Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.     

Pulmonary nocardiosis with bilateral diffuse granular lung shadows in a patient with subcutaneous panniculitic T-cell lymphoma

A 40-year-old woman undergoing prednisolone and cyclosporine therapy for subcutaneous panniculitic T-cell lymphoma complained of a cough for a few weeks. A chest X-ray revealed bilateral diffuse granular shadows. Additionally, the patient was discovered to have multiple subcutaneous abscesses. Gram-stained smears of sputum and pus from the abscess showing branched gram-positive rods led to a diagnosis of pulmonary nocardiosis with dissemination to the lungs and subcutaneous tissues. Combination therapy consisting of sulfamethoxazole/trimethoprim and panipenem/betamipron produced rapid improvement of radiographic abnormalities. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of diffuse granular shadows on chest X-rays, especially in immunocompromised patients.     

Imaging analysis of the brain in a primate model of cerebral malaria

This paper reviews our studies concerning imaging analysis of the brain in a primate model of cerebral malaria. To elucidate the clinical features of cerebral malaria, we performed positron emission tomography with ¹⁸F-fluorodeoxyglucose (FDG-PET) scanning and magnetic resonance imaging (MRI) of the brain in Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi, a primate model of severe human malaria with cerebral involvement. On FDG-PET scanning, we observed diffuse and heterogeneous reduction of metabolism in the cerebral cortex in the acute phase of malaria infection. Although the monkey exhibited severe clinical signs, MR imaging did not reveal any significant changes during the course of infection. Histopathologic examination frequently revealed preferential sequestration of PRBCs in the cerebral and cerebellum capillaries, but neither parenchymal injury nor neuronal necrosis was found in the tissues. These results suggest that heterogeneous metabolic reduction and lack of abnormalities on MRI in the acute phase of CM may be due to any avoidance mechanisms from ischemia caused by sequestration. This may be one reason why more than half of CM patients have no neurological sequelae following recovery.     

Taeniasis and cysticercosis in Asia and the Pacific: present state of knowledge and perspectives

Several topics on taeniasis and cysticercosis in Asia and the Pacific are overviewed. In Asia and the Pacific, three human taeniid species have been recognized: Taenia solium, Taenia saginata and Taenia asiatica. The first topic is on evolution of T. solium. Mitochondrial DNA polymorphisms of T. solium worldwide are discussed with emphasis of two specific genotypes: American-African and Asian. The second topic is recent major advances in sero- and molecular-diagnosis of T. solium cysticercosis in humans, pigs and dogs. The third is the present situation of T. solium taeniasis/cysticercosis in Papua (Irian Jaya), Indonesia. The forth is the present situation of T. solium cysticercosis and T. saginata taeniasis in Bali, Indonesia. The fifth is the present situation of T. asiatica taeniasis in Asia and the Pacific and in North Sumatra, Indonesia. The sixth is on the debate of the exact definition of T. asiatica. Because T. asiatica can not be differentiated from T. saginata morphologically, it is time to re-evaluate T. saginata in Asia and the Pacific. New and broad-based surveys across this region are necessary from epidemiological and public health perspectives, based on evidence.     

Possibility of ex vivo animal training model for colorectal endoscopic submucosal dissection

Purpose

Colorectal endoscopic submucosal dissection (ESD) has not been standardized due to technical difficulties and requires extensive training for reliability. Ex vivo animal model is convenient, but has no blood flow. The objective of this study is to evaluate the characteristics of various ex vivo animal models including a blood flow model for colorectal ESD training and the usefulness of practicing endoscopic hemostasis and closure using an animal model.

Methods

Harvested porcine cecum, rectum, and stomach and bovine cecum and rectum were analyzed regarding ease of mucosal injection, degree of submucosal elevation, and status of the proper muscle layer. Ex vivo animal model with blood flow was made using the bovine cecum. The vessel around the cecum was detached, and red ink was injected. Endoscopic hemostasis for perioperative hemorrhage and endoscopic closure for perforation were performed in this model.

Results

Mucosal injection was easily performed in the bovine cecum and rectum. Submucosal elevation was low in the bovine cecum, while the proper muscle layer was not tight in the porcine rectum and bovine cecum. Endoscopic hemostasis were accomplished in six (60 %) out of ten procedures of the ex vivo blood flow model. In two non-experts, the completion rates of endoscopic closure were 40 and 60 % in the first five procedures. These rates became 100 % in the last five procedures.

Conclusions

We have evaluated the characteristics of various ex vivo animal models and shown the possibility of training for endoscopic hemostasis and endoscopic closure in the ex vivo animal model.     

Anti-CYP2D6 antibodies detected by quantitative radioligand assay and relation to antibodies to liver-specific arginase in patients with autoimmune hepatitis.

BACKGROUND: Antibodies to cytochrome P4502D6 (CYP2D6) were measured and their prevalence compared with that of antibodies to liver-specific arginase in patients with autoimmune hepatitis (AIH). METHODS: Anti-CYP2D6 antibodies were measured by sensitive radioligand assay and enzyme-linked immunosorbent assay (ELISA), and anti-arginase antibodies were measured by ELISA in 132 patients (definite AIH 11, probable AIH 36, hepatitis C 20, hepatitis B 23, other autoimmune diseases 42) and 50 healthy controls. RESULTS: CYP2D6 index (radioligand assay) was significantly higher in all groups of patients than those in healthy controls. A higher index than the cut-off value (mean+3 S.D. in healthy controls) was found in 36.4%, 44.4%, 25.0%, 17.4% and 28.6% of patients with definite AIH, probable AIH, hepatitis C, hepatitis B and other autoimmune diseases, respectively. CYP2D6 index was not related to serum IgG, anti-nuclear antibody or AIH scores, and was weakly correlated with anti-arginase antibody activity. When CYP2D6 index and anti-arginase antibodies were combined, 55.3% of AIH patients were positive for either one or both antibodies. CONCLUSIONS: Anti-CYP2D6 antibodies by radioligand assay were frequently present in patients with AIH. Combined tests for anti-CYP2D6 radioligand assay and anti-arginase antibodies resulted in detection of 55% of AIH patients.     

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1–2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickned and extended throughout the antrum, with the complete picture shown in 1.5–5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.     

Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

BackgroundWe recently reported that severe asthma patients with frequent exacerbations showed high blood eosinophil counts (Eo) and fractions of exhaled nitric oxide (FeNO) compared with non-exacerbators. However, we did not determine exact cutoff values related to exacerbation. The aim of this study was to determine the cutoff values of Eo and FeNO that could be related to the exacerbation of severe asthma. We also aimed to confirm the clinical utility of Th2 markers related to exacerbation.MethodsThis study included 105 severe asthma patients who completed a three-year follow-up of a severe asthma cohort study, including smokers. Three Th2 markers were selected, viz., Eo, FeNO, and positive atopic status. Regarding Eo and FeNO, we determined the cutoff values for the definition of “positive” Th2 features using receiver operating characteristic curve analyses, based on the comparisons between frequent exacerbators and other patients.ResultsThe cutoff values for positive Th2 features were Eo ≥ 250 cells/μL and FeNO ≥31 ppb. Sixteen patients (15.2%) had no Th2 features, 40 (38.1%) had one, 25 (23.8%) had two, and 24 (22.9%) had three. A high number of positive Th2 features was significantly associated with exacerbation frequencies over three years (p < 0.05). Similarly, compared to patients with one or no Th2 features, those with three Th2 features had a significantly higher probability of having more than one exacerbation (p < 0.05).ConclusionsThe cutoff values determined in the current analysis were good predictors of future exacerbations in severe asthma patients.     

Efficacy of magnifying endoscopy with flexible spectral imaging color enhancement in the diagnosis of colorectal tumors

Background

Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is an image-enhanced endoscopy that captures the surface and vascular patterns of colorectal tumors. We evaluated and compared FICE magnification to narrow-band imaging (NBI) magnification.

Methods

Flexible spectral imaging color enhancement or NBI magnification was performed to the visualize surface and vascular patterns of colorectal tumors, classified into 4 types: Type A, Type B, Type C1/C2, and Type C3, as previously reported. A total of 235 colorectal tumors were examined. The correlations between classifications found by FICE or NBI magnification and histopathological diagnoses were examined. Image evaluation was validated by assessing inter-observer and intra-observer agreements on examinations.

Results

Twenty-eight hyperplastic polyps (HPs), 115 tubular adenomas (TAs), 72 mucosal and slightly invaded submucosal cancers (M-sSM), and 20 massively invaded submucosal cancers (mSM) were diagnosed. By FICE magnification, HP and TA were observed in 93.3 and 6.7% of Type A (15 lesions), respectively. TA, M-sSM, and HP were observed in 82.6, 15.4, and 2.0% of Type B (52 lesions), respectively. M-sSM, TA, and mSM were observed in 50.0, 46.0, and 4.0% of Type C1/2 (50 lesions), respectively. mSMs were observed in all 7 Type C3 lesions. In diagnosing mSM in Type C3, the sensitivity and specificity of FICE magnification were 77.7 and 100%, respectively, compared to those of NBI, at 63.6 and 99.0%, respectively. Imaging evaluation was validated accurately by intra- and intra-observer measurements showing consistent results.

Conclusions

The classification of colorectal tumors by FICE magnification correlated well with the histopathological diagnoses, similar to findings for NBI magnification. FICE magnification can be evaluated accurately with the same diagnostic classifications as those used for NBI magnification.