FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

FMS‐like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co‐altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co‐alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non‐FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.     

Performance of dedicated breast positron emission tomography in the detection of small and low-grade breast cancer

Breast Cancer Research and Treatment - This study compares the sensitivity of dedicated breast positron emission tomography (DbPET) and whole body positron emission tomography (WBPET) in detecting...     

Clinical usefulness of cell-free and concentrated ascites reinfusion therapy (CART) in combination with chemotherapy for malignant ascites: a post-marketing surveillance study

International Journal of Clinical Oncology - Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with...     

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection

Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. Conclusion: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.     

Candesartan cilexetil in the management of blood pressure for acute and recurrent stroke in Japan: the Challenge-Stroke study

The Challenge-Stroke study was conducted in Japanese patients initiated on candesartan cilexetil therapy within 3 months of suffering a stroke to investigate the clinical use of candesartan and its efficacy/safety in this therapeutic setting. A total of 869 patients formed the safety analysis set. In total, 79.6% of patients with brain hemorrhage (BH) and 60.2% with brain infarction (BI) began candesartan before post-stroke day 3 and 7, respectively. Baseline average blood pressure (BP) was 152.0/83.2 mmHg in the BH group and 165.2/89.8 mmHg in the BI group; this was reduced to 125.8/75.4 mmHg and 136.3/78.1 mmHg, respectively, at 1 year. The incidence of adverse drug reactions was 6.7 and 8.0%, respectively. There were 12 recurrent strokes in the BH group and 11 in the BI group after 1 year. The risk of recurrent stroke was significantly higher for BH patients with a final systolic BP ≥150 mmHg than for those with a final systolic BP <130 mmHg (hazard ratio: 6.807; p = 0.004). Aggressive antihypertensive therapy is currently employed in Japanese patients with acute stroke. Candesartan was safe and effective for BP control in acute stroke patients. Strict BP management may be useful for secondary prevention of stroke after BH.     

Clinical analysis of risk factors for falls in home-living stroke patients using functional evaluation tools

Wada N, Sohmiya M, Shimizu T, Okamoto K, Shirakura K. Clinical analysis of risk factors for falls in home-living stroke patients using functional evaluation tools.

Objectives

To identify risk factors associated with falls in home-living stroke patients and to predict falls using patient information and functional evaluation tools.

Design

Cohort study.

Setting

Community.

Participants

We recruited 101 home-living stroke patients who had hemiparesis and could walk independently with or without supporting devices. Disease duration ranged from 1 to 22 years (mean, 6.1y).

Interventions

Not applicable.

Main Outcome Measures

The score of each item of the Stroke Impairment Assessment Set (SIAS), and the FIM instrument, sex, age, duration of disease, stroke type, affected side of the body, frequency of rehabilitation, use of sedatives, and Mini-Mental State Examination score were evaluated and the occurrence of falls was observed prospectively for 12 months.

Results

Forty-five (44.6%) participants fell, 20 of whom fell repeatedly. A logistic model for predicting falls was refined until it included 4 predictors: memory score on the FIM, range of motion of the lower extremities on the SIAS, duration of disease, and affected side. The predictive value of the logistic model was 86.7%.

Conclusions

Evaluation tools were useful for predicting falls and devising preventive strategies in the high-risk group of home-living stroke patients.     

Effects of vitamin D2 analogs on calcium metabolism in vitamin D-deficient rats and in MC3T3-E1 osteoblastic cells

The effects of 1α-hydroxyvitamin D₂ on calcium metabolism in vivo and of 1α,25-dihydroxyvitamin D₂, which is an active metabolite of 1α-hydroxyvitamin D₂, on bone metabolism in vitro was studied and compared with that of 1α-hydroxyvitamin D₃ or 1α,25-dihydroxyvitamin D₃. 1α-Hydroxyvitamin D₂ and 1α-hydroxyvitamin D₃ was equally potent in stimulating intestinal calcium transport by using the everted sac method and of calcium mobilization from bone in vitamin D-deficient rats. On the other hand, the hypercalcemic activity of 1α-hydroxyvitamin D₂ was much lower than that of 1α-hydroxyvitamin D₃ in normal mice and rats. 1α,25-Dihydroxyvitamin D₂ and 1α,25-dihydroxyvitamin D₃ stimulated alkaline phosphatase activity in ostoblastic MC3T3-E1 cells and bone resorption in newborn mouse calvaria maintained in organ culture. These results show that 1α-hydroxyvitamin D₂ as well as 1α-hydroxyvitamin D₃ promote calcium absorption and may accelerate bone remodelling via direct action on osteoblasts. In addition, they suggest that 1α-hydroxyvitamin D₂ may be more useful than 1α-hydroxyvitamin D₃ for the treatment of senile osteoporosis, because hypercalcemia is one of the major side effects of 1α-hydroxyvitamin D₃.     

Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.