Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer.However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Recent First Line Eradication Rate of Helicobacter pylori Infection: Single Center Experience

BACKGROUND/AIMS: For more than a decade, triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) has been the first line eradication regimen for Helicobacter pylori infection in Korea. However, recent studies have proven that its' efficacy is no longer tolerable due to increased resistance of antibiotics. This study is aimed to investigate the current status of triple therapy, quadruple therapy and dual therapy as first line regimen for H. pylori infection in single medical center. MATERIALS AND METHODS: Medical records of patients who received urea breath test after first line eradication therapy from August 2011 to November 2014 were retrospectively analyzed. Patients were divided into three groups according to the first line treatment regimen; triple therapy (proton pump inhibitor (PPI)+clarithromycin+amoxicillin), quadruple therapy (PPI+bismuth+tetracycline+metronidazole), dual therapy (PPI+amoxicillin). RESULTS: A total of 557 patients were reviewed and 429 patients (77.0%) had successful eradication. Among 511 patients who received triple therapy, the eradication rates were 77.1% (394 patients). Eradication rates were 95.2% among quadruple therapy group. Dual therapy group had exceptionally low eradication rates (60.0%). CONCLUSIONS: Even though triple therapy has been recommended as first line regimen in Korea, eradication rates were below 80%. Quadruple therapy as first line regimen showed promising future reaching over 90% eradication rates. However, due to the small number of patients in our study, further studies are necessary to estimate usefulness of quadruple therapy as first line regimen.

A Clinical Study of Mandibular Angle Fracture / 대한악안면성형재건외과학회지

PURPOSE: To establish management protocol for mandibular angle fracture, we describe pertinent factors including cause, impacted third molar and recent treatment tendency. METHODS: We examined the records of 62 patients who had unilateral mandibular angle fracture. Sixty patients who had open reduction surgery were examined at postoperative weeks 1, 4, 8, 12, and 28. RESULTS: Left mandibular angle fracture is frequent in younger males. Presence of the mandibular third molar can increase fracture risk. Because of attached muscle, favorable fractures occurred primarily in the mandibular angle area. CONCLUSION: Extracting the mandibular third molar can prevent angle fractures, and open reduction with only one plate adaptation is generally the proper treatment method for mandibular angle fracture.

Left Ventricular Dyssynchrony in Patients Showing Diastolic Dysfunction without Overt Symptoms of Heart Failure

BACKGROUND/AIMS: Few studies have assessed left ventricular (LV) dyssynchrony in cases of diastolic dysfunction that do not include overt symptoms of heart failure. We hypothesized that systolic or diastolic dyssynchrony involves unique features with respect to the degree of diastolic impairment in isolated diastolic dysfunction. METHODS: We examined 105 subjects with no history of overt symptoms of heart failure and a left ventricular ejection fraction > 50% for mechanical dyssynchrony using tissue Doppler imaging. RESULTS: In terms of longitudinal dyssynchrony, four cases showed (6.3%) LV intraventricular systolic dyssynchrony (SDS(LV)), whereas none had LV intraventricular diastolic dyssynchrony (DDS(LV)) or co-existing systolic dyssynchrony. Radial dyssynchrony (RD) was found in six cases (9.4%). After adjusting for age, SDS(LV) and DDS(LV) were found to be significantly related to increases in the E/E' ratio (r = 0.405 and p < 0.001 vs. r = 0.216 and p = 0.045, respectively). RD at the base and apex was also significantly related to increases in E/E' (r = 0.298 and p = 0.002 vs. r = 0.196 and p = 0.045, respectively). CONCLUSIONS: Systolic and diastolic dyssynchrony in subjects with isolated diastolic dysfunction but without overt symptoms of heart failure was not as common as in patients with diastolic heart failure; however, the systolic and diastolic intraventricular time delay increased with increases in the E/E' ratio, an indicator of diastolic dysfunction.

A Case of Peritoneal Mesothelioma with Direct Invasion to Gastric Mucosa / 대한소화기학회지

Mesothelioma is a rare aggressive tumor arising from the mesothelial cell and regarded as universally fatal disease with average survival around 1 year. The incidence rate is varied from one to forty per million in different countries and increasing by the year. The most common site of tumor origin is the pleura and only 20% to 33% of mesothelioma arise from the peritoneum. There are increasing reports of malignant mesothelioma with forty to fifty fatal cases per year in Korea. Histological studies with immunohistochemical stain is helpful for the diagnosis of peritoneal mesothelioma and imaging modality alone is not sufficient for diagnosis, so it is difficult to confirm diagnosis. A 64-year-old male patient was admitted to the hospital with a palpable mass on abdomen. The 6x6 cm sized huge mass was seen on the body of stomach adjacent to the peritoneum. We report a case of malignant peritoneal mesothelioma without evident exposure to asbestos, of which direct invasion to the gastric mucosa was confirmed by endoscopic biopsy and immunohistochemical stain.

Calcifying Fibrous Pseudotumor of the Stomach That Was Diagnosed by Endoscopic Submucosal Dissection / 대한소화기내시경학회지

Calcifying fibrous pseudotumor (CFPT) is very rare and especially at an intrinsic visceral location such as the stomach. The CFPT is generally located in the subcutaneous or deep soft tissue and the subserosal area of organs and it is mainly diagnosed during childhood or young adulthood. The etiology and pathophysiology of CFPT are unclear. Herein we describe a case of gastric CFPT and we review the related literature. A thirty-year-old asymptomatic female patient visited our hospital for the evaluation of a submucosal tumor that was seen on previous endoscopy. On the endoscopic ultrasonography (EUS), a subepithelial lesion was found at the gastric angle and it was a slightly hypoechoic, homogenous mass located at the submucosal layer of the gastric wall. Endoscopic submucosal dissection was performed under the suspicion of carcinoid. On the microscopic findings, most of the tissue was composed of hyalinized collagenous tissue. Mild lymphocytic infiltration and several dystrophic calcifications were also seen. Immunohistochemically, bcl-2 and CD34 staining was negative, so we diagnosed the mass as CFPT.

A Case of Lymphoepithelial Cyst in the Lower Esophagus / 대한소화기내시경학회지

Lymphoepithelial cyst is a rare benign cystic tumor that is composed of a squamous epithelial cyst surrounded by lymphoid tissue, and this type of cyst is histologically similar to the branchial cleft cysts of the lateral neck. It is most often found in the head and neck and it is only rarely found in the pancreas, mediastinum and hypopharynx. Lymphoepithelial cysts of the esophagus have been described in Japan by Kataoka and Asami. We report here on a case of esophageal lymphoepithelial cyst that was removed endoscopically without serious complications.

Characteristics of Myocardial Deformation and Rotation in Subjects With Diastolic Dysfunction Without Diastolic Heart Failure

BACKGROUND AND OBJECTIVES: There have been very few pathophysiologic studies on isolated diastolic dysfunction. We hypothesized that the characteristics of isolated diastolic dysfunction would be located, on the clinical continuum, between those of a normal heart and diastolic heart failure. SUBJECTS AND METHODS: We enrolled 102 subjects who had no history of overt symptoms of heart failure and who had a left ventricular ejection fraction of more than 50%. They were examined for myocardial deformation and rotation using the two-dimensional speckle tracking image (2D-STI) technique. RESULTS: The circumferential strains and radial strain at the apical level (RS(apex)) were related to the ratio of the transmitral early peak velocity over the early diastolic mitral annulus velocity (E/E'). After adjustment for age, the RS(apex) showed a positive relationship with the E/E' ratio; whereas, the circumferential strains did not. Instead, the circumferential strains demonstrated a significant correlation with age. Basal rotation and left ventricular (LV) torsion were also related to age, but had no relationship with the E/E' ratio. However, as the E/E' ratio value increased, systolic mitral annular velocity decreased. CONCLUSION: Except for the RS(apex), LV myocardial deformation and rotation did not vary with the degree of E/E' ratio elevation when there was no associated diastolic heart failure. Additionally, in clinical situations such as isolated diastolic dysfunction, the advancement of age has a relatively greater influence on characteristics of LV myocardial deformation and rotation rather than on the E/E' ratio.

A Case of Sclerosed Hemangioma Mimicking Intrahepatic Cholangiocarcinoma / 대한소화기학회지

Hemangioma is one of the most frequently encountered benign hepatic neoplasm which can develop secondary degeneration. Sclerosed hemangioma is a rare disease histologically characterized by large amount of collagen and elastic fibril between sclerosed small vessels. Its differential diagnosis is very difficult. It should be included in the differential diagnosis of other hepatic lesions such as hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic hepatic tumor. A 77-year old male was admitted with upper abdominal discomfort. Abdominal ultrasonography revealed GB stone, dilated common bile duct with bile duct stone, and a 4.6 cm sized hyperechoic mass at segment 5 and 6 of the liver. Abdominal dynamic computed tomography demonstrated dilated intrahepatic bile ducts and a 5x5 cm sized mass which showed minimally delayed enhancement. Abdominal magnetic resonance imaging revealed the mass with low signal intensity in T1 weighted image, high signal intensity and focal low signal in T2 weighted image which showed minimal enhancement. We removed common bile duct stone with endoscopic retrograde cholangiopancreatography then decided to undergo right lower segmentectomy of liver due to possibility of cholangiocarcinoma. Histopathological examination of hepatic mass showed large amount of fibrous tissue with occasional residual vascular channels. We describe one case of sclerosed hemangioma mimicking cholangiocarcinoma.

Characteristics of QT Interval and QT Dispersion in Exercise Electrocardiogram: Healthy Persons versus Stable Angina Patients

BACKGROUND AND OBJECTIVES: The QT interval (QTi) and QT dispersion (QTd), which represent the myocardial electrical heterogeneity of repolarization, were studied to recognize the differences between normal controls (n=32) and stable angina patients (n=78). SUBJECTS AND METHODS: During the treadmill exercise test, standard 12 lead Electrocardiogram (ECG) was obtained at every stage, with the QTi and QTd measured. The corrected QT interval (cQTi) and QT dispersion (cQTd) were calculated using Bazett's formula, with the Delta QT interval (DeltaQTi) measured on leads V5 and aVF. RESULTS: During exercise, the QTi had a reverse relationship with the heart rate in both groups, but was decreased by a lesser extent in the patient group. The QTd also had a tendency to decrease according to increasing heart rate in both groups and was significantly greater in the patient group. The corrected QTi increased during exercise in both groups, and reached maximum during the pre-peak stage, but was minimized during a 1 minute recovery stage in the patient group. The corrected QTd reached a maximum during the peak exercise stage in both groups, but the values between the two groups were significantly different. Both the QTi and cQTi had tendencies to increase according to the number of vessels with stenosis. The DeltaQTi tended to reflect a regional ischemia in a single vessel disease. CONCLUSION: The QTi, QTd, cQTi and cQTd were increased in the stable angina patients compared with the normal controls, and augmented during the exercise test.