Voiding Dysfunction after Total Mesorectal Excision in Rectal Cancer

Purpose The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). Methods This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. Results A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. Conclusions Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition

Chest Computed Tomography (CT) Immediately after CT-Guided Transthoracic Needle Aspiration Biopsy as a Predictor of Overt Pneumothorax

BACKGROUND/AIMS: This study examined the correlation between pneumothorax detected by immediate post-transthoracic needle aspiration-biopsy (TTNB) chest computed tomography (CT) and overt pneumothorax detected by chest PA, and investigated factors that might influence the correlation. METHODS: Adult patients who had undergone CT-guided TTNB for lung lesions from May 2003 to June 2007 at Seoul National University Bundang Hospital were included. Immediate post-TTNB CT and chest PA follow-up at 4 and 16 hours after CT-guided TTNB were performed in 934 patients. RESULTS: Pneumothorax detected by immediate chest CT (CT-pneumothorax) was found in 237 (25%) and overt pneumothorax was detected by chest PA follow-up in 92 (38.8%) of the 237 patients. However, overt pneumothorax was found in 18 (2.6%) of the 697 patients without CT-pneumothorax. The width and depth of CT-pneumothorax were predictive risk factors for overt pneumothorax. CONCLUSIONS: CT-pneumothorax is very sensitive for predicting overt pneumothorax, and the width and depth on CT-pneumothorax are reliable risk factors for predicting overt pneumothorax.ope

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT

A Degenerative Intraspinal Cyst Mimicking a Nerve Root: A Case Report on an Intraoperative Challenge

Various intraspinal cysts have been described in the literature. Sometimes these cysts are difficult to recognize intraoperative and can place a surgeon in dilemma. We report a case of a degenerative intraspinal cyst with severe adhesion with dura, which was mimicking as a nerve root and posed a diagnostic dilemma during surgery. A Sixty-year-old man presented with insidious onset, gradually progressing lower back pain, right leg pain and neurological claudication of six months duration. The pain radiated to the right S1 dermatome. Right side straight leg raise test was positive at 45°. Sensations were diminished over the right L5 and S1 dermatomes. Motor function was normal. MRI showed a large cystic lesion at right L5-S1 level. The cyst appeared to compress the dural sac and traversing right S1 root at L5-S1 level. The lesion was isointense on T1-weighted image and hyperintense on T2-weighted image. While treating this condition using the uniportal full endoscopic technique the cyst appeared as nerve root. Meticulous dissection was required to separate the cyst from neural structures. Histology confirmed the diagnosis of a degenerative intraspinal cyst. The patient had significant improvement after surgery and at six months follow up he was completely asymptomatic. Various cysts can occur in the intraspinal canal, and careful attention should be paid to minimize the nerve injury in the presence of severe adhesions

Morphine Postconditioning Attenuates ICAM-1 Expression on Endothelial Cells

The purpose of this study is to determine 1) whether morphine postconditiong (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 µM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a µ-OR antagonist naloxone, a κ-OR antagonist nor-binaltorphimine, and a δ-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 µM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by coadministering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the κ and δ-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway

Femtosecond laser driven high-flux highly collimated MeV-proton beam

金沢大学先端科学・社会共創推進機構Highlly collimated energetic protons whose energies are up to 4 MeV are generated by an intense femtosecond Titanium Sappheire laser pulse interacting with a 7.5, 12.5, and 25 μm-thick Polyimide tape target and 5 μm-thick copper target. We find no clear difference on the proton spectra from 7.5, 12.5, and 25 μm Polyimide tape target. The highest conversion efficiency from laser energy into protons of ∼3% is observed with a 7.5 μm thick Polyimide target. The quality of the proton beam is good enough to obtain a clear projection image of a mesh having 10 μm line and space structure, installed into the passage of the beam. We obtain clear vertical lines on the proton intensity profiles from the copper target, which are considered to be transferred from the surface of the copper target. From it, we can restrict the size of the proton emitting region to be ∼20μm. © 2008 American Institute of Physics.Embargo Period 12 month

An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe