Invasive middle ear cholesterol granuloma involving the basal turn of the cochlea with profound sensorineural hearing loss.

STUDY DESIGN: A retrospective surgical case review. SETTING: A tertiary-care, university teaching hospital. PATIENTS: The authors describe a unique case operated on for a middle ear cholesterol granuloma, which had invaded the cochlea and vestibule causing profound sensorineural deafness. INTERVENTIONS: Extended radical mastoidectomy and labyrinthectomy with musculofascial seal. RESULTS: Successful postoperative outcome with no recurrence seen after 2 years of follow up. CONCLUSION: To the authors' knowledge, this is the first reported case of a primary middle ear cholesterol granuloma with direct invasion into the cochlea. Such invasion of the otic capsule by cholesterol granulomas is rare and presents a diagnostic challenge to the attending otologist and radiologist. Salient points of the case history, pathogenesis, imaging studies, histopathology, and management are presented with a review of the current literature.     

Myositis ossificans of the chest wall simulating malignant neoplasm

Myositis ossificans originating from the chest wall is extremely rare. We report a case of myositis ossificans occurring in a young woman with progressive painful swelling in the chest wall. Preoperative examination suggested a malignant neoplasm originating from soft tissue. Although rare, myositis ossificans is one of the potential causes of painful swelling in the chest wall, and can be mistaken for a malignant neoplasm.     

Intrarenal pseudoaneurysms complicating renal choriocarcinoma metastases: treatment with coil embolization

Most intrarenal pseudoaneurysms result from a laceration of the renal artery or its branches. However, tumor-induced renal pseudoaneurysm is very rare. We report a case in which embolization of an intrarenal pseudoaneurysm complicating renal metastases resulting from a choriocarcinoma was successful.     

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.