Low-grade Group Research Articles

Expression of GLUT3 and HIF-1α in Meningiomas of Various Grades Correlated with Peritumoral Brain Edema.

Aim To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. Methods In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. Results The proportion of GLUT3-positive staining in tumors sized <4 cm, 4–6 cm, and>6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P = 0.007). The proportion of HIF-1α-positive staining in tumors sized <4 cm, 4–6 cm, and >6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P = 0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P < 0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P = 0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P < 0.001, α/6 = 0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P = 0.003, α/6 = 0.008). Spearman's correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r = 0.463, P < 0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P < 0.05). Conclusions GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.

Abstract 2293: A urine-based liquid biopsy method for detection of upper tract urinary carcinoma

Abstract Background: Upper tract urinary carcinoma (UTUC) includes renal pelvic cancer and ureteral cancer. For its diagnosis, ureteroscopy is the only method to obtain pathological result before surgery. However, there are also some problems with ureteroscopy. In addition to the trauma and infection risks, the possibility of exudation and adhesion of surrounding tissues after ureteroscopy is significantly increased, hypertension in the cavity may cause tumor spread, and the use of ureteroscopy and biopsy may cause recurrence of bladder tumors after surgery. These unfavorable factors make clinically urgent need for a sensitive and non-invasive method for the diagnosis of UTUC. Materials and Methods: In this study, 150 hematuria patients with upper tract urinary disease and 100 healthy people were enrolled. Among the patients, 75 were pathologically confirmed with upper tract urinary carcinoma while 75 with benign urinary diseases. A Genetron Urinary Assay was designed to maximize the number of unique driver gene variants of UTUC by a limited number of amplicons. Next-generation sequencing libraries were constructed using multiplex PCR methods. We also detected CpG-sites on ONECUT2 gene by performing bisulfite-specific real-time PCR for bisulfite converted DNA. Furthermore, we developed a prediction model based on several significant features to evaluate the risk of UTUC. Results: 234 samples were available for analysis. Our liquid biopsy assay demonstrated a sensitivity of 94%, a specificity of 96%, a positive predication value (PPV) of 92% and a negative predication value(NPV) of 98% in this study. By using a decision tree model, we found age, gene mutations of HRAS, TERT and TP53 and methylation of ONECUT2 did place at some key nodes to classify the risk of patients of UTUC, and age around 48.5, the frequencies of mutated genes above certain value and ΔCt value of ONECUT2 about 7.6 would be good cutoffs. This model was able to stratify patients into a low or high-risk group with an accuracy score at 94%. After further analysis, we found that ONECUT2 methylation and TP53 mutations were more common in high grade UTUC (p&amp;lt;0.01), while AKT1 and FGFR3 (trend, but no statistical significance) mutations were more often shown in low grade group. No significant difference of gene mutations frequency was found between non muscle invasive and muscle invasive group, but FGFR3 as well as TERT and PIK3CA gene showed a trend of higher occurrence. Conclusion: In this study, Genetron Urinary Assay has a good performance in the diagnostic of UTUC. Its high sensitivity, high specificity, and non-invasiveness make it a potential clinical alternative to ureteroscopy. Further validation in a large prospective cohort of wide population is necessary to prove the true clinical value of this newly developed method. Citation Format: Xin Ma, Yansheng Xu, Hongzhao Li, Xing Ai, Jiangping Gao, Yiming Liang, Qiaosong Zheng, Kaisheng Mao, Tonghui Ma, Xu Zhang. A urine-based liquid biopsy method for detection of upper tract urinary carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2293.

THE EFFECT OF LOW-DOSE INTRAVESICAL BACILLUS CALMETTE-GUÉRIN (BCG) INFUSION THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

(Objective) Bacillus Calmette-Guérin (BCG) intravesical infusion therapy plays an important role in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Our institute performs low-dose (40 mg) BCG intravesical infusion therapy (completed 8 times) to reduce side effects. We retrospectively investigated its efficacy and side effects. (Patients and methods) We analyzed the response, non-recurrence, and side effect rates by risk stratification in 179 patients who received low-dose BCG intravesical infusion therapy from September 2003 to November 2018 in Nagano Municipal Hospital. Complications were classified using the Common Terminology Criteria for Adverse Events version 4.0. (Results) The median age was 73 years, and the male/female ratio was 137:42. The median observation period was 32 months, and infusion was completed 8 times in 149 cases (83.2%). The overall response rate was 88.8%. The response rate was significantly higher in the low-grade pathology group than in the high-grade group. However, no significant differences in G1/G2/G3 side effects, sex, age, presence of carcinoma in situ (CIS), depth of invasion, purpose of administration, and grade of side effects were observed. The overall non-recurrence rates were 91.8%, 76.7%, and 71.3% at 1, 3, and 5 years, respectively. Nevertheless, there were no significant differences in the non-recurrence rates with respect to depth of penetration, the degree of dysmorphism, purpose of administration, presence of CIS, and completed of infusion. A total of 71 G2 side effects (39.7%) were identified, and 3 cases of G3 side effects required hospitalization. (Conclusion) In our institution, the completion rate of low-dose BCG intravesical infusion therapy was high, with few side effects. Furthermore, it demonstrated similar therapeutic effect to that reported with standard-dose administration. Low-dose BCG intravesical infusion therapy may be an effective treatment, particularly for pathologically low-grade NMIBC.

Does the change in volumetric functional MR metrics post-TACE predict histopathologic grading of hepatocellular carcinoma?

To evaluate whether the change in volumetric ADC (vADC) and volumetric venous enhancement (vVE) after transarterial chemoembolization (TACE) can predict the histologic grading of hepatocellular carcinoma (HCC). This HIPPA-compliant retrospective study was approved by our institutional review board. The study population included 106 HCC patients (147 index lesions) who had MR imaging within 3months before and after TACE and pathologic report of the HCC either by biopsy or liver transplantation/resection between 2001 and 2017. Volumetric measurements of venous enhancement (VE) and apparent diffusion coefficient (ADC) were performed on baseline and post-TACE MRI. The tumors were histologically classified into two low-grade and high-grade groups. The parameters between two groups were compared using bivariate and multivariate analyses. Median change in vADC, vVE, and absolute vADC skewness after TACE was higher in low-grade HCCs as compared with high-grade HCCs (p < 0.001, p = 0.005, p = 0.04, respectively). Combining ΔvADC, ΔvVE, and the etiology for background liver disease in multivariate analysis had the highest accuracy in distinguishing high-grade tumors (AUC = 91%). ΔvADC and ΔvVE after TACE are potential predictors of HCC histopathological grading. Combining functional MRI biomarkers with the etiology of liver disease can enhance the accuracy in assessing degree of differentiation. • Change in volumetric functional MRI biomarkers after TACE can be a non-invasive method to evaluate tumor histopathology in HCC. • The etiology of background liver disease might be a predictor of tumor degree of differentiation.

Shear Wave Elasticity Differentiation Between Low- and High-Grade Bladder Urothelial Carcinoma and Correlation With Collagen Fiber Content.

To investigate the differences in the shear wave elasticity and collagen fiber content between low- and high-grade bladder urothelial carcinoma and study the relationship between elasticity and the content of collagen fiber. A total of 66 patients with bladder tumors who were referred to our hospital underwent transrectal or transvaginal conventional ultrasound and shear wave elasticity examinations. After bladder urothelial carcinoma was pathologically confirmed, 34 cases of low-grade and 32 cases of high-grade carcinoma were enrolled. The specimens underwent Masson trichrome staining, and image-processing software was used to quantitatively analyze the area of collagen fiber. Based on conventional ultrasound, the low- and high-grade groups were similar in the number, location, interior echoes, basal portion, size, and vascularity (P > .05); nevertheless, the difference in the surface condition (smooth or rough) was statistically significant (P = .03). The high-grade group had significantly higher maximum and mean elasticity than the low-grade group (P < .01). The percentage of the collagen fiber area in the high-grade group was significantly higher than that in the low-grade group (mean ± SD, 11.45% ± 1.66% versus 7.64% ± 0.70%; P = .01). There was a positive correlation between maximum elasticity, mean elasticity, and the percentage of the collagen fiber area (r = 0.75 and 0.52, respectively; P < .01). Shear wave elasticity can be used to differentiate between low- and high-grade bladder urothelial carcinoma. The elasticity of lesions has a close correlation with the content of collagen fiber, which may have an important impact on tissue stiffness and the development of bladder cancer.

Synovial Fluid Biomarkers in the Osteoarthritic Knee: Differences in Concentration with Progression of Radiographic Severity

Objectives:The purpose of the current study was to analyze the synovial fluid concentrations of known inflammatory biomarkers in the setting of symptomatic osteoarthritis (OA) of the knee and assess for any differences in biomarker concentrations based on the extent of radiographic disease.Methods:Patients presenting with knee complaints were invited to provide synovial fluid samples from the symptomatic knee during their initial office visit. For this study, a subset of patients with OA was analyzed. The concentration of 16 synovial fluid biomarkers was measured, including TIMP-1, TIMP-2, TIMP-3, MMP-13, IL-6, MCP-1, MIP-1β, VEGF, bFGF, eotaxin, IL-1Ra, MMP-1, MMP-3, MMP-9, RANTES, and TSG-6. Samples were analyzed using a multiplex magnetic bead immunoassay. Patients were divided into a low-grade OA group (K-L ≤ 2 or OARSI ≤ 1) or a high-grade cartilage OA group (K-L ≥ 3 or OARSI ≥ 2).Results:101 patients were included in this analysis. There was a significant difference in MIP-1β (p=0.025) and bFGF (p=0.015) concentrations between OARSI grade groups. Patients with high-grade joint space narrowing had significantly greater concentrations of MIP-1β (p=0.022) and bFGF (p=0.003). There was a significant difference in MIP-1β concentration between K-L grade groups (p=0.013). Patients in the high-grade K-L group had a significantly greater concentration of MIP-1β (p=0.020).Conclusions:The synovial fluid concentrations of two synovial fluid biomarkers were found to differ significantly based on the extent of radiographic OA present. MIP-1β is a pro-inflammatory growth factor known to induce the synthesis of other inflammatory factors including interleukins and TNF-α. bFGF is a growth factor that is known to promote chondrogenesis, angiogenesis, wound healing, and granulation tissue formation. Continued study of synovial fluid biomarkers in the setting of symptomatic OA may improve our understanding of the pathogenesis of disease and identify treatment targets in an attempt to halt disease progression.

Diffusion Weighted Imaging of Brain Gliomas in the Differential Diagnosis Value

Background: To evaluate the diagnostic value of diffusion weighted imaging (DWI) and apparent diffusion coefficient measurement (ADC) in glioma. cient measurement (ADC) in glioma. Methods: Thirty two low-grade glioma patients and 31 high-grade glioma patients who were confirmed by pathology in Lanzhou University Second Hospital, Lanzhou, China from February 2016 to January 2019 were selected. The other 30 patients with brain metastases were selected as a control group. DWI imaging data of the three groups were collected, and ADC, relative ADC (rADC) values in tumor parenchyma, peritumor edema area, and contralateral normal white matter area were measured, and the levels of n-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr) of tumor metabolites were analyzed. Results: rADC values in the peri-tumor edema areas of the high-grade glioma group were significantly lower than those in the low-grade group and the metastatic group （P=0.011）, and the low-grade group was significantly lower than that in the metastatic group (P &lt; 0.05). NAA/Cho and NAA/Cr in parenchymal and peritumor edema areas of patients in the advanced group were significantly lower than those in the metastatic group (P &lt; 0.05), and Cho /Cr was significantly higher than those in the metastatic group (P &lt; 0.05). Conclusion: the rADC value, NAA/Cho, NAA/Cr and Cho/Cr in parenchymal and peritumor edema areas of the tumor can help to distinguish high-grade glioma, low-grade glioma and brain metastases.

Magnetic Resonance Diffusion Kurtosis Imaging versus Diffusion-Weighted Imaging in Evaluating the Pathological Grade of Hepatocellular Carcinoma.

PurposeTo investigate the diagnostic efficacy of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) for pathological grading.MethodsFrom December 2015 to January 2017, consecutive patients suspected of having hepatocellular carcinoma (HCC) without prior treatment were prospectively enrolled in this study. MRI examinations were performed before surgical treatment. HCC patients confirmed by surgical pathology were included in the study. The mean diffusivity (MD) values, mean kurtosis (MK) values, and apparent diffusion coefficient (ADC) were calculated. The differences and correlations of these parameters among different pathological grades were analyzed. The diagnostic efficiency of DKI and DWI for predicting high-grade HCC was evaluated by receiver operating characteristic (ROC) curves. Logistic regression analyses were used to evaluate the predictive factors for pathological grade.ResultsA total of 128 patients (79 males and 49 females, age: 56.9±10.9 years, range, 32–80) with primary HCC were included: grade I: 22 (17.2%) patients, grade II: 37 (28.9%) patients, grade III: 43 (33.6%) patients, grade IV: 26 (20.3%) patients. The MK values of stage I, II, III, and IV were 0.86±0.13, 1.06±0.11, 1.27±0.17, and 1.57±0.13, respectively. The MK values were significantly higher in the high-grade group than in the low-grade group and were positively correlated with pathological grade (rho =0.7417, P<0.001). The MK value demonstrated a larger area under the curve (AUC), with a value of 0.93 than the MD value, which had an AUC of 0.815 (P<0.001), and ADC, which had an AUC of 0.662 (P=0.01). The MK value (>1.19), ADC (≤1.29×10–3 mm2/s), and HBV (+) were independent predictors for the pathological grade of HCCs.ConclusionThe MK values derived from DKI and the ADC values obtained from traditional DWI were more valuable than the MD values in predicting the histological grade of HCCs and could potentially guide clinical treatment before surgery.

Multiple mathematical models of diffusion-weighted imaging for endometrial cancer characterization: Correlation with prognosis-related risk factors

PurposeTo investigate mono-exponential, bi-exponential, and stretched-exponential models of diffusion-weighted imaging (DWI) for evaluation of prognosis-related risk factors of endometrial cancer (EC). MethodSixty-one consecutive patients with EC who preoperatively underwent pelvic MRI with multiple b value DWI between September 2016 and May 2018 were enrolled. The apparent-diffusion-coefficient (ADC), bi-exponential model parameters (D, D* and f) and stretched-exponential model parameters (DDC and α) were measured and compared to analyze the following prognosis-related risk factors confirmed by pathology: histological grade, depth of myometrial invasion, cervical stromal infiltration (CSI) and lymphovascular invasion (LVSI). A stepwise multilvariate logistic regression and the receiver operating characteristic (ROC) curves were performed for further statistical analysis. ResultsLower ADC, D, f, and DDC were observed in tumor with high grade compared with a low-grade group, and the largest area under curve (AUC) was obtained when combining f and DDC values. ADC, D, f, DDC, and α were significantly different in patients with deep myometrial invasion (DMI) compared to those without DMI; the combination of f, DDC and α showed the highest AUC. Significantly different ADC and f were found between patients’ presence and absence CSI; the f values showed the highest diagnostic performance with an AUC of 0.825. Regarding the LVSI, ADC, D*, f, and DDC were significantly lower in tumors with LVSI compared to those without LVSI; the combination of f and DDC showed the largest AUC. ConclusionMultiple mathematical DWI models are a useful approach for the prediction of prognosis-related risk factors in EC.

Application of the amide proton transfer-weighted imaging and diffusion kurtosis imaging in the study of cervical cancer.

To analyze the value of amide proton transfer-weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) in differentiating cervical cancer (CC) pathological type, grade, and stage. One hundred and twelve women underwent pelvic APTWI and DKI. The magnetization transfer ratio asymmetry (MTRasym, 3.5ppm), apparent kurtosis coefficient (Kapp), and non-Gaussian diffusion coefficient (Dapp) were calculated by histological subtype, grade, and stage. The differences, efficacy, and correlation between parameters were determined. The MTRasym(3.5ppm) and Dapp values of the adenocarcinoma (CA) group were higher than those of the cervical squamous carcinoma (CSC) group, while the Kapp values were lower than those of the CSC group. The MTRasym(3.5ppm) and Kapp values of the high-grade group were higher than those of the low-grade group, while the Dapp values were lower than those of the low-grade group. The Dapp values of the advanced-stage group were lower than those of the early-stage group, while the Kapp values were greater than those of the early-stage group. The Kapp showed the highest efficacy in differentiating CSC and CA, high- and low-grade CC, and advanced- and early-stage CC. In the CSC and CA groups, both the Kapp and Dapp were highly correlated with pathological grade, and the MTRasym(3.5ppm) was weakly correlated with pathological grade. The Kapp, Dapp, and MTRasym(3.5ppm) were all weakly correlated with pathological stage. Both DKI and APTWI can be used in preliminary evaluations of CC, but DKI has advantages in the identification of pathological type, grade, and stage. • PTWI and DKI provide new information regarding cervical cancer. • MTRasym(3.5ppm), Dapp, and Kapp are valid parameters to characterize tissue microstructure. • DKI is superior to APTWI in the study of cervical cancer.

Biportal endoscopic discectomy for high-grade migrated lumbar disc herniation.

Although endoscopic procedures for lumbar disc herniation have improved greatly and offer many advantages, the indications are limited mostly to nonmigrated or low-grade migrated disc herniation. Endoscopic application in migrated disc herniation cases is still challenging and technically demanding. The goal in this study was to determine the feasibility of biportal endoscopic discectomy for removal of high-grade migrated disc herniation. A retrospective review was performed in 262 patients who had undergone biportal endoscopic discectomy after the diagnosis of lumbar herniated disc. According to preoperative MRI findings, disc herniation was classified into 5 zones based on the direction and distance from the disc space. Patients were divided into 2 groups-a high-grade migration group and a low-grade migration group. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified Macnab criteria, and those outcomes and operation time were compared between the 2 groups. There were 10 patients with "high-grade up," 8 with "low-grade up," 98 with disc-level, 102 with "low-grade down," and 44 with "high-grade down" herniation, thereby yielding 54 patients in the high-grade group and 208 in the low-grade group. Demographic data for the 2 groups showed no significant difference. There was no significant difference between the 2 groups in ODI, VAS, and modified Macnab criteria. Operation time between the 2 groups was not significantly different (60.74 vs 65.63 minutes, p > 0.05). Biportal endoscopic discectomy can be effective for high-grade migrated lumbar disc herniation with no prolonged operation time and satisfactory clinical outcomes.

Predictive Values of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Other Prognostic Factors in Pediatric Patients With Bell's Palsy.

Bell's palsy (BP) is the most frequent cause of unilateral facial paralysis, and inflammation is believed to play an important role in pathogenesis. Due to its rarity, however, no consensus has been reached regarding optimum treatment or factors affecting prognosis. In the present study, treatment outcomes and prognostic factors of BP were investigated in pediatric patients who underwent steroid therapy. The goal was to investigate the relationship between BP and inflammation using multiple inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and red cell distribution width (RDW). In all, 54 patients diagnosed with BP and 39 healthy randomly selected controls were enrolled in this retrospective study. Demographic characteristics and complete blood cell count test results were compared. In addition, prognostic factors were sought by dividing the 54 patients with BP into 2 groups according to the House-Brackmann grading system: low grade BP (grades II and III) and high grade BP (grades IV and V). Serum samples were analyzed retrospectively on initial presentation and 6 months after the symptom begins. Meaningful hematological parameters include NLR, PLR, MPV, and RDW. The NLR values in the BP group were significantly higher than in the control group. The NLR value in the 2 groups of patients with BP differed significantly. The mean PLR value in the BP group was higher than in the control group; however, there were no significant differences between the low-grade and high-grade BP groups nor were there any statically significant differences in the other characteristics. The NLR and PLR values are readily accessible parameters that may be useful prognostic markers in pediatric patients with BP. Further studies are required to confirm these results and their utility in predicting prognosis and treating pediatric patients with BP.

Molecular characterization of prostate cancer in Middle Eastern population highlights differences with Western populations with prognostic implication.

To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western population. Immunohistochemistry for ERG, PTEN and SPINK1 was performed in a cohort of localized PCA (n = 340). The data were correlated to pathological and clinical outcomes and compared to Western populations. ERG expression and PTEN loss were noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression was assessed in a subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in the lower grade groups (1-3 vs 4-5; p = 0.04). In contrast to the Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI 1.10-726, p = 0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI 0.98-7.33, p = 0.05), after adjusting for GG, path stage and surgical margin. This study documents significant differences in key molecular events in PCA in Middle Eastern population compared to Western populations that could explain differences in PCA incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest risk for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCA and add further insight to understanding PCA molecular pathways.

Prediction of surgical difficulty in minimally invasive surgery for rectal cancer by use of MRI pelvimetry.

BackgroundTechnical difficulties in rectal surgery are often related to dissection in a limited surgical field. This study investigated the clinical value of MRI pelvimetry in the prediction of surgical difficulty associated with minimally invasive rectal surgery.MethodsPatients with rectal cancer who underwent laparoscopic or robotic total mesorectal excision between 2005 and 2017 were reviewed retrospectively and categorized according to surgical difficulty on the basis of duration of surgery, conversion to an open procedure, use of the transanal approach, postoperative hospital stay, blood loss and postoperative complications. Preoperative clinical and MRI‐related parameters were examined to develop a prediction model to estimate the extent of surgical difficulty, and to compare anastomotic leakage rates in the low‐ and high‐grade surgical difficulty groups. Prognosis was investigated by calculating overall and relapse‐free survival, and cumulative local and distant recurrence rates.ResultsOf 121 patients analysed, 104 (86·0 per cent) were categorized into the low‐grade group and 17 (14·0 per cent) into the high‐grade group. Multivariable analysis indicated that high‐grade surgical difficulty was associated with a BMI above 25 kg/m2 (odds ratio (OR) 4·45, P = 0·033), tumour size 45 mm or more (OR 5·42, P = 0·042), anorectal angle 123° or more (OR 5·98, P = 0·028) and pelvic outlet less than 82·7 mm (OR 6·62, P = 0·048). All of these features were used to devise a four‐variable scoring model to predict surgical difficulty. In patients categorized as high grade for surgical difficulty, the anastomotic leakage rate was 53 per cent (9 of 17 patients), compared with 9·6 per cent (10 of 104) in the low‐grade group (P < 0·001). The high‐grade group had a significantly higher local recurrence rate than the low‐grade group (P = 0·002).ConclusionThis study highlights the impact of clinical variables and MRI pelvimetry in the prediction of surgical difficulty in minimally invasive rectal surgery.

MP62-04 ONCOLOGICAL PROGNOSIS AND PATHOLOGICAL FEATURE AFTER RADICAL PROSTATECTOMY ACCORDING TO THE ZONAL ORIGIN OF HIGH GRADE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Staging I (MP62)1 Apr 2020MP62-04 ONCOLOGICAL PROGNOSIS AND PATHOLOGICAL FEATURE AFTER RADICAL PROSTATECTOMY ACCORDING TO THE ZONAL ORIGIN OF HIGH GRADE PROSTATE CANCER Jung Jun Kim*, Sung Kyu Hong, and Seok Soo Byun Jung Jun Kim*Jung Jun Kim* More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , and Seok Soo ByunSeok Soo Byun More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000937.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We assessed the impact of prostatic zone tumor origin on pathological prognostic features and subsequent biochemical outcomes after radical prostatectomy. METHODS: A total of 3,823 patients who underwent radical prostatectomy between 2003 and 2018 were divided into two grade group. A high grade group was defined as Gleason sum ≥ 4+3 and ISUP (International Society of Urological Pathology) groups 3 to 5. A low grade group was defined as Gleason sum ≤ 3+4, and ISUP groups 1/2. The patients was also classified according to the location of index lesion which is transition zone and peripheral zone. The Kaplan-Meier method was used to determine differences in biochemical recurrence-free survival. RESULTS: The presence of high grade index lesion at transition zone cancer was associated with significantly increased prostate specific antigen, tumor volume and incidence of positive surgical margins but a lower incidence of extraprostatic extension, seminal vesicle invasion, lymph node involvement and biochemical failure after radical prostatectomy compared with high grade peripheral zone cancer (Table 1&2). And the outcome was consisitent regardless of surgical margin (Figure). The zonal origin could not differ the recurrence of low grade cases(Table 2). however, the patients with low grade prostate cancer demonstrated good pathology and decent oncological prognosis regardless of tumor origin. CONCLUSIONS: Among high grade cancer, high grade transition zone index lesion independently impact better biochemical outcome in spite of some worse clinical and pathological prognostic factors. To predict prognosis of high grade cancer patients after prostatectomy, the location of index lesion is definitely one of the factor to consider. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e946-e947 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jung Jun Kim* More articles by this author Sung Kyu Hong More articles by this author Seok Soo Byun More articles by this author Expand All Advertisement PDF downloadLoading ...

Serum and Urine Levels of Vascular Endothelial Growth Factor as Prognostic Markers in Patients with Bladder Cancer

Background: Bladder cancer is the second most common urinary cancer after prostate cancer. Recent studies have shown higher serum and urinary vascular endothelial growth factor (VEGF) in increased angiogenesis. In this study, the mean serum and urine level of VEGF was assessed in patients with bladder cancer. Methods: In this case-control study, 46 patients with bladder cancer referred to Imam-Khomeini Hospital in Tehran, Iran and 38 subjects as control, were enrolled and the mean serum and urine level of VEGF was assessed and compared between the groups. Results: The mean serum level of VEGF was 478.7, 518.4, and 648.1 in control, low-grade, and high-grade groups, respectively, with no significant difference (P=0.175). The mean urine level of VEGF was 414.2, 968.3, and 848.4 in control, low-grade, and high-grade groups, respectively, with significant difference (P=0.010). Conclusion: The mean urine level of VEGF in patients with bladder cancer is higher than healthy subjects.

The Expression and Prognostic Significance of Claudin-8 and Androgen Receptor in Breast Cancer.

PurposeClaudin-8 (CLDN8) has been identified as an androgen-regulated gene in prostate cancer. However, the role of CLDN8 has not been fully explored in breast cancer. We aimed to explore the expression of CLDN8 and androgen receptor (AR), determine the correlation between CLDN8 and AR, assess the prognostic value of CLDN8 and AR co-expression, and investigate the possible CLDN8 expression molecular mechanism in breast cancer.Materials and MethodsTwenty-eight pairs of fresh tumor tissues and adjacent noncancerous tissues were evaluated by Western blot for CLDN8. Then, 142 breast cancer samples were determined by immunohistochemistry for CLDN8 and AR. The association of clinicopathological features with CLDN8, AR and CLDN8, and AR co-expression was examined. The Cancer Genome Atlas (TCGA) was used to demonstrate the expression of CLDN8 and correlation between CLDN8 and AR. Kaplan–Meier survival analysis was performed to assess the prognostic impact of CLDN8 and AR co-expression. The mechanisms related to CLDN8 expression in breast cancer were explored by Gene Set Enrichment Analysis (GSEA).ResultsCLDN8 was downregulated in breast cancer tissues and positively correlated with none lymph node metastasis (P=0.016), low histological grade (P=0.006), positive ER (P=0.014), positive PR (P=0.003), low Ki-67 index (P=0.017) and molecular subtypes (P=0.012). CLDN8 level was significantly associated with AR level (r=0.348; P<0.001). CLDN8 and AR co-expression was positively correlated with none lymph node metastasis (P=0.007), low histological grade (P=0.017), positive ER (P=0.019), positive PR (P=0.015) and low Ki-67 index group (P=0.038). CLDN8 and AR co-expression had a better clinical prognosis.ConclusionThe expression of CLDN8 is directly related to the expression of AR. CLDN8 and AR co-expression might be a potential prognostic evaluation factor for breast cancer patients.

Role of baseline volumetric functional MRI in predicting histopathologic grade and patients' survival in hepatocellular carcinoma.

We aimed to evaluate the role of volumetric ADC (vADC) and volumetric venous enhancement (vVE) in predicting the grade of tumor differentiation in hepatocellular carcinoma (HCC). The study population included 136 HCC patients (188 lesions) who had baseline MR imaging and histopathological report. Measurements of vVE and vADC were performed on baseline MRI. Tumors were histologically classified into low-grade and high-grade groups. The parameters between the two groups were compared using Mann-Whitney U and chi-square tests for continuous and categorical parameters, respectively. Area under receiver operating characteristic (AUROC) was calculated to investigate the accuracy of vADC and vVE. Logistic regression and multivariable Cox regression were used to unveil the potential parameters associated with high-grade HCC and patient's survival, respectively. Lesions with higher vADC values and a higher absolute vADC skewness were more likely to be high grade on histopathology assessment (p = 0.001 and p = 0.0291, respectively). Also, vVE showed a trend to be higher in low-grade lesions (p = 0.079). Adjusted multivariable model including vADC, vVE, and vADC skewness could strongly predict HCC degree of differentiation (AUROC=83%). Additionally, a higher Child-Pugh score (HR = 2.39 [p = 0.02] for score 2 and HR = 3.47 [p = 0.001] for score 3), vADC skewness (HR = 1.52, p = 0.02; per increments in skewness), and tumor volume (HR = 1.1, p = 0.001; per 100cm3 increments) showed the highest association with patients' survival. vADC and vVE have the potential to accurately predict HCC differentiation. Additionally, some imaging features in combination with patients' clinical characteristics can predict patient survival. • Volumetric functional MRI metrics can be considered as non-invasive measures for determining tumor histopathology in HCC. • Estimating patient survival based on clinical and imaging parameters can be used for modifying management approach and preventing unnecessary adverse events.

Histogram analysis in predicting the grade and histological subtype of meningiomas based on diffusion kurtosis imaging.

Presurgical grading is particularly important for selecting the best therapeutic strategy for meningioma patients. To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the differentiation of grades and histological subtypes of meningiomas. A total of 172 patients with histopathologically proven meningiomas underwent preoperative magnetic resonance imaging (MRI) and were classified into low-grade and high-grade groups. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) histograms were generated based on solid components of the whole tumor. The following parameters of each histogram were obtained: 10th, 25th, 75th, and 90th percentiles, mean, median, maximum, minimum, and kurtosis, skewness, and variance. Comparisons of different grades and subtypes were made by Mann-Whitney U test, Kruskal-Wallis test, ROC curves analysis, and multiple logistic regression. Pearson correlation was used to evaluate correlations between histogram parameters and the Ki-67 labeling index. Significantly higher maximum, skewness, and variance of MD, mean, median, maximum, variance, 10th, 25th, 75th, and 90th percentiles of MK were found in high-grade than low-grade meningiomas (all P < 0.05). DKI histogram parameters differentiated 7/10 pairs of subtype pairs. The 90th percentile of MK yielded the highest AUC of 0.870 and was the only independent indicator for grading meningiomas. Various DKI histogram parameters were correlated with the Ki-67 labeling index (P < 0.05). The histogram analysis of DKI is useful for differentiating meningioma grades and subtypes. The 90th percentile of MK may serve as an optimal parameter for predicting the grade of meningiomas.

Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles

AbstractThe genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%. To investigate the genetic background of localized-stage FL, patient cohorts with advanced-stage FL or localized-stage FL, uniformly treated within phase 3 trials of the German Low-Grade Lymphoma Study Group, were comparatively analyzed. Targeted gene expression (GE) profiling of 184 genes using nCounter technology was performed in 110 localized-stage and 556 advanced-stage FL patients. By penalized Cox regression, a prognostic GE signature could not be identified in patients with advanced-stage FL, consistent with results from global tests and univariate regression. In contrast, it was possible to define robust GE signatures discriminating localized-stage and advanced-stage FL (area under the curve, 0.98) by penalized logistic regression. Of note, 3% of samples harboring an “advanced-stage signature” in the localized-stage cohort exhibited inferior failure-free survival (hazard ratio [HR], 7.1; P = .0003). Likewise, in the advanced-stage cohort, 7% of samples with a “localized-stage signature” had prolonged failure-free survival (HR, 2.3; P = .017) and overall survival (HR, 3.4; P = .072). These data support the concept of a biological difference between localized-stage and advanced-stage FL that might contribute to the superior outcome of localized FL.