Multilocular Cystic Renal Neoplasm of Low Malignant Potential: A Case Report and Literature Review.

Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) is a rare subtype of renal cell carcinoma that has a favorable outcome. Most cases of MCRNLMP usually present as distinct multilocular cystic lesions; however, they may appear as small complicated cysts with hemorrhagic components. Herein, we present a case of MCRNLMP and provide a review of the literature.

Effects of Vagus Nerve Stimulation on Sleep-Disordered Breathing, Daytime Sleepiness, and Sleep Quality in Patients With Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) on sleep-disordered breathing (SDB), daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy (DRE). It also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. METHODS: Twenty-four patients were recruited. Paired t-tests and multiple linear regression analyses were performed to determine how the demographic and clinical characteristics of the patients influenced the variables that changed significantly after VNS treatment. RESULTS: After VNS, the patients showed significant increases in the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), apnea index, hypopnea index, and oxygen desaturation index (ODI), as well as a significant decrease in the lowest arterial oxygen saturation (SaO2 nadir) (p<0.05). The multiple linear regression analyses demonstrated that the predictor of larger increases in AHI and RDI was being older at baseline, and that the predictor of a larger increase in apnea index was a longer epilepsy duration. The strongest predictor of a larger increase in ODI was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. The strongest predictor of a larger decrease in SaO2 nadir was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. CONCLUSIONS: This study has confirmed that VNS improves seizure control in patients with DRE, whereas it increases obstructive sleep apnea (OSA). Furthermore, the increase in OSA is affected by age and the duration of epilepsy. Therefore, careful observation and monitoring of SDB is recommended in patients who undergo VNS.

Synergism of a novel MCL­1 downregulator, acriflavine, with navitoclax (ABT­263) in triple­negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.

Myeloid cell leukemia sequence 1 (MCL­1), an anti­apoptotic B­cell lymphoma 2 (BCL­2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL­1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL­1 blockers, the present study presented acriflavine (ACF) as a novel MCL­1 inhibitor in triple­negative breast cancer (TNBC). Further evaluation of its treatment potential on lung adenocarcinoma and glioblastoma multiforme (GBM) was also investigated. The anticancer effect of ACF on TNBC cells was demonstrated when MDA­MB­231 and HS578T cells were treated with ACF. ACF significantly induced typical intrinsic apoptosis in TNBCs in a dose­ and time­dependent manner via MCL­1 downregulation. MCL­1 downregulation by ACF treatment was revealed at each phase of protein expression. Initially, transcriptional regulation via reverse transcription­quantitative PCR was validated. Then, post­translational regulation was explained by utilizing an inhibitor against protein biosynthesis and proteasome. Lastly, immunoprecipitation of ubiquitinated MCL­1 confirmed the post­translational downregulation of MCL­1. In addition, the synergistic treatment efficacy of ACF with the well­known MCL­1 inhibitor ABT­263 against the TNBC cells was explored [combination index (CI)<1]. Conjointly, the anticancer effect of ACF was assessed in GBM (U87, U251 and U343), and lung cancer (A549 and NCI­H69) cell lines as well, using immunoblotting, cytotoxicity assay and FACS. The effect of the combination treatment using ACF and ABT­263 was estimated in GBM (U87, U343 and U251), and non­small cell lung cancer (A549) cells likewise. The present study suggested a novel MCL­1 inhibitory function of ACF and the synergistic antitumor effect with ABT­263.

Comparing Ictal Cardiac Autonomic Changes in Patients with Frontal Lobe Epilepsy and Temporal Lobe Epilepsy by Ultra-Short-Term Heart Rate Variability Analysis.

Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey-Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.

Effect of Long-Term Treatment with Vagus Nerve Stimulation on Mood and Quality of Life in Korean Patients with Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) treatment on suicidality, mood-related symptoms, and quality of life (QOL) in patients with drug-resistant epilepsy (DRE). We also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. METHODS: Among 35 epilepsy patients who underwent VNS implantation consecutively in our epilepsy center, 25 patients were recruited to this study for assessing the effects of VNS on suicidality, mood-related symptoms, and QOL. The differences in these variables between before and after VNS treatment were analyzed statistically using paired t-tests. Multiple linear regression analyses were also performed to determine how the patients' demographic and clinical characteristics influenced the variables that showed statistically significant changes after long-term VNS treatment. RESULTS: After VNS, our patients showed significant improvements not only in the mean seizure frequency but also in suicidality, depression, and QOL. The reduction in depression was associated with the improvement in QOL and more-severe depression at baseline. The reduction in suicidality was associated with higher suicidality at baseline, smaller changes in depression, and less-severe depression at baseline. Improved QOL was associated with lower suicidality at baseline. CONCLUSIONS: This study found that VNS decreased the mean seizure frequency in patients with DRE, and also improved their depression, suicidality, and QOL. These results provide further evidence for therapeutic effect of VNS on psychological comorbidities of patients with DRE.

A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice.

Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer. The anti-neu antibody inhibited tumor growth and enhanced anti-tumor immunity in HER2/neu+ breast cancer TUBO models, whereas GDC-0941 or A66 alone did not. Anti-neu antibody and PI3K inhibitor synergistically promoted anti-tumor immunity by increasing functional T cell production. In the presence of the anti-neu antibody, A66 was more effective than GDC-0941 at increasing the fraction of CD4+, CD8+, and IFN-γ+CD8+ T cells in the tumor-infiltrating lymphocyte population. Detection of IFN-γ levels by enzyme-linked immunospot assay showed that the numbers of tumor-specific T cells against neu and non-neu tumor antigens were increased by combined PI3K inhibitor plus anti-neu antibody treatment, with A66 exhibiting more potent effects than GDC-0941. In a TUBO (neu+) and TUBO-P2J (neu-) mixed tumor model representing immunohistochemistry 2+ tumors, A66 suppressed tumor growth and prolonged survival to a greater extent than GDC-0941 when combined with anti-neu antibody. These results demonstrate that a PI3K p110α-isoform-selective inhibitor is an effective adjunct to trastuzumab in the treatment of HER2-positive breast cancer.

Transitional cell carcinoma arising in a calyceal cyst mimicking a cystic renal tumour.

Solitary renal cysts are relatively common. The occurrence of transitional cell carcinoma (TCC) in a renal cyst is rare. We present the case of a 59-year-old man with a medical history of viral hepatitis B. During a workup for his hepatitis, a computed tomography scan revealed a large cystic tumour in the upper region of the left kidney. A radical left nephrectomy was performed. Microscopic examination of the cystic tumour revealed a grade 2 TCC. The cyst was lined by transitional epithelium. This is a case of a TCC growing within a renal calyceal cyst.

Extramedullary plasmacytoma of the pancreas diagnosed using endoscopic ultrasonography-guided fine needle aspiration.

Extramedullary plasmacytoma involves organs outside the bone marrow; however, involvement of the pancreas is rare. We recently experienced a case of extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). EUS-FNA, which has a high diagnostic accuracy and an excellent safety profile, is the modality of choice for establishing tissue diagnosis. We report a case of extramedullary plasmacytoma of the pancreas diagnosed using EUS-FNA.

CXC motif ligand 12 as a novel diagnostic marker for papillary thyroid carcinoma.

BACKGROUND: We subjected chemokine (C-X-C motif) ligand 12 (CXCL12) to immunohistochemistry to determine its utility as a novel diagnostic marker for papillary thyroid carcinoma (PTC) in comparison to cytokeratin 19 (CK19), Hector Battifora mesothelial epitope-1 (HBME-1), and galectin-3. METHODS: We analyzed the expressions of CXCL12, CK19, HBME-1, and galectin-3 using immunohistochemical staining in 258 cases of thyroid lesions (196 PTCs and 62 thyroid lesions excluding PTC). RESULTS: Remarkably, CXCL12 expression was exclusively found in PTC compared to other thyroid lesions (90.8% vs 3.2%; p < .001). In total, 91.1% (62 of 68) of the variant PTCs and 90.6% of conventional type (116 of 128) were associated with CXCL12 immunohistochemical expression, irrespective of the histological subtype. In contrast, very few of the thyroid lesions, excluding PTC, were positive for CXCL12 (2 of 62; 3.2%). Diagnostic performances for PTCs were as follows: sensitivity, 90.8%; specificity, 96.8%; positive predictive value, 98.9%; negative predictive value, 76.9%; and diagnostic accuracy, 92.2%. CONCLUSION: Our findings indicate that CXCL12 might serve as an effective novel supplementary diagnostic marker for PTC.

Strong cytoplasmic expression of COX2 at the invasive fronts of gallbladder cancer is associated with a poor prognosis.

AIM: The significance of cell cycle proteins, p21 and p53, and cyclo-oxygenase-2 (COX2) is still controversial in gallbladder adenocarcinoma. Conflicting results exist with regard to the prognostic significance of p21 and p53 expression, and the strong association of gallbladder cancer with chronic inflammation makes it only natural that COX2 negativity is rarely encountered, even in non-neoplastic biliary epithelia. METHODS: The authors explored whether the p21 and p53-labelling indices (LI) and strong cytoplasmic COX2 expression differ in the central parts (TC) and invasive fronts (IF) of gallbladder cancer. Paraffin-embedded whole tissue sections of 67 gallbladder cancers were immunohistochemically analysed for p21, p53 and COX2-LI at the IF and TC, and results were correlated with the clinicopathological features. RESULTS: Significantly higher LI was seen in IF compared with TC for p21, p53 and COX2. COX2-LI-IF showed significant positive correlations with perineural and lymphatic invasion, higher T and N stages, and non-papillary gross morphology. Gall-bladder cancers with COX2-LI-IF≥30% showed decreased overall and disease-free survival, and COX2-LI-IF≥30% was an independent poor prognostic factor on multivariable analysis. Gall-bladder cancers with high COX2 and p21-LI-IF showed decreased overall and disease-free survival. CONCLUSIONS: The IF of gallbladder cancer is characterised by significantly increased expression of p21, p53 and strong COX2 expression, and strong cytoplasmic COX2 expression at IF is associated with a poorer prognosis. Heterogeneity between TC and IF should be considered in in situ molecular studies, especially during interpretation of immunohistochemical stain results and tissue microarray construction.

Hypocomplementemic urticarial vasculitis in systemic lupus erythematosus.

Urticarial vasculitis is characterized clinically by urticarial skin lesions and histologically by leukocytoclastic vasculitis. Hypocomplementemic urticarial vasculitis is associated with connective tissue diseases such as systemic lupus erythematosus (SLE). We report a case of urticarial vasculitis that preceded manifestations of SLE.