Imaging of malignant lymphomas with F-18 FDG coincidence detection positron emission tomography

PURPOSE: The authors evaluated the utility of F-18 fluorodeoxyglucose (FDG) coincidence detection (CoDe) positron emission tomography (PET) for staging, post-treatment evaluation, and follow-up assessment of patients with malignant lymphomas. MATERIALS AND METHODS: Fifty-eight patients with histologically proved malignant lymphomas (4 Hodgkin's disease, 54 non-Hodgkin's lymphoma) underwent CoDe PET using F-18 FDG. CoDe PET was performed using a dual-head gamma camera equipped with coincidence detection circuitry. Of the 87 CoDe PET studies, 26 were performed for staging, 38 for post-treatment evaluation, and 23 for follow-up evaluation of recurrence. The entire trunk, from the cervical to the inguinal regions, or selected regions were scanned with the patient in the supine position. No attenuation correction was made and reconstruction was performed using filtered back-projection rather than iterative reconstruction. CoDe PET findings were compared with corresponding results of computed tomographic (CT) and magnetic resonance imaging (MRI), tissue biopsy, or clinical follow-up. RESULTS: For staging, 52 sites were positive on CoDe PET or CT-MRI. CoDe PET detected 49 sites (94%), and CT-MRI showed 47 sites (90%). CoDe PET detected five more lymphomatous lesions and missed three lesions. For post-treatment evaluation, CoDe PET showed a positive predictive value of 100% and a negative predictive value of 83%, but the validated cases numbered only 11. For follow-up for recurrence, CoDe PET had a negative predictive value of 90%, but frequent false-positive findings were noted in the head and neck region as a result of underlying inflammatory changes. CONCLUSIONS: For staging, FDG CoDe PET alone without attenuation correction is not sensitive enough to be used as an independent imaging method, especially for small abdominal lesions. However, it appears to be an accurate method for assessing residual disease and for patient follow-up.     

HLA‐A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein–Barr virus type 1 (EBV‐1) infection. We carried out a genome‐wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA‐A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10^?9). HLA‐A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA‐A‐aa‐site‐99} = 3.79 × 10^?8, p_rs1136697 = 3.79 × 10^?8) and T‐cell receptor binding site (p_{HLA‐A‐aa‐site‐145} = 1.41 × 10^?4, p_rs1059520 = 1.41 × 10^?4) of the HLA‐A. We also detected strong association signals in the 5′‐UTR region with predicted active promoter states (p_rs41545520 = 7.91 × 10^?8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520‐G correlated with reduced HLA‐A expression. Multivariate logistic regression diminished the effects of HLA‐A amino acid variants and SNPs, indicating a correlation with the effects of HLA‐A*11:01, and to a lesser extent HLA‐A*02:07. We report the strong genetic influence of HLA‐A on NPC susceptibility in the Malaysian Chinese.     

Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells

Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benefits such CML‐LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW‐7197, an orally bioavailable transforming growth factor‐β signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML‐LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW‐7197 to CML‐affected mice significantly delayed disease relapse and prolonged survival. Notably, combined treatment with EW‐7197 plus TKI was effective in eliminating CML‐LICs even if they expressed the TKI‐resistant T315I mutant BCR‐ABL1 oncogene. Collectively, these results indicate that EW‐7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML‐LICs.     

Hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation in adult patients with idiopathic aplastic anemia

We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n = 19/260) of patients. Classical Cy (200 mg/m²)-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m² conditioning (p = 0.035), classical Cy-ATG conditioning (p = 0.007), and horse ATG conditioning (p < 0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR = 3.484; 95% CI 1.226–9.904; p = 0.002). Rabbit ATG (HR 12.719; 95% CI 2.332–69.373; p = 0.003) and weight gain > 10% (HR 35.655; 95% CI 2.208–575.805; p = 0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p < 0.001; Fig. 2) in the SOS group.     

Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells

Here, we demonstrate that kinetin riboside (KR), a cytokinin analog, induces apoptosis in HeLa and mouse melanoma B16F-10 cells. KR disrupted the mitochondrial membrane potential and induced the release of cytochrome c and activation of caspase-3. Bad were upregulated while Bcl-2 was down-regulated under KR exposure. A tumor growth in mice was dramatically suppressed by KR. In contrast, human skin fibroblast CCL-116 and bovine primary fibroblast cells show resistances to KR and no significant changes in Bad, Bcl-X(L,) and cleaved PARP were observed. Our data suggest that KR selectively induces apoptosis in cancer cells through the classical mitochondria dependent apoptosis pathway.     

Percutaneous Transhepatic Treatment of Benign Bile Duct Strictures Using Retrievable Covered Stents: Long-Term Outcomes in 148 Patients

ObjectiveTo investigate the long-term outcomes of percutaneous treatment of benign biliary strictures using temporary placement of a retrievable expanded polytetrafluoroethylene (PTFE) covered stent.Materials and MethodsWe retrospectively analyzed the outcomes of 148 patients (84 male and 64 female; age range, 11–92 years) who underwent percutaneous transhepatic placement and removal of a retrievable PTFE-covered stent for the treatment of benign biliary strictures between March 2007 and August 2019 through long-term follow-up. Ninety-two patients had treatment-naïve strictures and 56 had recurrent/refractory strictures.ResultsStent placement was technically successful in all 148 patients. The mean indwelling period of the stent was 2.4 months (median period, 2.3 months; range, 0.2–7.7 months). Stent migration, either early or late, occurred in 28 (18.9%) patients. Clinical success, defined as resolution of stricture after completing stent placement and removal, was achieved in 94.2% (131 of 139 patients). The overall complication rate was 15.5% (23 of 148 patients). During the mean follow-up of 60.2 months (median period, 52.7 months; range, 1.6–146.1 months), 37 patients had a recurrence of clinically significant strictures at 0.5–124.5 months after removal of biliary stent and catheter (median, 16.1 months). The primary patency rates at 1, 3, 5, 7, and 10 years after removal of biliary stent and catheter were 88.2%, 70.0%, 66.2%, 60.5%, and 54.5%, respectively. In the multivariable Cox proportional hazard regression analysis, sex, age, underlying disease, relation to surgery, stricture type, biliary stones, history of previous treatment, and stricture site were not significantly associated with the primary patency.ConclusionLong-term outcomes suggest that percutaneous treatment of benign biliary strictures using temporary placement of retrievable PTFE-covered stents may be a clinically effective method.     

Brachial-ankle pulse wave velocity as a predictor of long-term cardiovascular events in 2174 subjects with type 2 diabetes mellitus: A retrospective cohort study

The prognostic value of arterial stiffness in patients with diabetes mellitus (DM) remains unclear. The aim of this study was to investigate the association between brachial-ankle pulse wave velocity (baPWV) and the occurrence of cardiovascular events in people with DM. A total of 2714 subjects (mean age, 63.6 years; males, 59.3%) with type 2 DM and without documented cardiovascular disease and stroke were analyzed. The primary end-point of this study was composite cardiovascular events of cardiac death, non-fatal myocardial infarction, coronary revascularization and stroke. There were 118 composite events (4.3%) during a median follow-up period of 3.84 years (interquartile range, 1.60–5.52 years). In multivariable Cox regression analysis, higher baPWV (≥1672 cm/s) was associated with composite events even after controlling for potential confounders (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.31–3.07; P = .001). Compared to the lowest baPWV tertile, both middle (HR, 1.84; 95% CI, 1.03–3.27; P = .037) and the highest (HR, 2.97; 95% CI, 1.69–5.22; P < .001) tertile of baPWV were associated with increased risk of cardiovascular events in the same multivariable model. In conclusion, the baPWV was associated with cardiovascular events in people with type 2 DM. Considering the simplicity and convenience of baPWV measurement, baPWV may be useful for risk stratification of people with type 2 DM.     

Inpatients with shoulder osteoarthritis who received integrative Korean medicine treatment: Long-term follow-up of an observation study

This study aimed to investigate the long-term clinical efficacy of and satisfaction with integrative Korean medicine (KM) treatment in patients with shoulder osteoarthritis (SOA). We conducted a prospective observational study of patients with SOA. Patients aged 19 years and older who underwent inpatient treatment for more than 1 week were eligible for enrollment in the study. The primary evaluation index was the numeric rating scale for shoulder pain. Sub-evaluation indices included the Shoulder Pain and Disability Index for shoulder function, EuroQol-5-dimension score for overall quality of life, and Patient Global Impression of Change. Outcome measures were assessed at admission, discharge, and follow-up. For the follow-up questionnaire survey, the following information was collected: current status, surgery after discharge, reasons for finding integrative KM treatment satisfactory/unsatisfactory, and quality of life after discharge. In total, 186 patients were enrolled in the primary analysis, and 103 patients completed the follow-up survey. The mean number of days of follow-up was 1019 ± 439. Compared with the baseline, the mean differences in the numeric rating scale and Shoulder Pain and Disability Index were 3.05 ± 0.34 and 36.06 ± 5.53, respectively. Regarding the Patient Global Impression of Change, 89 out of 103 (86.4%) patients chose “minimally improved” or better. Furthermore, the EuroQol-5-dimension score also increased, showing an improvement of health-related quality of life after treatment. Integrative KM treatment is a potential option for reducing pain severity and improving function and health-related quality of life in patients with SOA. Prospective randomized studies would support this finding for the next step.