Inflammation plays a key role in the pathophysiology of hepatic ischemia–reperfusion (I/R) injury. However, the mechanism by which hepatic I/R induces inflammatory responses remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by I/R is mediated through a multiple-protein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in hepatic I/R injury and found that hepatic I/R stimuli upregulated the inflammasome-component molecule, nucleotide-binding oligomerization domain–like receptor (NLR) family pyrin domain–containing 3 (NLRP3), but not apoptosis-associated speck–like protein containing a caspase recruitment domain (ASC). NLRP3−/− mice, but not ASC−/− and caspase-1−/− mice, had significantly less liver injury after hepatic I/R. NLRP3−/− mice showed reduced inflammatory responses, reactive oxygen species production, and apoptosis in I/R liver. Notably, infiltration of neutrophils, but not macrophages, was markedly inhibited in the I/R liver of NLRP3−/− mice. Bone marrow transplantation experiments showed that NLRP3 not only in bone marrow–derived cells, but also in non-bone marrow–derived cells contributed to liver injury after I/R. In vitro experiments revealed that keratinocyte-derived chemokine–induced activation of heterotrimeric G proteins was markedly diminished. Furthermore, NLRP3−/− neutrophils decreased keratinocyte-derived chemokine–induced concentrations of intracellular calcium elevation, Rac activation, and actin assembly formation, thereby resulting in impaired migration activity. Taken together, NLRP3 regulates chemokine-mediated functions and recruitment of neutrophils, and thereby contributes to hepatic I/R injury independently of inflammasomes. These findings identify a novel role of NLRP3 in the pathophysiology of hepatic I/R injury.

Evaluation of pathologic predictors of metastases in T1 stage colorectal cancer may be difficult with hematoxylin and eosin (HE) staining alone. The aim of this study was to clarify the role of pathologic predictors by using immunohistochemical staining and Elastica van Gieson (EVG) staining. One hundred and twenty-four patients who underwent bowel resection for single T1 stage colorectal cancer from 1990 to 2004 in 1 institution were studied. D2-40, EVG staining, and CAM5.2 were used to detect lymphatic invasion, venous invasion, and tumor budding, respectively. These 3 factors were separately evaluated based on HE staining. Histology was reviewed by 1 pathologist. Lymph node metastases in the surgical specimen were the standard reference, and distant metastases were identified by periodic computed tomography for 2 years or more after surgery. A logistic regression model was applied to analyze risk factors for lymph node metastases and a Cox regression model for distant metastases. In predicting lymph node metastases, univariate analysis demonstrated significance for all predictors except venous invasion by HE staining. Multivariate analysis showed that venous invasion by EVG and tumor budding by HE showed significance as predictors. In predicting distant metastases, univariate analysis showed significance for lymphatic invasion shown by D2-40, tumor budding shown by CAM5.2 and HE, and lymph node metastases. Multivariate analysis showed only venous invasion by EVG stain as being significantly associated with distant metastases (P=0.001). In conclusion, venous invasion evaluated shown by EVG staining is a useful pathologic predictor for metastases in T1 stage colorectal cancer.

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Esophagojejunostomy using DST with OrVil is useful in performing a minimally invasive procedure but carries a high risk of anastomotic stenosis.

This is the first study to use a magnetic tracer to identify sentinel lymph nodes in patients with breast cancer. This new technique may alter the role of radioisotopes with further refinement and experience.