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Duodenal neuroendocrine tumors (NETs) are rare subepithelial tumors that arise from the neuroendocrine cells beneath the epithelial layer. However, an accurate histopathological diagnosis is difficult when tissue samples are obtained using conventional endoscopic forceps biopsy alone. This study aimed to evaluate the magnifying endoscopy with narrow-band imaging (ME-NBI) findings of duodenal NETs. We retrospectively analyzed a database of 22 duodenal NETs from 21 patients who underwent ME-NBI between January 2011 and June 2022. The ME-NBI, endosonographic, and histopathologic findings of duodenal NETs were analyzed. Nineteen lesions were located in the bulb, two were located in the superior duodenal angle, and one was located in the second portion of the duodenum. Eighteen lesions (82%) had IIa morphology, and nine (41%) had central depression on the surface. On endoscopic ultrasonography, almost all lesions (20/22, 91%) were located in the second and/or third layers, and the median tumor size was 6 mm. During ME-NBI, the microsurface pattern was regular in 18 lesions (82%) and absent in 4 (18%). The microvascular pattern was regular in 17 lesions (77%), irregular in 4 (18%), and absent in 1 (5%). Thickened subepithelial vessels were observed in 15 (68%) lesions. There was no difference in tumor size according to the presence or absence of thickened subepithelial vessels (6.1 ± 1.8 mm vs. 5.9 ± 3.8 mm, p = 0.860). In conclusion, the characteristic ME-NBI findings of duodenal NETs were regular microsurface and microvascular patterns and the presence of thickened subepithelial vessels. These ME-NBI features may be useful for differentiating duodenal NETs from other duodenal subepithelial lesions.

PDF - 1244K, BRD7 mediated reduction of MMP2 require beta-catenin pathway. A2780 (A) or SKOV3 (B) cells were co-transfected with BRD7 plasmid and beta-catenin siRNA. After 36 hours, whole mRNA was isolated and cDNA was synthesized. Semi-quantitative PCR was performed to estimate the expression of MMP2 mRNA.

Purpose: Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in epithelial ovarian cancer.Experimental Design: We analyzed the expression of BRD7 in human ovarian tissues with real-time PCR. To investigate the functional role of BRD7, we transfected ovarian cancer cells (A2780 and SKOV3) with BRD7 plasmid and checked the cell viability, apoptosis, and invasion. The activities of BRD7 in the signaling pathways associated with carcinogenesis were also tested. In addition, we used the orthotopic mouse model for ovarian cancer to evaluate tumor growth-inhibiting effect by administration of BRD7 plasmid.Results: The BRD7 expression was downregulated in the ovarian cancer tissues compared with normal (P < 0.05), high-grade serous cancer exhibited significantly decreased expression of BRD7 compared with low-grade (P < 0.01) serous cancer. Transfection of BRD7 plasmid to A2780 (p53-wild) or SKOV3 (p53-null) ovarian cancer cells showed the tumor suppressive effects assessed by cell viability, apoptosis, and invasion assay and especially significantly decreased tumor weight in orthotopic mouse model (A2780). Moreover, we found that tumor suppressive effects of BRD7 are independent to the presence of p53 activity in ovarian cancer cells. BRD7 negatively regulated β-catenin pathway, resulting in decreased its accumulation in the nucleus.Conclusions: These results suggested that BRD7 acts as a tumor suppressor in epithelial ovarian cancers independently of p53 activity, via negative regulation of β-catenin pathway. Clin Cancer Res; 20(3); 565–75. ©2013 AACR.

PDF - 1246K, Western blot analysis was used to determine expression levels of MEK1 and p-ERK (1/2) when two ovarian cancer cells were transfected with BRD7 plasmid.

PDF - 57K, Information of the cell lines used in experiments.

PDF - 1513K, BRD7 mediated tumor suppressive effects are not correlated with cell cycle. A, Cell cycle distributions of A2780 (marked as A) and SKOV3 (marked as S) cells measured by flow cytometry. Cell number histograms plot (upper panel) show the distribution of cells on the basis of DNA contents as determined by PI fluorescence intensity. Left peak represents cells in the G1/G0 phases, hatched area represents cells in S phase, and peak on right represents cells in the G2 and M phases. The expression levels of BRD7 mRNA among phases of cell cycle show no significant differences in both A2780 and SKOV3 cell line (.lower panel). Values are expressed as means of three independent experiments plus or minus SD. B, Western blot analysis was used to determine expression levels of Cyclin B1, D1 or E2.

PDF - 856K, Western blot analysis was used to determine expression levels of alpha-catenin when two ovarian cancer cells were transfected with BRD7 plasmid.

We aimed to evaluate whether adding a sustained-release (SR) formula of mosapride to proton-pump inhibitors (PPIs) would be more effective in controlling symptoms than PPI alone in patients with gastroesophageal reflux disease (GERD). Sixty patients with heartburn and/or regurgitation were randomly assigned to two groups: mosapride SR 15 mg combined with esomeprazole 20 mg once daily (ME group) and esomeprazole 20 mg once daily alone (E group). The primary endpoint was the complete-resolution rate of GERD symptoms after eight-week medication, and the secondary endpoints were the complete-resolution rate of GERD symptoms after four-week medication, symptom-improvement rates ≥ 50% after four- and eight-week medication, and change in reflux-disease-questionnaire (RDQ) and GERD-health-related quality-of-life (GERD-HRQL) scores from baseline at four- and eight-week medication. No significant differences in complete-symptom-resolution rates at eight weeks and four weeks or in the changes in RDQ and GERD-HRQL scores from baseline at four- and eight-week medication were observed between the ME and E groups. The symptom-improvement rate of ≥50% after four and eight weeks was comparable between both groups. Adding mosapride SR to esomeprazole in patients with GERD provides no additional benefits in controlling GERD symptoms.

Purpose Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. Materials and methods We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. Results Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023). Conclusion PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

Data concerning the long-term outcomes of endoscopic submucosal dissection (ESD) versus surgery for early gastric cancer (EGC) are limited. We aimed to compare the long-term outcomes of ESD and surgery for patients with EGC. Data were reviewed from patients treated by ESD or surgery for EGC in 2005–2010. The primary outcome was overall survival (OS). Secondary outcomes were disease-specific survival (DSS), disease-free survival (DFS), recurrence-free survival (RFS), treatment-related complications, and hospital stay duration. Among 617 patients, 342 underwent ESD and 275 underwent surgery. The 5-year OS rates were similar between the ESD group and the surgery group (96.9% vs 98.1%, P = 0.581). In a propensity-score-matched analysis of 117 pairs, there were no significant differences in the OS rates (96.5% vs 99.1%, P = 0.125) and DSS rates (100% vs 99.1%, P = 0.317) between the ESD group and the surgery group. The ESD group had a significantly lower DFS rate (90.3% vs 98.0%, P = 0.002), a significantly lower RFS rate (95.1% vs 98.0%, P = 0.033), a significantly higher early complication rate (6.7% vs 1.5%, P

Although the concurrent use of a chemotherapeutic agent and radiotherapy improves survival in patients with locally advanced or recurrent cervical cancer, severe side effects related to chemotherapy are frequent and may result in a low quality of life for the patients. In this study, we investigated the effects of a combination of Wee1 inhibitor (AZD1775) and irradiation in cervical cancer. In vitro effects of AZD1775 with irradiation in human cervical cancer cells were assessed by clonogenic survival and apoptosis assays. The effects on DNA damage response signaling and the cell cycle were also explored. Tumor growth delay was evaluated to investigate the in vivo effects of AZD1775 with irradiation in cervical cancer mouse models, including xenografts and patient-derived xenografts (PDXs). The co-treatment of AZD1775 and irradiation significantly decreased clonogenic survival and increased apoptosis in cervical cancer cells. These effects were associated with G2 checkpoint abrogation which resulted in persistent DNA damage. Both in the xenografts and the PDXs, the co-treatment significantly decreased tumor growth compared tothe irradiation alone (p

When it comes to indoor Real-Time Location Systems (RTLS) for an Automatic Guided Vehicle (AGV), the most important factor is to minimize the location estimation error. In industrial sites, centimetre-level accuracy is required for the AGV. Since the duration for measuring the position of an AGV is slower than the speed of arriving RF signals, the margin of error inevitably becomes larger than in systems that use low-speed media such as ultrasonic waves. To minimize such errors, a short-range location estimation Recursive RF Active Echo (RRFAE) algorithm is presented. Increasing the time ratio by repeatedly and interactively reflecting the signal can reduce measurement error. That is, there is an effect of expanding the measurement distance by the number of iterations. We propose and implement a precise positioning algorithm in an indoor environment where many reflections exist. The error analysis of the RRFAE algorithm after hardware correction shows that the level of the RRFAE's errors is only one tenth that of an RTLS system that uses other RF signals.

BACKGROUND/AIMS The gastroesophageal junction is an important barrier against gastroesophageal ref lux. Endoscopic grading of gastroesophageal f lap valve is simple, reproducible, and may predict reflux activity. We investigated the correlation between gastroesophageal flap valve grade and the gastroesophageal junction's structural properties using abdominal computed tomography. METHODS A total of 138 patients with early gastric cancer who underwent both pre-treatment esophagogastroduodenoscopy and water-distended stomach two-phase computed tomography were enrolled. Endoscopic gastroesophageal f lap valve grade and abdominal computed tomography findings were analyzed to assess anatomical factors including the gastroesophageal junction and related organs. RESULTS The angle of His increased significantly with gastroesophageal flap valve grade (grade I, 65.2˚ ± 19.6˚; grade II, 66.6˚ ± 19.8˚; grade III, 76.7˚ ± 11.9˚; grade IV, 120.0˚ ± 30.3˚; p < 0.001), as did the size of the diaphragmatic hiatus (grade I, 213.0 ± 53.8 mm2 ; grade II, 232.6 ± 71.0 mm2 ; grade III, 292.3 ± 99.2 mm2 ; grade IV, 584.4 ± 268.3; p < 0.001). The length of the abdominal esophagus decreased as gastroesophageal flap valve grade increased (grade I, 34.6 ± 5.8 mm; grade II, 32.0 ± 6.5 mm; grade III, 24.6 ± 7.8 mm; grade IV, -22.6 ± 38.2 mm; p < 0.001). There was no significant relationship between gastroesophageal flap valve grade and visceral and subcutaneous fat areas (p = 0.877 and p = 0.508, respectively). CONCLUSIONS Endoscopic grading of the gastroesophageal flap valve is well correlated with anatomical changes around the gastroesophageal junction on abdominal computed tomography, and it can provide useful information about the anti-reflux barrier.

PURPOSE This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. MATERIALS AND METHODS The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively. RESULTS Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05). CONCLUSION V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.

Background/Aims: Proton pump inhibitors are widely used to prevent gastric endoscopic submucosal dissection (ESD)- related bleeding, but no standard administration regimens have been established. We aimed to prospectively compare the effects of continuous infusion and intermittent dosing with pantoprazole on preventing gastric ESD-related bleeding. Additionally, we analyzed the risk factors for bleeding. Methods: From April 2012 to May 2013, patients with a gastric epithelial neoplasm scheduled for ESD in the Pusan National University Hospital were randomly assigned to one of two groups according to the pantoprazole administration regimen (continuous infusion or intermittent dosing). The primary outcomes measured were intra- and postprocedural bleeding events. Results: The final analysis included 401 patients. The rate of significant intraprocedural bleeding was 25.4% in the C group and 24.0% in the I group, with no significant difference (p=0.419). In addition, there was no significant difference in the postprocedural bleeding rate between the C and I groups (11.7% vs 10.2%, p=0.374). Multivariate analysis showed that intraprocedural bleeding was associated with the proximal tumor location, the presence of fibrosis, and the size of the resected specimen, whereas postprocedural bleeding was associated with the size of the resected specimen and the procedure/coagulation time. Conclusions: Intermittent dosing with pantoprazole is sufficient and cost-effective for the prevention of gastric ESD-related bleeding. Operators should consider tumor characteristics when planning ESD to minimize the risk of intraprocedural bleeding, and patients with large iatrogenic ulcers should be carefully monitored for postprocedural bleeding. (Gut Liver 2019;13:40-47)

This study was designed to investigate whether proton pump inhibitors (PPI, V-ATPase blocker) could increase the effect of cytotoxic agents in chemoresistant epithelial ovarian cancer (EOC). Expression of V-ATPase protein was evaluated in patients with EOC using immunohistochemistry, and patient survival was compared based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or PPI (omeprazole) pretreatment. Cell survival and apoptosis was assessed using MTT assay and ELISA, respectively. In vivo experiments were performed to confirm the synergistic effect with omeprazole and paclitaxel on tumor growth in orthotopic and patient-derived xenograft (PDX) mouse models. Expression of V-ATPase protein in ovarian cancer tissues was observed in 44 patients (44/59, 74.6%). Higher expression of V-ATPase mRNA was associated with poorer overall survival in TCGA data. Inhibition of V-ATPase by siRNA or omeprazole significantly increased cytotoxicity or apoptosis to paclitaxel in chemoresistant (HeyA8-MDR, SKOV3-TR) and clear cell carcinoma cells (ES-2, RMG-1), but not in chemosensitive cells (HeyA8, SKOV3ip1). Moreover, the combination of omeprazole and paclitaxel significantly decreased the total tumor weight compared with paclitaxel alone in a chemoresistant EOC animal model and a PDX model of clear cell carcinoma. However, this finding was not observed in chemosensitive EOC animal models. These results show that omeprazole pretreatment can increase the effect of chemotherapeutic agents in chemoresistant EOC and clear cell carcinoma via reduction of the acidic tumor microenvironment.

We assessed the anti-proliferative activity of itraconazole using an EOC cell line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways to determine the mechanism of action of itraconazole. Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as well as patient-derived xenografts (PDXs). Itraconazole treatment inhibited proliferation of endothelial cells in a dose-dependent manner, but had no effect on EOC cells. The endothelial cell antiproliferative effect was associated with inhibition of hedgehog, and mTOR pathways and angiogenesis. In xenograft models of EOC using SKOV3ip1 or HeyA8, mice treated with the combination of itraconazole and paclitaxel had significantly decreased tumor weight than the control, paclitaxel-alone, or itraconazole-alone groups. Tissue derived from these tumors had significantly lower microvessel density than tissue from the other groups as well as hedgehog and mTOR pathway inhibition. We confirmed those effects in two EOC PDX models. These results suggest that itraconazole selectively inhibits endothelial cells rather than cancer cells by targeting multiple pathways including hedgehog, and mTOR pathways and angiogenesis.

Application of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancers (EGCs) remains controversial owing to limited data regarding long-term outcomes. We aimed to evaluate the feasibility of ESD for undifferentiated-type EGCs that meet the expanded criteria (EC). We performed a retrospective analysis of 66 patients who underwent ESD for undifferentiated-type EGC between January 2005 and December 2014. We evaluated the rates of en bloc, complete, and curative resections along with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). Of the 66 patients, the EC group included 38 patients and the beyond-EC group included 28 patients. The overall rates of en bloc, complete, and curative resection of the 66 lesions were 92.4% (61/66), 65.2% (43/66), and 48.5% (32/66), respectively. Of the 34 patients with non-curative resection, 18 underwent additional surgery. Local remnant cancer was detected in 1 patient (1/18, 5.6%), and none of the 18 patients had lymph node metastasis. On multivariate analysis, tumors > 2 cm [odd ratio (OR) 6.183, 95% confidence interval (CI) 1.279–29.880, p = 0.023) and submucosal invasion depth (OR 6.226, 95% CI 1.881–20.606, p = 0.003) were independent predictors of incomplete resection. All 26 patients with more than 1 year of follow-up after curative resection survived without any evidence of local or distant recurrences over a median follow-up period of 36 months. The OS, DSS, and RFS rates of patients with curative ESD were 93.8, 100, and 100%, respectively. ESD may have favorable long-term outcomes in patients with undifferentiated-type EGC after curative resection.

Sphingosine kinase 1 (SK1) is over-expressed in multiple types of human cancer. SK1 has growth-promoting effects and has been proposed as a potential therapeutic target. We investigated the therapeutic effects of SK1 inhibition in epithelial ovarian carcinoma (EOC). SK1 siRNA or inhibitors were tested in EOC cell lines, including A2780, SKOV3ip1, A2780-CP20, SKOV3-TR, ES2 and RMG2. Cells were treated with SK inhibitor or FTY720, and cell proliferation, apoptosis, angiogenesis and invasion were examined by MTT, FACS, ELISA and wound-healing assays, respectively. In vivo experiments were performed to test the effects of FTY720 on tumor growth in orthotopic mouse xenografts of EOC cell lines A2780 or SKOV3ip1 and a patient-derived xenograft (PDX) model of clear cell ovarian carcinoma (CCC). Blocking SK1 with siRNA or inhibitors significantly reduced proliferation, angiogenesis and invasion, and increased apoptosis in chemosensitive (A2780 and SKOV3ip1) and chemoresistant (A2780-CP20, SKOV3-TR, ES2 and RMG2) EOC cells. SK1 inhibitors also decreased the intracellular enzymatic activity of SK1. Furthermore, FTY720 treatment significantly decreased the in vivo tumor weight in xenograft models of established cell lines (A2780 and SKOV3ip1) and a PDX model for CCC compared to control (p

Objective The renin–angiotensin system (RAS) influences cardiovascular homeostasis, and Angiotensin II type 1 receptor (AGTR1) is the main effector of RAS, and AGTR2 antagonizes AGTR1. Accumulating evidence supports the role of RAS in the paracrine regulation of tumorigenesis in several cancer types. Although treatment with AGTR1 antagonist (losartan) or AGTR2 agonist (CGP42112A) inhibits tumor progression in several cancer cells, their combined treatment has not been reported. Methods In this study, we estimated the expression of AGTR1 and AGTR2 in epithelial ovarian cancer cells and tissues. Then, we evaluated the anti-cancer effects of combined treatment with losartan and/or CGP42112A in ovarian cancer cells and human umbilical vein endothelial cells (HUVEC). Results AGTR1 protein was detected in 86% of ovarian cancer tissues, while AGTR2 was not detected in immunohistochemistry. The mRNA expression of AGTR1 obtained from the cancer genome atlas (TCGA) dataset showed that AGTR1 overexpression was correlated with poor survival. Treatment with either losartan or CGP42112A reduced the angiotensin II (Ang II)-mediated cell survival in both ovarian cancer cells and HUVEC. Combined treatment with losartan and CGP42112A synergistically decreased cell survival. As a downstream pathway, phosphorylation of phospholipase C β3 (PLC β3) and expression of vascular endothelial growth factor (VEGF) decreased synergistically in combined treatment. Conclusion The results suggest that dual regulation of AGTR1 and AGTR2 may be a novel therapeutic strategy for epithelial ovarian carcinoma through inhibition of cancer cell survival as well as anti-angiogenesis. Translational relevance This study investigated the expressions of AGTR1 and AGTR2 in epithelial ovarian carcinoma and the therapeutic potential of AGTR modulation with specific antagonist and/or agonist in epithelial ovarian cancer cells. Treatment of AGTR1 antagonist, losartan and/or AGTR2 agonist, CGP42112A synergistically mediated anti-cancer effects including the decrease of cell survival and down-regulation of VEGF.

Background The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer. Methods A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique. Results After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level ≥2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level

Surgical resection for esophagogastric junction (EGJ) tumors is more aggressive and worsens the quality of life of the patients and leads to poor prognosis even after surgery compared with tumors in other sites of the stomach. Endoscopic submucosal dissection (ESD) is a widely accepted treatment modality for premalignant lesions and early cancers in the stomach. However, EGJ tumor is one of the most technically difficult lesions to resect by ESD. Therefore, this study aimed to evaluate the therapeutic outcomes of ESD for EGJ epithelial neoplasms and to assess the predictive factors for incomplete resection. We conducted a retrospective observational study of 48 patients who underwent ESD for adenomas and early cancers of the EGJ between March 2006 and November 2015 at the Pusan National University Hospital. Therapeutic outcomes of ESD and procedure-related adverse events were analyzed. En bloc resection, complete resection, and curative resection rates were 96, 77, and 71%, respectively. Multivariate analyses showed that the presence of ulceration was an independent predictive factor for incomplete resection (odds ratio 21.3, 95% confidence interval 1.51–298.49; p = 0.023). The procedure-related bleeding, perforation, and stenosis rates were 8, 4, and 0%, respectively; none of the adverse events required surgical intervention. During a median follow-up period of 25 months (range 6–72 months), local recurrence occurred in four patients with incomplete resection. ESD is an effective, safe, and feasible treatment for EGJ epithelial neoplasms. However, the complete resection rate decreases for tumors with ulceration.

A method of the ultrasonic transmission time difference (ToF) flow measurement is the one which is mainly applied to large diameter flow meters by incorporating high power digital signal processing devices. In this paper, we propose a ToF-type ultrasonic water meter which can be applied to small diameter flow meters such as water meters at home. Unlike the existing ToF method, a differential ToF (dToF) algorithm is proposed to calculate the flow rate irrespective of the water temperature. We have also focused on low-power design by minimizing the computational portion of the micro-controller. To do this, a measuring principle using dToF has been implemented with a single front-end chip and a single MCU.

Background/aims Globus is a persistent or intermittent non-painful sensation of a lump or foreign body in the throat. Given the benign nature of the condition and the association of gastroesophageal reflux disease, empirical therapy with proton pump inhibitor seems reasonable for patients with typical globus. The aim of this study was to investigate the clinical predictors for symptom response to short-term proton pump inhibitor treatment in patients with globus symptom. Methods Fifty-four patients with globus symptom were enrolled prospectively. All patients were treated with pantoprazole 40 mg daily for 4 weeks. Treatment response was defined as a > 50% reduction in symptom scores between symptom assessments. Univariate and multivariate logistic regression analysis between responders and non-responders was performed to identify variables predicting response to pantoprazole treatment. Results Of the 54 consecutive patients considered, 13 were excluded on the basis of exclusion criteria and/or refusal to participate in the study. Finally, 41 patients were included in this study. After 4-week pantoprazole treatment, 22 patients (53.7%) were classified as responders. On multivariate analysis, the presence of reflux symptom was associated with a higher response rate to 4-week pantoprazole treatment (OR, 68.56; P = 0.043), and long symptom duration (≥ 3 months) were associated with a lower response rate to pantoprazole treatment (OR, 0.03; P = 0.034). Conclusions Presence of reflux symptom and short symptom duration were independent predictors of responsiveness to 4-week pantoprazole treatment in patients with globus.

Galectin 1 is a 14-kd laminin-binding lectin involved in important biologic mechanisms of tumors, including neoplastic transformation, cell survival, angiogenesis, cell proliferation, and metastasis. In this study, we investigated the role of galectin 1 in cell survival and metastasis in cervical cancer. The expression of galectin 1 was determined in 73 formalin-fixed, paraffin-embedded cervical cancer tissues using an immunohistochemical method and compared with clinicopathologic risk factors for recurrence after surgery. To evaluate the role of galectin 1 in cell proliferation and invasion, we performed proliferation and invasion assays with galectin 1 small interfering RNA (siRNA) using cervical cancer cell lines, including HeLa and SiHa cells. Immunohistochemical analysis revealed that galectin 1 expression was found in most peritumoral stroma samples (72/73; 98.6%). Galectin 1 expression was significantly correlated with the depth of invasion in the cervix (P=.015) and lymph node metastasis (P=.045) on univariate analysis. When progression-free survival of all of the patients studied was analyzed based upon galectin 1 expression, galectin 1 expression was not correlated with progression-free survival (P=.32). Down-regulation of galectin 1 using small interfering RNA resulted in the inhibition of cell growth and proliferation of HeLa and SiHa cells. Moreover, the ability of cells to invade was significantly reduced by galectin 1 small interfering RNA. Our results revealed that high galectin 1 expression in peritumoral stroma was significantly correlated with depth of invasion in cervical lesions and lymph node metastasis of cervical cancer and that galectin 1 may be functionally involved in cell proliferation and invasion.

Papillary adenocarcinoma of the stomach has been treated according to the same endoscopic submucosal dissection (ESD) indication criteria as other differentiated-type adenocarcinomas. We aimed to compare lymph node metastasis (LNM) in patients with early gastric cancer (EGC) with papillary adenocarcinoma (EGC-P) with that in patients with EGC with nonpapillary adenocarcinoma (EGC-NP) and to consider the potential limitation of current ESD indication criteria in the treatment of EGC-P. In total, 1583 patients who underwent gastrectomy for EGC from 2005 to 2014 were included. Clinicopathologic characteristics of 56 patients with EGC-P were compared with those of 1527 patients with EGC-NP. The safety of ESD was evaluated, by application of current ESD indication criteria to EGC-P. The frequency of submucosal invasion was significantly higher in EGC-P than in both EGC-NP with differentiated-type histologic appearance and EGC-NP with undifferentiated-type histologic appearance (71.4% vs 50.8% and 37.6%, respectively). In addition, the frequency of LNM in EGC-P was 17.9%, higher than that in both EGC-NP with differentiated-type histologic appearance and EGC-NP with undifferentiated-type histologic appearance (9.7% and 11.1%, respectively). When the current ESD indication criteria were applied to the 56 patients with EGC-P, 17 patients met the current indications. Of these patients, two (11.8%) had LNM and three (17.6%) had lymphovascular invasion (LVI). When LNM and LVI were combined, one of seven patients (16.7%) meeting the absolute ESD indications and three of ten patients (30.0%) meeting the expanded ESD indications would not be cured after ESD. The use of ESD should be more carefully applied in patients with EGC-P meeting the ESD indication criteria, especially the expanded indication criteria, after pretreatment workup compared with other differentiated-type adenocarcinomas, owing to the higher frequencies of submucosal invasion, LNM, and LVI in EGC-P.