The Immunomodulatory Effects of Lipoteichoic Acid from Lactobacillus reuteri L1 on RAW264.7 Cells and Mice Vary with Dose.

The probiotic properties of Lactobacillus reuteri (L. reuteri) and its impact on immune function are well-documented. Lipoteichoic acid (LTA) is a crucial immune molecule in Gram-positive bacteria. Despite extensive research on LTA's structural diversity, the immunomodulatory mechanisms of L. reuteri LTA remain largely unexplored. This study investigates the immunomodulatory effects of L. reuteri L1 LTA at various concentrations on RAW 264.7 cells and mice under normal and inflammatory conditions. We found that LTA does not significantly affect healthy subjects; however, low-concentration LTA can reduce inflammation induced by LPS in cells and mice, enhancing the abundance of dominant intestinal bacteria. In contrast, high-concentration LTA exacerbates intestinal damage and dysbiosis. Creatinine may play a role in this differential response. In summary, while LTA does not alter immune homeostasis in healthy organisms, low-concentration LTA may mitigate damage from immune imbalance, but high-concentration LTA can worsen it. This suggests a quantitative requirement for probiotic intake. Our study provides critical theoretical support for understanding the immunomodulatory effects of probiotics on the host and paves the way for future research into the immune mechanisms of probiotics.

PiR-hsa-23533 promotes malignancy in head and neck squamous cell carcinoma via USP7.

BACKGROUND: With regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. METHODS: Differentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. RESULTS: piR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. CONCLUSIONS: These findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

Dietary Nucleotides Promote Neonatal Rat Microbiota-Gut-Brain Axis Development by Affecting Gut Microbiota Composition and Metabolic Function.

A variety of active factors in milk and foods have been proven to serve as microbial nutrients that regulate the formation of early gut microbiota (GM), thereby ensuring the healthy development of infants. This study demonstrated that dietary nucleotides (NTs), one of the main nitrogen-containing substances in human milk, promoted the neurodevelopment of neonatal rats and the expression of Sox2, Dcx, Tuj1, and NeuN in the prefrontal cortex and hippocampus, but had no significant regulatory effects in the striatum. 16s rRNA sequencing and metabolomics of the colon contents of neonatal rats at different developmental stages showed that the early intake of NTs promoted an increase in the abundance of beneficial microorganisms related to neurodevelopment, digestion, and gut absorption, such as g_Romboutsia and g_Akkermansia. Changes in the ability of the GM to regulate folate synthesis, riboflavin metabolism, and other processes were also observed. Further analysis revealed significant correlations between the level of characteristic metabolites, namely, trans-3-indoleacrylic acid, urocanic acid, inosine, and adenosine, in the gut with neurodevelopment and characteristic GM components. These findings suggest that NTs in milk may affect neurodevelopment and maturation in early life by regulating the GM composition-gut-brain axis.

Combined signature of N7-methylguanosine regulators with their related genes and the tumor microenvironment: a prognostic and therapeutic biomarker for breast cancer.

Background: Identifying predictive markers for breast cancer (BC) prognosis and immunotherapeutic responses remains challenging. Recent findings indicate that N7-methylguanosine (m7G) modification and the tumor microenvironment (TME) are critical for BC tumorigenesis and metastasis, suggesting that integrating m7G modifications and TME cell characteristics could improve the predictive accuracy for prognosis and immunotherapeutic responses. Methods: We utilized bulk RNA-sequencing data from The Cancer Genome Atlas Breast Cancer Cohort and the GSE42568 and GSE146558 datasets to identify BC-specific m7G-modification regulators and associated genes. We used multiple m7G databases and RNA interference to validate the relationships between BC-specific m7G-modification regulators (METTL1 and WDR4) and related genes. Single-cell RNA-sequencing data from GSE176078 confirmed the association between m7G modifications and TME cells. We constructed an m7G-TME classifier, validated the results using an independent BC cohort (GSE20685; n = 327), investigated the clinical significance of BC-specific m7G-modifying regulators by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and performed tissue-microarray assays on 192 BC samples. Results: Immunohistochemistry and RT-qPCR results indicated that METTL1 and WDR4 overexpression in BC correlated with poor patient prognosis. Moreover, single-cell analysis revealed relationships between m7G modification and TME cells, indicating their potential as indicators of BC prognosis and treatment responses. The m7G-TME classifier enabled patient subgrouping and revealed significantly better survival and treatment responses in the m7Glow+TMEhigh group. Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups. Conclusions: The m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies.

The efficacy and safety of telerehabilitation for patients following total knee arthroplasty: a overviews of systematic reviews.

BACKGROUND: Studies evaluating the effectiveness and safety of telerehabilitation in patients undergoing total knee arthroplasty (TKA) have increased. However, the study quality and results differ, systematic reviews are limited. We aimed to synthesise systematic reviews and meta-analyses to assess the effects of telerehabilitation in patients post-TKA. MATERIALS AND METHODS: Systematic reviews and meta-analyses regarding the effectiveness and safety of TKA telerehabilitation were retrieved from eight databases from establishment to 18 December 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS) and GRADE system were used to evaluate results, methods, bias and evidence quality. RESULTS: Thirteen systematic reviews and meta-analyses were analysed. The AMSTAR 2 showed low methodological quality in seven studies and very low quality in six. Among the key items, item 2 had been registered on website before systematic review in four reviews. Concerning item 4, did not provide a comprehensive search strategy in 4 reviews. For item 7, none of the reviews provided a list of reasons for excluding an article. For item 9, regarding whether appropriate tools were used to assess the risk of bias of each included study, one review was assessed as 'partially yes', one review only included RCTs, and the remainder were assessed as 'yes'. For item 11, one review did not specify the statistical methods used, and three reviews did not conduct a meta-analysis. For item 13, four reviews considered the risk of bias when interpreting or discussing the study results. For item 15, seven reviews did not evaluate publication bias. The PRISMA scores of the 13 reviews ranged from 17.5 to 26.0. The PRISMA indicated that 69.2% had no protocol registration, 38.5% did not provide other materials and evidence certainty, 23.1% did not provide certainty assessment, 30.8% did not report study bias. According to the ROBIS scale, diferrent domains have diferrent risks in all the reviews. CONCLUSION: Telerehabilitation positively affects walking ability, knee extension and patient costs post-TKA surgery. Regarding the quality of life, patient satisfaction and the WOMAC, telerehabilitation had similar effects to conventional rehabilitation. Owing to the low quality of the studies, these conclusions should be interpreted cautiously, high-quality studies are needed in the future.

Clinical study on single-port endoscopic resection via a gasless transaxillary approach in the treatment of breast fibroadenoma in adolescents.

BACKGROUND: Breast fibroadenoma is the most common benign breast tumour. This study aimed to investigate the advantages and disadvantages of endoscopic-assisted resection via a gas-less transaxillary single-port approach for breast fibroadenoma in adolescent patients, compared with a traditional approach. METHODS: The clinical data of 83 patients with breast fibroadenoma treated in our hospital from October 2019 to October 2021 were collected for retrospective analysis. These patients were divided into an endoscopic-assisted surgery (ES) group (n = 39) and a traditional open surgery (OS) group (n = 44) according to the surgical approach. The operative time, intraoperative blood loss, incision length, postoperative complications, and patient satisfaction were compared between the two groups. RESULTS: The surgical cost was (5.1 ± 0.6) thousand Yuan [(0.7 ± 0.1) thousand US dollars] in the ES group and (3.5 ± 2.7) thousand Yuan [(0.5 ± 0.4) thousand US dollars] in the OS group, showing a statistically significant difference (p < 0.001). There was no significant difference in surgical time, intraoperative blood loss, incision length, or the rate of postoperative complications between the two groups. Stratified analysis revealed that the ES group had a significantly shorter operative time [(57.00 ± 10.26) min vs. (78.27 ± 7.63)] (p < 0.001), a smaller incision length [(3.73 ± 0.34) cm vs. (4.42 ± 0.44) cm] (p < 0.001), and a lower complication incidence rate (11.1% vs. 63.6) (p = 0.011) than the OS group in the cases with a nodule number ≥ 3. The satisfaction score using the BREAST-Q scale indicated that psychosocial well-being and patient satisfaction with the breast in the ES group were significantly superior to those in the OS group [(91.18 ± 3.12) points vs. (87.00 ± 4.45) points and (91.03 ± 6.80) points vs. (84.45 ± 6.06) points, respectively] (p < 0.001). CONCLUSION: ES is a safe and effective method for the treatment of fibroadenoma. In patients with multiple fibroadenomas (≥ 3 tumours), ES has a shorter operative time and fewer postoperative complications. ES demonstrates a significant, prominent advantage in cosmetic appearance. However, it should be noted that ES is associated with higher costs than OS.

The E3 ubiquitin ligase MIB1 suppresses breast cancer cell migration through regulating CTNND1 protein level.

Breast cancer is one of the most common invasive cancers among women. The leading cause of difficulty in treating breast cancer patients is metastasis. Because cell migration is closely related to breast cancer metastasis, elucidating the detailed mechanism by which breast cancer cells promote their migration is crucial for improving the prognosis of patients. In this study, we investigated the relationship between breast cancer cell migration and Mind bomb1 (MIB1), an E3 ubiquitin ligase. We found that the downregulation of MIB1 promotes the cell migration of MCF7, a breast cancer-derived cell line. Furthermore, knockdown of MIB1 caused a reduction in CTNND1 and thereby impaired E-cadherin membrane localization in the cell boundary region. Taken together, our data suggest that MIB1 might play a role in suppressing breast cancer cell migration.

Topological polarization singular lasing with highly efficient radiation channel.

Bound states in the continuum (BICs) in photonic crystals describe the originally leaky Bloch modes that can become bounded when their radiation fields carry topological polarization singularities. However, topological polarization singularities do not carry energy to far field, which limits radiation efficiencies of BICs for light emitting applications. Here, we demonstrate a topological polarization singular laser which has a topological polarization singular channel in the second Brillouin zone and a paired linearly polarized radiation channel in the first Brillouin zone. The presence of the singular channel enables the lasing mode with a higher quality factor than other modes for single mode lasing. In the meanwhile, the presence of the radiation channel secures the lasing mode with high radiation efficiency. The demonstrated topological polarization singular laser operates at room temperature with an external quantum efficiency exceeding 24%. Our work presents a new paradigm in eigenmode engineering for mode selection, exotic field manipulation and lasing.

Identification of WRKY transcription factor family genes in Pinus massoniana Lamb. and their expression patterns and functions in response to drought stress.

BACKGROUND: Pinus massoniana Lamb. is the timber species with the widest distribution and the largest afforestation area in China, providing a large amount of timber, turpentine and ecological products. Seasonal drought caused by climate warming severely constrains the quality and growth of P. massoniana forests. WRKY transcription factors play an important role in plant responses to abiotic stress. In this study, the molecular mechanisms by which P. massoniana responds to drought stress were analysed based on the P. massoniana WRKY (PmWRKY) family of genes. RESULTS: Forty-three PmWRKYs are divided into three major families, 7 sub-families, and the conserved motifs are essentially the same. Among these 43 PmWRKYs express under drought stress but with different expression patterns in response to stress. PmWRKYs respond to drought stress induced by exogenous hormones of SA, ABA, and MeJA. The expression of PmWRKY6, PmWRKY10, and PmWRKY30 up-regulate in different families and tissues under drought stress, while PmWRKY22 down-regulate. Transgenetic tobaccos of PmWRKY31 are with lower malondialdehyde (MDA) content and higher proline (Pro) content than wild type (WT) tobaccos. In transgenic tobaccos of PmWRKY31, expression levels of related genes significantly improve, and drought tolerance enhance. CONCLUSIONS: This study analysed the molecular biological characteristics of PmWRKYs and investigated the expression patterns and functions of PmWRKYs in response to drought stress in P. massoniana. The results of this study provide a basis for in-depth research of the molecular functions of PmWRKYs in response to drought stress.

Chitosan oligosaccharides exert neuroprotective effects via modulating the PI3K/Akt/Bcl-2 pathway in a Parkinsonian model.

Parkinson's disease (PD), the second most common neurodegenerative disease, is a threat to patients due to the inability to prevent or decelerate disease progression. Currently, most clinical drugs for the treatment of PD are synthetic drugs that always present undesirable adverse or toxic effects. Chitosan oligosaccharide (COS) is a natural oligosaccharide that has been considered relatively safe and studied in the therapeutic effects on different types of neuronal disorders. In this study, we separated four COS monomers (COSs) including chitobiose (COS2), chitotriose (COS3), chitotetraose (COS4) and chitopentaose (COS5) to explore their structure-activity relationship in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Techniques including TLC, HPLC, MS, and NMR were applied to investigate the purity and structure of the COSs. After the oral administration of COSs, behavior indexes, pathological indexes, cytokines, and expression of proteins in the nigrostriatal pathway of the mice were analyzed. The results showed that the four COSs were fully deacetylated and the purity was >90%. Additionally, the neurobehavioral deficits of the PD mice were improved by treatment with COSs. The results further proved that COSs could protect the TH-labelled dopaminergic neurons via reducing the overexpression of α-synuclein, alleviating neuroinflammation, and activating the PI3K/Akt/Bcl-2 pathway to reduce apoptosis. COS3 exhibited a better effect on protecting dopaminergic neurons; however, COS2 provided a better effect on reducing the overexpression of α-synuclein. To conclude, the neuroprotective activity makes COSs a viable candidate as an ingredient for healthcare products.

IGF-1R/YAP signaling pathway is involved in collagen V-induced insulin biosynthesis and secretion in rat islet INS-1 cells.

PURPOSE: Type V collagen (collagen V) is one of the important components of extracellular matrix (ECM) in pancreas. We previously reported that pre-coating collagen V on the culture dishes enhanced insulin production in INS-1 rat pancreatic ß cells. In this study, we investigate the underlying mechanism. RESULTS: Insulin biosynthesis and secretion are both increased in INS-1 cells cultured on collagen V-coated dishes, accompanied by the reduced nuclear translocation of Yes-associated protein (YAP), a transcriptional co-activator. YAP, the downstream effector of Hippo signaling pathway, plays an important role in the development and function of pancreas. Inhibition of YAP activation by verteporfin further up-regulates insulin biosynthesis and secretion. Silencing large tumor suppressor (LATS), a core component of Hippo pathway which inhibits activity of YAP by phosphorylation, by siRNA transfection inhibits both insulin biosynthesis and secretion. In the present study, the protein level of insulin-like growth factor 1 receptor (IGF-1 R), detected as the upstream molecule of YAP, is reduced in the INS-1 cells cultured on the dishes coated with collagen V. The silencing of IGF-1 R by siRNA transfection further enhances insulin biosynthesis and secretion. IGF-1 treatment reduces collagen V-induced up-regulation of insulin biosynthesis and secretion, accompanying the increased nuclear YAP. CONCLUSION: Inhibition of IGF-1 R/YAP signal pathway is involved in collagen V-induced insulin biosynthesis and secretion in INS-1 cells.

Ultrasound-guided microwave ablation for multiple benign breast lesions: A prospective study.

AIM: To provide medical evidence for the feasibility and clinical efficacy of microwave ablation (MWA) in the treatment of benign breast lesions, especially multiple benign breast lesions. METHODS: We included patients with multiple benign breast lesions who were seen at our hospital during the period from June 2016 to December 2017. After signed informed consent had been obtained and core breast biopsy, all included patients who underwent MWA at 2450 MHz with 30 W power adjustment. Postoperative follow-up was performed for 1 year, at 3-month intervals. Ablation time, complications, volume-reduction ratio (VRR), and lesion residuals after ablation were analyzed. RESULTS: We ultimately included 1274 lesions from 164 cases in the study with a median follow-up time of 13.6 months. For a single lesion, the median ablation time was 36 s. Pain, fat liquefaction, and skin scalding were the most common complications. The overall complete disappearance rate was 92.1% (1173/1274), with the highest complete disappearance rate observed among those patients with lesions <10 mm in diameter (942/968, 97.3%). For lesions that persisted at 12 months after MWA, the average the volume-reduction ratio (VRR) was 87.5%. CONCLUSIONS: For multiple benign lesions of the breast, especially lesions with the longest diameter <10 mm, ultrasound guided MWA is a minimally invasive, relatively quick therapeutic strategy associated with accuracy in treatment and few complications.

Utility of noncontrast MRI in the detection and risk grading of gastrointestinal stromal tumor: a comparison with contrast-enhanced CT.

BACKGROUND: Recently developed adjuvant therapies for gastrointestinal stromal tumor (GIST) have been shown to improve patient survival. Guidelines currently recommend contrast-enhanced computed tomography (CECT) for GIST detection and surveillance. Patients with moderate-to-high risk GISTs require more frequent surveillance due to a higher 5-year recurrence rate. Our study aimed to compare noncontrast magnetic resonance imaging (MRI) with CECT for GIST detection, and evaluate volumetric apparent diffusion coefficients (ADCs) for risk stratification of GIST. METHODS: We retrospectively enrolled 83 patients with histopathologically confirmed GISTs for lesion detection efficiency analysis between noncontrast MRI and matched CECT studies. A 5-point scale was used by two independent reviewers to determine if the lesion was present or absent. Another cohort, comprising 28 patients with pathologically confirmed primary GISTs, was further screened for risk stratification, with a comparison of volumetric ADC parameters between the pathologically very-low-to-low risk and moderate-to-high risk GIST patients. RESULTS: For identifying GISTs, the sensitivity and specificity of noncontrast MRI were 83.6% and 89.3% for reader 1 respectively, and 81.8% and 92.9% for reader 2 respectively; the sensitivity and specificity of CECT were 76.4% and 89.3% for reader 1 respectively, and 76.4 and 78.6% for reader 2 respectively. Tumor volumetric ADC histogram parameters, including ADCmax, ADCstdev, 90th and 95th percentiles, inhomogeneity, and entropy, were positively correlated with a higher risk grade of GIST (r=0.421-0.758). The receiver operator characteristic curve analysis showed ADCmax achieved the highest area under the curve value of 0.938 for discriminating very-low-to-low risk versus moderate-to-high risk GISTs. CONCLUSIONS: Noncontrast MRI was an efficient technique for identifying GIST patients. The combination of CECT and noncontrast MRI can improve the reliability of diagnosis. For patients with contraindications to CECT, noncontrast MRI may be a comparable alternative. Volumetric ADC histogram parameters may be useful in differentiating very-low-to-low risk from moderate-to-high risk primary GISTs.

Circular RNA DHX33 promotes malignant behavior in ccRCC by targeting miR-489-3p/MEK1 axis.

Mounting evidence indicates that circular RNAs modulate the initiation of clear cell renal cell carcinoma (ccRCC). However, their specific roles in the malignancy of ccRCC is understudied. Here, we present a novel circular RNA, circDHX33, that is up-regulated in ccRCC cell lines and tissues. Upregulated circDHX33 in ccRCC patients significantly correlates with advanced TNM stage and metastasis. Suppressing circDHX33 expression inhibits the proliferation and invasion of cultured cells, and suppresses tumor growth in vivo. Mechanistically, we show that circDHX33 promotes ccRCC progression by sponging miR-489-3p and modulating MEK1 expression. In conclusion, our findings suggest that circDHX33 plays a role in promoting ccRCC via the miR-489-3p/MEK1 axis and may serve as a novel therapeutic target for the treatment of ccRCC patients.

WHSC1 promotes wnt/ß-catenin signaling in a FoxM1-dependent manner facilitating proliferation, invasion and epithelial-mesenchymal transition in breast cancer.

Objectives: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1) is highly expressed in various malignant tumors. We investigated the correlation and regulatory pathway of WHSC1 in the progression of breast cancer (BC).Methods: The expression and distribution of WHSC1 in the BC tissues and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining. Spearman correlation analysis demonstrated the correlation between WHSC1 high expression level and the clinical characteristics of BC patients. The effects of WHSC1 on the proliferation, apoptosis, migration and invasion of BC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, and transwell. Furthermore, the expression of Forkhead box M1 (FoxM1) and the location of ß-catenin were detected by qRT-PCR and western blot.Results: Firstly, WHSC1 expression was up-regulated in BC tissues and cell lines. The high expression of WHSC1 in BC is associated with the tumor size (p = 0.027), metastasis (p = 0.018) and pathological stages (p = 0.025) of the BC patients. The knockdown of WHSC1 inhibited the growth, proliferation migration, invasion and EMT of BC cell lines. Furthermore, WHSC1 could promote the expression of FoxM1 in BC cells and tissues. WHSC1 enhanced the expression of FoxM1, and promoted the nuclear localization of ß-catenin, and thus activated the downstream genes expression of Wnt/ß-catenin signaling pathway to regulate the development of BC.Conclusion: In summary, our study elucidates the correlation and specific regulatory mechanism between WHSC1 and the progression of BC, thus implying that WHSC1 may function as molecular diagnosis, prognosis and molecular targeted therapy of BC.

Prospective comparison of diffusion-weighted magnetic resonance enterography and contrast enhanced computed tomography enterography for the detection of ileocolonic Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic and relapsing course with various status of different segments, and there were no investigations comparing the lesion detection between magnetic resonance (MR) and computed tomography (CT) in term of the severity of CD. We aim to assess the performances of diffusion-weighted MR enterography (DW-MRE) and contrast enhanced CT enterography (CTE) for detecting different grade lesions in ileocolonic CD. METHODS: Forty-one consecutive patients finally diagnosed with ileocolonic CD were included. All the patients prospectively underwent DW-MRE, contrast enhanced CTE, and ileocolonoscopy within 2 weeks. DW-MRE and CTE images were interpreted for the presence or absence of active CD segments by two experienced radiologists independently. Ileocolonic segments (terminal ileum, right colon, transverse colon, left colon, and rectum) were graded as inactive (0-2), mild (3-6), or moderate-severe (≥ 7) by the simplified endoscopic score for CD (SES-CD). Diagnostic efficiencies of DW-MRE and CTE for mild and/or moderate-severe CD segments were calculated and compared, using ileocolonoscopy as reference standard. RESULTS: According to SES-CD, 190 ileocolonic segments from 41 CD patients were scored as 91 inactive, 68 mild, and 31 moderate-severe CD lesions. The sensitivity of DW-MRE for detecting active from inactive segments was higher than that of CTE, and the specificities of them had no significant differences. As for the subgroup analysis, DW-MRE was more sensitive for mild CD lesions than CTE (76.5% vs 60.3%; P = 0.019), while the sensitivities for moderate-severe CD were similar between these two modalities (96.8% for DW-MRE and 93.5% for CTE; P = 1.00). CONCLUSIONS: Both DW-MRE and CTE had comparably excellent performances for moderate-severe CD detection; DW-MRE demonstrated better sensitivity in mild lesions compared with CTE and could be more suitable for the diagnosis of mild CD.

Apparent diffusion coefficient-based histogram analysis differentiates histological subtypes of periampullary adenocarcinoma.

BACKGROUND: For periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes. AIM: To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC. METHODS: Between January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter. RESULTS: In total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s). CONCLUSION: Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

Assessment of tumor heterogeneity: Differentiation of periampullary neoplasms based on CT whole-lesion histogram analysis.

PURPOSE: To investigate the utility of whole-lesion histogram analysis from multidetector computed tomography (MDCT) for discrimination of duodenal adenocarcinoma (DAC), pancreatic ductal adenocarcinoma (PDAC) and gastrointestinal stromal tumor (GIST) around the periampullary area. MATERIALS AND METHODS: 171 patients suspicious of periampullary tumors were examined by MDCT (arterial and venous phases) and treated with surgery. A total of 74 patients were finally included in this retrospective study (26 DACs, 20 PDACs, and 28 GISTs). The interobserver agreement was evaluated by intra-class correlation coefficient (ICC) test between two radiologists. Volumetric histogram analysis based on CT Kinetics software was performed on enhanced MDCT images that recorded different histogram parameters of arterial and venous phases, including mean, median, 10th, 25th, 75th, and 90th percentiles, as well as skewness, kurtosis and entropy. The extracted histogram parameters were compared between DAC, PDAC and GIST respectively by Mann-Whitney U tests with Bonferroni corrections. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic ability of each significant parameter and the area under the curve (AUC) was calculated. RESULTS: The whole-lesion CT histogram analysis demonstrated significant differences between DAC, PDAC, and GIST with different histogram features on both arterial and venous phase scans (all P < 0.05). In the ROC analysis, the 90th percentile of venous phase demonstrated the highest AUC of 0.854 (P < 0.001) for discriminating DAC from PDAC. Excellent discriminators of periampullary tumors were noted among the histogram features, namely the 90th percentile of arterial phase, which demonstrated AUCs of 0.809 and 0.936 (P < 0.001) respectively for distinguishing DAC and PDAC from GIST. CONCLUSION: The whole-lesion CT histogram analysis could be useful for differential diagnosis of DAC, PDAC and GIST arising from the periampullary area. Further assessment is warranted to investigate the clinical role of histogram analysis based on MDCT.

Differentiation of atypical pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinomas: Using whole-tumor CT texture analysis as quantitative biomarkers.

BACKGROUND: To explore the application value of computed tomography (CT) texture analysis in differentiating atypical pancreatic neuroendocrine tumors (pNET) from pancreatic ductal adenocarcinomas (PDAC). MATERIALS AND METHODS: This single-center retrospective study was approved by local institutional review board, and the requirement for informed consent was waived. We retrospectively analyzed 127 patients with 50 PDACs and 77 pNETs in pathology database between January 2012 and May 2017.These patients successfully finished preoperative contrast-enhanced CT test. Texture parameters (mean, median, 5th, 10th, 25th, 75th, 90th percentiles, skewness, kurtosis and entropy) were extracted from portal images and compared between PDAC and 77 pNET groups using proper statistical method. The optimal parameters for differentiating PDACs and atypical pNETs were gained through receiver operating characteristic (ROC) curves. RESULTS: On the basis of arterial enhancement, 52 pNETs (67%, 52/77) were typical hypervascular and 25 pNETs (32%, 25/77) were atypical hypovascular. Compared with PDACs, atypical pNETs had statistically higher mean, median, 5th, 10th, and 25th percentiles (P = 0.006, 0.024, 0.000, 0.001, 0.021, respectively) and statistically lower skewness (P = 0.017). However, there were no difference for 75th, 90th percentiles, kurtosis and entropy between these two tumors (P = 0.232, 0.415, 0.143, 0.291, respectively). For differentiating PDACs and atypical pNETs, 5th percentile and 5th+skewness were optimal parameters for alone and combined diagnosis, respectively. CONCLUSION: Volumetric CT texture features, especially combined diagnosis of 5th+skewness can be used as a quantitative tool to distinguish atypical pNETs from PDACs.