Ultrasonographic evaluation of gastrointestinal graft‐versus‐host disease after hematopoietic stem cell transplantation

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a major and life‐threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI‐GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI‐GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI‐GVHD. Severity of GI‐GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI‐GVHD into four US grades. There was a significant correlation between clinical stage of GI‐GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI‐GVHD upon treatment. Thus, US is an effective and efficient non‐invasive means of identifying the extent and severity of GI‐GVHD and monitoring response to treatment.     

Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene.

Endothelial progenitor cells (EPCs) are present in the mononuclear cells (MNCs) of umbilical cord blood and peripheral blood. To establish the efficiency of angiogenic cell and gene therapies, we transfected the human vascular endothelial growth factor (hVEGF) gene into cord blood MNCs to enhance endothelialization. MNCs from cord blood and peripheral blood were isolated and transfected with pCR3 expressing hVEGF165 or GFP by the Hemagglutinating Virus of Japan (HVJ)-envelope and the cells were cultured in endothelium basal medium-2. The number of attached cells from cord blood was higher than that from peripheral blood. Attached cells expressed Flk-1, VE-cadherin, PECAM-1, CD34, and Tie-2. The increase in the number of attached cells was transient with the transfection of vascular endothelial growth factor (VEGF) gene early in the experimental period. Flt-1 mRNA was not expressed early in the culture period, but was expressed at 2 weeks after separation. VEGF gene transfer into MNCs at 12 days after separation, i.e., when Flt-1 mRNA was expressed continuously, increased the number of attached cells. We evaluated the effects of the transplantation of cord blood MNCs expressing the hVEGF gene on regional blood flow in an ischemic area in a rat model of chronic hindlimb ischemia. Blood flow was significantly improved in nude rats that received transplanted control MNCs. Transplantation of cord blood MNCs transfected with the hVEGF gene yielded greater improvements in blood flow. These results indicate that the hVEGF gene enhances endothelialization of EPCs, and that the transplantation of cord blood MNCs transfected with the VEGF gene may be feasible for the treatment of ischemic diseases as a type of angiogenic cell and gene therapy.     

Acute myeloid leukaemia blast cells with a tyrosine kinase domain mutation of FLT3 are less sensitive to lestaurtinib than those with a FLT3 internal tandem duplication

FLT3 tyrosine kinase domain mutations (FLT3/TKDs) are associated with a favourable prognosis in acute myeloid leukaemia (AML), unlike FLT3 internal tandem duplications (FLT3/ITDs) that have a poor prognosis. Whilst FLT3/ITD+ cells are more susceptible to the cytotoxic effects of FLT3 inhibitors than wild type (WT) cells, the sensitivity of FLT3/TKD+ cells to therapeutic agents is unclear, as is the importance of the mutant level. We therefore studied the effect of cytarabine and the FLT3 inhibitor lestaurtinib, either alone or in combination, on in vitro survival of blast cells from 36 cases of AML (14 FLT3/WT, 11 FLT3/ITD+ and 11 FLT3/TKD+). All three groups showed similar sensitivity to the cytotoxic effects of cytarabine but FLT3/ITD mutant level was inversely correlated with cytarabine cytotoxicity (P = 0.04) whereas FLT3/TKD mutant level had no impact. FLT3/TKD+ cells showed a similar response to lestaurtinib as FLT3/WT cells, whereas FLT3/ITD+ cells were more sensitive (P = 0.004). There was no correlation between mutant level and lestaurtinib sensitivity for either FLT3/ITD+ or FLT3/TKD+ cells. Synergistic cytotoxicity of lestaurtinib plus cytarabine was demonstrated in all three groups. These results suggest that FLT3/TKD+ and FLT3/WT cases should not be differentiated when considering patients for treatment with FLT3 inhibitors.     

Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

Synthesis and Characterization of Polymerized Ionic Liquids: Mechanical and Thermal Properties of a Novel Type of Hydrogels

An easy and efficient route to synthesize gel materials based on polymeric ionic liquids (PILs) is presented. The radical polymerization of imidazolium (Im)‐based ionic liquids (ILs) bearing a vinyl group ([VEIm][Br], [VEIm][Ac], [VBIm][Br], [VBIm][Cl]) with crosslinker (CL) N,N′‐methylenebisacrylamide (Bis) in water results in polyionic liquid hydrogels. Thermal and mechanical properties (tensile and compression tests) are investigated and compared with two different types of hydrogels. One is a polyacrylamide (PAAm) hydrogel having covalent‐type crosslinking. The other is an alginate‐based hydrogel having ionic‐type crosslinking. Prepared IL‐hydrogel materials provide favorable flexibility, adjustable by varying the CL ratio and water content. The higher the CL ratio is, the higher the fragility of the gel matrix. The gelation time of the hydrogels depends on the alkyl chain length, as well as the size of the anion.

     

Contralateral glissonian pedicle occlusion in a case of portal vein tumor thrombosis

To dissect portal vein branches directly and encircle them separately is a common procedure that is performed to control back flow bleeding during operations for hepatocellular carcinoma with portal vein tumor thrombosis. However, this technique has an increased risk of injuring contralateral portal branches and disseminating thrombosis fragments to the remnant liver. We present an alternative technique using right-sided glissonian pedicle occlusion for hepatocellular carcinoma with left portal vein tumor thrombosis due to complex anatomical vasculatures of the hepatic pedicle. This technique would be very useful for liver resection of hepatocellular carcinoma with the major type of portal vein tumor thrombosis.