Measurement of spinal cord blood flow by an inhalation method and intraarterial injection of hydrogen gas

AbstractPurpose: This study was performed to determine spinal cord blood flow using the H2 clearance method.Methods: In 12 dogs we measured blood flow determined by hydrogen clearance techniques (BF) in both gray and white matter by spinal cord puncture, and compared the results with BF measured by a catheter inserted intrathecally to avoid spinal cord injury. We studied direct intraarterial and intravenous injection of hydrogen in addition to the inhalation method because hydrogen is an explosive gas.Results: BF measured intrathecally with catheters adherent to either the ventral or the dorsal funiculus did not differ significantly from that of the gray matter. BF measured with a catheter inserted into the epidural space was about one fourth of the BF measured intrathecally. Values measured by the intraarterial injection method did not differ significantly from those obtained by the inhalation method.Conclusions: BF measured with a catheter inserted intrathecally reflects blood flow in the gray matter of the spinal cord. Using intraarterial injection of H2, BF was safely and accurately measured while avoiding the risk of explosion. (J Vasc Surg 1997;26:623-8.

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

医薬保健研究域医学系Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subunit of polycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor suppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16INK4a, E-cadherin, and p21were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. © 2009 Japanese Cancer Association

Local balance of transforming growth factor-β1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma

金沢大学大学院医学系研究科がん細胞学Tumor-stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal-derived factor-1 (SDF-1) and transforming growth factor (TGF)-β1. Two cell lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF-β1 treatment, and coculture with CC cells and anti-TGF-β1 neutralizing antibody restored the decreased SDF-1 expression, suggesting that TGF-β1 secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF-β1 in CC cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF-β1 secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be involved in invasion of CC cells. © 2006 Japanese Society of Pathology

Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines

The aim of this article is to propose new criteria for the diagnosis and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts. A working group reviewed articles with regard to the diagnosis and treatment of acute cholecystitis and extracted the best current available evidence. In addition to the evidence and face-to-face discussions, domestic consensus meetings were held by the experts in order to assess the results. A provisional outcome statement regarding the diagnostic criteria and criteria for severity assessment was discussed and finalized during an International Consensus Meeting held in Tokyo 2006. Patients exhibiting one of the local signs of inflammation, such as Murphy’s sign, or a mass, pain or tenderness in the right upper quadrant, as well as one of the systemic signs of inflammation, such as fever, elevated white blood cell count, and elevated C-reactive protein level, are diagnosed as having acute cholecystitis. Patients in whom suspected clinical findings are confirmed by diagnostic imaging are also diagnosed with acute cholecystitis. The severity of acute cholecystitis is classified into three grades, mild (grade I), moderate (grade II), and severe (grade III). Grade I (mild acute cholecystitis) is defined as acute cholecystitis in a patient with no organ dysfunction and limited disease in the gallbladder, making cholecystectomy a low-risk procedure. Grade II (moderate acute cholecystitis) is associated with no organ dysfunction but there is extensive disease in the gallbladder, resulting in difficulty in safely performing a cholecystectomy. Grade II disease is usually characterized by an elevated white blood cell count; a palpable, tender mass in the right upper abdominal quadrant; disease duration of more than 72 h; and imaging studies indicating significant inflammatory changes in the gallbladder. Grade III (severe acute cholecystitis) is defined as acute cholecystitis with organ dysfunction

Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines

The Tokyo Guidelines formulate clinical guidance for healthcare providers regarding the diagnosis, severity assessment, and treatment of acute cholangitis and acute cholecystitis. The Guidelines were developed through a comprehensive literature search and selection of evidence. Recommendations were based on the strength and quality of evidence. Expert consensus opinion was used to enhance or formulate important areas where data were insufficient. A working group, composed of gastroenterologists and surgeons with expertise in biliary tract surgery, supplemented with physicians in critical care medicine, epidemiology, and laboratory medicine, was selected to formulate draft guidelines. Several other groups (including members of the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery) have reviewed and revised the draft guidelines. To build a global consensus on the management of acute biliary infection, an international expert panel, representing experts in this area, was established. Between April 1 and 2, 2006, an International Consensus Meeting on acute biliary infections was held in Tokyo. A consensus was determined based on best available scientific evidence and discussion by the panel of experts. This report describes the highlights of the Tokyo International Consensus Meeting in 2006. Some important areas focused on at the meeting include proposals for internationally accepted diagnostic criteria and severity assessment for both clinical and research purposes

Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis

There are no evidence-based-criteria for the diagnosis, severity assessment, of treatment of acute cholecysitis or acute cholangitis. For example, the full complement of symptoms and signs described as Charcot’s triad and as Reynolds’ pentad are infrequent and as such do not really assist the clinician with planning management strategies. In view of these factors, we launched a project to prepare evidence-based guidelines for the management of acute cholangitis and cholecystitis that will be useful in the clinical setting. This research has been funded by the Japanese Ministry of Health, Labour, and Welfare, in cooperation with the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. A working group, consisting of 46 experts in gastroenterology, surgery, internal medicine, emergency medicine, intensive care, and clinical epidemiology, analyzed and examined the literature on patients with cholangitis and cholecystitis in order to produce evidence-based guidelines. During the investigations we found that there was a lack of high-level evidence, for treatments, and the working group formulated the guidelines by obtaining consensus, based on evidence categorized by level, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence of May 2001 (version 1). This work required more than 20 meetings to obtain a consensus on each item from the working group. Then four forums were held to permit examination of the Guideline details in Japan, both by an external assessment committee and by the working group participants (version 2). As we knew that the diagnosis and management of acute biliary infection may differ from country to country, we appointed a publication committee and held 12 meetings to prepare draft Guidelines in English (version 3). We then had several discussions on these draft guidelines with leading experts in the field throughout the world, via e-mail, leading to version 4. Finally, an International Consensus Meeting took place in Tokyo, on 1–2 April, 2006, to obtain international agreement on diagnostic criteria, severity assessment, and management

Techniques of biliary drainage for acute cholangitis: Tokyo Guidelines

Biliary decompression and drainage done in a timely manner is the cornerstone of acute cholangitis treatment. The mortality rate of acute cholangitis was extremely high when no interventional procedures, other than open drainage, were available. At present, endoscopic drainage is the procedure of first choice, in view of its safety and effectiveness. In patients with severe (grade III) disease, defined according to the severity assessment criteria in the Guidelines, biliary drainage should be done promptly with respiration management, while patients with moderate (grade II) disease also need to undergo drainage promptly with close monitoring of their responses to the primary care. For endoscopic drainage, endoscopic nasobiliary drainage (ENBD) or stent placement procedures are performed. Randomized controlled trials (RCTs) have reported no difference in the drainage effect of these two procedures, but case-series studies have indicated the frequent occurrence of hemorrhage associated with endoscopic sphincterotomy (EST), and complications such as pancreatitis. Although the usefulness of percutaneous transhepatic drainage is supported by the case-series studies, its lower success rate and higher complication rates makes it a second-option procedure

Techniques of biliary drainage for acute cholecystitis: Tokyo Guidelines

The principal management of acute cholecystitis is early cholecystectomy. However, percutaneous transhepatic gallbladder drainage (PTGBD) may be preferable for patients with moderate (grade II) or severe (grade III) acute cholecystitis. For patients with moderate (grade II) disease, PTGBD should be applied only when they do not respond to conservative treatment. For patients with severe (grade III) disease, PTGBD is recommended with intensive care. Percutaneous transhepatic gallbladder aspiration (PTGBA) is a simple alternative drainage method with fewer complications; however, its clinical usefulness has been shown only by case-series studies. To clarify the clinical value of these drainage methods, proper randomized trials should be done. This article describes techniques of drainage for acute cholecystitis

Antimicrobial therapy for acute cholangitis: Tokyo Guidelines

Antimicrobial agents should be administered to all patients with suspected acute cholangitis as a priority as soon as possible. Bile cultures should be performed at the earliest opportunity. The important factors which should be considered in selecting antimicrobial therapy include the agent’s activity against potentially infecting bacteria, the severity of the cholangitis, the presence or absence of renal and hepatic diseases, the patient’s recent history of antimicrobial therapy, and any recent culture results, if available. Biliary penetration of the microbial agents should also be considered in the selection of antimicrobials, but activity against the infecting isolates is of greatest importance. If the causative organisms are identified, empirically chosen antimicrobial drugs should be replaced by narrower-spectrum antimicrobial agents, the most appropriate for the species and the site of the infection