Diagnostic accuracy of functional imaging modalities for chondrosarcoma: A systematic review and meta-analysis.

INTRODUCTION: The distinction between low-grade (grade 1) chondrosarcoma and its benign counterparts can be challenging. This systematic review aims to quantify the diagnostic accuracies of all functional imaging modalities used in the diagnosis of chondrosarcoma. METHODS: Medline and Embase were searched in February 2019. We included studies of either retrospective or prospective design if the results of functional scans were compared with pre-determined reference standards. Studies had to be primary diagnostic reports on patients with chondral tumours at first diagnosis. Two review authors independently performed study selection, extracted data and assessed the methodological quality. We calculated diagnostic accuracy measures for each included study. RESULTS: Four functional imaging modalities were identified across thirteen studies that met the inclusion criteria. 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) was a sensitive and specific test. Technetium-99 m with methylene diphosphonate (Tc-99 m MDP) had an overall low specificity of 4%. Thallium-201 scintigraphy demonstrated high positive predictive values across the studies. The negative predictive values of Technetium-99 m pentavalent dimercaptosuccinic acid (Tc-99 m DMSA (V)) were consistently 100%. CONCLUSIONS: Low-grade chondrosarcomas continue to pose a diagnostic dilemma. FDG-PET demonstrated superior diagnostic accuracy compared to Tc-99 m MDP, Thallium-201 and Tc-99 m DMSA (V). Characteristic uptake patterns of Thallium-201 and Tc-99 m DMSA (V) may provide additional metabolic information to guide the diagnosis in this challenging group of tumours.

Hemosuccus Pancreaticus in the Simple Mucinous Cyst of the Pancreas.

Hemosuccus pancreaticus is an unusual gastrointestinal hemorrhage through the main pancreatic duct. We report a rare case of hemosuccus pancreaticus due to a simple mucinous cyst of the pancreas. A 52-year-old man who had been followed-up for a suspected branch duct intraductal papillary mucinous neoplasm (IPMN) visited the emergency room due to hematochezia. Endoscopy showed active bleeding from the ampulla. Computed tomography revealed hemorrhage in a 2.0-cm cystic mass in the pancreatic body. The patient was diagnosed with hemosuccus pancreaticus caused by bleeding into the main pancreatic duct from suspected IPMN. Elective laparoscopic distal pancreatectomy was performed. The histopathological diagnosis was a simple mucinous cyst with squamous metaplasia based upon the pathological finding involving the absence of ovarian-type stroma. In conclusion, it should be recognized that a pancreatic cyst including simple mucinous cyst may cause hemosuccus pancreaticus, and these cysts should be viewed as neoplastic and approached similarly as other mucinous pancreatic neoplasms.

Botulinum Toxin Therapy versus Anterior Belly of Digastric Transfer in the Management of Marginal Mandibular Branch of the Facial Nerve Palsy: A Patient Satisfaction Survey.

BACKGROUND: Botulinum toxin (BT) chemodenervation and anterior belly of digastric muscle (ABD) transfer are both treatment options in the management of an isolated marginal mandibular branch of the facial nerve (MMB) palsy. We compare the patient satisfaction following either BT injections or ABD transfer in the management of their isolated MMB palsy. METHODS: Patients in the ABD-arm of the study were identified retrospectively from September 2007 to July 2014. The patients in the BT-arm of the study were identified prospectively from those attending the clinic. Both groups of patients completed a validated patient satisfaction survey. Statistical analysis was performed and a P-value <0.05 was considered statistically significant. RESULTS: Seven patients were in the ABD-arm and 11 patients in the BT-arm of the study. The patient satisfaction in both groups was high with 45% of ABD-arm patients and 40% of BT-arm patients rating their overall outcome as 'better' or 'much better', which was significantly more than the proportion rating their outcome as 'worse' or 'much worse' (P<0.001), although there was a significant trend towards those in the ABD-arm being more likely to be dissatisfied with their outcome (P=0.01). CONCLUSIONS: BT therapy is a good first-line intervention in the management of isolated MMB palsy. We have, however, shown that the overall satisfaction in both groups is high. Therefore, in patients who would prefer a more permanent solution to manage their facial asymmetry, ABD transfer remains a satisfactory treatment option with a good level of patient satisfaction.

Correlation of Primary Tumor FDG Uptake with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.

PURPOSE: The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. METHODS: We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUVmax) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. RESULTS: The high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUVmax compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. CONCLUSIONS: In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer.

High uric acid level associated with increased arterial stiffness in apparently healthy women.

OBJECTIVES: Increased serum uric acid level is regarded as a risk factor for cardiovascular disease, and found to be associated with increased arterial stiffness. While previous studies investigated the relationship between serum uric acid and arterial stiffness, most did not exclude the confounding factors, such as history or medications of hypertension, diabetes, dyslipidemia and hyperuricemia. The aim of this study was to explore the association of uric acid with arterial stiffness in an apparently healthy population. METHODS: This cross-sectional study enrolled 7025 participants during health examinations from October 2006 to August 2009. A total of 5150 apparently healthy subjects were enrolled in the final analysis. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV). Uric acid was divided into quartiles in men (Q1: 59.5-333.1, Q2: 333.2-380.7, Q3: 380.8-428.3, Q4: 428.4-701.9 µmol/L) and women (Q1: 113.0-236.4, Q2: 236.5-273.6, Q3:273.7-315.2, Q4:315.3-585.0 µmol/L). RESULTS: Uric acid level was significantly different between women with and without increased arterial stiffness, but not in men. ANCOVA showed that women with Q3 and Q4 of serum uric acid had greater baPWV level. In multiple logistic regression analysis, Q4 (OR = 1.53, 95% CI = 1.04-2.26) of uric acid was positively associated with increased baPWV in women, but not in men. In addition, age and high blood pressure were also independently associated factors of increased arterial stiffness for both genders. CONCLUSION: In apparently healthy women, high-normal serum uric acid or greater was associated with greater risk of arterial stiffness. However, the relationship between hyperuricemia and increased arterial stiffness was not significant in men.

Association of human adenovirus-36 in overweight Korean adults.

BACKGROUND: Although human adenovirus-36 (Ad-36) has been reported to be associated with obesity in US adults and children, Korean children and the Italian population, the association has not been found in Dutch or Belgian populations or in US military subjects. Therefore, we examined whether Ad-36 infection is associated with obesity in Korean adults. METHODS: A total of 540 age- and sex-matched individuals, who were normal weight, overweight or obese, were selected from participants in routine health examinations at the Ewha Womans University Medical Center. Overweight participants were defined as those with a body mass index (BMI) of 23 ≤ BMI<25 kg m(-2) and obese subjects were those with BMI ≥ 25 kg m(-2), according to the International Obesity Task Force definition. Ad-36 antibody was measured using a serum neutralization assay. RESULTS: Although more overweight participants than normal or obese subjects tested positive for the Ad-36 antibody (40%, 32.8% and 30%, respectively), the differences were not significant. The participants who tested positive for Ad-36 antibody had lower levels of triglycerides (TG) in each of the three groups, higher total cholesterol (TC) in the obese group and higher high-density lipoprotein-cholesterol (HDL-C) in both the normal and obese groups. The odds ratio (OR) for Ad-36 antibody positivity was greater in overweight than in normal subjects (OR=2.03; 95% confidence interval (CI), 1.16-3.55) after adjusting for age, sex and waist circumference. However, this OR was non-significant in the obese group (OR=1.56; 95% CI, 0.67-3.67). CONCLUSION: Ad-36 seems to be strongly associated with overweight, but not obese, Korean adults.

Association between human adenovirus-36 and lipid disorders in Korean schoolchildren.

BACKGROUND: Although the human adenovirus-36 (Ad-36) has been associated with obesity and related lipid disorders in the United States, this association has yet to be identified in other countries. Therefore, we tried to determine whether Ad-36 is associated with obesity or lipid disorders in Korean schoolchildren. METHOD: A total of 318 Korean schoolchildren aged 6-15 years, who participated in the Ewha Womans University Obesity Research Study, were selected for a community-based cohort study. Non-obese and obese were defined as body mass index (BMI) <85th and > or = 95th percentiles of the Korean reference BMI-for-age curves, respectively, according to International Obesity Task Force definitions. The cutoff points for lipid disorders were modified from the age-modified standards of the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP) III metabolic syndrome criteria. The Ad-36 antibody was measured using a serum neutralization assay. RESULTS: More obese participants than non-obese participants tested positive for the Ad-36 antibody (28.57 vs 13.56%, respectively; P = 0.0174). Within the obese group, the participants who tested positive for the Ad-36 antibody had higher levels of triglycerides (TG) and total cholesterol than those who tested negative for the Ad-36 antibody (P<0.001). However, these associations were not present in the non-obese group. The unadjusted odds ratio (OR) for Ad-36 antibody positivity was greater in obese participants than non-obese participants (OR = 2.550, 95% confidence interval (CI): 1.154-5.633). However, this OR seemed to be nonsignificant when age, sex and lipid variables were included in the analysis (OR = 1.752, 95% CI: 0.763-4.020). The unadjusted OR for the elevated TG was significantly higher in participants who were Ad-36 antibody-positive than those who were Ad-36 antibody-negative (OR = 2.511, 95% CI: 1.448-4.353). This trend remained constant even after adjustment for age, sex and obesity (OR = 2.328, 95% CI: 1.296-4.181). CONCLUSION: Ad-36 seems to be strongly associated with lipid disorders in Korean schoolchildren regardless of obesity.

AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex.

We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes purified from rat kidney IMCD contain the type II protein kinase A (PKA) regulatory subunit (RII), protein phosphatase (PP)2B, PKCzeta, and an RII-binding protein (relative molecular mass ~90 kDa) representing a putative A kinase anchoring protein (AKAP). Affinity chromatography of detergent-solubilized endosomes on cAMP-agarose permits recovery of a protein complex consisting of the 90-kDa AKAP, RII, PP2B, and PKCzeta. With the use of small-particle flow cytometry, RII and PKCzeta were localized to an identical population of endosomes, suggesting that these proteins are components of an endosomal multiprotein complex. (32)P-labeled aquaporin-2 (AQP2) present in these PKA-phosphorylated endosomes was dephosphorylated in vitro by either addition of exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar to that described previously in hippocampal neurons. This signaling complex potentially mediates the phosphorylation of AQP2 to regulate its trafficking into the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling complex could also dephosphorylate AQP2 in vivo.

High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells.

OBJECTIVE: Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). METHODS: The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. RESULTS: After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% +/- 19%, p = 0.006) as compared with the control and mannitol (85% +/- 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% +/- 49%) than in the control and mannitol (94% +/- 18%) groups. CONCLUSION: High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.

Nongenomic stimulation of nitric oxide release by estrogen is mediated by estrogen receptor alpha localized in caveolae.

Acute administration of 17beta-estradiol (E(2)) exerts antiatherosclerotic effects in healthy postmenopausal women. The vasoprotective action of E(2) may be partly accounted for by a rapid increase in nitric oxide (NO) levels in endothelial cells (ECs). However, the signaling mechanisms producing this rise are unknown. In an attempt to address the short-term effect of E(2) on endothelial NO production, confluent bovine aortic endothelial cells (BAECs) were incubated in the absence or presence of E(2), and NO production was measured. Significant increases in NO levels were detected after only 5 min of E(2) exposure without a change in the protein levels of endothelial NO synthase (eNOS). This short-term effect of estrogen was significantly blunted by various ligands which decrease intracellular Ca(2+) concentration. Furthermore, plasma membrane-impermeable BSA-conjugated E(2) (E(2)BSA) stimulated endothelial NO release, indicating that in the current system the site of action of E(2) is on the plasma membrane rather than the classical nuclear receptor. The partial antagonist tamoxifen did not block E(2)-induced NO production; however, a pure estrogen receptor alpha (ERalpha) antagonist ICI 182,780 completely inhibited E(2)-stimulated NO release. The binding of E(2) to the membrane was confirmed using FITC-labeled E(2)BSA (E(2)BSA-FITC). Western blot analysis showed that plasmalemmal caveolae possess ERalpha in addition to well-known caveolae-associated proteins eNOS and caveolin. This study demonstrates that the nongenomic and short-term effect of E(2) on endothelial NO release is Ca(2+)-dependent and occurs via ERalpha localized in plasmalemmal caveolae.

Phosphorylation of aquaporin-2 does not alter the membrane water permeability of rat papillary water channel-containing vesicles.

Antidiuretic hormone modulates the water permeability (Pf) of epithelial cells in the rat kidney by vesicle-mediated insertion and removal of the aquaporin-2 (AQP-2) water channel. AQP-2 possesses a single consensus cAMP-dependent protein kinase A (PKA) phosphorylation site (Ser-256) hypothesized to regulate channel Pf(Kuwahara, M., Fushimi, K., Terada, Y., Bai, L., Sasaki, S., and Marumo, F. (1995) J. Biol. Chem. 270, 10384-10387). To test whether PKA phosphorylation of AQP-2 alters channel Pf, we compared the Pf values of purified AQP-2 endosomes after incubation with either PKA or alkaline phosphatase. Studies using [gamma-32P]ATP reveal that AQP-2 endosomes contain endogenous PKA and phosphatase activities that add and remove 32P label from AQP-2. However, the Pf (0.16 +/- 0.06 cm/s) of endosomes containing phosphorylated AQP-2 (0.7 +/- 0. 3 mol of PO4/mol of protein) is not significantly different from the same AQP-2 endosomes where 95 +/- 8% of the phosphate has been removed (Pf 0.14 +/- 0.06 cm/s). These data do not support a role for PKA phosphorylation in alteration of AQP-2's Pf. Instead, AQP-2 phosphorylation by PKA may modulate AQP-2's distribution between plasma membrane and intracellular vesicle compartments.

Demonstration of an insulin-insensitive storage pool of glucose transporters in rat hepatocytes and HepG2 cells.

The subcellular distribution of glucose transporters in rat hepatocytes and HepG2 cells was studied in the absence and in the presence of insulin. Glucose transporters were quantitated by measuring glucose-sensitive cytochalasin B binding and by protein immunoblotting using isoform-specific antibodies. Plasma membrane contamination into subcellular fractions was assessed by measuring distribution of 5'-nucleotidase and cell surface carbohydrate label. In hepatocytes, GLUT-2 occurred in a low-density microsomal (LDM) fraction at a significant concentration, and as much as 15% of cellular GLUT-2 was found intracellularly that cannot be accounted for by plasma membrane contamination. In HepG2 cells which express GLUT-1 and GLUT-2, the two isoforms showed distinct subcellular distribution patterns: GLUT-2 was highly concentrated in LDM while very little GLUT-1 was found in this fraction, indicating that a large portion of GLUT-2 occurs in intracellular organelles. Insulin treatment did not change the subcellular distribution patterns of glucose transporters in both cell types. Our results suggest that rat hepatocytes and HepG2 cells possess an intracellular storage pool for GLUT-2, but lack the insulin-responsive glucose transporter translocation mechanism.

Anion carrier in the human erythrocyte exists as a dimer.

The in situ state of assembly of the human erythrocyte anion carrier (band 3) has been investigated by applying target size analysis on the radiation-induced inactivation of anion flux and degradation of polypeptide band 3. Irradiation with a high energy electron beam resulted in inactivation of carrier-mediated anion flux in intact cells, in inside-out vesicles devoid of cytoskeletal and cytoplasmic proteins, and in inside-out vesicles whose band 3 protein has been partially proteolyzed, with little change in leak pathway. The inactivation showed a single exponential function of radiation dose from which the target size of the anion carrier was estimated to be 210,000, 220,000, and 98,000 daltons in intact cells, in the inside-out vesicles, and in the vesicles after a limited proteolysis, respectively. Irradiation also resulted in degradation of the band 3 of the inside-out vesicles, as detected on sodium dodecyl sulfate-gel electrophoresis, with a dose dependence characteristic of a target size of 220,000 daltons. It is suggested that the human erythrocyte anion carrier exists in situ as a dimer of band 3.