Sonographic Differentiation Between Angiolipomas and Superficial Lipomas.

OBJECTIVES: The purpose of this study was to compare the sonographic findings of angio lipomas with those of superficial lipomas. METHODS: Preoperative sonograms of 26 angiolipomas from 18 patients and 47 superficial lipomas from 43 patients that were confirmed by biopsy were reviewed retrospectively. The echo texture, echogenicity, internal echogenic stranding, vascularity, visualization of lateral and superficial-deep tumor capsules, shape, and tumor length, width, and length-to-width ratio were evaluated and compared between angiolipomas and superficial lipomas. RESULTS: Angiolipomas frequently appeared as heterogeneous (19 of 26 [73.1%]), hyperechoic (23 of 26 [88.5%]), and ovoid (17 of 26 [65.4%]) masses with lesser visualized lateral tumor capsules (6 of 26 [23.1%]), whereas superficial lipomas appeared as homogeneous (36 of 47 [76.6%]), isoechoic (35 of 47 [74.5%]), and spindle-shaped (23 of 47 [48.9%]) masses with well-visualized lateral capsules (33 of 47 [70.2%]), and the differences were statistically significant (P < .001). Vascularity was seen in 4 angiolipomas (16.7%) and in no superficial lipomas (0%). The mean length and width ± SD of angiolipomas (2.2 ± 1.02 and 0.6 ± 0.27 cm, respectively) were smaller than those of superficial lipomas (4.2 ± 1.52 and 1.1 ± 0.51 cm), with statistical significance (P< .001). The other sonographic findings did not reveal statistically significant differences between the tumor types. CONCLUSIONS: Sonography might help differentiate angiolipomas from superficial lipomas.

Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

We report here an ectopic case of Fasciola hepatica infection confirmed by recovery of an adult worm in the mesocolon. A 56-year-old female was admitted to our hospital with discomfort and pain in the left lower quadrant of the abdomen. Abdominal CT showed 3 abscesses in the left upper quadrant, mesentery, and pelvic cavity. On surgical exploration, abscess pockets were found in the mesocolon of the sigmoid colon and transverse colon. A leaf-like worm found in the abscess pocket of the mesocolon of the left colon was diagnosed as an adult fluke of F. hepatica. Histologically, numerous eggs of F. hepatica were noted with acute and chronic granulomatous inflammations in the subserosa and pericolic adipose tissues. Conclusively, a rare case of ectopic fascioliasis has been confirmed in this study by the adult worm recovery of F. hepatica in the mesocolon.

Salivary duct carcinomas: clinical and CT and MR imaging features in 20 patients.

INTRODUCTION: Salivary duct carcinoma (SDC) is an uncommon high grade adenocarcinoma of the salivary gland with a grave prognosis. The aim of this study was to investigate the clinical and CT and MR imaging features of SDC. METHODS: We retrospectively evaluated the clinical and CT and MR imaging findings in 20 patients (14 men and six women; mean age, 59 years) with histologically proved SDC. We also tried to correlate clinicoradiological tumor staging with pathologic tumor staging in 17 patients who underwent surgery. RESULTS: The tumor originated in the parotid gland (n = 11; 55%), the submandibular gland (n = 7; 35%) and the buccal space along the distal Stensen's duct (n = 2; 10%). Locoregional recurrence occurred in 41% and distant metastasis in 47%. Fifty-eight percent died of the disease with a mean survival period of 32 months after diagnosis. On CT and MR images, SDC was mostly seen as an ill-defined (85%) and infiltrative (60%) mass with frequent calcification (50%) and necrosis (80%). Although various signal intensities were seen on MR images, six of nine tumors contained the areas of marked hypointensity on T2-weighted images. Clinicoradiological tumor staging correlated well with pathologic tumor staging in 82% of the patients. CONCLUSION: Ill-defined, infiltrative mass with calcification on CT scans and the areas of marked hypointensity on T2-weighted MR images may be useful radiologic features to suggest the diagnosis of SDC. CT and MR imaging are useful for staging of SDC.

Extended gastritis cystica profunda associated with Epstein-Barr virus-positive dysplasia and carcinoma with lymphoid stroma.

We report a case of gastritis cystica porfunda (GCP) associated with gastric carcinoma with lymphoid stroma (CLS). There was dysplastic change in the transitional area between GCP and CLS. Epstein-Barr virus (EBV) in situ hybridization (ISH) revealed positive reaction at the dysplastic area as well as at the CLS area. Immunohistochemical staining disclosed that dysplastic epithelium was similar to GCP in CK 20, MUC5AC, and E-cadherin expression, but similar to CLS in MUC6, CEA, p53, c-erb-B2, and EBV-ISH expression. Results of the EBV-ISH suggested that EBV infection may play a role in dysplastic change.

Clinicopathologic and molecular characteristics of lung adenocarcinoma arising in young patients.

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.

Reclassifying formerly indeterminate thyroid FNAs using the Bethesda system reduces the number of inconclusive cases.

OBJECTIVE: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. STUDY DESIGN: According to the BSRTC, we reclassified cytologic samples originally diagnosed as 'indeterminate' with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as 'atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)'. RESULTS: According to the BSRTC, 154 'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused inconclusive diagnoses. CONCLUSION: The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto's thyroiditis precluded cytopathologists from making definitive diagnoses.

Beyond hydrophilic polymers in amphiphilic polymer-based self-assembled NanoCarriers: Small hydrophilic carboxylate-capped disulfide drug delivery system and its multifunctionality and multispatial targetability.

Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic molecule-stabilized NPs for effective intracellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic molecule-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hydrophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multiple disulfide-containing poly(ε-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic molecules represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers.

Predicting idiopathic toxicity of cisplatin by a pharmacometabonomic approach.

Cisplatin has been one of the most widely used anticancer agents, but its nephrotoxicity remains a dose-limiting complication. Here, we evaluated the idiopathic nature and the predose prediction of cisplatin-induced nephrotoxicity using a nuclear magnetic resonance (NMR)-based pharmacometabonomic approach. Cisplatin produced serious toxic responses in some animals (toxic group), but had little effect in others (nontoxic group), as judged by hematological and histological results. The individual metabolic profiles, assessed by urine NMR spectra, showed large differences between the post-administration profiles of the two groups, indicating the relevance of the NMR approach. Importantly, multivariate analysis of the NMR data showed that the toxic and nontoxic groups can be differentiated based on the pretreatment metabolite profiles. Leave-one-out analysis, performed to evaluate the practical performance of our approach, gave a 66% accuracy rate in predicting toxic responses based on the pretreatment metabolite profiles. Hence, we provide a working model that can explain the idiopathic toxicity mechanism based on marker metabolites found by NMR analysis consistent with tissue NADH measurements. Thus, a pharmacometabonomic approach using pretreatment metabolite profiles may help expedite personalized chemotherapy of anticancer drugs.

PPARgamma agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis.

The peroxisome proliferator activated receptor (PPAR)gamma agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARgamma agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-beta1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-beta/Smad2 in the treated groups, PAI-1 and TGF-beta are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARgamma agonist might be used in the treatment of renal fibrotic disease.

Cytomorphologic features of small cell carcinoma of lung in effusion fluid using a liquid-based cytology technique.

BACKGROUND: Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations. METHODS: Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients. RESULTS: LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP. CONCLUSION: LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP. Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions.

SB365 induces apoptosis and suppresses proliferation of glioblastoma cells.

CONTEXT: Glioblastoma is a malignant brain tumor with limited treatment modalities due to its nature. SB365, Pulsatilla saponin D, is known to induce apoptosis and inhibit the growth of many cancer cells. AIM: We elucidated the anticancer effects of SB365 in glioblastoma cells. METHODS: We examined the antiproliferative activity of SB365 in human glioblastoma cell lines. Apoptosis was evaluated using the Hoechst assay, TUNEL assay, DAPI nuclear staining, and Western blotting analysis. To test the antimetastatic capacity of SB365, cell migration assay was conducted, and hypoxia-inducible factor-1 alpha (HIF-1α) expression and vascular endothelial growth factor (VEGF) level were determined under hypoxic conditions. STATICAL ANALYSIS: Significance of the results was confirmed by a one-way analysis of variance analysis. RESULTS: SB365 treatment suppressed the growth of glioblastoma cells and resulted in apoptotic morphological features such as nuclear condensation and fragmentation, enhancing the expression of cleaved poly (ADP-ribose) polymerase and caspase-3. It also significantly delayed cell migration and decreased the HIF-1α expression and VEGF secretion. CONCLUSION: Our findings thus demonstrate that SB365 induced apoptosis and delayed the growth and migration of human glioblastoma cells. It is considered that SB365 would be a promising therapeutic option for glioblastoma.

Protective effect of morin on dimethylnitrosamine-induced hepatic fibrosis in rats.

Morin, a plant-derived flavonoid, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of morin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Oral administration of morin remarkably prevented weight loss in the body and liver from DMN and inhibited the elevation of serum alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin levels. For the evaluation of hepatic fibrosis-related factors, we investigated expressions of collagen type I, transforming growth factor beta(1) (TGF-beta(1)), and alpha-smooth muscle actin (alpha-SMA) in mRNA and protein levels. We observed that morin significantly reduced the expression of collagen type I, TGF-beta(1), and alpha-SMA on hepatic fibrosis induced by DMN. Taken together, this study demonstrated that morin showed hepatoprotective and antifibrogenic effects against DMN-induced hepatic injury. This suggests that morin may be useful in preventing the development of hepatic fibrosis and cirrhosis.

Tongue base varix as a source of oral bleeding: A case report.

RATIONALE: Oral bleeding is usually diagnosed after by referral to other department for the differential diagnosis of hematemesis or hemoptysis. If a patient presents with blood in the oral cavity with no obvious source, generally upper airway, pulmonary, or gastroesophageal lesions are considered likely bleeding foci. The tongue base is an unusual site for laryngopharyngeal varices and only a few cases have been reported. PATIENT CONCERNS: Although varix at the tongue base in patients with liver cirrhosis has been rarely described, physicians must consider variceal bleeding from the tongue base when presented with oral bleeding. In such cases, bleeding foci can be identified and controlled by laryngoscopy. We describe the case of a 42-year-old woman complaining of small amount of hemoptysis with variceal bleeding at the tongue base controlled by laryngoscopic excision and cauterization. DIAGNOSIS: A diagnosis of tongue base varix was made based on medical history, clinical manifestations, laryngoscopic findings and pathologic features for the patient. INTERVENTIONS: The successful laryngoscopic procedures were performed. OUTCOMES: The patient has shown no recurrent oral bleeding during follow-up. LESSONS: Variceal bleeding in the tongue base is likely to cause serious massive hemorrhage. We need to consider this possibility when presented with a patient with intraoral bleeding but no evidence of hemoptysis or hematemesis.

Severe paradoxical reaction requiring tracheostomy in a human immunodeficiency virus (HIV)-negative patient with cervical lymph node tuberculosis.

During drug treatment of tuberculous lymphadenitis, paradoxical response (PR) may occasionally occur. Continued treatment or lymph node aspiration improves PR without severe sequelae. However, we report a case of severe PR in a patient with cervical lymph node tuberculosis causing airway obstruction due to retropharyngeal lymph node swelling during antituberculous treatment. Tracheostomy and drainage of the node were performed to secure the airway. Possible airway obstruction due to PR must be suspected when cervical lymph node tuberculosis involves the retropharyngeal lymph node.

Morin protects acute liver damage by carbon tetrachloride (CCl(4)) in rat.

The purpose of this study was to investigate possible beneficial effects of morin on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL-1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta, IL-6, and iNOS.

Antitumor effect of the paclitaxel-eluting membrane in a mouse model.

Local treatment of primary bile duct cancer, which grows locally at the primary lesion and seldom metastasizes to distant sites, is challenging. The present study evaluated the antitumor effect, systemic toxicity, biodistribution and survival benefit of the paclitaxel-eluting polyurethane membrane in a tumor model. Membranes containing various amounts of paclitaxel (0, 100, 300, 600 and 1,200 µg/disc) were inserted beneath the tumor mass in mouse models. Tumor size and body weight of the tumor models were monitored for 26 days after insertion of the membrane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was performed in the tumor tissues. High-performance liquid chromatography was performed for evaluation of paclitaxel concentration in peripheral tissues. Tumor volumes on day 26 of membrane treatment were decreased in a dose-dependent manner. No significant difference in body weight was observed in the groups. A greater number of apoptotic cells were counted per high power field in tumor tissues following an increase of paclitaxel concentration. In the 1,200 µg-group, concentrations of paclitaxel were significantly higher in tumors compared with those of other tissues and serum. The paclitaxel-eluting membrane demonstrated a significant and dose-dependent antitumor activity, and did not exert systemic toxicity in the tumor model.

Prevention of tracheal inflammation and fibrosis using nitinol stent coated with doxycycline.

OBJECTIVES: This study was conducted to determine whether a nitinol stent coated with doxycycline prevents tracheal inflammation and fibrosis in a rabbit. METHODS: A nitinol stent coated with doxycycline was designed by us. Twelve rabbits were divided into three groups: normal, control (nondoxycycline-coated stent), and doxycycline-coated stent group. The stents were inserted into the tracheal lumen through the oral cavity. Tracheal granulation was evaluated and graded by laryngoscopy. Histological examinations evaluated the inflammatory response and fibrosis. Real-time polymerase chain reaction (PCR) and Western blot assessed the changes to the extracellular matrix (ECM). RESULTS: Endoscopic findings showed that the nitinol stent coated with doxycycline resulted in lesser granulation tissue in the trachea than the noncoated stent. Histologic examination further revealed that the doxycycline-coated stent was associated with decreased inflammatory cells and reduced fibrosis, compared to the noncoated stent. In PCR and Western blot, the doxycycline-coated stent showed lower expression of ECM components inducing fibrosis. CONCLUSION: A nitinol stent coated with doxycycline showed favorable effects in reducing tracheal inflammation and fibrosis in a rabbit model. Further research is required to study the beneficial effects of local application of doxycycline for prevention of tracheal stenosis. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1558-1563, 2018.

Aß pathology downregulates brain mGluR5 density in a mouse model of Alzheimer.

The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([18F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniques. The non-displaceable binding potential values for mGluR5 was estimated by the Logan's graphical analysis. Brain PET imaging revealed that radioactivities in the hippocampus and the striatum were significantly lower in 5xFAD mice compared to control animals. Binding values were also significantly lowered in 5xFAD mice. This decline was validated by immunoblotting of protein isolates from brain tissues, as the mean band density for 5xFAD mice had a lower mGluR5 intensity than for wild type mice. These results indicated that mGluR5 levels in 5xFAD mice were down regulated in the limbic system.

Protein complexed with chondroitin sulfate in poly(lactide-co-glycolide) microspheres.

Chondroitin sulfate (CsA) is an acidic mucopolysaccharide, which is able to form ionic complexes with positively charged proteins. In this study, a protein-CsA complex was constructed to nano-sized particles. Zeta potential measurements revealed that a CsA-to-protein fraction of greater than 0.1 results in a neutralization of the positive charge on lysozyme (Lys). Based on this preliminary study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring Lys/CsA complexes via the multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of Lys release from the PLGA microspheres evidenced nearly zero-order kinetics, depending on the quantity of CsA. An in vivo fluorescent image of experimental mouse tissue showed that the PLGA microspheres with the Lys/CsA complex had released the entirety of their Lys without no residual amount after 23 days, but microspheres without the complex harbored a great deal of residual Lys, which is attributable to its degradation by acidic PLGA degradates. The tissue reaction evidenced by the PLGA microspheres stabilized with CsA showed minimal foreign body reaction and little configuration of immune cells including neutrophils and macrophages, but the reactions of the PLGA microspheres without CsA were characterized by a relatively elevated inflammation. These results show that CsA is a viable candidate for long-acting micro-particular protein delivery.