Background
Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual ...IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts.
Methods
Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19‐9 levels, and age).
Results
In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19‐9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788.
Conclusions
External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.
Antecedentes
La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales.
Métodos
Se recogieron datos clínico‐patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19‐9, y edad).
Resultados
En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19‐9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788.
Conclusión
La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.
A nomogram to predict individual intraductal papillary mucinous neoplasm (IPMN) malignancy risk was released, with good diagnostic performance based on a cohort of 2258 Korean or Japanese patients with IPMN. This study validated a nomogram to predict malignancy risk and invasiveness of IPMN, using Eastern and Western cohorts. External validation of the nomogram showed good performance in predicting malignancy and invasive cancer in both Eastern and Western patients with IPMN. The nomogram could be applicable globally to decide customized treatment options for patients with IPMN.
Useful for patients with IPMN
Background
Recently, aging has been shown to be associated with sarcopenic obesity (SO), of which decreased muscle mass and increased fat mass are features. Sarcopenia and obesity alone are known to ...be associated with abnormal lipid metabolism. However, it remains unclear whether SO has greater adverse effects on dyslipidemia than on sarcopenia or obesity alone.
Aim
We aimed to investigate the association between SO and dyslipidemia in elderly Koreans.
Subjects and methods
This study was based on data collected during the 2008–2010 Korea National Health and Nutrition Examination Survey. We included 1,466 men and 2,017 women aged 65 years and over. Sarcopenia was indicated in participants with height- or weight-adjusted appendicular skeletal muscle that was 1 standard deviation below the sex-specific mean for the young reference group, and obesity was defined as a body mass index ≥25 kg/m
2
. Dyslipidemia was defined according to the National Cholesterol Education Program-Adult Treatment Panel III.
Results
After adjusting for confounding factors, the SO group had a higher risk for dyslipidemia odds ratio (OR) 2.82 (95 % confidence interval 1.76–4.51) than the obese group 2.12 (1.11–4.07) and sarcopenic group 1.46 (1.01–2.11) (
p
< 0.001) only in men. Furthermore, the SO group in men had the highest OR for hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, hyper-low-density lipoprotein cholesterolemia, and a high ratio of triglyceride to high-density lipoprotein cholesterol even after further adjustments.
Conclusions
In Korean elderly men, SO was associated with an increased risk for dyslipidemia compared with sarcopenia or obesity alone.
Summary
Patients with pyogenic vertebral osteomyelitis (PVO) are at greater risk of bone loss. However, treatment guidelines for bone loss have been lacking. Early bisphosphonate treatment within ...6 weeks after PVO diagnosis was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment.
Introduction
Due to absence of concern and proper guidelines, management of bone loss or osteoporosis in PVO is often neglected or delayed. A retrospective cohort study was planned to investigate differences in bone mineral density (BMD) in PVO patients with osteoporosis according to the timing of osteoporosis treatment.
Methods
The PVO cohort consisted of 192 patients with osteoporosis who visited our institution between January 2003 and March 2015 and received bisphosphonate treatment for osteoporosis. According to the interval between PVO diagnosis and initiation of bisphosphonate, the patients were divided into three groups: group A (within 6 weeks after PVO diagnosis), group B (between 6 weeks and 3 months after diagnosis), and group C (more than 3 months after PVO diagnosis).
Results
The percent increase in total femoral BMD in group A was significantly larger than that in group B at 2-year follow-up (
p
= 0.036). Similarly, the percent increase in trochanteric (
p
= 0.008) and total femoral (
p
= 0009) BMD in group A was significantly larger than that in group C at 2-year follow-up. Even after multivariate adjustment, total femoral BMD changes were significantly associated with the treatment group. Group B (odds ratio = 2.824,
p
= 0.013) and group C (odds ratio = 3.591,
p
= 0.001) were more significantly associated with total femoral BMD decreases at 2-year follow-up compared with group A.
Conclusions
Early bisphosphonate treatment within 6 weeks after PVO diagnosis (group A) was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment (groups B and C).
InAs quantum dashes (Qdash) engineered to emit near 2 μm are envisioned to be promising quantum emitters for next-generation technologies in sensing and communications. In this study, we explore the ...effect of punctuated growth (PG) on the structure and optical properties of InP-based InAs Qdashes emitting near the 2-μm wavelength. Morphological analysis revealed that PG led to an improvement in in-plane size uniformity and increases in average height and height distribution. A 2 × boost in photoluminescence intensity was observed, which we attribute to improved lateral dimensions and structural stabilization. PG encouraged formation of taller Qdashes while photoluminescence measurements revealed a blue-shift in the peak wavelength. We proposed that the blue-shift originates from the thinner quantum well cap and decreased distance between the Qdash and InAlGaAs barrier. This study on the punctuated growth of large InAs Qdashes is a step toward realizing bright, tunable, and broadband sources for 2-μm communications, spectroscopy, and sensing.
The autocrine and paracrine activation of the renin–angiotensin system (RAS) within cells of the kidney plays a role in the overall pathophysiology of the renal disease due to diabetes. In this ...study, we focus on components of the RAS in the podocyte as these cells are important in the pathogenesis of glomerulosclerosis and proteinuria. Immortalized mouse podocytes were exposed to media containing normal glucose (NG) or high glucose (HG) for in vitro studies. In vivo studies utilized kidney tissue obtained from rats treated for 3 months with streptozotocin to induce diabetes. Angiotensinogen (AGT) and the angiotensin II (AII) type 1 receptor mRNA and protein were significantly increased in the podocytes cultured under the high glucose conditions. Both angiotensins I and II levels were significantly higher in cell lysates and the conditioned media of cells grown in high glucose. There were no differences in renin activity, angiotensin-converting enzyme level, or AII type 2 receptor level. Glomerular AGT and AII type 1 receptor assessed by means of immunohistochemistry were increased in diabetic rats compared with the control rats. Other measured components of the RAS within the glomeruli were not different. We suggest that increased AGT, an attendant increase in AII and increased AII type 1 receptor in podocytes experiencing diabetic conditions play an important role in the pathogenesis of diabetic nephropathy.
This case report follows a 10-year-old castrated male Miniature Schnauzer dog presented with a history of incomplete surgical resection of an oral malignant melanoma (amelanotic type) on the right ...mandible. Melanoma vaccine therapy was administered due to incomplete surgical resection, however, new masses were detected on the contralateral mandible and suspected pulmonary metastasis occurred at 2 weeks and 7 months, respectively, following the first melanoma vaccination. At the time of detecting the pulmonary metastasis, targeted chemotherapy was initiated with the owner's consent using imatinib (10 mg/kg/day, p.o.), a tyrosine kinase inhibitor (TKI). The patient did not show any significant adverse events related to both anticancer treatments. Three months following the first dose of imatinib, the absence of the suspected pulmonary metastatic nodules on radiography indicated complete remission. In conclusion, this report describes the achievement of clinical remission of suspected pulmonary metastatic oral malignant melanoma and an extension of survival time in a dog given a combination treatment of immunotherapy and tyrosine kinase inhibitor.
Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to ...be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.
We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.
Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.
Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.
Summary
Background Allergic contact dermatitis (ACD) is a delayed type of T cell‐mediated cutaneous inflammatory response, in which multiple cell types are involved. Dasatinib and LCB 03‐0110 are ...small molecule multityrosine kinase inhibitors, and they share remarkably similar target kinases such as the c‐Src family, Btk and Syk, which play key roles in the cell signalling of T cells and other inflammatory cells.
Objectives To test the anti‐ACD activity of dasatinib and LCB 03‐0110 and compare it with that of tacrolimus (FK506) and triamcinolone acetonide (a glucocorticoid), which are widely used for topical treatment of ACD, and to examine the two compounds for their capacity to induce skin atrophy, a side‐effect.
Methods ACD was induced on the ears of mice by repeated topical application of oxazolone. Each test compound was then topically applied on the ear. Ear swelling, epidermal thickness and levels of inflammatory cytokines were measured. The skin atrophy induced by the compounds was tested during prolonged application on the dorsal skin of hairless mice, followed by haematoxylin and eosin staining.
Results Dasatinib and LCB 03‐0110 suppressed the symptoms of ACD such as ear swelling, increase in epidermal thickness and synthesis of inflammatory cytokines (i.e. interleukin‐1β, tumour necrosis factor‐α and interferon‐γ) in a dose‐dependent manner. The two compounds showed near‐equal potency to tacrolimus; however, their potency was lower than that of triamcinolone acetonide. Prolonged treatment with the two compounds did not induce any skin atrophy, whereas use of steroidal agents induced severe atrophy.
Conclusions Dasatinib and LCB 03‐0110 could be used as effective agents for the treatment of ACD without the adverse side‐effect of skin atrophy.
The epigenetic information present in mammalian gametes and whether it is transmitted to the progeny are relatively unknown. We find that many promoters in mouse sperm are occupied by RNA polymerase ...II (Pol II) and Mediator. The same promoters are accessible in GV and MII oocytes and preimplantation embryos. Sperm distal ATAC-seq sites containing motifs for various transcription factors are conserved in monkeys and humans. ChIP-seq analyses confirm that Foxa1, ERα, and AR occupy distal enhancers in sperm. Accessible sperm enhancers containing H3.3 and H2A.Z are also accessible in oocytes and preimplantation embryos. Furthermore, their interactions with promoters in the gametes persist during early development. Sperm- or oocyte-specific interactions mediated by CTCF and cohesin are only present in the paternal or maternal chromosomes, respectively, in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. Thus, mammalian gametes contain complex patterns of 3D interactions that can be transmitted to the zygote after fertilization.
Display omitted
•ATAC-seq accessibility at sperm and oocyte promoters is maintained in the embryo•Sperm enhancers containing transcription factors are conserved in mammals•Accessible sperm enhancers are also open in oocytes and preimplantation embryos•Interactions mediated by FoxA1 and CTCF and cohesin persist from gametes to embryos
Jung et al. show that sperm and oocyte promoters and enhancers contain ATAC-seq accessible sites suggesting the presence of Pol II, Foxa1, ERα, and AR. Accessibility in gametes persists in early embryos. Interactions mediated by CTCF in gametes are inherited from each parent and become the same in 8-cell embryos.
Rectal carcinoid tumors are often found incidentally during screening colonoscopy and can be resected using various endoscopic techniques. This study aimed to compare the safety and efficacy of ...endoscopic submucosal dissection (ESD) with endoscopic mucosal resection (EMR) for rectal carcinoid tumors.
Between January 2003 and June 2009, 74 patients (74 lesions) underwent either EMR (n = 28) or ESD (n = 46) for rectal carcinoid tumors. The rate of endoscopic complete resection, pathological complete resection, procedure complications, and tumor recurrence were analyzed retrospectively.
The endoscopic complete resection rate was significantly higher in the ESD group (46 lesions, 100 %) compared with the EMR group (25 lesions, 89.3 %) ( P = 0.049). The pathological complete resection rate was higher in the ESD group (38 lesions, 82.6 %) compared with the EMR group (18 lesions, 64.3 %); however, this difference was borderline significant ( P = 0.067). Overall complication rate was not significantly different between the EMR group (3.6 %) and the ESD group (6.3 %). There was one case of remnant lesion in the EMR group, which was managed by ESD, and no recurrence has been detected in either the EMR or ESD groups.
This study suggests that ESD might be a feasible treatment technique for small rectal carcinoid tumors. It showed superior efficacy and comparable safety to EMR.
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