The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms.

BACKGROUND: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. METHODS: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. RESULTS: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12-0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12-5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02-0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06-0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79-0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70-0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08-0.99). CONCLUSION: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms.

BACKGROUND: Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). METHODS: A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. RESULTS: Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p <  0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01-1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78-17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19-9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19-9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). CONCLUSIONS: Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. MATERIALS AND METHODS: 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients' demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. RESULTS: The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58-163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16-268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs. CONCLUSIONS: HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.

Role of Aspergillus fumigatus-Specific IgE in the Diagnosis of Allergic Bronchopulmonary Aspergillosis.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) has been regarded as a rare disease in China due to the lack of quantitative detection of Aspergillus fumigatus-specific IgE (sIgE). We compared the diagnostic rate of ABPA among asthma patients with or without A. fumigatus-sIgE screening tests to evaluate the benefit of the tests in diagnosing ABPA. METHODS: We reviewed the detection rate of A. fumigatus-sIgE and the diagnostic rate of ABPA in 1842 asthma patients in the First Affiliated Hospital of Zhejiang University from 2014 to 2016. Additionally, we collected 144 asthma cases from November 2016 to March 2017 to detect the total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract, the ABPA diagnostic rate of these patients was then compared with the total cohort. Total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract were also tested in 30 patients identified with Aspergillus-positive sputum culture to analyze the incidence of ABPA. RESULTS: Among the 1,842 asthma cases, 566 were inspected for total IgE; 308 (55.40%) were total IgE-positive and 58 (10.43%) had total IgE > 1,000 IU/mL. In contrast, only 126 cases were tested for A. fumigatus-sIgE (6.84%), and 28 had A. fumigatus-sIgE > 0.35 kUA/L (22.22%). Eleven patients were finally diagnosed with ABPA. Of 1,842 asthma patients, only 0.6% were diagnosed with ABPA if the A. fumigatus-sIgE was not detected at first. Moreover, among the 144 asthma cases that were selected for total IgE, A. fumigatus-sIgE, and sIgE against mixed mold extract screening tests, 12 had total IgE > 1,000 IU/mL (8.33%), 11 had A. fumigatus-sIgE > 0.35 kUA/L (7.64%), and 14 had sIgE against mixed mold extract > 0.35 (9.72%); 7 of these patients were confirmed as having ABPA according to the ISHAM guidelines (4.86%) but only 2 without A. fumigatus-sIgE screening test were diagnosed with ABPA (1.39%) (p = 0.000). Of the 30 Aspergillus-positive sputum culture cases, 4 had A. fumigatus-sIgE > 0.35 kUA/L (13.33%), but none was diagnosed with ABPA. CONCLUSIONS: Routine A. fumigatus-sIgE screening for asthma patients can significantly improve the diagnostic rate of ABPA.

Differentiation of intrapancreatic accessory spleen from small hypervascular neuroendocrine tumor of the pancreas: textural analysis on contrast-enhanced computed tomography.

BACKGROUND: Intrapancreatic accessory spleens (IPASs) are usually misdiagnosed as pancreatic neuroendocrine tumors (PNETs). Texture analysis is valuable in tumor detection, diagnosis, and staging. PURPOSE: To identify the potential of texture features in differentiating IPASs from small hypervascular PNETs. MATERIAL AND METHODS: Twenty-one patients with PNETs and 13 individuals with IPASs who underwent pretreatment dynamic contrast-enhanced computed tomography (CT) were retrospectively analyzed. The routine imaging features-such as location, size, margin, cystic or solid appearance, enhancement degree and pattern, and lymph node enlargement-were recorded. Texture features, such as entropy, skewness, kurtosis, and uniformity, on contrast-enhanced images were analyzed. Receiver operating characteristic (ROC) analysis was performed to differentiate IPASs from PNETs. RESULTS: No significant differences were observed in margin, enhancement degree (arterial and portal phase), lymph node enlargement, or size between PNETs and IPASs (all P > 0.05). However, IPASs usually showed heterogeneous enhancement at the arterial phase and the same degree of enhancement as the spleen at the portal phase, both of which were greater than those of PNETs (69% vs. 35%, P = 0.06; 100% vs. 29%, P = 0.04). Entropy and uniformity were significantly different between IPASs and PNETs at moderate (1.5) and high sigma values (2.5) (both P < 0.01). ROC analysis showed that uniformity at moderate and high sigma had the highest area under the curve (0.82 and 0.89) with better sensitivity (85.0-95.0%) and acceptable specificity (75.0-83.3%) for differentiating IPASs from PNETs. CONCLUSIONS: Texture parameters have potential in differentiating IPASs from PNETs.

[Influence of As2O3-lipiodol emulsion via transarterial embolization on a VX2 liver tumor model in rabbits].

OBJECTIVE: To investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model. METHODS: VX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis. RESULTS: The growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05]. CONCLUSION: As2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.

[Diffusion weighted imaging combined with dynamic contrast enhanced magnetic resonance imaging in monitoring therapeutic efficacy for hepatocellular carcinoma after transcatheter arterial chemoembolization].

OBJECTIVE: To evaluate the diagnostic value of diffusion weighted imaging (DWI) combined with dynamic contrast-enhanced (DCE) MRI in monitoring the efficacy for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: MRI and CT scan were performed 4-6 weeks after TACE in 31 patients.With digital signature algorithm (DSA) examination as the reference standard, the value in detection of the residue and recurrence of HCC was compared between MRI and CT results. RESULTS: Seventy-three lesions were detected in 31 patients. Fourteen lesions confirmed by DSA had no tumor staining, and 59 lesions had tumor staining. Diagnostic sensitivity and specificity of DCE-CT were 78.0% and 85.7%, respectively; while those of DWI combined with DCE-MRI were 100% and 92.9% (P<0.001). CONCLUSION: DWI combined with DCE-MRI is more effective than DCE-CT in detecting the residue and recurrence of HCC after TACE.

The impact of bacillus pumilus TS2 isolated from yaks on growth performance, gut microbial community, antioxidant activity, and cytokines related to immunity and inflammation in broilers.

Intensive poultry farming faces challenges like gut inflammation in the absence of antibiotics, resulting in reduced productivity, heightened susceptibility to enteric diseases, and other complications. Alternative strategies are needed to manage inflammation and maintain sustainable poultry production. Yaks living in high-altitude hypoxic environments have specialized gut microbes. However, yak probiotics remain largely uncharacterized. We previously isolated a strain of Bacillus pumilus (named TS2) from yaks and demonstrated its potential as a probiotic in vitro. Therefore, in this study, we evaluated the in vivo growth-promoting, antioxidant, immune, and anti-inflammatory effects of Bacillus pumilus isolated from yaks in broilers. We demonstrated the safety of TS2 isolated from yaks in broilers. Furthermore, we found that TS2 increased the average daily weight gain (ADWG) and reduced the feed conversion ratio (FCR). Supplementation with TS2 also improved the mucosal morphology, the ratio of villi to crypt cells, and enzyme activity. High-throughput sequencing showed that the abundance of Lactobacillus was higher in the TS2 treated broilers. Importantly, the serum level of malondialdehyde (MDA) was reduced and the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were increased in the low-dose TS2 group, while the inflammatory factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were downregulated compared with the control group. We demonstrated that TS2 supplementation can increase the overall growth performance and ameliorate the blood parameters related to inflammation and immunity in broilers.

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

PURPOSE: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). METHODS: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. RESULTS: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). CONCLUSIONS: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Computed tomography texture-based models for predicting KIT exon 11 mutation of gastrointestinal stromal tumors.

Background: KIT exon 11 mutation in gastrointestinal stromal tumors (GISTs) is associated with treatment strategies. However, few studies have shown the role of imaging-based texture analysis in KIT exon 11 mutation in GISTs. In this study, we aimed to show the association between computed tomography (CT)-based texture features and KIT exon 11 mutation. Methods: Ninety-five GISTs confirmed by surgery and identified with mutational genotype of KIT were included in this study. By amplifying the samples using over-sampling technique, a total of 183 region of interest (ROI) segments were extracted from 63 patients as training cohort. The 63 new ROI segments were extracted from the 63 patients as internal validation cohort. Thirty-two patients who underwent KIT exon 11 mutation test during 2021-2023 was selected as external validation cohort. The textural parameters were evaluated both in training cohort and validation cohort. Least absolute shrinkage and selection operator (LASSO) algorithms and logistic regression analysis were used to select the discriminant features. Results: Three of textural features were obtained using LASSO analysis. Logistic regression analysis showed that patients' age, tumor location and radiomics features were significantly associated with KIT exon 11 mutation (p < 0.05). A nomogram was developed based on the associated factors. The area under the curve (AUC) of clinical features, radiomics features and their combination in training cohort was 0.687 (95 % CI: 0.604-0.771), 0.829 (95 % CI: 0.768-0.890) and 0.874 (95 % CI: 0.822-0.926), respectively. The AUC of radiomics features in internal validation cohort and external cohort was 0.880 (95 % CI: 0.796-0.964) and 0.827 (95%CI: 0.667-0.987), respectively. Conclusion: The CT texture-based model can be used to predict KIT exon 11 mutation in GISTs.

The association between pain and WHO grade of pancreatic neuroendocrine neoplasms: A multicenter study.

BACKGROUND: Abdominal or back pain is a common symptom in pancreatic diseases. However, the role of pain in pancreatic neuroendocrine neoplasm (PNENs) has not been clarified. OBJECTIVE: In this study, we aimed to show the association between the pain and the grade of PNENs. METHODS: A total of 186 patients with pathologically confirmed PNENs were included in this study. Clinical features and histological or radiological findings (size, location, and vascular invasion and local organs invasion and distal metastasis) were collected. Logistic regression analyses were used to show the association between pain and grade of PNENs. Nomogram was developed based on associated factors to predict the higher grade of PNENs. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of size and nomogram model. RESULTS: The prevalence of pain in the cohort was 30.6% (n= 57). The vascular invasion and G3 PNENs were more common in the pain group (P= 0.02, P< 0.01). The tumor size was larger and incident of higher grade of PNENs was higher in the pain group than the non-pain group (p< 0.01). Age, pain and size were independent risk factors for G2/G3 or G3 PNENs. The odds ratio was 3.03 (95% CI: 1.67-7.91) and 3.32 (95% CI: 1.42-7.79) for pain, respectively. The nomogram model was developed to predict the G2/G3 or G3 PNENs. The area under the curve (AUC) of the nomogram model was 0.84 (95% CI, 0.77-0.91) in predicting the G2/G3 PNENs, and was 0.84 (95% CI, 0.78-0.91) in predicting the G3 PNENs. CONCLUSION: Abdominal or back pain is associated with the grade of PNENs. The nomograms based on clinical features may be a powerful numerical tool for predicting the grade of PNENs.

Bone Loss in Patients with Pancreatic Neuroendocrine Tumors.

Background: Pancreatic diseases may affect nutritional status, which is one of the important associated factors of bone health. High prevalence of osteoporosis or osteopenia has been reported in patients with pancreatitis. The bone loss in pancreatic neuroendocrine tumors (PNETs) has not been reported. In this study, we showed the prevalence of bone loss and possible associated factors in PNET patients. Methods: A total of 91 PNET patients were included. Bone status was evaluated based on computed tomography (CT) attenuation (Housfield units, HU): >160 HU, normal bone mineral density; osteopenia, 135 HU ≤ CT value ≤ 160 HU; osteoporosis, <135 HU. Associated factors for bone loss were identified by logistic regression analyses. Results: The average age was 55.76 years old in PNET patients. The prevalence of osteoporosis and low bone mass was 37.4% and 60.4%, respectively. Higher prevalence of osteoporosis was observed in patients older than 50 years (64.0%). Multivariate logistic analysis showed that age was an associated factor for low bone mass (odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04−1.22) and osteoporosis (OR = 1.14, 95% CI: 1.03−1.20). Diabetes was also associated with bone loss in PNET patients after adjusting with confounders (OR = 13.56, 95% CI: 1.02−132.4). Conclusions: Our data show that bone loss is common in patients with PNETs. Age and diabetes are associated with bone loss in PNET patients.

Microscopic Invasion of Nerve Is Associated With Aggressive Behaviors in Pancreatic Neuroendocrine Tumors.

OBJECTIVES: The role of neural invasion has been reported in cancers. Few studies also showed that neural invasion was related to survival rate in patients with pancreatic neuroendocrine tumor (PNET). The aim of this study is to explore the association between neural invasion and aggressive behaviors in PNET. METHODS: After excluding those patients with biopsy and with missing histological data, a total 197 patients with PNET who underwent surgery were retrospectively analyzed. The demographic data and histological data were obtained. Aggressive behavior was defined based on extra-pancreatic extension including vascular invasion, organ invasion and lymph node metastases. Logistic regression analyses were used to identify risk factor for aggressive behavior. Receiver operating characteristic (ROC) curves were performed to show the performance of nomograms in evaluating aggressive behavior of PNET. RESULTS: The prevalence of neural invasion in the cohort was 10.1% (n = 20). The prevalence of lymph node metastasis, organ invasion, and vascular invasion in PNET patients with neural invasion was higher than those in patients without neural invasion (p < 0.05). Neural invasion was more common in grade 3 (G3) tumors than G1/G2 (p < 0.01). Tumor size, tumor grade, and neural invasion were independent associated factors of aggressive behavior (p < 0.05) after adjusting for possible cofounders in total tumors and G1/G2 tumors. Two nomograms were developed to predict the aggressive behavior. The area under the ROC curve was 0.84 (95% confidence interval (CI): 0.77-0.90) for total population and was 0.84 (95% CI: 0.78-0.89) for patients with G1/G2 PNET respectively. CONCLUSIONS: Neural invasion is associated with aggressive behavior in PNET. Nomograms based on tumor size, grade and neural invasion show acceptable performances in predicting aggressive behavior in PNET.

Diabetes in Patients With Pancreatic Neuroendocrine Neoplasms.

Objective: Diabetes mellitus (DM) is probably a risk factor for pancreatic neuroendocrine neoplasms (PNENs). However, the prevalence of DM in PNEN patients remains inconclusive. In the present study we observed the prevalence of DM and possible risk factors in PNEN patients. Methods: After excluding those with insulinoma, a total of 197 patients with PNENs were included. The demographic data, pathological characteristics, and data of blood biochemical tests were recorded. DM was considered if there was evidence of a fasting plasma glucose level of ≥7.0 mmol/L or a 2-h plasma glucose level of ≥11.1 mmol/L, or a history of DM at the time of PNEN diagnosis. Impaired fasting glucose was considered if fasting plasma glucose level was between 6.1 and 7.0 mmol/L. Results: The prevalence of DM, new-onset DM, and impaired fasting glucose were 17.26, 9.14, and 7.1%, respectively. The prevalence of DM was 26.0% in patients ≥60 years old (19/73) and 12.1% in patients <60 years old. Multivariable logistic regression analysis demonstrated that age, tumor size, and nerve invasion were independent risk factors for DM and impaired fasting glucose + DM (p < 0.05). Age, organs and nerve invasion were independent risk factors for impaired fasting glucose. Low high-density lipoprotein (HDL) was also a risk factor for incident of DM (OR = 0.15, 95%CI: 0.03-0.66). G2/G3 was an independent risk factor for DM in women. Conclusion: Our data shows that the prevalence of DM is 17.26% in patients with PNENs and is 26.0% in patients ≥60 years of age after excluding insulinoma. Age, nerve invasion, tumor size, and HDL are risk factors for DM in PNEN patients.

Treatment for Liver Tumor Using Combined Transarterial Embolization and Interaarterial Transfecting HIF-1α shRNA in a Rabbit VX2 Model.

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) has been selected as therapeutic gene in gene therapy. The aim of this study was to explore the treatment effect of combined transarterial embolization using microsphere treatment (MD) and intraarterial transfecting HIF-1α shRNA on hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Rabbit skin fibroblast was transfected with HIF-1α shRNA to evaluate the knocking down efficiency. Sixteen rabbit VX2 liver tumor models were randomly divided into four groups: the control group without any treatment, the MD group, the shRNA group (HIF-1α shRNA transfection by transcatheter intraarterial infusion), and the shRNA+MD group. The necrotic score, mitotic count and expression of HIF-1α, vascular endothelial growth factor (VEGF), CD34 and periodic acid-Schiff (PAS) stain were evaluated at the 14th and 28th day after treatment. The expression of HIF-1α and VEGF of VX2 tumors was also evaluated by real-time polymerase chain reaction on the 28th day. RESULTS: The expression of HIF-1α-mRNA was lower in HIF-1α shRNA group than the control (p < 0.01). The tumor size was smaller in the shRNA + MD group than the shRNA group and the MD group (p < 0.05) on the 28th day. The growth rate of tumors in the shRNA + MD group was also lower than in other groups. The gene and protein expressions of both HIF-1α and VEGF in the shRNA + MD group were lower than the MD group, shRNA group and control group on the 28th day (p < 0.05). The necrotic score was higher in the shRNA + MD group than the MD group and control group (p < 0.05). The mitotic count and PAS-positive cells in shRNA + MD group were lower and CD34 was higher than the other three groups (p < 0.05). CONCLUSION: Compared to therapy with MD or HIF-1α shRNA with transcatheter intraarterial transfection alone, the combined treatment has a better effect on HCC.

CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms.

PURPOSE: CD56 is a neural cell adhesion molecule that plays a role in the cohesiveness of neuroendocrine cells. The aim of this study was to explore the biological values of CD56 expression in pancreatic neuroendocrine neoplasms (PNENs) and its role in predicting PNENs grades. PATIENTS AND METHODS: A total of 138 patients with histological-proven PNENs was included (66 G1, 46 G2 and 26 G3). The clinicopathological characteristics, including mitosis count, ki67 index, chromogranin A (CgA), synaptophysin (Syn) and CD56 expression, were evaluated. We assessed the diagnostic performance of markers in predicting PNEN G3 and the association between CD56 expression and risk of G3 or organs invasion. RESULTS: Lack of CD56 immunoreaction (CD56-) was more common in PNEN G3 than G1/G2 (31% vs 0-2%, p < 0.01). The sizes of CD56- tumors were larger than CD56 positive tumors in PNEN G3 (p < 0.01). The odds ratio (OR) of CD56- expression was 13.6 [95% confidence interval (CI): 2.1-88.1] in predicting PNEN G3. The OR of CD56- expression was 6.5 (95% CI: 1.1-38.6) and 31.9 (95% CI: 1.09-938.3) in predicting organs invasion and neuroendocrine carcinoma in PNEN G3, respectively. Tumor size (area under the curve [AUC] = 0.77 and size+CD56- expression [AUC = 0.84]) had acceptable performance in predicating PNEN G3. CONCLUSION: Lack of CD56 immunoreaction may be a predictor and biological behavior marker for PNEN G3.

Textural analysis on contrast-enhanced CT in pancreatic neuroendocrine neoplasms: association with WHO grade.

PURPOSE: Grades of pancreatic neuroendocrine neoplasms (PNENs) are associated with the choice of treatment strategies. Texture analysis has been used in tumor diagnosis and staging evaluation. In this study, we aim to evaluate the potential ability of texture parameters in differentiation of PNENs grades. MATERIALS AND METHODS: 37 patients with histologically proven PNENs and underwent pretreatment dynamic contrast-enhanced computed tomography examinations were retrospectively analyzed. Imaging features and texture features at contrast-enhanced images were evaluated. Receiver operating characteristic curves were used to determine the cut-off values and the sensitivity and specificity of prediction. RESULTS: There were significant differences in tumor margin, pancreatic duct dilatation, lymph nodes invasion, size, portal enhancement ratio (PER), arterial enhancement ratio (AER), mean grey-level intensity, kurtosis, entropy, and uniformity among G1, G2, and pancreatic neuroendocrine carcinoma (PNEC) G3 (p < 0.01). Similar results were found between pancreatic neuroendocrine tumors (PNETs) G1/G2 and PNEC G3. AER and PER showed the best sensitivity (0.86-0.94) and specificity (0.92-1.0) for differentiating PNEC G3 from PNETs G1/G2. Mean grey-level intensity, entropy, and uniformity also showed acceptable sensitivity (0.73-0.91) and specificity (0.85-1.0). Mean grey-level intensity was also showed acceptable sensitivity (91% to 100%) and specificity (82% to 91%) in differentiating PNET G1 from PNET G2. CONCLUSIONS: Our data indicated that texture parameters have potential in grading PNENs, in particular in differentiating PNEC G3 from PNETs G1/G2.

A nomogram based on bi-regional radiomics features from multimodal magnetic resonance imaging for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

BACKGROUND: We aimed to develop and validate a nomogram combining bi-regional radiomics features from multimodal magnetic resonance imaging (MRI) and clinicoradiological characteristics to preoperatively predict microvascular invasion (MVI) of hepatocellular carcinoma (HCC). METHODS: A total of 267 HCC patients were divided into training (n=194) and validation (n=73) cohorts according to MRI data. Bi-regional features were extracted from whole tumors and peritumoral regions in multimodal MRI. The minimum redundancy maximum relevance (mRMR) algorithm was applied to select features and build signatures. The predictive performance of the optimal radiomics signature was further evaluated within subgroups defined by tumor size and alpha fetoprotein (AFP) level. Then, a radiomics nomogram including the optimal radiomics signature, radiographic descriptors, and clinical variables was developed using multivariable regression. The nomogram performance was evaluated based on its discrimination, calibration, and clinical utility. RESULTS: The fusion radiomics signature derived from triphasic dynamic contrast-enhanced (DCE) MR images can effectively classify MVI and non-MVI HCC patients, with an AUC of 0.784 (95% CI: 0.719-0.840) in the training cohort and 0.820 (95% CI: 0.713-0.900) in the validation cohort. The fusion radiomics signature also performed well in the subgroups defined by the two risk factors, respectively. The nomogram, consisting of the fusion radiomics signature, arterial peritumoral enhancement, and AFP level, outperformed the clinicoradiological prediction model in the validation cohort (AUCs: 0.858 vs. 0.729; P=0.022), fitting well in the calibration curves (P>0.05). Decision curves confirmed the clinical utility of the nomogram. CONCLUSIONS: The radiomics nomogram can serve as a visual predictive tool for MVI in HCCs, and thus assist clinicians in selecting optimal treatment strategies to improve clinical outcomes.

Pancreatic neuroendocrine tumor: prediction of the tumor grade using magnetic resonance imaging findings and texture analysis with 3-T magnetic resonance.

PURPOSE: The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) findings and texture parameters for prediction of the histopathologic grade of pancreatic neuroendocrine tumors (PNETs) with 3-T magnetic resonance. PATIENTS AND METHODS: PNETs are classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity. A total of 77 patients with pathologically confirmed PNETs met the inclusion criteria. Texture analysis (TA) was applied to T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) maps. Patient demographics, MRI findings, and texture parameters were compared among three different histopathologic subtypes by using Fisher's exact tests or Kruskal-Wallis test. Then, logistic regression analysis was adopted to predict tumor grades. ROC curves and AUCs were calculated to assess the diagnostic performance of MRI findings and texture parameters in prediction of tumor grades. RESULTS: There were 31 G1, 29 G2, and 17 G3 patients. Compared with G1, G2/G3 tumors showed higher frequencies of an ill-defined margin, a predominantly solid tumor type, local invasion or metastases, hypo-enhancement at the arterial phase, and restriction diffusion. Four T2-based (inverse difference moment, energy, correlation, and differenceEntropy) and five DWI-based (correlation, contrast, inverse difference moment, maxintensity, and entropy) TA parameters exhibited statistical significance among PNETs (P<0.001). The AUCs of six predicting models on T2WI and DWI ranged from 0.703-0.989. CONCLUSION: Our data indicate that MRI findings, including tumor margin, texture, local invasion or metastases, tumor enhancement, and diffusion restriction, as well as texture parameters can aid the prediction of PNETs grading.

The differentiation of pancreatic neuroendocrine carcinoma from pancreatic ductal adenocarcinoma: the values of CT imaging features and texture analysis.

BACKGROUND: Imaging findings for pancreatic neuroendocrine carcinoma (PNEC) and pancreatic ductal adenocarcinoma (PDAC) often overlap. The aim of this study was to demonstrate the value of computed tomography (CT) imaging features and texture analysis to differentiate PNEC from PDAC. METHODS: Twenty-eight patients with pathologically-proved PDAC and 14 patients with PNEC were included in this study. CT imaging findings, including tumor boundary, size, enhancement degree, duct dilatation and parenchymal atrophy were used to compare PDAC and PNEC. CT texture features were extracted from CT images at the arterial and portal phases. RESULTS: More PNEC than PDAC had well-defined margins (57.1% vs 25.0%, p = 0.04). Parenchymal atrophy was more common in PDAC than in PNEC (67.9% vs 28.1%, p = 0.02). CT attenuation values (HU) and contrast ratios of PNEC inthe arterial and portal phases were higher than those of PDAC (p < 0.05 or 0.01). Entropy was lower and uniformity was higher in PNEC compare to PDAC at the arterial phase (p < 0.05). Contrast ratio showed the highest area under curve (AUC) for differentiating PNEC from PDAC (AUC = 0.98-0.99). Entropy and uniformity also showed an acceptable AUC (0.71-0.72). CONCLUSIONS: Our data indicate that CT imaging features, including tumor margin, enhanced degree and parenchymal atrophy, as well as texture parameters can aid in the differentiation of PNEC from PDAC.