients' endoscopic findings, initial hemostasis, complications, rebleeding rates, and bleeding-related death rates were reviewed. RESULTS Hemostasis was achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2% (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow-up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%), spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%). A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous history of variceal bleeding (p < 0.001) were significant risk factors for rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p < 0.001) were the risk factors most closely associated with bleeding-related death. CONCLUSIONS This study provides a comprehensive overview of the outcomes and prognostic factors of patients with GVH. The results may help in the selection of effective treatment strategies for patients with GVH.

Gastrointestinal xanthomas are characterized by foamy cytoplasmic cells containing lipid in lamina propria, and occur almost in the gastric mucosa. Colonic xanthomas have been described in rare case. All reported colonic xanthomas were located in rectosigmoid. Rectosigmoid xanthomas have tended to exhibit small polypoid lesion, on the contrary flat in stomach. We report a case of xanthoma on ascending colon presenting as a laterally spreading tumor resected by endoscopic mucosal resection method.

Purpose To evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart. Materials and Methods A total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group (3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed. Conclusion Modified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease that is misdiagnosed as malignancy or inflammatory bowel disease because of similarities in clinical and endoscopic manifestations. Furthermore, SRUS with ulcerative colitis (UC) is extremely rare. To date, two cases have been reported in the medical literature. We report an additional case of SRUS with UC that was misdiagnosed as rectal cancer. A 61-year-old man was admitted to our hospital with rectal bleeding. Colonoscopy showed a well-demarcated, shallow, ulcerative lesion with polypoidal growth involving the entire circumference of the rectal lumen. Findings from imaging studies, including abdominal computed tomography (CT) and positron emission tomography (PET)/CT resembled those of rectal cancer. Surgical resection was performed because clinical symptoms persisted despite medical treatment and because occult rectal cancer could not be ruled out. Histopathological examination of the resected specimen revealed fibromuscular obliteration of the lamina propria and crypt abscesses, characteristics compatible with SRUS and UC.

The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapy-induced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.

Background: Hepatocellular carcinoma (HCC) is worldwide one of the most common and lethal malignant tumors despite at- tempts at treatment using various therapeutic modalities. Combination of transarterial chemoembolization (TACE) and radiofre- quency ablation (RFA) can have expanded indication as curative therapy in patients with larger size HCC (2 - 5 cm) that is unsuitable for RFA alone, but there are few studies showing long-term survival and larger sample size. Objectives: The goal of this study was to evaluate the long-term ecacy and safety of combined TACE with RFA, and TACE alone in hepatocellular carcinoma of 2 to 5 cm. Patients and Methods: This was a retrospective study including 207 consecutive patients who were enrolled using computerized hepatocellular carcinoma database consisting of 105 patients who underwent combined TACE with RFA, and 102 patients who un- derwent TACE alone with long-term follow-up. Results: The complete remission rate was meaningfully higher in the combination group (97.1%, 102/105) than in the TACE group (54.9%, 56/102) (P < 0.001). The mean follow-up periods of the combination group and the TACE group were 49.3 16.9 months and 46.3 26.7 months, respectively. The TACE group (90.2%, 92/102) showed significantly higher tumoral recurrence or persistence than the combination group (59.0%, 62/105) during follow-up periods (P < 0.001). The cumulative survival rates at 1, 2, 3, 4, and 5 years were 88.6, 82.9, 79.0, 75.2, and 74.3%, respectively in the combination group and 93.1, 73.5, 59.8, 50.0, and 45.1%, respectively in the TACE group. Independent factors associated with improved overall survival were the combination group, Child-Pugh class A, complete remission at 1 month, negative intrahepatic new tumors, and no adverse event. Conclusions: Complete local tumor control by combination of TACE with RFA could improve overall survival in comparison with TACE alone for long-term follow-up. The combination of TACE with RFA should be considered for achieving complete local tumor control before progression to advanced stage in HCC of 2 to 5 cm.

Capsaicin is known to have tumor suppressive effects. However, the molecular mechanisms and targets of capsaicin involved in exerting anticancer activity are complex and remain to be clarified. The aim of the current study was to investigate the effects of capsaicin on human gastric cancer cells (AGS cells) and demonstrate that capsaicin induced apoptosis in AGS cells. Results of the MTT assay and flow cytometry revealed that capsaicin potentially inhibited the proliferation of AGS cells and induced apoptosis in vitro in a dose-dependent manner. Cleaved caspase-3 was increased and Bcl-2 was reduced by treatment with capsaicin in AGS cells. Capsaicin treatment decreased the expression of phosphorylated ERK 1/2, p38 MAPK or JNK in AGS cells. The results of this study suggest that capsaicin may serve as an anti-tumorigenic agent in human gastric cancer.

We report the first case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid cyst in a 67-year-old man. Laboratory investigation revealed increased serum amylase and lipase, increased serum ionized calcium and parathyroid hormone (PTH) levels, and decreased serum phosphate, indicating pancreatitis and primary hyperparathyroidism (PHPT). Abdominal computed tomography (CT) revealed mild swelling of the pancreatic head with peri-pancreatic fat infiltration and fluid collection around the pancreatic tail. Ultrasonography and CT of the neck showed a cystic lesion at the inferior portion of the left thyroid gland, suggesting a parathyroid cyst. There was no evidence of parathyroid adenoma by 99mTc sestamibi scintigraphy. PHPT caused by a functioning parathyroid cyst was suspected. The patient underwent surgical resection of the functioning parathyroid cyst owing to his prolonged hypercalcemia. At 3 weeks after the operation, his serum levels of PTH, total calcium, ionized calcium, inorganic phosphate, amylase, and lipase were normalized. At the follow-up examinations, he has remained asymptomatic.

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 non‑metastatic 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.

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.

Rationale: Radiofrequency ablation (RFA) is a safe and effective local treatment modality with a low complication rate and is commonly used to treat hepatocellular carcinoma (HCC). The clinical outcome of RFA may be closely related to the location, size, and shape of index tumors, and major complications, including hemorrhage, liver abscess, infarction, visceral organ perforation, hemothorax, pneumothorax, tumoral seeding, and hepatic failure. Cardiac tamponade is a rare and serious life-threatening complication associated with RFA. To date, a review of the medical literature reported 5 cases of cardiac tamponade after RFA for HCC. Herein, we report another case of cardiac tamponade after RFA for HCC in a 56-year-old man. Patient concerns: He had suffered from liver cirrhosis due to alcohol abuse. He had chronic obstructive pulmonary disease. Magnetic resonance imaging showed a 3.0-cm exophytic subcapsular HCC in segment IVa of left hepatic lobe. As the patient was at high risk for surgery because of poor lung function, RFA was selected as the treatment of choice. The index tumor was located in the vicinity of the diaphragm and colon. During RFA procedure, thermal injury to the adjacent diaphragm and colon was minimized by introducing artificial ascites. Bleeding or tumoral seeding was prevented by ablating the electrode track during electrode retraction. Diagnosis: Two hours after RFA, the patient presented with dyspnea, chest discomfort, and low blood pressure (80/60 mm Hg), suggesting cardiac tamponade. Immediate follow-up contrast-enhanced computed tomography image depicted the slightly high attenuated hemopericardium. Transthoracic echocardiography (TTE) showed a moderate amount of pericardial effusion with tamponade and a large hematoma. Interventions: Under fluoroscopy and portable echocardiography guidance, a cardiologist immediately inserted a 7-French pigtail catheter into the pericardial space and collected more than 200 cc of bloody pericardial fluid. Outcomes: After pericardiocentesis, the patient's symptoms and hemodynamic status were dramatically improved. Follow-up TTE showed scanty amount of pericardial effusion and the drainage catheter was removed. The patient was discharged. Lessons: When treating HCC in the left lobe (especially segments II and IVa), attention should be paid to cardiac tamponade. The early diagnosis and immediate treatment of cardiac tamponade may increase the chance of cure.

Colorectal laterally spreading tumors (LSTs) are large and flat elevated neoplasms with diameters of at least 10 mm. Endoscopic resection of LSTs, with their large size and broad base, is difficult and dangerous compared with the resection of polypoid neoplasms. This study aimed to determine the risk factors for procedure-related complications including bleeding and perforation after endoscopic resection of LSTs. Patients with colorectal LST undergoing endoscopic resection at 5 university hospitals in Honam Province of South Korea were enrolled, and their records about patients, lesions, and procedure parameters associated with the occurrence of complications were reviewed retrospectively. Logistic regression analysis was performed to identify risk factors for complications. The frequency of comorbidities in bleeding group was significantly higher than in the no bleeding group. The frequency of bleeding was significantly higher in lesions with adenocarcinoma than in lesions with low or high-grade dysplasia. The frequency of bleeding was significantly higher in piecemeal resection than in en bloc resection. The frequency of perforation was significantly higher in endoscopic mucosal resection-precutting (EMR-P) than in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection. The mean procedure duration was significantly longer in the perforation group than in the no perforation group. On multivariate analysis, patient comorbidity and histologic grade of the lesion were significant independent risk factors for bleeding, whereas EMR-P was a significant independent risk factor for perforation after endoscopic resection. This study demonstrated that patient comorbidity and histologic grade of lesion were significant independent risk factors for bleeding, and EMR-P was a significant independent risk factor for perforation after endoscopic resection of colorectal LSTs.

Irritable bowel syndrome (IBS) is a common, functional gastrointestinal disorder, which affects approximately 10–20% of the general population.1–3 Despite its high prevalence, the pathogenesis of IBS is still very little understood, and seems to be multi-factorial disease.1–3 Many factors have been proposed to contribute to the pathogenesis of IBS, including visceral hypersensitivity, gastrointestinal dysmotility, activation of mucosal immune system, alterations of the gut microbiota, and impaired intestinal barrier function, as well as psychosocial distress.1–3 Recently, a newly identified cause for IBS is infectious gastroenteritis.1–3 About 10% of patients with IBS develop the symptoms consistent with diarrhea-predominant IBS (IBS-D) after an episode of infectious gastroenteritis and these patients are designated as postinfectious IBS (PI-IBS).4–6 Jalanka-Touvinene et al7 investigated the alteration of fecal microbiota composition and its association with clinical features in patients with PI-IBS. Compositional analysis of fecal microbiota showed the 27 discriminant bacterial groups, providing an index of microbial dysbiosis (IMD), which significantly separated the fecal microbial profile of PI-IBS patients from that of healthy control (HC), and the fecal microbiota of PI-IBS resembled that of IBS-D. The major differences in the fecal microbiota of PI-IBS compared to HC were the increase of the several members of Bacteroides and decrease of uncultured Clostridiales compared with HC. These descriminant microbial profiles, creating IMD positively correlated with intestinal symptoms, but not psychological symptoms. Also, IMD correlated with host mucosal gene expression including amino acid synthesis for gut integrity, cell junction pathways and inflammatory cytokine production, indicative of an increased inflammatory response and impaired intestinal barrier function in PI-IBS. The authors concluded that the fecal microbiota composition of patients with PI-IBS differs from that of HC, and resembles that of IBS-D. Host-microbe associations between host gene expression and altered fecal microbiota suggest that impaired intestinal barrier function may underlie both immunological and microbiological deviations in the pathogenesis of PI-IBS.

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.

Background/Aims Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions. Methods In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured. Results The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively). Conclusions A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.

The aim of this study was to compare the efficacy, rebleeding rates, survival, and complications of endoscopic variceal ligation (EVL) with those of endoscopic variceal obliteration (EVO) in patients with acute type 1 gastroesophageal variceal (GOV1) bleeding. Data were collected retrospectively at a single center. A total of 84 patients were selected (20 patients underwent EVL; 64 patients underwent EVO) from February 2004 to September 2011. Their clinical characteristics, laboratory results, vital signs, Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and overall mortality were evaluated. There were no significant differences in baseline characteristics between the two groups. The success rate in initial control of active bleeding was not significantly different between the EVL and EVO groups (18/20 EVL, or 90.0%, compared with 62/64 EVO, or 96.9%; p=0.239). The early rebleeding rate was also not significantly different between the groups (3/18 EVL, or 16.7% compared with 17/62 EVO, or 27.4%; p=0.422). The late rebleeding rate of the EVL group was lower than that of the EVO group (3/18 EVL, or 16.7%, compared with 26/59 EVO, or 44.1%; p=0.042). The time-to-rebleeding was 594 days for the EVL group and 326 days for the EVO group (p=0.054). In the multivariate analysis, portal vein thrombosis (PVT) was a significant risk factor for early rebleeding. Hepatocellular carcinoma (HCC) and previous history of bleeding were significant risk factors for very late rebleeding. In conclusion, EVL is better than EVO in reducing late rebleeding in acute GOV1 bleeding. HCC, PVT, and previous bleeding history were significant risk factors for rebleeding.

There are still concerns about the oncologic safety of stent insertion for colorectal cancer obstruction. This study investigated whether the use of stents as a bridge to surgery negatively affect the long-term outcome compared to curative surgery for left-sided colorectal cancer obstruction. Between January 2004 and December 2009, patients with left-sided colorectal cancer obstruction without distant metastasis were retrospectively reviewed. Forty-three patients underwent radical resection after preoperative stent insertion (stent group), whereas 48 underwent emergency surgery with curative intent (surgery group). The short- and long-term outcomes between the two groups were compared. The stent and surgery groups had similar demographics. There were no significant differences in primary anastomosis, laparoscopic-assisted surgery, operation time, time until first defecation and oral intake after surgery, postoperative hospital stay, and reoperation. The stent group had an average hospital stay 7 days longer than the surgery group. During the median follow-up period of 48.1 months, the 5-year disease-free survival rates were not significantly different between the stent and surgery groups (47.2 vs. 48.9 %, respectively; p = 0.499). Overall, the 5-year survival rate was also similar in the two groups (70.4 vs. 76.4 %, respectively; p = 0.941). For left-sided colorectal cancer obstruction, stent insertion followed by surgery showed short-term advantages and similar oncologic outcomes compared to surgery without preoperative intervention. Stent insertion as a bridge to surgery is a safe and feasible treatment option for patients with colorectal cancer obstruction.

Background and study aims: Post-polypectomy coagulation syndrome (PPCS) is a well known complication of colonoscopic polypectomy. However, no previous studies have reported on the clinical outcomes or risk factors of PPCS. The aim of the current study was to analyze the clinical outcomes and risk factors of PPCS developing after a colonoscopic polypectomy. Patients and methods: Data for all patients who underwent colonoscopic polypectomies and required hospitalization in nine university hospitals were analyzed retrospectively. The incidence, clinicopathological characteristics, and clinical outcomes of PPCS cases were examined. Additionally, patients who developed PPCS were compared with controls who were matched by age and sex, in order to assess for possible risk factors. Results: The rate of PPCS that required hospitalization after colonoscopic polypectomy was 0.7/1000. All patients with PPCS were treated medically without the need for surgical interventions. The median durations of therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively. The rates of major PPCS and mortality were 2.9 % and 0 %, respectively. On multivariate analysis, hypertension (OR = 3.023, 95 %CI 1.034 – 8.832), large lesion size (OR = 2.855, 95 %CI 1.027 – 7.937), and non-polypoid configuration (OR = 3.332, 95 %CI 1.029 – 10.791) were found to be independent risk factors related to the development of PPCS. Conclusions: In this study, the rates of major PPCS and mortality were only 2.9 % and 0 %, respectively. Hypertension, large lesion size, and non-polypoid configuration of the lesion were independently associated with PPCS. Therefore, patients may be reassured by the excellent prognosis of PPCS, while endoscopists should be especially careful when performing colonoscopic polypectomies in patients with hypertension or large and non-polypoid lesions.

Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in epithelial tumor carcinogenesis. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the induction of RON and tumor growth in human gastric cancer. EGCG inhibited phorbol 12-myristate 13-acetate (PMA)-induced RON expression and reduced RON transcriptional activity. However, (-)-epigalloca-techin (EGC), (-)-epicatechin gallate (ECG) and (-)‑epicatechin (EC) did not affect RON expression. Experiments with deleted and site-directed mutagenesis of the RON promoter indicated that Egr-1 binding sites in the RON promoter may be the EGCG‑response element acting as a cis-element in gastric cancer cells. EGCG also inhibited PMA-induced Egr-1 expression and DNA binding in a dose-dependent manner. Furthermore, gastric cancer cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by EGCG and siRNA-targeted RON and Egr-1. EGCG significantly reduced tumor growth in an in vivo tumor model, whereas RON expression was downregulated. These results suggest that EGCG may exert at least part of its anticancer effect by controlling RON expression through suppression of Egr-1 activation.

Background/Aims Researches on the potential risk factors for the development of erosive esophagitis have been conducted extensively, however, the results are conflicting. The aim of this multicenter study was to identify the prevalence rate and risk factors of erosive esophagitis and their interactions with residency status. Methods A total of 4,023 eligible subjects at 8 tertiary health care centers were evaluated using questionnaires, laboratory tests and endoscopy. Univariate and multivariate analyses were conducted to identify independent risk factors for erosive esophagitis. Results The prevalence rate of reflux esophagitis was 8.8%. Los Angeles grade A was common type of erosive esophagitis. Residence in a large urban areas was negatively associated with the development of erosive esophagitis (OR, 0.60; 95% CI, 0.40-0.90). The high body mass index (≥ 25 kg/m2) was more frequent in residents of small and medium-sized cities than those in big cities (38.8% and 26.9%, respectively; P < 0.001). Seronegativity of Helicobacter pylori was associated with increased erosive esophagitis (OR, 1.91; 95% CI, 1.48-2.46). Triglyceride ≥ 150 mg/dL (OR, 1.65; 95% CI, 1.08-2.07), fasting glucose level ≥ 126 mg/dL (OR, 1.73; 95% CI, 1.06-2.81), and hiatal hernia (OR, 3.11; 95% CI, 1.87-5.16) were also associated with erosive esophagitis. Conclusions The prevalence rate of erosive esophagitis and its risk factors in this study were similar to the result of 8.0% of nationwide study in 2006. Residency and obesity are more important independent risk factors than H. pylori infection status for development of erosive esophagitis in Korea. These results suggest that the prevalence rate of erosive esophagitis in Korea might not increase as in the Western countries.

The purpose of this study was to review the computed tomography (CT) features of thyroglossal duct cysts (TDCs) in children less than 11 years of age. A retrospective chart review was performed at Chonnam National University Hospital for the period of March 2005 to June 2011. CT scans of 16 patients having TDCs were evaluated for the following features: site of the mass, relationship to the midline, walls, margins, internal septa, rim enhancement, internal density, and the presence or absence of the thyroid gland. Of the 16 lesions, 8 (50%) were located in the midline and 12 (75%) were infrahyoid in location. Twelve (75%) of the 16 patients had well-circumscribed walls and peripheral rim enhancement. Internal septa were seen in four of the cysts, and all but one of the cysts demonstrated homogeneous or low-density attenuation. The most common CT findings of TDCs in children less than 11 years of age were a homogeneous or low-density lesion. TDCs in children under the age of 11 years were mostly located in the infrahyoid neck.

Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating cancer metastasis. Recently, microRNA-375 (miR-375) was reported to be downregulated in many types of cancers, including gastric cancer. Increase in the expression of Recepteur d’Origine Nantais (RON), a receptor tyrosine kinase, has been reported in tumors. However, the function of miR-375 and RON expression in gastric cancer metastasis has not been sufficiently studied. In silico analysis identified miR-375 binding sites in the 3′-untranslated regions (3′-UTR) of the RON-encoding gene. Expression of miR-375 resulted in reduced activity of a luciferase reporter containing the 3′-UTR fragments of RON-encoding mRNA, confirming that miR-375 directly targets the 3′-UTR of RON mRNA. Moreover, we found that overexpression of miR-375 inhibited mRNA and protein expression of RON, which was accompanied by the suppression of cell proliferation, migration, and invasion in gastric cancer AGS and MKN-28 cells. Ectopic miR-375 expression also induced G1 cell cycle arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of RON by RNAi, similar to miR-375 overexpression, suppressed tumorigenic properties and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of Rb. Thus, our study provides evidence that miR-375 acts as a suppressor of metastasis in gastric cancer by targeting RON, and might represent a new potential therapeutic target for gastric cancer.

The number of patients with10 adenomas is relatively small, and few studies have investigated the risk of colorectal neoplasm (CRN) in these patients. Thus, we aimed to investigate the risk of developing CRN in patients with10 adenomas and to compare their risk with that of patients with 3-10 adenomas.A retrospective multicenter cohort study that included 214 patients with10 adenomas on index colonoscopy performed between January 2009 and December 2011, and underwent follow-up colonoscopy until December 2015 was conducted. The risk of developing advanced CRN (cancer or advanced adenoma with a diameter of ≥10 mm or with a villous component, or high-grade dysplasia) was investigated and compared with that in patients with 3-10 adenomas (n = 975).Among the 214 patients with10 adenomas, the mean age was 62.9 years and the mean number of adenomas on index colonoscopy was 14.2. Overall, 57 patients (26.6%) developed an advanced CRN after a mean of 4.3 years from baseline colonoscopy. The respective 3- and 5-year cumulative risks of advanced CRN were 6.8% (95% confidence interval [CI] 2.9-10.7) and 28.7% (95% CI 20.8-36.5), higher than those in the group with 3-10 adenomas (n = 975, P = 0.001). Having10 adenomas on index colonoscopy was an independent risk factor for developing advanced CRN (odds ratio 2.25, 95% CI 1.49-3.38).The risk of developing advanced CRN in patients with10 adenomas was high and statistically higher than that in patients with 3-10 adenomas. Further prospective studies are needed to investigate whether a more intensive surveillance is needed in this group.

// Young-Lan Park 1, * , Sun-Young Park 1, * , Seung-Hyun Lee 1 , Rul-Bin Kim 1 , Joong-Keun Kim 1 , Sung-Yoon Rew 1 , Dae-Seong Myung 1 , Sung-Bum Cho 1 , Wan-Sik Lee 1 , Hyun-Soo Kim 1 , Young-Eun Joo 1 1 Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea * These authors contributed equally to this work Correspondence to: Young-Eun Joo, email: yejoo@chonnam.ac.kr Keywords: FILIP1L, cell survival, angiogenesis, prognosis, colorectal neoplasm Received: June 06, 2016 Accepted: October 10, 2016 Published: October 14, 2016 ABSTRACT Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells. FILIP1L knockdown enhanced angiogenesis by increasing VEGF-A and HIF-1α levels and decreasing angiostatin level. FILIP1L overexpression suppressed angiogenesis by decreasing VEGF-A and -D l level and increasing angiostatin and endostatin levels. Phosphorylated β-catenin levels decreased and phosphorylated Akt and GSK-3β levels increased following FILIP1L knockdown. FILIP1L overexpression had the opposite effects. FILIP1L expression was associated with reductions in tumor size, cell differentiation, lymphovascular invasion, stage, invasion depth and lymph node metastasis, and with longer overall survival. Mean Ki-67 labeling indexes and microvessel density values were lower in FILIP1L-positive tumors than in FILIP1L-negative tumors. These results indicate that FILIP1L suppresses tumor progression by inhibiting cell proliferation and angiogenesis in colorectal cancer.

To elucidate the rate and risk factors of HBV reactivation in patients with chronic HBV infection with low replicative state and resolved HBV infection undergoing allogenic/autologous hematopoietic stem-cell transplantation (HSCT) in Korea. The medical charts of 506 patients who underwent allogenic/autologous HSCT from January 2008 to December 2013 were analyzed retrospectively. We examined the reactivation rate and variables related to the risk of HBV reactivation, with a median follow-up period of 41.8 (1–245) months. Univariate analysis was used to identify any factors associated with HBV reactivation. Factors that were significant in the univariate analysis were entered into a stepwise multivariate analysis to find the most significant risk factors associated with HBV reactivation. The reactivation rate of HBV in patients who underwent HSCT was 4.2 % (21/506). In subgroup analysis, the HBV reactivation rate (14.3 %) was the highest among HBsAg(+) patients (5/35). The reactivation rate of HBV in patients with resolved HBV infection [HBsAg(−)/HBcAb(+) with or without anti-HBs antibody] was 5.9 % (10/171). In univariate analysis for risk factors of HBV reactivation in patients who underwent HSCT, initial detectable HBV DNA (p = 0.004), age (≥60 years) (p = 0.012), recipient hepatitis B surface antigen-positive (HbsAg)(+) before HSCT (p = 0.004), recipient hepatitis B surface antibody-negative (HBsAb)(−) before HSCT (p = 0.005), recipient hepatitis B core antibody-positive (HbcAb)(+) before HSCT (p = 0.013), and donor HBsAg(+) (p

Background The purpose of this study was to investigate expression of recepteur d'origine nantais (RON) in human hypopharyngeal squamous cell carcinoma (SCC) and to determine whether RON affects tumor cell behavior in hypopharyngeal SCC cell line and if this would serve as a target for molecular therapy in a preclinical model. Methods Reverse transcriptase-polymerase chain reaction, immunohistochemistry, Western blotting, cell invasion, migration, proliferation, and apoptosis assays were used to assess alteration of RON expression and its impact to cancer progression in human hypopharyngeal SCC. Results Immunoreactivity of RON was observed in hypopharyngeal SCC tissues relative to adjacent normal mucosa in all cases. RON protein expression was significantly increased in metastatic lymph nodes than nonmetastatic lymph nodes by Western blotting. Knockdown of RON resulted in significantly reduced cell invasion, migration, and proliferation in human hypopharyngeal SCC cells. Knockdown of RON enhanced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP-ribose polymerase (PARP). Conclusion These results indicate that knockdown of RON expression may be associated with the reversal of invasive phenotype in hypopharyngeal SCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Metastasis to the ampulla of Vater from renal cell carcinoma (RCC) is rarely encountered. We present the case of a 50-year-old male admitted with complaints of right upper quadrant pain and jaundice. The medical history consisted of a right radical nephrectomy, right adrenalectomy, and brain mass excision for RCC and metastasis. An esophagogastroduodenoscopy revealed a round ampullary mass with ulceration. An abdominal computed tomography scan revealed an enhancing mass in the ampulla of Vater, total pancreas, and left adrenal gland. Pathologic examination of a biopsy specimen was compatible with metastatic RCC of the clear cell type. A percutaneous transhepatic cholangiogram revealed complete obstruction of the distal common bile duct. A metal stent was inserted for bile drainage via the percutaneous transhepatic route. Patients with a history of RCC should undergo a careful long-term follow-up to detect and evaluate metastasis to usual and unusual sites.

Background/Aims: Gastroesophageal reflux (GER) has been implicated in the pathogenesis of chronic cough. The aims of this study were to evaluate the diagnostic usefulness of multichannel intraluminal impedance combined with pH monitoring (MII/pH monitoring) in patients with suspected symptoms of gastroesophageal reflux disease (GERD) and to assess the correlation between GER symptoms and refl ux nature. Methods: Seventy patients with suspected symptoms of GERD (such as heartburn, acid regurgitation, noncardiac chest pain, globus and chronic cough) were enrolled. All patients were asked to discontinue medications that would infl uence esophageal motor function and gastric acid secretion at least one week ago. All subjects underwent MII/pH monitoring. Results: Forty-five patients (64.3%) were diagnosed with GERD. Among these patients, eleven patients (15.7%) had pathologic acid refl ux by pH data and thirty-four patients (48.6%) had pathologic bolus exposure by impedance. Subjects with chronic cough had a higher De- Meester score (p=0.009), percentage of acid exposure time (p=0.007), acid bolus exposure % time (p=0.027), distal acid refl ux episodes (p=0.015) and proximal acid refl ux episodes (p=0.030) than subjects without chronic cough. Conclusions: The results of this study showed that the impedance monitoring enhanced diagnostic sensitivity than pH-monitoring alone by 48.6%. In addition, refl ux episodes at the distal and proximal esophagus were noted to be important factors associated with chronic cough. (Gut Liver 2012;6:197-202)

Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in carcinogenesis of epithelial tumors. RON expression was induced by the tumor promoter, phorbol 12-myristate 13-acetate (PMA), in gastric adenocarcinoma AGS cells. Studies with deleted and site-directed mutagenesis of Egr-1 promoter and with expression vectors encoding Egr-1 confirmed that Egr-1 is essential for RON expression. In addition, AGS cells pretreated with PMA showed remarkably enhanced invasiveness, which was partially abrogated by siRNA-targeted RON and Egr-1. These results suggest that tumor promoter induces RON expression via Egr-1, which, in turn, stimulates cell invasiveness in AGS cells. J. Cell. Biochem. 113: 1217–1223, 2012. © 2011 Wiley Periodicals, Inc.

We describe the clinical and radiographic characteristics of fungus balls in the bilateral paranasal sinuses. The medical records of 8 of 245 patients with fungus balls of the bilateral paranasal sinuses between 2000 and 2010 were retrospectively reviewed. The incidence of bilateral paranasal sinus fungus balls was 3.3%. Fungus balls were located in the maxillary sinuses bilaterally in 4 cases (50%), followed by the maxillary sinus and contralateral sphenoid sinus in 3 cases (37.5%), and the sphenoid sinuses bilaterally in 1 case (12.5%). There were no predisposing anatomic variations for the occurrence of bilateral paranasal fungus balls. Although the presenting symptoms and signs were non-specific, CT findings were helpful in the diagnosis of bilateral fungus balls. Endonasal removal by an endoscopic approach was performed in all patients. No peri-operative complications or recurrences were noted. Fungus balls in the bilateral paranasal sinuses are most frequently found in the maxillary sinuses bilaterally. Because symptoms of bilateral paranasal fungus balls and findings on nasal endoscopic examination are frequently non-specific, a high index of suspicion is needed and imaging studies, such as CT, are essential to establish the correct pre-operative diagnosis.

Background In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). Methods We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. Results SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and −7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. Conclusions SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1875-8) contains supplementary material, which is available to authorized users.

Knowledge of the intraoperative location of lesions is a prerequisite for deciding the proper extent of gastric resection or the choice of anastomosis technique during totally laparoscopic distal gastrectomy (TLDG) for early gastric cancer (EGC). In this study we introduce a novel tumor localization method for TLDG: endoscopic blood tattooing.Twenty-three consecutive patients scheduled for TLDG for EGC were enrolled in this prospective study. The day before surgery, 2-3 ml of autologous blood was injected into the gastric muscle layer at 3-4 cm proximal to the lesion during endoscopy.The study subjects consisted of 15 males and 8 females with a mean age of 61 ± 10.4 years. During surgery, the endoscopic blood tattooed sites were successfully identified in all 23 patients. No complications associated with the procedure occurred, and no patient had microscopic residual tumor cells at the proximal resection margin, with a mean proximal margin length of 3.3 ± 2.7 cm. Eighteen patients underwent TLDG with Billroth II anastomosis, four patients with Roux-en-Y gastrojejunostomy, and one patient with laparoscopic total gastrectomy. At final pathologic examinations, 20 patients were of stage IA and 3 were of stage IB according to the UICC TNM classification (6th ed.).Endoscopic blood tattooing provides a simple and useful means of localizing lesions during TLDG for EGC. Although the superiority of this technique over other localization methods needs to be evaluated further, the authors recommend endoscopic blood tattooing as an alternative to other intraoperative localization methods for laparoscopic surgery for EGC.

The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expression with various clinicopathological parameters in gastric cancer. The biological role of RON in tumor cell behaviors and oncogenic signaling pathways was investigated by using small interfering RNA in gastric cancer cell lines including AGS and MKN28. The expression of RON in gastric cancer tissues was investigated by using reverse transcription polymerase chain reaction and immunohistochemistry. Knockdown of RON suppressed tumor cell migration and invasion in AGS and MKN28, induced apoptosis through modulation of anti-apoptotic and pre-apoptotic genes and induced cell cycle arrest by decreasing cyclin D1, cyclin D3 and CDK4, and by inducing p21 and p27 expression. Signaling cascades, including Akt and mitogen-activated protein kinase (MAPK), were significantly blocked by knockdown of RON. Expression of RON was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.

Background Clinical demand for total colonoscopy is increasing. Several articles have reported on the usefulness of a cap for faster cecal intubation and reduced patient discomfort, but results for polyp and adenoma detection have been inconsistent. Objective To assess the efficacy of a cap attached to the tip of a colonoscope for detection and resection of polyps by experienced colonoscopists. Design Prospective, randomized, controlled trial. Setting A tertiary referral center. Patients and Intervention A total of 329 patients who underwent colonoscopic EMR were randomized to cap-assisted colonoscopy (CAC) (CAC group, n=166) or regular colonoscopy (RC) (RC group, n=163). Main Outcome Measurements Cecal intubation time, total procedure time, required time for colonoscopic EMR of each polyp, and missing polyp rate. Results The cecal intubation time in the CAC group and RC group was 5.3 ± 3.3 minutes and 5.8 ± 3.7 minutes, respectively ( P = .170). The total procedure time in the CAC group and RC group was 23.0 ± 15.5 minutes and 29.2 ± 13.4 minutes, respectively ( P = .626). The time required for colonoscopic EMR of each polyp in the CAC group and RC group was 3.5 ± 4.5 minutes and 4.2 ± 5.1 minutes, respectively ( P = .010). The number of polyps during the initial colonoscopy in the CAC group and RC group was 2.2 ± 1.7 and 2.0 ± 1.8, respectively ( P = .221). The number of detected polyps during colonoscopic EMR in the CAC group and RC group was 3.4 ± 2.7 and 2.7 ± 1.9 ( P = .003). The number of missed polyps in the CAC group and RC group was 1.1 ± 1.5 and 0.8 ± 0.9 ( P = .024). Limitation Single-center experience. Conclusions CAC may reduce the time required for colonoscopic EMR of each polyp and may also improve the polyp detection rate.

Purpose The aims of this study were to compare the clinical outcomes of the preoperative drainage methods in patients with obstructive jaundice awaiting panreaticoduodenectomy and to determine, which procedure would be more effective for preoperative drainage. Methods Among 239 patients undergoing pancreaticoduodenectomy for periampullary cancer, 77 with obstructive jaundice underwent percutaneous transhepatic biliary drainage (PTBD, n=34) or endoscopic biliary drainage (EBD, n=43). Results Median rate of decrease in bilirubin was 0.65 mg/d in PTBD group and 0.34 mg/d in EBD group (P=0.003). Median interval from preoperative drainage to pancreaticoduodenectomy were 11 days in PTBD group and 18 days in EBD group (P=0.009). Overall indwelling catheter-related complication rates were higher in "EBD" group compared with "PTBD" group (23.3% vs. 2.9%, P=0.019). No catheter occlusion developed in "PTBD" group, but 6 stent occlusions (13.3%) developed in "EBD" group (P=0.031). The mortality rate was not significantly different between the 2 groups. Conclusions Percutaneous biliary drainage may be preferred for preoperative drainage in patients with obstructive jaundice awaiting pancreaticoduodenectomy due to rapid biliary decompression and lower frequency of catheter-related complications.

Objective:We report an extremely rare case of a fungus ball within a mucocele of the sphenoid sinus and infratemporal fossa.Case report:A 62-year-old woman was referred for evaluation of a mass lesion in the left sphenoid sinus and infratemporal fossa. Endoscopic examination of the nasal cavity was unremarkable. Computed tomography showed a non-enhancing, expansile mass with calcifications in the sphenoid and infratemporal fossa; T2-weighted magnetic resonance imaging revealed marked hypointense signals within the sphenoid sinus mass, with an intermediate signal intensity. A presumptive diagnosis of a mucocele was made. During surgery, a profuse amount of yellow fluid was drained from the mucocele. Clay-like material was noted within the mucocele, corresponding to the hypointense magnetic resonance imaging signals; this was identified as aspergillus on histopathological examination. Radiological findings for a fungus ball within a mucocele can be similar to those for allergic fungal sinusitis, which shows mixed low and high attenuation on computed tomography and low-signal intensity on T2-weighted magnetic resonance imaging, within an expansile, cystic lesion.Conclusion:Although an association between a fungus ball and a mucocele is rare in the paranasal sinuses, this disease entity should be considered in the differential diagnosis of expansile, cystic sinus lesions.