BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

PURPOSE: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. MATERIALS AND METHODS: Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. RESULTS: In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. CONCLUSION: The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.
Brain ; Carcinoma, Non-Small-Cell Lung ; Compliance ; Hippocampus ; Lung Neoplasms ; Neoplasm Metastasis ; Prospective Studies ; Radiation Oncology ; Radiotherapy

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of PKCβII on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral PKCβII gene transfer and pharmacological inhibitors, the role of PKCβII on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by PKCβi (10 nM), a selective inhibitor of PKCβII. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by PKCβi. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of PKCβII inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of PKCβII using adenoviral PKCβII increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, PKCβII-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that PKCβII plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of PKCβII-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.
Endothelial Cells* ; Gene Silencing ; Inflammation ; Intercellular Adhesion Molecule-1 ; Mitochondria ; Monocytes ; Phosphorylation ; Protein Kinase C beta* ; Protein Kinase C* ; Protein Kinases* ; Reactive Oxygen Species ; Superoxide Dismutase

Hiatal hernia and Morgagni hernia are sorts of diaphragmatic hernias that are rarely detected on transthoracic echocardiography. Although echocardiographic findings have an important role for differential diagnosis of cardiac masses, we often might overlook diaphragmatic hernia. We report three cases of diaphragmatic hernias having specific features. The first case is huge hiatal hernia that encroaches left atrium with internal swirling flow on transthoracic echocardiography. The second case is a hiatal hernia that encroaches on both atria, incidentally detected on preoperative echocardiography. The third case is Morgagni hernia which encroaches on the right atrium only. So, we need to consider possibility of diaphragmatic hernia when we find a cardiac mass with specific echocardiographic features.
Diagnosis, Differential ; Echocardiography ; Heart Atria ; Hernia ; Hernia, Diaphragmatic* ; Hernia, Hiatal

BACKGROUND: Anthocyanins have been shown to inhibit cancer cell growth by suppressing oxidative stress and inflammatory responses. The purpose of this study was to investigate the effects of an anthocyanin-rich extract (AE) from black soybean coat on intestinal carcinogenesis. METHODS: APC(Min/+) mice were fed a diet of 0.2% or 0.5% AE for 7 weeks. We analyzed the number of intestinal tumors, oxidative stress and inflammatory markers associated with beta-catenin and cytosolic phospholipase A2 (cPLA2) signals. The number of intestinal tumors, and cellular expression of beta-catenin were determined. RESULTS: The number of intestinal tumors was significantly lower in mice fed a 0.5% AE diet compared to those of the other groups. Cytosolic beta-catenin expression was significantly decreased in the AE supplemented groups compared to that of the control animals. In addition, mucosa expression of cyclooxygenase-2 and cPLA2 were also significantly decreased in the 0.5% AE group, by 32% and 62%, respectively, compared to the control group. CONCLUSIONS: These results suggest that dietary AE reduced the development of intestinal tumors, possibly through the ability to suppress oxidative stresses, decreasing inflammatory responses mediated by beta-catenin associated signals.
Animals ; Anthocyanins ; beta Catenin ; Carcinogenesis ; Cyclooxygenase 2 ; Cytosol ; Diet ; Inflammation ; Intestinal Polyposis* ; Mice ; Mucous Membrane ; Oxidative Stress ; Phospholipases A2 ; Soybeans*

BACKGROUND: We investigated the effects of the combined administration of nefopam, a N-methyl-D-aspartate receptor antagonist and low dose remifentanil, on early postoperative pain and analgesic requirement. METHODS: Fifty patients scheduled to undergo mastoidectomy and tympanoplasty were randomized to be given either nefopam 40 mg mixed with normal saline 100 ml (Group N) or an equal amount of normal saline (Group C) before anesthesia induction. Anesthesia was maintained with 5-6 vol% desflurane and remifentanil 0.05-0.15 microg/kg/min during the surgery. Postoperative pain was controlled by titration of ketorolac in the postanesthesia care unit (PACU) and ward. We evaluated the intraoperative remifentanil dose, recovery profiles, ketorolac demand in the PACU and ward, numeric rating scale (NRS) for pain at time intervals of every 10 min for 1 h in the PACU, 6, 12, 18 and 24 h in a ward, as well as the time to first analgesic requirement in the PACU and ward. RESULTS: Ketorolac demand and NRS in the PACU were significantly lower in Group N than Group C (P = 0.002, P = 0.005, respectively). The time to first analgesic requirement in the PACU in Group N were significantly longer than Group C (P = 0.046). There were no significant differences in intraoperative remifentanil dose, ketorolac demand, NRS, and the time to first analgesic requirement in the ward between the groups. CONCLUSIONS: Nefopam administration combined with low dose remifentanil infusion reduces pain and analgesic consumption during the immediate postoperative period in patients undergoing middle ear surgery under desflurane anesthesia.
Anesthesia* ; Ear, Middle* ; Humans ; Ketorolac ; N-Methylaspartate ; Nefopam* ; Pain, Postoperative ; Postoperative Period ; Tympanoplasty

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I (AT1R) inhibitor, valsartan (10 microM), but not by the AT2R inhibitor, PD123319. TSA (1~10 microM) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing AT1R. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through AT1R.
Angiotensin II ; Angiotensins* ; Animals ; Aorta ; Aortic Coarctation ; Blood Pressure* ; Histone Deacetylases ; Hypertension ; Models, Animal ; Muscle, Smooth, Vascular ; NAD ; Phosphorylation ; Rats ; Reactive Oxygen Species ; Vasoconstriction* ; Valsartan

Posaconazole is a new oral triazole with broad-spectrum antifungal activity. Posaconazole has also shown a significant advantage of preventing invasive fungal infection compared to fluconazole or itraconazole in patients with prolonged neutropenia. Indeed, posaconazole has been commonly used for antifungal prophylaxis in patients undergoing remission induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the first reported case of fatal breakthrough mucormycosis in a patient receiving posaconazole prophylaxis during remission induction chemotherapy in Korea. This case demonstrated that breakthrough fungal infection can occurs in patients receiving posaconazole prophylaxis because of its limited activity against some mucorales.
Drug Therapy ; Fluconazole ; Humans ; Itraconazole ; Korea ; Leukemia, Myeloid, Acute* ; Mucorales ; Mucormycosis* ; Myelodysplastic Syndromes ; Neutropenia ; Remission Induction

The use of neuraxial anesthesia has traditionally been contraindicated in patients with severe aortic stenosis. However, general anesthesia can be riskier than neuraxial anesthesia for severe aortic stenosis patients undergoing spinal surgeries in the prone position as this can cause a major reduction in cardiac output secondary to diminished preload. In addition, general anesthesia, muscle relaxation, and positive-pressure ventilation can decrease venous return and reduce vascular tone, further compromising cardiac output. Combined spinal-epidural anesthesia with closely monitored, careful titration of the local anesthetic dose can be an efficient and safe anesthetic method for managing such patients. We describe the successful management of combined spinal-epidural anesthesia in an asymptomatic severe aortic stenosis patient scheduled for lumbar discectomy.
Anesthesia* ; Anesthesia, Conduction ; Anesthesia, General ; Aortic Valve Stenosis* ; Cardiac Output ; Dexmedetomidine ; Diskectomy* ; Humans ; Muscle Relaxation ; Positive-Pressure Respiration ; Prone Position

BACKGROUND: The standard bifrontal application of the bispectral index (BIS) sensor interferes with the operative field in neurosurgery and plastic surgery. The aim of this study was to compare the standard frontal BIS sensor position with an alternative position across the mandible. METHODS: Two BIS(TM) Quatro sensors (Aspect Medical Systems, Newton, MA, USA) mounted on the frontal and mandibular regions were connected to BIS Vista(TM) monitors on each patient during general anesthesia. Data from each position were collected at awake, loss of consciousness, intubation, incision, every 30 minutes during the intraoperative period and emergence. These data were compared using Bland-Altman and scatter plot analyses. RESULTS: Scatter plot analysis revealed a significant correlation between BIS values of frontal and mandibular positions (R = 0.869, P = 0.000), except during emergence (R = 0.253, P = 0.077). Bland-Altman analysis revealed a negative bias of 3.2 with a limit of agreement of 16.5/-22.9, in which 3.7% of the values were outside of the limit of agreement. Additional values included -2.9 (14.1/-8.3) while patients were awake, -21.7 (14.9/-58.3) at loss of consciousness, -1.8 (9.0/-12.5) during maintenance, and -1.9 (14.9/-18.8) during emergence. CONCLUSIONS: Overall, BIS values do not agree between the standard frontal position and an alternative mandibular position. However, during the anesthesia maintenance period, the mandibular position can be availably used as an alternative position if the operative field renders the standard frontal position unavailable.
Anesthesia ; Anesthesia, General ; Bias (Epidemiology) ; Consciousness Monitors ; Electroencephalography ; Humans ; Intraoperative Period ; Intubation ; Mandible ; Neurosurgery ; Surgery, Plastic ; Unconsciousness