Laparoscopic microwave coagulation therapy for hepatocellular carcinoma

BACKGROUND AND STUDY AIMS: Several different effective forms of treatment are available, singly or in combination, for patients with hepatocellular carcinoma (HCC). These include surgical resection, transcatheter arterial embolization, percutaneous ethanol injection, and percutaneous microwave coagulation therapy. In this study, we carried out laparoscopic microwave coagulation therapy (LMCT), using laparoscopic microwave electrodes to treat HCC. PATIENTS AND METHODS: Under local anesthesia, 24 patients with HCCs located on or near the liver surface underwent LMCT under direct laparoscopic vision, with ultrasound guidance. LMCT was performed using microwave electrodes with tips ranging from 15-45 mm in length, and the effectiveness of the treatment was confirmed using contrast-enhanced computed tomography (CT) within two weeks of the LMCT procedure. RESULTS: The mean longest axis of the 26 HCC nodules in 24 patients was 20 mm, and that of the coagulated areas including the nodules was 40 mm, with additional therapy being required in two patients. Complete efficacy of the treatment was observed in 21 patients (87.5%), but local recurrences were seen in three of them one year after LMCT. The three-year survival rate was 92%, but the number of patients included in the study was small. Hemostasis was complete, but mild pneumothorax occurred in three patients. CONCLUSIONS: LMCT under local anesthesia is a minimally invasive and effective therapy when carried out on a single occasion to treat HCCs located near the liver surface, and it can be safely performed under direct visual guidance.     

Prostaglandin D2-induced eosinophilic airway inflammation is mediated by CRTH2 receptor

Mast cell-derived prostaglandin D(2) (PGD(2)) is one of the essential modulators of eosinophilic airway inflammation in asthma and allergic rhinitis. Two G protein-coupled receptors for PGD(2), prostaglandin D(2) receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th(2) cells (CRTH2), are both expressed on the surface of eosinophils, and CRTH2 has been demonstrated to mediate PGD(2)-induced eosinophil mobilization in vitro. However, it has not yet been determined whether PGD(2) and its receptors mediate in vivo eosinophil trafficking into the airways or other organs. We demonstrated that intratracheal administration of PGD(2) in rats pretreated with systemic interleukin-5 (IL-5) injection induced marked airway eosinophilia, determined by the differential counts of cells in bronchoalveolar lavage (BAL) fluid and lung histology, within 2 h. Systemic IL-5 alone significantly increased the number of eosinophils in the peripheral blood but showed no effect on airway eosinophilia. Three CRTH2-specific agonists (13,14-dihydro-15-keto-PGD(2), 11-deoxy-11-methylene-15-keto-PGD(2), and indomethacin) demonstrated equivalent induction of BAL eosinophilia to that of PGD(2), but a DP agonist (BW 245C [5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin]) or a thromboxane A(2) receptor (TP) agonist ([1S-1alpha,2beta(5Z), 3alpha(1E,3R*),4alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-heptenoic acid) showed no effect. PGD(2) or CRTH2 agonist-induced BAL eosinophilia was almost completely inhibited by pretreatment with a CRTH2/TP antagonist, ramatroban [BAY-u3405; (+)-(3R)-3-(4-fluorobenzenesulfonamido)-1,2,3,4-tetra-hydrocarbazole-9-propionic acid], whereas a TP-specific antagonist, SQ29,548 (5-heptenoic, 7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]-hept-2-yl]-[1S-[1alpha,2alpha(Z),3alpha,4alpha]]), or a DP-specific antagonist, BW A868C [3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexy-2-hydroxyethylamino)-hydantoin], did not inhibit the effects of PGD(2). These results suggest that CRTH2 plays a significant role in the eosinophil trafficking from the bloodstream into the airways in PGD(2)-related airway inflammation.     

Visualization of bacteriophage P1 infection by cryo-electron tomography of tiny Escherichia coli

Bacteriophage P1 has a contractile tail that targets the conserved lipopolysaccharide on the outer membrane surface of the host for initial adsorption. The mechanism by which P1 DNA enters the host cell is not well understood, mainly because the transient molecular interactions between bacteriophage and bacteria have been difficult to study by conventional approaches. Here, we engineered tiny E. coli host cells so that the initial stages of P1-host interactions could be captured in unprecedented detail by cryo-electron tomography. Analysis of three-dimensional reconstructions of frozen-hydrated specimens revealed three predominant configurations: an extended tail stage with DNA present in the phage head, a contracted tail stage with DNA, and a contracted tail stage without DNA. Comparative analysis of various conformations indicated that there is uniform penetration of the inner tail tube into the E. coli periplasm and a significant movement of the baseplate away from the outer membrane during tail contraction.     

Alleviation of Experimental Ulcerative Colitis with the Synthetic Peptide,F2A4-K-NS (Fibratide)

Recombinant fibroblast growth factors (FGFs) maintain the integrity of the gut epithelium and reduce mucosal injury in experimental inflammatory bowel disease (IBD). Chemically synthesized FGF mimetics could potentially extend the utility of FGFs by tailoring them for optimal bioactivity and oral administration, for example. Here, F2A4-K-NS (Fibratide), a synthetic FGF mimetic peptide, alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in mice when delivered systemically and, to a lesser extent, orally. Intraperitoneal injection of Fibratide (1 or 5 mg/kg/day) ameliorated DSS-induced ulcerative colitis, resulting in reduced weight loss, decreased colon wall thickening, and increased colon length. Fibratide also improved epithelial integrity by reducing histological-detectable crypt damage and inflammation. Orally administered Fibratide (1 mg/kg/day) was also effective in ameliorating symptoms with effects generally similar to those of intraperitoneal injection. In vitro studies were conducted to help clarify how Fibratide might act in vivo. Fibratide exhibited a modest enhancement of epithelial cell proliferation. On the other hand, Fibratide doubled the rate of epithelial cells migration and restitution in a cell culture model of wound repair. Collectively, the results indicate that Fibratide reduced the severity of experimental ulcerative colitis and may be potentially useful in the treatment of IBD.     

Plummer-Vinson syndrome successfully treated by endoscopic dilatation

Plummer-Vinson (Paterson-Brown-Kelly) syndrome is uncommon nowadays. Although iron repletion improves its symptoms, endoscopic dilatation of associated esophageal webs is sometimes required. The case is described of a 69-year-old woman with Plummer-Vinson syndrome who was successfully treated by endoscopic bougienage. The patient had a longstanding history of anemia and slowly progressive dysphagia of solid food. Laboratory data on admission showed iron deficiency anemia (red blood cell count 402 x 10(4)/microL, hemoglobin 6.8 g/dL, serum iron 8 microg/dL, and serum ferritin 2.4 ng/mL). Radiographic esophagography revealed two circumferential webs at the level of the cervical esophagus. Upper gastrointestinal endoscopy showed a severe upper esophageal stricture caused by a smooth mucosal diaphragm. The patient was prescribed 40 mg of intravenous iron supplements daily for 30 days; her anemia improved but the dysphagia did not. Endoscopic bougienage was performed with the use of Celestin dilators of serially increasing diameters. The webs were easily disrupted without complications. The patient's dysphagia resolved shortly after the treatment and did not recur. This experience indicates that endoscopic bougienage is safe, effective, and relatively easy to perform in patients with severe esophageal stenosis.