Malignant Potential In Patients Research Articles

Clonal Bronchopulmonary B-Cell Proliferations of Indeterminate Malignant Potential in Patients with Common Variable Immune Deficiency (CVID) associated Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)

Abstract Introduction/Objective Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is often challenging to distinguish from reactive nodular lymphoid hyperplasia, and assessing B-cell clonality in such cases is crucial in making the distinction. However, patients with common variable immune deficiency (CVID) can harbor clonal or oligoclonal lymphoid populations in their tissues, particularly in association with granulomatous lymphocytic interstitial lung disease (GLILD), making the distinction from MALT lymphoma extremely challenging. We report six cases of GLILD with clonal or oligoclonal B cell infiltrates in lung wedge resection specimens and describe their clinicopathologic characteristics, management, and outcomes. Methods/Case Report A retrospective review was performed to collect lung wedge resection specimens from patients with CVID showing atypical B-cell infiltrates associated with GLILD between 01/2015 and 08/2023. The clinicopathologic findings, management, and response to treatment were studied. Results (if a Case Study enter NA) A total of six GLILD cases were identified with variable degrees of architectural and cytologic lymphoid atypia. Clonality of the lymphoid infiltrate was assessed by kappa/lambda in situ hybridization staining in all six, flow cytometry in 3/6, and IGH gene rearrangement in 4/6 cases. The infiltrate showed frank lambda restriction in 1/6, lambda predominance in 1/6, polytypic expression in 1/6, and no significant plasmacytic component in 3/6 cases. Flow cytometry detected atypical light chain skewed B-cell populations in 3/3 of cases. IGH was positive for clonality in 3/4 and oligoclonal in 1/4 cases. Four patients received therapeutic intervention for GLILD, including one with Rituximab monotherapy, two with Rituximab+Azathioprine, and one with Rituximab+Mycophenolate leading to marked symptomatic and radiologic improvement in all four patients. The remaining two patients were observed to have stable disease. Conclusion Patients with CVID can harbor clonal B-cell populations due to their underlying immune dysfunction. Studies have shown that these can be transient and may not always progress to overt lymphoma. In the setting of GLILD, detecting these populations makes the distinction from MALT lymphoma very challenging. Given that the first- line therapy for both GLILD and MALT is anti-CD20 therapy, the malignant potential of these clones remains uncertain and can only be determined with long-term clinical follow-up.

A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study

BackgroundDifferential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging. We evaluated the accuracy of a clinical and ultrasound based algorithm in predicting mesenchimal uterine malignancies (MUMs), including smooth muscle tumors of uncertain malignant potential (STUMPs). MethodsWe report the twelve-months follow-up of an observational, prospective, single-centre study that included women with at least one myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a three-class diagnostic algorithm, using symptoms and ultrasound features. “White” patients underwent annual telephone follow-up for 2 years, “Green” patients underwent a clinical and ultrasound follow-up at 6, 12 and 24 months and “Orange” patients underwent surgery. We further developed a risk class system to stratify the malignancy risk. Findings2,268 women were included andtarget lesion was classified as benign in 2,158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (OR 1.05 (95% CI 1.03-1.07), tumor diameter >8 cm (OR 5.92 (95% CI 2.87-12.24), irregular margins (OR 2.34 (95% CI 1.09-4.98), color score=4 (OR 2.73 (95% CI 1.28-5.82), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (OR 0.39 (95% CI 0.19-0.82). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best AUC (0.87 (95% CI 0.82-0.91)). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1,093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%). ConclusionThe preoperative three-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicentre study, will permit differentiation between benign and MUMs allowing a personalized clinical approach. FundingNothing to declare.

Local cytokine concentration in patients with non-muscle invasive bladder cancer of low malignant potential and with varying rates of recurrence

Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence. Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.

Development and validation of an EUS-based nomogram for prediction of the malignant potential in gastrointestinal stromal tumors

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract that require different therapeutic interventions according to the malignancy. We aim to develop and validate a EUS (endoscopic ultrasonography)-based nomogram to predict malignant potential in patients with GIST. Methods 258 patients with pathological diagnosis of gastric GISTs were enrolled retrospectively in our hospital from June 2015 to October 2020. Patients were randomly divided into the development cohort (DC, n = 179) and the validation cohort (VC, n = 79). We established a nomogram using lasso regression based on DC data. The predictive effectiveness of the nomogram was evaluated by the area under the receiver operating characteristic curve (AUC). Through bootstrapping, a consistency index (C-index) and calibration chart are developed to evaluate the reliability and accuracy of the nomogram. Results A total of 192 patients with low-malignant potential (very low and low-risk) GISTs and 66 patients with high-malignant potential (intermediate and high-risk) GISTs were included in this study. The nomogram was constructed with the following 6 EUS indicators: ulceration, hemorrhage, tumor shape, irregular border, transverse diameter, and necrosis. Internal and external validation showed that the nomogram had a good ability to predict the malignant potential of GISTs (AUC = 0.881 and 0.908, respectively). The calibration curve shows that the nomogram has a good agreement between predicted and actual probabilities for differentiating GISTs malignancy (C-index = 0.868 and 0.907, respectively). Conclusions This study developed and verified a EUS-based nomogram, which can effectively predict the malignant potential of patients with gastric GISTs.

An Extreme Case of Liver Adenomatosis: Are They All the Same?

Hepatocellular adenoma (HCA) is a rare and benign liver tumor that affects predominantly young and middle-aged women, especially between 30–40 years old. Liver adenomatosis (LA) is defined as the presence of 10 or more HCA. There are authors that report eight different subtypes of HCA, that correlates with clinical and histopathological features, being the inflammatory subtype the most common. We present a case of a 32-year-old Caucasian woman with a history of self-limited episodes of right abdominal pain and an abdominal ultrasound with multiple hypoechogenic liver nodules, suspected of metastasis. She was taking combined oral contraceptive for 6 years. Magnetic Resonance Imaging (MRI) disclosed around 40 nodules, suggestive of HCA. Liver biopsy confirmed HCA, inflammatory subtype. Oral contraceptive was stopped and control MRI 6 months later disclosed reduction of nodules’ dimensions. Management of patients with LA should be based on the size of the largest tumor, as clinical presentation and risk of bleeding or malignancy do not differ between patients with single or multiple HCAs. However, even with biopsy, there is a risk of missampling, raising concern about the real risk of bleeding and malignant potential in patients with different subtypes coexisting in the same liver.

Strategy for Discriminating Intraductal Papillary Neoplasm of the Bile Duct (IPNB) in Different Anatomical Locations Based on Clinicopathological Features and Outcomes

Introduction: In the statement by the Japan-Korea expert pathologists, it was described that Intraductal papillary neoplasm of bile duct (IPNB) can be subclassified into two types. Each of these two types has a different tendency in the anatomical location and invasiveness. The present study assessed the clinical features and outcomes of intra-/extra- hepatic IPNB to establish optimal therapeutic strategies for IPNB. Method: The present study included 28 cases who were pathologically diagnosed with IPNB. These cases were classified by the anatomical location where it arises (intrahepatic-IPNB 7 cases/ extrahepatic-IPNB 21 cases). Furthermore, we attempted to further clarify the characteristics of intrahepatic IPNB by comparing with intrahepatic cholangiocarcinoma (ICC). Results: Superficial extension was significantly more frequent in extrahepatic type with 17 cases (p=0.003). Pathologically, lymphatic invasion was significantly more frequent in the extrahepatic type (p=0.033), and mucus production tended to be more frequent in intrahepatic type (p=0.063). In terms of prognosis, recurrence was observed in 9 cases of extrahepatic type. As compared with 26 cases of ICC, preoperative intrahepatic (p=0.026) and extrahepatic (p<0.01) biliary dilatation and histological mucus production (p<0.01) were significantly found in primary hepatic IPNB. ICC group significantly showed CA19-9 >100 (p=0.043), portal invasion (p<0.01) and recurrence (p<0.01). Conclusions: Preoperative diagnosis of intrahepatic IPNB is possible because of the relatively common and characteristic imaging findings. However, considering the malignant potential in patients with high tumor markers and portal vein invasion, as well as the characteristics of horizontal extension of IPNB, systematic hepatectomy with adequate bile duct resection are recommended.

Management of indeterminate hepatic nodules and evaluation of factors predicting their malignant potential in patients with colorectal cancer

Some liver nodules remain indeterminate despite hepatocyte-specific contrast MRI in patients with colorectal liver metastasis (CRLM). Our objective was to study the natural course and evaluate possible treatment strategies for indeterminate nodules. We retrospectively evaluated patients in whom MRI revealed ‘indeterminate’ or ‘equivocal’ nodules between January 2008 and October 2018. Patients were followed up until October 2019 or until death (median, 18 months; (1–130 months)). The incidence of patients with indeterminate nodules on MRI was 15.4% (60 of 389). The sensitivity and specificity of intraoperative ultrasound for detecting indeterminate nodules were 73.68% and 93.75%, respectively, with a positive predictive value of 96.6%. Over half of the patients followed up had benign nodules (58.8%). By comparing characteristics of patients with benign or malignant nodules in the follow up group, the ratio of positive lymph nodes to total number of lymph nodes resected (pLNR) was significantly greater in patients with malignant nodules (P = 0.006). Intraoperative ultrasound could be considered as an adjunct to MRI in patients with indeterminate nodules owing to its high positive predictive value. The pLNR could be used to help select which patients can undergo conservative therapy, at least in metachronous CRLM.

Pre-operative nomogram predicting malignant potential in the patients with intraductal papillary mucinous neoplasm of the pancreas: focused on imaging features based on revised international guideline.

To clarify the pre-operative imaging and clinical features differentiating malignant from benign intraductal papillary mucinous neoplasm (IPMN) of the pancreas and develop a nomogram for estimating the individualized risk of malignant IPMN. One hundred twenty-six patients with IPMN (72 benign and 54 malignant) who underwent pre-operative contrast-enhanced CT or MRI from 2010 to 2018 were retrospectively evaluated in two tertiary institutions. All lesions were pathologically proven by surgery or biopsy. Significant imaging and clinical findings for malignancy were assessed by univariate and multivariable logistic regression analyses. Based on the significant variables in the multivariable analysis, we developed a nomogram to predict malignant potential in patients with IPMNs, and the area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic value. Multivariable analysis revealed that enhancing mural nodule ≥ 5mm (odds ratio (OR), 48.30; 95% confidence interval (CI), 11.69-199.49), increased serum carbohydrate antigen 19-9 (CA19-9) (OR, 8.69; 95% CI, 2.04-36.92), main pancreatic duct (MPD) diameter ≥ 10mm (OR, 6.34; 95% CI, 1.21-33.30), and acute pancreatitis (OR, 4.77; 95% CI, 1.12-20.36) were independent significant parameters to predict malignant IPMN. Among them, enhancing mural nodule ≥ 5mm showed the highest OR and predictor point on the nomogram. The AUC for the nomogram was 0.955 (95% CI, 0.903-0.984). Pre-operative imaging findings could aid in predicting malignant potential of IPMN using the significant findings of enhancing mural nodule ≥ 5mm, increased serum CA19-9, MPD diameter ≥ 10mm, and acute pancreatitis. • Among pre-operative imaging and clinical features, enhancing mural nodule ≥ 5mm, increased serum CA19-9, main pancreatic duct diameter ≥ 10mm, and acute pancreatitis were independent significant parameters to predict malignant IPMN. • Enhancing mural nodule ≥ 5mm was a single predictor for malignant IPMN, with the highest diagnostic values compared to other significant parameters. • A constructed nomogram using these parameters could aid in predicting malignant potential in patients with IPMN of the pancreas.

Development and validation of a nomogram based on CT images and 3D texture analysis for preoperative prediction of the malignant potential in gastrointestinal stromal tumors

BackgroundGastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the digestive system, are treated varyingly according to the malignancy. The purpose of this study is to develop and validate a nomogram for preoperative prediction of the malignant potential in patients with GIST.MethodsA total of 440 patients with pathologically confirmed GIST after surgery in our hospital from January 2011 to July 2019 were retrospectively analyzed. They were randomly divided into the training set (n = 308) and validation set (n = 132). CT signs and texture features of each patient were analyzed and predictive model were developed using the least absolute shrinkage and selection operator (lasso) regression. Then a nomogram based on selected parameters was developed. The predictive effectiveness of nomogram was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). Concordance index (C-index) and calibration plots were formulated to evaluate the reliability and accuracy of the nomogram by bootstrapping based on internal (training set) and external (validation set) validity. The clinical application value of the nomogram was determined through the decision curve analysis (DCA).ResultsTotally 156 GIST patients with low-malignant (very low and low risk) and 284 ones with high-malignant potential (intermediate and high risk) are enrolled in this study. The prediction nomogram consisting of size, cystoid variation and meanValue had an excellent discrimination both in training and validation sets (AUCs (95% confidence interval(CI)): 0.935 (0.908, 0.961), 0.933 (0.892, 0.974); C-indices (95% CI): 0.941 (0.912, 0.956), 0.935 (0.901, 0.982); sensitivity: 81.4, 90.6%; specificity: 75.0, 75.7%; accuracy: 88.0, 88.6%, respectively). The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating GIST malignancy. Decision curve analysis demonstrated that the nomogram was clinically useful.ConclusionThis study presents a prediction nomogram that incorporates the CT signs and texture parameter, which can be conveniently used to facilitate the preoperative individualized prediction of malignancy in GIST patients.

Gas Chromatography-Mass Spectrometry Analysis of Urinary Steroid Metabolomics for Detection of Early Signs of Adrenal Neoplasm Malignancy in Patients with Cushing's Syndrome.

The metabolomics of urinary steroids was studied by gas chromatography-mass spectrometry in 25 patients with Cushing's syndrome without malignant potential and in 12 patients with malignant potential of adrenal neoplasms (Weiss score 1-3). Patients with adrenocortical adenoma (N=24) constituted the control group. In patients with Cushing's syndrome and malignant potential, increased urinary excretion of 16-oxo-androstendiol, tetrahydro-11-deoxycortisol, and 16-hydroxypregnendiol, which had 100% specificity and sensitivity >90% for the diagnosis of malignant potential. Additionally, non-classical 5-ene-pregnenes (16-OHpregnenolone, 21-OH-pregnenolone, 3β,16,20-pregnentriol, and 3β,17,20-pregnentriol) were identified. The revealed changes in the metabolomics of steroids can be early signs of malignant potential in patients with Cushing's syndrome. In patients with malignant potential, three signs of reduced activity of 11β-hydroxysteroid dehydrogenase type 2 were detected and in patients without malignant potential, one sign was found. In patients with and without malignant potential, three signs increased activity of 5β-reductase were found.

PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer

ObjectivesPD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression. MethodsWe evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC). ResultsPD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023). ConclusionsDuring tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.

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Neutrophil to Lymphocyte Ratio is a Predictive Factor of Malignant Potential for Intraductal Papillary Mucinous Neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 (P = .001), prognostic nutritional index (PNI) < 45 (P = .016), CA 19-9 > 37 U/mL (P = .039), and cystic diameter ⩾ 30 mm (P = .010), and mural nodule (P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1

CT, MRI, and F-18 FDG PET for the detection of non-small-cell lung cancer (NSCLC): A protocol for a network meta-analysis of diagnostic test accuracy.

Background:Non-small-cell lung cancer (NSCLC) is a rare cancer in lung carcinomas and has been widely known as a difficult curable disease among all the tumors. However, early detection of malignant potential in patients with NSCLC has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET are all considered as good tests for diagnosing malignant NSCLC efficiently, but no recommended suggestion presents that which test among the 3 is the prior one in diagnose. We perform this study through network meta-analysis method, and to rank these tests using a superiority index.Methods and analysis:PubMed, Embase.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of CT, MRI, and F-18 FDG PET for diagnosing NSCLC. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index.Results:This study is ongoing, and will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide systematically suggestions to select different diagnostic measures for detecting the early NSCLC.Ethics and dissemination:Ethical approval and patient consent are not required since this study is a network meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication.PROSPERO registration number:PROSPEROCRD42018094542.

Overexpression of miR‑221 and miR‑222 in the cancer stroma is associated with malignant potential in colorectal cancer.

The cancer stroma is important in cancer development, however, whether the aberrant expression of microRNAs (miRNAs) in the cancer stroma is associated with cancer progression remains to be fully elucidated. The aim of the present study was to identify the miRNAs associated with liver metastasis in the cancer stroma of human colorectal cancer (CRC). Using laser capture microdissection, cancer stroma was obtained from the primary lesion of six patients with CRC with liver metastasis (CRCwLM) and six patients with CRC without liver metastasis (CRCwoLM), and miRNA microarray analysis was performed. Candidate miRNA expression status in the stroma was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis in 40CRC cases (wLM, n=20; woLM, n=20), and the association between miRNA expression and clinicopathological factors was assessed in 101 advanced CRC samples. The localization of candidate miRNAs in CRCs was analyzed using insitu hybridization analysis (ISH). The microarray analysis identified six miRNAs with expression differing between the CRCwLM and CRCwoLM cancer stroma. Validation using RT‑qPCR analysis of the stroma showed that the expression levels of miR‑221 and miR‑222 in the cancer stroma were significantly higher in CRCwLM than in CRCwoLM. The RT‑qPCR analysis of 101 CRC samples showed that a high expression level of miR‑221 or miR‑222 in the cancer stroma was associated with liver metastasis, distant metastasis, and shorter overall survival rate of patients with CRC (P<0.05). Increased levels of miR‑221 and miR‑222 were observed in cancer cells and in fibroblasts in the stromal tissue in the ISH analysis. The results suggested that the overexpression of miR‑221 and miR‑222 in the cancer stroma is associated with the metastatic activity and malignant potential in patients with CRC.

F-18 FDG PET, CT, and MRI for detecting the malignant potential in patients with gastrointestinal stromal tumors: A protocol for a network meta-analysis of diagnostic test accuracy.

Background:Gastrointestinal stromal tumor (GIST) is a rare cancer in gastrointestinal carcinomas and has been widely known as a curable disease among all the digestive tumors. However, early detection of malignant potential in patients with GIST has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET are all considered as good tests for diagnosing malignant GIST efficiently, but no recommended suggestions presents which test among the 3 is the prior one in detecting the malignant potential of GIST. We perform this study to assess the accuracy between CT, MRI, and F-18 FDG PET through network meta-analysis method, and to rank these tests.Methods and analysis:PubMed, EMBASE.com, CNKI, and CBM databases will be searched without search date and language restrictions. We will include diagnostic tests which assessed the accuracy of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST. The risk of bias in each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index.Results:This study is ongoing, and will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide a comprehensive evidence summary of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST.

Multiple growth periods predict unfavourable pathology in patients with small renal masses.

To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy. Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low-grade pT1-2 renal cell carcinoma [RCC]) vs unfavourable (high-grade of any stage and low-grade pT3-4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran-Armitage trend test and Somers' D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology. Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2-66.0) vs 68.5 (61.5-77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively. While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses.

An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer.

β4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients, and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between β4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of β4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of β4 integrin, which, in turn, recruits FAK to β4 integrin and leads to FAK activation and signaling. Upon disruption of the β4 integrin/FAK complex, tumorigenesis and metastasis in triple-negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of β4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent β4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer.

MP49-02 RELATIONSHIPS BETWEEN C-FES EXPRESSION AND MALIGNANT AGGRESSIVENESS IN BLADDER CANCER IN VIVO AND IN VITRO

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-02 RELATIONSHIPS BETWEEN C-FES EXPRESSION AND MALIGNANT AGGRESSIVENESS IN BLADDER CANCER IN VIVO AND IN VITRO Akihiro Asai, Yasuyoshi Miyata, Kensuke Mitsunari, Tomohiro Matsuo, Kojiro Ohba, and Hideki Sakai Akihiro AsaiAkihiro Asai More articles by this author , Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , Kojiro OhbaKojiro Ohba More articles by this author , and Hideki SakaiHideki Sakai More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.506AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES c-Fes is a proto-oncogene encoded non-receptor protein-tyrosine kinase; however, genetic studies have implicated it also plays anti-tumorigenic roles in some cancers. On the other hand, pathological roles of c-Fes in bladder cancer is not fully understood. This study explored the relationship between c-Fes expression and clinical significance, pathological features, and malignant potential in patients with bladder cancer. In addition, such findings were confirmed by using bladder cancer cell line. METHODS Bladder cancer tissues from 202 patients were analyzed for the relationships between c-Fes expression and grade, pT stage, and metastasis. Our study population was composed of non-muscle invasive bladder cancer (NMIBC, n=165) and MIBC (n=37). Metastasis at diagnosis was detected in 15 patients (7.4%). Expression of c-Fes and proliferation index (PI, using anti-Ki-67 antibody) were investigated by immunohistochemical technique. In bladder cancer cell line (T24), c-Fes expression was examined by Western blotting and knock-down (KD) was performed using small interfering RNA (siRNA). Cancer cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) assay and cell migration was evaluated by in scratch assay. These results were compared between wild type (WT)- and KD-T24 cells. RESULTS Eighty-nine patients (44.1%) were judged as positive for c-Fes and its expression in low grade tumor (58/98, 59.2%) was significantly (P<0.001) higher than that in high grade one (31/104, 29.8%). However, c-Fes expression was not associated with pT stage and metastasis. On the other hand, when such association was analyzed in patients with high grade tumor, positive ratio of c-Fes expression in NMIBC (20.8%) was significantly (P < 0.001) lower than that in MIBC (50.0%). In regard to PI, there is no significant association in entire patients. However, PI in c-Fes-positive tumor (mean/SD = 27.6/8.6) was significantly (P=0.001) than those in negative one (22.9/7.3)in high grade tumors, but not in low grade tumor. In vitro study, c-Fes was strongly expressed in T24 cells. When c-Fes expression was decreased by si-RNA, cell proliferation was suppressed. In addition, cell maigration of KD-T24 was inhibited compared to WT. CONCLUSIONS c-Fes expression was negatively associated with grade, but not with pT stage. However, in high grade tumor, c-Fes was positively associated with pT stage. In vivo and in vitro studies showed such pathological role of c-Fes was speculated to be regulated by complex mechanism including cell proliferation in bladder cancer tissues. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e603 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Asai More articles by this author Yasuyoshi Miyata More articles by this author Kensuke Mitsunari More articles by this author Tomohiro Matsuo More articles by this author Kojiro Ohba More articles by this author Hideki Sakai More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prospective Evaluation of the Clinical Utility of 18-Fluorodeoxyglucose PET CT Scanning in Patients with Von Hippel-Lindau–Associated Pancreatic Lesions

The natural history of pancreatic neuroendocrine neoplasms (PNENs) in patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of patients with PNENs is challenging because there are no reliable preoperative criteria to detect malignant lesions, and the majority of resected tumors are found to be benign. The aim of this study was to determine whether 18-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) uptake predicts growth and detects malignant VHL-associated PNENs. We performed a prospective study of 197 patients with VHL-associated pancreatic lesions. Clinical and imaging characteristics were analyzed to study the associations between FDG-PET uptake, tumor growth, and the development of metastatic disease. One hundred nine of 197 patients had solid pancreatic lesions and underwent both CT and (18)FDG-PET scanning, which identified 165 and 144 lesions, respectively. Metastatic disease was detected by (18)FDG-PET in 3 patients in whom it was not detected by CT scan and suggested non-neoplastic disease in 3 patients. Maximum standardized uptake values (SUV) on (18)FDG-PET correlated with tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated with tumor growth (r = 0.36, p = 0.0062). No association was seen between (18)FDG-PET uptake and age, VHL genotype, or serum chromogranin A levels. Scanning with FDG-PET identifies metastatic disease not detected by CT scan and avoids resection of non-PNEN lesions that have no malignant potential in patients with VHL-associated PNENs. It should be considered as a valuable functional imaging modality in the clinical management of patients with VHL-associated PNENs.