Podoplanin expression in the cyst wall correlates with the progression of intraductal papillary mucinous neoplasm

A thickened, enhanced cyst wall on imaging examinations is one of the “worrisome features” described in the consensus guidelines for management of intraductal papillary mucinous neoplasm of the pancreas (IPMN). Podoplanin (PDPN) expression by cancer-associated fibroblasts is known to be an indicator of poor prognosis in some types of cancer. We performed immunohistochemical staining for alpha-smooth muscle actin (α-SMA) in IPMN lesions and determined the pathological wall thickness by measuring the thinnest and thickest α-SMA-positive parts of the wall of the largest cyst in each case, and the mean of these two values was recorded as the wall thickness. The thickness of the pathological wall increased with progression from IPMN with low-grade dysplasia to IPMN with an invasive carcinoma. The pathological wall was thicker in IPMN with main duct involvement, nongastric-type IPMN, and IPMN with mural nodules. We also stained for PDPN and assessed the thickness of cyst wall staining as for α-SMA. The thickness of the PDPN-positive cyst wall varied in a pattern similar to the thickness of the α-SMA-positive pathological cyst wall. PDPN-positive stromal fibroblasts in the invasive component of IPMN-IC were evaluated as a ratio to α-SMA-positive fibroblasts. A high ratio (>50 %) of PDPN-positive stromal fibroblasts was a predictor of poor outcome. PDPN expression in the cyst wall correlates with the progression of IPMN. PDPN may be a significant prognostic marker of IPMN-IC.     

Ethylmaltol Odor Enhances Salivary Hemodynamic Responses to Sucrose Taste as Detected by Near-Infrared Spectroscopy

The perceived intensity of the taste of a food is enhanced only if the odor of the food is perceptually similar to the taste. For example, a caramel-like odor enhances the perceived intensity of sweetness. The way gustatory and olfactory signals are integrated in the brain depends largely on one’s previous experiences with taste and odor pairings. To elucidate the effects of a sweet, sugary odor, ethylmaltol, on sucrose taste, as perceived by the central integration of flavor, we recorded salivary hemodynamic responses to the odor and taste pairings using near-infrared spectroscopy (NIRS) of seven panelists. First, we observed concentration-dependent increases in the amplitude of the responses to 0 to 6 % sucrose solutions. Second, when ethylmaltol odor was added to a 4 % sucrose solution, we observed a significant increase in the amplitude of the responses from all panelists. The addition of ethylmaltol to a tasteless solution caused no significant change in the amplitude of the salivary hemodynamic response. These results indicate that the sweet odor of ethylmaltol enhances the salivary hemodynamic response when combined with a sweet taste. Therefore, a congruent combination of sweet odor and taste greatly enhances salivary responses, which are dependent on the central integration of odor and taste.     

Impact of Less Invasive Treatments Including Sclerotherapy With a New Agent and Hemorrhoidopexy for Prolapsing Internal Hemorrhoids

Conventional hemorrhoidectomy is applied for the treatment of prolapsing internal hemorrhoids. Recently, less-invasive treatments such as sclerotherapy using aluminum potassium sulphate/tannic acid (ALTA) and a procedure for prolapse and hemorrhoids (PPH) have been introduced. We compared the results of sclerotherapy with ALTA and an improved type of PPH03 with those of hemorrhoidectomy. Between January 2006 and March 2009, we performed hemorrhoidectomy in 464 patients, ALTA in 940 patients, and PPH in 148 patients with second- and third-degree internal hemorrhoids according to the Goligher''s classification. The volume of ALTA injected into a hemorrhoid was 7.3 ± 2.2 (mean ± SD) mL. The duration of the operation was significantly shorter in ALTA (13 ± 2 minutes) than in hemorrhoidectomy (43 ± 5 minutes) or PPH (32 ± 12 minutes). Postoperative pain, requiring intravenous pain medications, occurred in 65 cases (14%) in hemorrhoidectomy, in 16 cases (1.7%) in ALTA, and in 1 case (0.7%) in PPH. The disappearance rates of prolapse were 100% in hemorrhoidectomy, 96% in ALTA, and 98.6% in PPH. ALTA can be performed on an outpatient basis without any severe pain or complication, and PPH is a useful alternative treatment with less pain. Less-invasive treatments are beneficial when performed with care to avoid complications.     

Linear ubiquitination: A novel NF-κB regulatory mechanism for inflammatory and immune responses by the LUBAC ubiquitin ligase complex [Review

The NF-κB pathway is a central signaling pathway for inflammatory and immune responses, and aberrant NF-κB signaling is implicated multiple disorders, such as cancer and autoimmune, chronic inflammatory and metabolic diseases. NF-κB is regulated by various post-translational modifications, including phosphorylation and multiple ubiquitinations. We determined that LUBAC (linear ubiquitin chain assembly complex), composed of SHARPIN, HOIL-IL and HOIP, generates a novel type of Met1-linked linear polyubiquitin chain and specifically regulates the canonical NF-κB pathway via the linear ubiquitination of NEMO and RIP1. In the absence of LUBAC components, NF-κB signaling was attenuated and induced apoptosis and inflammation. Many studies on the pathophysiological functions of LUBAC, such as in B cell development, innate immune response, carcinogenesis, and osteogenesis, have been performed recently. This review summarizes these new findings on LUBAC- and linear ubiquitination-mediated NF-κB regulation and their implications in disorders.