Brain metastases: An update on the multi-disciplinary approach of clinical management.

IMPORTANCE: Brain metastasis (BM) is the most common malignant intracranial neoplasm in adults with over 100,000 new cases annually in the United States and outnumbering primary brain tumors 10:1. OBSERVATIONS: The incidence of BM in adult cancer patients ranges from 10-40%, and is increasing with improved surveillance, effective systemic therapy, and an aging population. The overall prognosis of cancer patients is largely dependent on the presence or absence of brain metastasis, and therefore, a timely and accurate diagnosis is crucial for improving long-term outcomes, especially in the current era of significantly improved systemic therapy for many common cancers. BM should be suspected in any cancer patient who develops new neurological deficits or behavioral abnormalities. Gadolinium enhanced MRI is the preferred imaging technique and BM must be distinguished from other pathologies. Large, symptomatic lesion(s) in patients with good functional status are best treated with surgery and stereotactic radiosurgery (SRS). Due to neurocognitive side effects and improved overall survival of cancer patients, whole brain radiotherapy (WBRT) is reserved as salvage therapy for patients with multiple lesions or as palliation. Newer approaches including multi-lesion stereotactic surgery, targeted therapy, and immunotherapy are also being investigated to improve outcomes while preserving quality of life. CONCLUSION: With the significant advancements in the systemic treatment for cancer patients, addressing BM effectively is critical for overall survival. In addition to patient's performance status, therapeutic approach should be based on the type of primary tumor and associated molecular profile as well as the size, number, and location of metastatic lesion(s).

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer.

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

Imaging findings of primary hepatic angiosarcoma on gadoxetate disodium-enhanced liver MRI: comparison with hepatic haemangiomas of similar size.

AIM: To describe imaging characteristics of primary hepatic angiosarcoma on gadoxetate disodium-enhanced dynamic magnetic resonance imaging (MRI) and to determine features that differentiate angiosarcomas from similar-sized haemangiomas. MATERIALS AND METHODS: The study included 15 patients with hepatic angiosarcomas and 35 patients with size-matched hepatic haemangiomas who underwent gadoxetate disodium-enhanced liver MRI. The number, size, growth pattern, signal intensity (SI) characteristics, and SI changes on dynamic scans were evaluated and compared between the two entities. RESULTS: Overall, hepatic angiosarcomas significantly more often showed lesion multiplicity (86.7%), capsular retraction (40%), prominent intratumoural vessels (66.7%), vascular invasion (20%), heterogeneous SI on T2-weighted (100%) and hepatobiliary phase images (80%), and intralesional haemorrhage (60%, all p<0.05). On dynamic scans, angiosarcomas demonstrated enhancing foci of irregular or rim-like nodular/linear or bizarre (86.7%) shapes, with centrifugal or bizarre patterns of progressive enhancement (53.3%). Enhancement of angiosarcomas was less than that of the blood pool on visual grading, but the enhancement curves followed that of the aorta. Regardless of size, angiosarcomas showed heterogeneous T2 SI, intratumoural haemorrhage, and heterogeneity during the hepatobiliary phase, whereas these findings were more common in haemangiomas >6 cm in diameter. CONCLUSION: Gadoxetate disodium-enhanced dynamic liver MRI is capable of depicting vascular hallmarks of hepatic angiosarcomas. Heterogeneous SI on T2-weighted and hepatobiliary phase images, multiplicity, and an enhancement curve following that of the aorta are also distinctive features that differentiate angiosarcomas from haemangiomas.

Protective Role of Apelin Against Cyclosporine-Induced Renal Tubular Injury in Rats.

BACKGROUND: Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. METHODS: Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 µg/kg/day) for 7 days via subcutaneous injection. We performed serum and urinary assays of creatinine and neutrophil gelatinase-associated lipocalin (NGAL) to estimate renal injury and performed Western blotting for endothelial nitric oxide synthase and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) to document the underlying mechanism. RESULTS: The CsA-treated group showed increased urinary creatinine excretion, polyuria, and renal glycosuria without GFR reduction, suggesting adequate CsA-induced renal tubular injury. Urinary NGAL excretion also increased significantly in the CsA group. Conversely, apelin attenuated CsA-induced tubular injury and had no effect on urinary NGAL excretion. In histopathologic examination, the apelin-treated group had lower tubulo-interstitial injury scores compared with those in the CsA group. Regarding the effects of apelin, our results indicate that apelin provides protection against CsA-induced tubular injury by activating nitric oxide and/or the NFATc1 pathway. Notably, we also found that CsA inhibits renal glucose reabsorption by reducing Na+-K+ ATPase expression and that apelin reverses reduced renal glucose reabsorption by CsA in tubular cells. CONCLUSIONS: Our study demonstrates the renoprotective effect of apelin against CsA-induced renal tubular toxicity and provides novel insights into the effects of CsA and apelin on renal tubular cells.

Changing prevalence and treatment outcomes of patients with p16 human papillomavirus related oropharyngeal squamous cell carcinoma in New Zealand.

There has, to our knowledge, been no previous report of changes in the prevalence and outcomes of treatment of HPV-positive (+) oropharyngeal squamous cell carcinoma (SCC) in New Zealand. We identified all affected patients in the greater Wellington region between 1 January 1994 and 30 November 2014 from the New Zealand Cancer Registry. Their personal details, characteristics of their tumours, treatment, complications, and outcomes were collected retrospectively from their casenotes and the New Zealand Death Registry, followed by p16 immunohistochemical staining. Of the 161 patients included, 131 (81%) were men. p16 immunohistochemical staining was done routinely in 13 patients during investigations, and retrospectively for 135 patients. The proportion of p16+ oropharyngeal SCC increased from 24% during 1994-1999, to 76% during 2009-2014 (p<0.001). Oropharyngeal SCC among Europeans was more likely to be p16+ than in non-Europeans (67% compared with 44%, p=0.036). Patients with p16+ disease were younger (mean (SD) 56 (10) compared with 66 (9) years, p<0.01) with fewer coexisting conditions (mean (SD) Charlson Comorbidity Index: 2.45 (0.82) compared with 2.92 (1.16), p=0.01), and less likely to have smoked (57/81(70%) compared with 38/42 (91%) p=0.035), or misused alcohol (12/81 (15%) compared with 14/42 (31%), p=0.042), or both. They were also more likely to have poorly differentiated tumours (30/52 (58%) compared with 9/34 (26%), p=0.019) with nodal metastases (74/85 (87%) compared with 17/30 (57%), p=0.001). Overall 5-year all-cause survival was more favourable for patients with p16+ disease (65/86 (76%) compared with 15/49 (31%), p=0.000). Interestingly, all-cause age at death was younger in p16+ patients (62 (11.1) compared with 71 (11.2) years, p=0.001). The prevalence of p16+ oropharyngeal SCC had tripled in this population between 1994 and 2014, and affected patients have distinct characteristics and outcomes of treatment.

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.

Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by ß3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo ß3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and ß3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling.

Concurrent Post-Transplantation Diabetes Mellitus in Renal Allograft Recipients With Immunoglobulin A Nephropathy.

BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution. RESULTS: Sixteen patients (14.4%) had PTDM at the time of diagnosis of PTIgAN, which increased to 28 patients (25.2%) at the last follow-up (10.4 years after transplantation). Donor ages were younger in PTIgAN patients with concurrent PTDM. However, other clinical and demographic data were not significantly different between PTIgAN patients with and without PTDM. Histologically, Banff "mm" scores were higher and "M1" of the Oxford classification was more frequent in PTIgAN patients with concurrent PTDM than in patients without PTDM, but the difference did not reach statistical significance. Serum creatinine levels and proteinuria at the time of biopsy and overall graft survival did not vary according to the presence of PTDM both at biopsy and at the last follow-up. CONCLUSIONS: Concurrent PTDM does not significantly influence graft function or outcome for 10 years after transplantation in PTIgAN patients.

Deletion of Osr2 Partially Rescues Tooth Development in Runx2 Mutant Mice.

Tooth organogenesis depends on genetically programmed sequential and reciprocal inductive interactions between the dental epithelium and neural crest-derived mesenchyme. Previous studies showed that the Msx1 and Runx2 transcription factors are required for activation of odontogenic signals, including Bmp4 and Fgf3, in the early tooth mesenchyme to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 acts downstream of Msx1 to activate Fgf3 expression. Recent studies identified Osr2 as a repressor of tooth development and showed that inactivation of Osr2 rescued molar tooth morphogenesis in the Msx1(-/-) mutant mice as well as in mice with neural crest-specific inactivation of Bmp4. Here we show that Runx2 expression is expanded in the tooth bud mesenchyme in Osr2(-/-) mutant mouse embryos and is partially restored in the tooth mesenchyme in Msx1(-/-)Osr2(-/-) mutants in comparison with Msx1(-/-) and wild-type embryos. Whereas mandibular molar development arrested at the bud stage and maxillary molar development arrested at the bud-to-cap transition in Runx2(-/-) mutant mice, both mandibular and maxillary molar tooth germs progressed to the early bell stage, with rescued expression of Msx1 and Bmp4 in the dental papilla as well as expression of Bmp4, p21, and Shh in the primary enamel knot in the Osr2(-/-)Runx2(-/-) compound mutants. In contrast to the Msx1(-/-)Osr2(-/-) compound mutants, which exhibit nearly normal first molar morphogenesis, the Osr2(-/-)Runx2(-/-) compound mutant embryos failed to activate the expression of Fgf3 and Fgf10 in the dental papilla and exhibited significant deficit in cell proliferation in both the dental epithelium and mesenchyme in comparison with the control embryos. These data indicate that Runx2 synergizes with Msx1 to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 controls continued tooth growth and morphogenesis beyond the cap stage through activation of Fgf3 and Fgf10 expression in the dental papilla.

Immunohistochemical analysis of infiltrating inflammatory cells in the isolated v-lesion of allograft kidney.

The term "isolated v-lesion" was proposed at the 2009 Banff conference on allograft pathology. It is still debated whether the isolated v-lesion is a part of the antibody-mediated or T cell-mediated rejection and whether the isolated v-lesion has any prognostic significance of its own. To investigate the characteristics of the isolated v-lesion, we identified infiltrating inflammatory cells in renal allograft biopsy specimens with these lesions. We selected 11 allograft renal biopsy specimens which were compatible with the original definition of the isolated v-lesion (v1 or v2 with i ≤ 1 and t ≤ 1) and had enough paraffin-embedded tissue for immunohistochemistry. We performed immunohistochemistry for markers of T cells (CD3, CD4, and CD8), B cells (CD20), NK/T cells (CD56), and macrophages (CD68). The number of positive cells was counted in each compartment of the renal tissue including the arteries, peritubular capillaries, glomeruli, tubules, and interstitium. Arteries were infiltrated by CD3/CD8-positive T cells and CD68-positive macrophages. Three cases showed T cell-dominant infiltrates and four cases showed macrophage-dominant infiltrates. Glomeruli showed a similar inflammatory cell profile to that of arteries. Tubulitis was composed of CD3/CD8-positive T cells. The components of interstitial inflammation were more variable with the presence of CD20-positive B cells. In six cases, interstitial infiltrates were predominantly composed of CD3/CD8-positive T cells, and two of these cases showed almost exclusive infiltrates of T cells. However, four cases showed co-dominant infiltrates of T and B cells, and one case showed predominant B cell infiltrates. The isolated v-lesion has a heterogeneous pathogenesis, and B cell-predominant infiltrates in some cases suggest that this lesion could be related to an antibody-related process.

Estimated long-term dietary exposure to lead, cadmium, and mercury in young Korean children.

BACKGROUND: Controlling for day-to-day variation is a key issue in estimating long-term dietary exposure to heavy metals using 24-hour recall (24HR) data from a relatively small number of days. OBJECTIVES: This study was conducted to estimate long-term dietary exposure to lead, cadmium and mercury among Korean children using the Iowa State University (ISU) method and to assess the contributions of different food groups to heavy metal intake. METHODS: We analyzed 2 days of 24HR data from 457 children between 0 and 6 years of age in 2010. Using bootstrapped concentration data for 118 representative foods, 93.5% of total intake was included in the exposure estimates in this study. Using the 2-day exposure data, we estimated long-term exposure by controlling for within-individual variation using the ISU method. RESULTS: The long-term dietary exposure estimates (mean±standard deviation) for lead, cadmium, and mercury were 0.47±0.14, 0.38±0.20, and 0.22±0.08 µg/kg bw/day, respectively. For lead and cadmium, the percentages of children whose exposure was greater than the reference value were 35 and 42%, respectively. Fruits were an important source of lead exposure, and cereal and fish and shellfish made the greatest contributions to the total cadmium and mercury exposure. CONCLUSIONS: Our findings also suggest that the long-term exposure to lead and cadmium was somewhat greater than the reference values, whereas mercury exposure was well below than the reference value in this population. Further studies may be necessary to evaluate the food items contributing to heavy metal exposure, and continuous monitoring is needed to ensure the safety of food intake and dietary patterns among vulnerable groups in Korea.

Automated screening for tuberculosis by multiparametric analysis of data obtained during routine complete blood count.

INTRODUCTION: The main goal of this study was to develop a multiparametric cell population data (CPD) model that combines information from several morphologic parameters generated by DxH800, in addition to the traditional parameters regularly reported in the CBC-diff, and to test the performance of this model in screening the general population for primary tuberculosis (TB). METHODS: A total of 3741 study cases were divided into two groups, test and validation set at cut-off value of 6000 WBCs/µL. We developed multiparametric model for primary TB screening (TB hemeprint), selected CPD, and calculated parameters which could discriminate primary TB from other non-TB diseases and normal control in test set. We applied it to the validation set, which was a set of completely different samples, to test its reproducibility if applied to a routine laboratory test. RESULTS: After screening primary TB using TB hemeprint, sensitivity, specificity, PPV, and NPV were 85.4%, 89.6%, 31.1%, and 99.1%, respectively, in primary TB with lower than 6000 WBCs/µL of test set (test set-L). In primary TB with higher than 6000 WBCs/µL of test set (test set-H), those values were 83.1%, 85.6%, 29.7%, and 98.6%, respectively. There were only 0.4% (2/461) and 0.6% (2/326) of normal control samples included in test set-L and -H, respectively. Diagnostic efficiencies except sensitivity in each validation set were very comparable with those in each test set. CONCLUSION: Tuberculosis hemeprint may allow us to screen primary TB with acceptable sensitivity and specificity using combination of TB-specific CPD and calculated parameters.

Treatment of BK virus-associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single-center experience.

BACKGROUND: BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is a severe complication after hematopoietic stem cell transplantation (HSCT). Cidofovir (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but its use for BKV-HC in pediatric HSCT recipients has not yet been established as a standard therapy. PATIENT AND METHODS: We retrospectively investigated the efficacy and safety of CDV therapy for patients with BKV-HC at a single institution and analyzed the clinical management outcomes. RESULTS: From April 2009 to July 2011, 12 patients developed BKV-HC at a median of 37 days after transplant (range 15-59 days). The cumulative incidence was 9% and the median peak of the urine BKV load was 2.5 × 10(10) copies/mL (range 1.4 × 10(9) -1.2 × 10(11) copies/mL). Eleven patients received intravenous CDV (5 mg/kg/dose, with probenecid), whereas 1 patient received CDV (5 mg/kg/dose, without probenecid) intravesically. The median duration of therapy was 25 days (range 9-73 days), and a median of 2 doses was given (range 1-4). A reduction of ≥ 1 log in the BKV load was found in 11 patients, while 1 patient did not have any significant change in BKV load. Clinical improvement was observed in all cases, and no HC-related death was observed. CDV-related toxicity occurred in 1 patient (8%) and spontaneously resolved. CONCLUSIONS: CDV appears to be an effective and safe treatment for BKV-HC in pediatric HSCT recipients, but prospective trials are warranted to support its use.

Predicting portal hypertension as assessed by acoustic radiation force impulse: correlations with the Doppler ultrasound.

OBJECTIVE: The purpose of this study was to assess the value of acoustic radiation force impulse (ARFI) for evaluating portal hypertension by correlating the elasticity of liver cirrhosis, as measured by ARFI, with haemodynamic indices measured by Doppler ultrasound. METHODS: We evaluated the data of a total of 154 prospectively enrolled patients who underwent both duplex Doppler ultrasound and ARFI imaging. The duplex Doppler ultrasound indices, including the mean portal vein velocity, splenic index (SI) and splenoportal index (SPI) were evaluated to determine the statistical correlation with shear wave velocity (SWV) of ARFI. We also analysed the differences in the correlations between the SI, SPI and SWV of the group who had varices. The correlations were assessed with Spearman's rank correlation coefficients. RESULTS: There was an increase of SWV in parallel with the increase of the SI (ρ=0.409, p<0.01) and SPI (ρ=0.451, p<0.01). In the patient group who did not have varices (n=74), the Doppler indices were found to be more correlated with the SWV (SI: ρ=0.447, SPI: ρ=0.552, p<0.01). However, the group with varices showed no correlation between the SWV and the Doppler parameters. CONCLUSION: SWV of ARFI was well correlated statistically with Doppler parameters, but is of limited value in predicting portal hypertension directly owing to great variability of Doppler parameters. By evaluating the correlation between ARFI and Doppler ultrasound, we suggest that the SWV might be a non-invasive supplementary tool for predicting portal hypertension.

Synchronized ATP oscillations have a critical role in prechondrogenic condensation during chondrogenesis.

The skeletal elements of embryonic limb are prefigured by prechondrogenic condensation in which secreted molecules such as adhesion molecules and extracellular matrix have crucial roles. However, how the secreted molecules are controlled to organize the condensation remains unclear. In this study, we examined metabolic regulation of secretion in prechondrogenic condensation, using bioluminescent monitoring systems. We here report on ATP oscillations in the early step of chondrogenesis. The ATP oscillations depended on both glycolysis and mitochondrial respiration, and their synchronization among cells were achieved via gap junctions. In addition, the ATP oscillations were driven by Ca(2+) oscillations and led to oscillatory secretion in chondrogenesis. Blockade of the ATP oscillations prevented cellular condensation. Furthermore, the degree of cellular condensation increased with the frequency of ATP oscillations. We conclude that ATP oscillations have a critical role in prechondrogenic condensation by inducing oscillatory secretion.

Comparison of patient outcomes after implantation of Visian toric implantable collamer lens and iris-fixated toric phakic intraocular lens.

PURPOSE: We compared visual and refractive outcomes after implantation of Visian toric implantable collamer lenses (toric ICLs) and iris-fixated toric pIOLs (toric Artisans). PATIENTS AND METHODS: A comparative retrospective analysis was performed. Toric ICLs were implanted into 30 eyes of 18 patients, and toric Artisans into 31 eyes of 22 recipients. We measured the logarithms of the minimum angle of resolution of uncorrected visual acuity (logMAR UCVA), logMAR of best spectacle-corrected corrected VA (logMAR BSCVA), MR, SE, and astigmatism (by the power vector method) before surgery and 1, 3, and 6 months thereafter. Differences between patients receiving each type of lens were compared by using a mixed model of repeated measures. RESULTS: Visual improvements were evident after operation in both groups. By comparing the attempted to the achieved SE values, we were able to confirm that correction of refractive error was similar in both groups. However, the logMAR UCVA was significantly higher in the toric ICL group at all postoperative time points. Although manifest cylinder power and astigmatism (calculated by using the power vector method) gradually decreased in the toric ICL group, cylinder power 1 month postoperatively increased from -2.62 to -2.75 D; astigmatism was also increased at this time in the toric Artisan group. CONCLUSION: The two tested toric pIOLs were similar in terms of the ability to correct refractive error, as assessed 3 months postoperatively. However toric ICLs corrected astigmatism more rapidly and safely. Notably, the large difference in astigmatism level between the two groups 1 month postoperatively indicates that toric ICLs are more effective when used to correct astigmatism.

Omental infarction caused by laparoscopy-assisted gastrectomy for gastric cancer: CT findings.

AIM: To investigate the computed tomography (CT) imaging features of omental infarction in patients who underwent laparoscopy-assisted gastrectomy (LAG) for gastric cancer. MATERIALS AND METHODS: A retrospective study was performed on 390 patients who underwent LAG for gastric cancer. Two radiologists evaluated the CT images for the presence of omental infarction. The CT pattern was characterized at initial presentation and the evolutional changes were evaluated. The initial CT appearance of omental infarctions were categorized into the following four types: type 1 (ill-defined, heterogeneous, fat density lesion); type 2 (well-defined fat density lesion with rim enhancement); type 3 (well-defined heterogeneous lesion with fat component); and type 4 (well-defined heterogeneous lesion without a fat component). RESULTS: Of the 390 patients involved, nine patients (2.3%; six male and three female with a mean age of 57 years) were diagnosed with omental infarction. Infarctions averaged 4.1 cm (range 2-7.3 cm) in diameter. Among nine patients with omental infarction, two patients had type 1 lesions, two had type 2, two had type 3, and three type 4. All infarctions became smaller and better defined with evolution. In two patients who presented with type 1 lesions on initial CT, each lesion was progressed to type 2 and type 3 on follow-up CT. In two patients with type 3 lesions on initial CT, the lesions changed to type 4 on follow-up CT. CONCLUSION: An awareness of the various CT features and evolutional changes in omental infarction after LAG for gastric cancer can help ensure the correct diagnosis and to avoid misdiagnosis for omental implants.

Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation.

Tuberculosis (TB) is a rare infectious complication after hematopoietic stem cell transplantation (HSCT), but may be more significant in areas where the disease is endemic. Here, we present the clinical course of 2 children with acute lymphoblastic leukemia who were diagnosed with pulmonary TB after allogeneic HSCT. Both patients were treated for either probable or possible invasive fungal infection, as well as TB. One patient, diagnosed with TB 3 months after HSCT, showed remittent fever and symptoms that progressed to acute respiratory distress syndrome and death, despite 3 modifications to the anti-TB regimen. In contrast, another patient who was diagnosed with TB 8 months after transplantation, responded well to anti-TB medication and completed 1 year of treatment with resolution of lung lesions. Co-morbid opportunistic infections, profound host immunosuppression early after transplantation, and potential risk of multi-drug resistant-TB may act as major barriers to effective treatment of TB after HSCT despite appropriate anti-TB medication.