Additional Biopsies Research Articles

Comparison of cold biopsy forceps vs cold snare for diminutive colorectal polyp removal: A multicenter non-inferiority randomized controlled trial

European guidelines recommends the use of cold snare polypectomy (CSP) for removal of diminutive colorectal polyps (DCP). However, for DCP < 4 mm cold biopsy forceps (CBF) may be optional. We aimed to compare the efficacy of CSP with CBF for removal of DCP in routine colonoscopy. We conducted a multicenter non-inferiority randomized controlled trial. After screening, 123 patients were prospectively included and 180 DCPs were removed by either CBF or CSP after randomization (1:1). The primary end-point was the histological complete resection rate defined by negative additional biopsies taken from the edge of the polypectomy ulcer site. Among DCPs, 121 (67.2%) adenomas or sessile serrated lesions were considered for the analysis. Polyps were 4 [1-5] mm in size, mostly flat (55.4%) and located in the proximal colon (44.6%). The en bloc resection rate was higher in the CSP group than the CBF group (91.7% vs. 42.6%, p<0.001). The histological complete resection rate was comparable in the two groups (93.33% vs 90.16%; p=0.527), even for polyps < 4 mm (91.30% vs 91.30%; p=1). All specimens were retrieved and there was no difference in terms of procedure times and adverse events. Finally, univariate analysis did not identify any potential factor associated with complete resection rate. In this study, CSP was comparable to CBF for the removal of DCP. Therefore, CBF may be considered as an alternative technique for resection of DCP, together with CSP, ClinicalTrials.gov registry (NCT04727918).

Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients.

Two hundred twenty-four breast cancer patients with paired tissue and plasma samples were enrolled from 3 clinical centers to evaluate sensitivity and specificity of a digital PCR HER2 amplification assay. All patients were histologically confirmed diagnosis of locally advanced and recurrent or metastatic breast cancer with stage III/IV and had tissue HER2 status determinations using IHC/FISH. For the whole 224 advanced breast cancer patients, the sensitivity between dPCR in plasma and IHC/FISH in tissue samples is 43.75% (42/96), the specificity is 84.38% (108/128) and the overall concordance is 66.96% (150/224). Interestingly, when we looked at stage III, stage IV and recurrent or metastatic breast cancer separately, compared with IHC/FISH in tissue samples, the sensitivity of dPCR in plasma increases from 37.93% (11/29) for stage III to 41.67% (15/36) for stage IV cancer. Recurrent breast cancer patient had an increased sensitivity of 51.61% (16/31). This is consistent with our expectation sensitivity would increase concordantly as tumor burden goes up. On the other hand, specificity decreased from 92.68% (38/41) for stage III to 86.44% (51/59) for stage IV cancer. Recurrent breast cancer patient had a specificity of only 67.86% (19/28). This is, in part, due to inter- and intra-tumor heterogeneity. Many patients determined to be negative for HER2 amplification in tissue biopsy could have HER2 positive tumors at other sites, which was detected by the liquid biopsy. This study suggested the necessity of liquid biopsy for HER2 amplification detection and demonstrated digital PCR can be used as a companion diagnostic tool to determine HER2 amplification status. It also suggested that a liquid biopsy should follow a negative result from tissue biopsy to avoid false negative results especially for late-stage breast cancer patients and ones who experienced relapse or became resistant to current therapy. Future studies should focus on therapeutic effects on patients determined to be HER2 positive through liquid biopsy and collecting additional tissue biopsies to identify HER2 positive tumor when the original tissue biopsy and liquid biopsy don't agree.

A Tale of Two Pathologies

Background: In workup for a tumor in an individual, a second pathology is discovered at times, which can complicate further management. Cross-sectional imaging is widely utilized in gastrointestinal tumors leading to identification of incidentalomas, and we audited our multidisciplinary team (MDT) meeting data in order to analyze the implications and refine the approach in the presence of dual pathology. Materials and Methods: This study was a retrospective assessment of a prospectively maintained single institute gastrointestinal tumor board MDT database between June 2019 and June 2020. Results: Of the 76 patients discussed in the gastrointestinal MDT, 21 patients associated with clinically relevant second pathology were included in the study group. Positron emission tomography–computed tomography (PET-CT) was the most common modality responsible for detection of the second pathology. Additional workup to better characterize these findings was needed in 10 (47.6%) patients. Eleven patients had dual neoplasms, of which four accounted for dual malignant neoplasms. MDT resulted in a change in plan in 6 (28.6%) patients, which was mainly related to radiology review, thereby downstaging to the correct stage. Conclusions: PET-CT increases detection of a second pathology in gastrointestinal tumors. Appropriate review of radiology, supplementing with additional imaging and/or biopsy, and wait and reassess in selected situations in an MDT is pivotal in management of a double pathology.

Usefulness of grayscale values measuring hypoechoic lesions for predicting prostate cancer: An experimental pilot study.

BackgroundTo ensure reproducibility and representativeness of hypoechoic lesions in transrectal ultrasonography (TRUS), we used grayscale values and evaluated their usefulness in predicting prostate cancer (PCA).MethodsA total of 172 patients scheduled for prostate biopsy for suspected PCA between October 2016 and May 2018 were prospectively enrolled. Patients underwent 12 core target biopsies for hypoechoic lesions in 12 areas of the prostate and two additional target biopsy cores for two hypoechoic lesions. We estimated the grayscale value of the image using a red/green/blue scoring method through a function embedded in the picture archiving and communication system. Imaging data were analyzed using estimated grayscale values.ResultsOf the 127 patients (median age = 68.5 years, median prostate-specific antigen level = 6.19 ng/mL), 67 (52.8%) had PCA. Of 1778 biopsy lesions, 327 (18.4%) were PCA lesions. No differences in the grayscale values were found between PCA and benign lesions; however, the grayscale value between 28.0 and 57.0 for hypoechoic lesions was identified as a significant factor for predicting PCA in multivariable analysis (p=0.008). Multivariable analysis indicated a grayscale value between 34.0 and 48.0 as a predicting factor for clinically significant PCA (cs-PCA: Gleason grade group ≥2) (p=0.001). The area under the curve (AUC) for predicting cs-PCA was higher for combined clinical and grayscale value parameters than for TRUS grayscale values (0.780 vs. 0.561, p<0.001).ConclusionsHypoechoic lesions that meet the quantitative criteria seem useful for predicting cs-PCA. The presence of hypoechoic lesions is not a predicting factor for PCA.

Magnetic resonance imaging-guided biopsies in children.

BackgroundMagnetic resonance imaging (MRI) is used far less as an imaging-guided method for percutaneous biopsies than computed tomography (CT) and ultrasound (US), despite its imaging benefits, particularly in children.PurposeTo evaluate the feasibility, accuracy and safety of MRI-guided biopsies in paediatric patient population.Material and MethodsThe retrospective study included 57 consecutive paediatric patients (<18 years old). A percutaneous core needle biopsy (PCNB) or trephine biopsy was performed in 53 cases, and an additional fine-needle aspiration biopsy (FNAB) in 26 cases. In 4 cases, a stand-alone FNAB was taken. Biopsies were performed with 0.23 T open and 1.5 T closed MRI scanners. Statistical methods used for confidence intervals and p-values were Wilson score method and chi-square test.ResultsThe overall diagnostic accuracy of histologic biopsy was 0.94, with sensitivity 0.82, specificity 1.00, positive predictive value (PPV) 1.00 and negative predictive value (NPV) 0.92. In histological bone biopsies, diagnostic accuracy was 0.96, with sensitivity 0.86, specificity 1.00, PPV 1.00 and NPV 0.94. The FNAB sample diagnosis was associated with the histological diagnosis in 79% of cases. There were no major primary complications and only a few late complications. After biopsy, 83% of the children were ambulatory in 6 h. Anti-inflammatory drugs and paracetamol provided satisfactory pain relief in 96% of the patients after biopsy. Most outpatients (71%) were discharged from hospital either on the same day or 1 day later.ConclusionMRI is a technically feasible, accurate and safe guidance tool for performing percutaneous biopsies in children.

Preoperative MRI in breast cancer: effect of breast density on biopsy rate and yield.

Preoperative breast MRI is used to evaluate for additional cancer and extent of disease for newly diagnosed breast cancer, yet benefits and harms of preoperative MRI are not well-documented. We examined whether preoperative MRI yields additional biopsy and cancer detection by extent of breast density. We followed women in the Breast Cancer Surveillance Consortium with an incident breast cancer diagnosed from 2005 to 2017. We quantified breast biopsies and cancers detected within 6months of diagnosis by preoperative breast MRI receipt, overall and by breast density, accounting for MRI selection bias using inverse probability weighted logistic regression. Among 19,324 women with newly diagnosed breast cancer, 28% had preoperative MRI, 11% additional biopsy, and 5% additional cancer detected. Four times as many women with preoperative MRI underwent additional biopsy compared to women without MRI (22.6% v. 5.1%). Additional biopsy rates with preoperative MRI increased with increasing breast density (27.4% for extremely dense compared to 16.2% for almost entirely fatty breasts). Rates of additional cancer detection were almost four times higher for women with v. without MRI (9.9% v. 2.6%). Conditional on additional biopsy, age-adjusted rates of additional cancer detection were lowest among women with extremely dense breasts, regardless of imaging modality (with MRI: 35.0%; 95% CI 27.0-43.0%; without MRI: 45.1%; 95% CI 32.6-57.5%). For women with dense breasts, preoperative MRI was associated with much higher biopsy rates, without concomitant higher cancer detection. Preoperative MRI may be considered for some women, but selecting women based on breast density is not supported by evidence. ClinicalTrials.gov: NCT02980848; registered 2017.

Accuracy of Prostate Multiparametric MRI in Identification of Intraprostatic Tumor Deposits Validated on Transperineal Biopsies

To determine the accuracy of prostate multiparametric (mp) MRI in identification of intraprostatic tumor deposits using a systematic and targeted MR-guided transperineal prostate biopsy technique as a reference.One hundred sixty patients underwent a combined systematic and targeted MRI-guided prostate biopsy using a transperineal approach under general anesthesia. For each patient, a pre-biopsy mpMRI scan was obtained and imported into a prostate biopsy planning system. Transverse images were then reoriented from the supine to dorsal lithotomy position. Dividing the prostate into an apical and base section, a systematic array of transperineal biopsies spaced approximately 10mm apart was planned with additional biopsies targeting mpMRI-identified PI-RADS 3, 4 or 5 lesions. Biopsy procedures were carried out in the dorsal lithotomy position using a transrectal ultrasound with stepper-stabilizer and template grid. Matching of the planning mpMRI images to live ultrasound images was achieved using the template grid as a reference.All patients successfully underwent their biopsy procedure as planned. An average of 26 biopsy specimens were obtained per patient (range 11-44). Twenty-nine percent (15/52) of PI-RADS 3 lesions, 49% (46/94) of PI-RADS 4 lesions, and 76% (39/51) of PI-RADS 5 lesions were pathologically confirmed prostate cancer. Forty-two percent (67/160) of patients harbored mpMRI-unidentified prostate cancer. Twenty-two percent (36/160) of patients harbored mpMRI-unidentified GS≥7 disease and four percent (7/160) of patients harbored mpMRI-unidentified GS≥8 disease.Using prostate mpMRI to identify intraprostatic tumor deposits without pathologic confirmation would lead to significant numbers of false positive mpMRI identified lesions and miss clinically significant prostate cancer outside of mpMRI identified lesions in over 20% of patients. Use of systematic prostate biopsy information appears necessary to significantly improve the accuracy of mpMRI identification of intraprostatic tumor deposits.

The Role of Prostate Combination Biopsy Consisting of Targeted and Additional Systematic Biopsy.

Background: To identify the role of combination biopsy, which consists of both targeted and additional systematic cores, in the diagnosis of clinically significant prostate cancer (csPCa). Methods: We retrospectively reviewed patients with PSA levels 2.5–15 ng/mL who have a suspicious prostate lesion (with the Prostate Imaging Reporting and Data System (PI-RADS) ≥ 3) on multiparametric MRI (mpMRI) between January 2016 and December 2018. We analyzed biopsy results by PI-RADS score and biopsy methods (systematic, targeted, and combination biopsy). Results: Of the 711 total patients, an average of 4.0 ± 1.8 targeted and 8.6 ± 3.1 additional systematic biopsies were performed. The additional systematic biopsies were sampled outside the targeted biopsy area. The combination biopsies detected more csPCa (201 patients, 28.3%) than did the targeted (175 patients, 24.6%) or systematic (124 patients, 17.4%) biopsies alone (p < 0.001). In the initial biopsy samples, there was a 7% increase in the detection of csPCa than in targeted biopsy (62% to 69%). It increased by 11% in repeat biopsy (46% to 57%). There was no statistical significance in both groups (p = 0.3174). Conclusions: Combination biopsy has the benefit of detecting csPCa in both initial and repeat biopsy when there is a suspicious lesion on mpMRI.

S79 Safety and Efficacy of Fluoroscopic Forceps Biopsy of Indeterminate Biliary Strictures

Introduction: Fluoroscopy-guided forceps biopsy (FGFB) of indeterminate biliary strictures is one method of tissue acquisition performed at ERCP. Endoscopic techniques for FGFB have not been standardized. There are theoretical benefits to individual devices stemming from their construction, design, diameter, and maneuverability. There are no studies comparing different biopsy forceps for yield or safety. We aim to compare the safety and yield of three different biopsy forceps for FGFB at ERCP. Methods: We conducted an observational retrospective study at a tertiary care center of patients undergoing ERCP for indeterminate biliary stricture with FGFB between 01/2018 and 05/2021. Endoscopy documentation software was queried for “stricture” and “biopsy” in patients who had ERCP. Biopsy forceps type were recorded (RadialJaw 4™ (Boston Scientific Corp, Boston, MA) jumbo, large, and pediatric corresponding to a forceps length of 2.8, 2.4 and 2.0mm, respectively, with the first two including a needle). Data points included location and length of stricture, additional biopsy modalities, cytology and pathology results, tumor markers, and clinical course. Diagnoses were considered definitive if pathology returned positive for malignancy. A benign diagnosis was determined after 6 months of follow up without concerns of cancer. Results: 88 patients had FGFB of indeterminate biliary strictures using jumbo (n=36), large (n=9), pediatric (n=40), and a combination of pediatric and large (n=3) forceps, respectively. Definitive diagnoses were made in 30% of individuals (Table). There was no difference in diagnostic yield amongst the different biopsy forceps [X2(3) = 1.675 (P=0.642)]. Univariable analysis of stricture length, stricture location and presence of a mass on imaging was not associated with a definitive tissue diagnosis on biopsy. In those with negative biopsies, but in whom malignancy was identified, brush cytology most commonly yielded the diagnosis. Three patients had post-ERCP pancreatitis (all had pediatric forceps used for FGFB). No patients had biopsy induced bleeding or perforation. Conclusion: Forceps size does not affect outcome of fluoroscopy-guided forceps biopsy of biliary strictures with an overall yield of 30%. Adverse events are rare with fluoroscopic biopsy. Expansion of this dataset may offer further insights into the safety and efficacy of this procedure.Table 1.: Biopsy Forceps Size and Tissue Diagnosis Yield.

Systematic tissue collection during clinical breast biopsy is feasible, safe and enables high-content translational analyses

Systematic collection of fresh tissues for research at the time of diagnostic image-guided breast biopsy has the potential to fuel a wide variety of innovative studies. Here we report the initial experience, including safety, feasibility, and laboratory proof-of-principle, with the collection and analysis of research specimens obtained via breast core needle biopsy immediately following routine clinical biopsy at a single institution over a 14-month period. Patients underwent one or two additional core biopsies following collection of all necessary clinical specimens. In total, 395 patients were approached and 270 consented to the research study, yielding a 68.4% consent rate. Among consenting patients, 238 lesions were biopsied for research, resulting in 446 research specimens collected. No immediate complications were observed. Representative research core specimens showed high diagnostic concordance with clinical core biopsies. Flow cytometry demonstrated consistent recovery of hundreds to thousands of viable cells per research core. Among a group of HER2 + tumor research specimens, HER2 assessment by flow cytometry correlated highly with immunohistochemistry (IHC) staining, and in addition revealed extensive inter- and intra-tumoral variation in HER2 levels of potential clinical relevance. Suitability for single-cell transcriptomic analysis was demonstrated for a triple-negative tumor core biopsy, revealing substantial cellular diversity in the tumor immune microenvironment, including a prognostically relevant T cell subpopulation. Thus, collection of fresh tissues for research purposes at the time of diagnostic breast biopsy is safe, feasible and efficient, and may provide a high-yield mechanism to generate a rich tissue repository for a wide variety of cross-disciplinary research.

Does fine needle aspiration from a different nodule other than the dominant nodule provide additional benefit in thyroid diseases with nodules?

Objectives: The incidence of thyroid nodules has increased significantly and malignancy detected in 5-15% of them. While biopsy is recommended for all nodules larger than 1 cm in multinodular goiter, this is practically not possible in many patients. In addition, the relationship between nodule size and malignancy is not clear. We aimed to examine the value of additional biopsy from a nondominant nodule in terms of changing treatment and follow-up decisions and the relationship between nodule size and malignancy risk.&#x0D; Material and Method: Patients (n=2,541) with thyroid nodules who applied to our clinic for various indications and performed fine needle aspiration between January 1, 2016 and March 1, 2021 were included in the study. Some of our patients with multinodular goiter were biopsied from a second additional nodule. Cytologic evaluations reported according to the Bethesta system. Pathology reports of the operated patients were scanned retrospectivelly.&#x0D; Results: Fine needle aspiration biopsy was performed from a total of 3382 nodules of 2541 patients. The average age of our patient group was 56 (46-65) and 79% of them were women. When a comparison was made between nodule size and malignancy rate; the highest malignancy rate was detected in nodules between 1-2 cm (61,8%). Finally, a diagnosis of Bethesta-4,-5,-6 was reached in only 7 (0.9%) of 823 patients who underwent additional biopsy from nondominant nodule.&#x0D; Conclusion: The value of an additional biopsy from a second nodule in terms of changing follow-up is very low and not significant and most of the cancers arise from nodules between 1-2 cm. According to our study, the assumptions that the malignancy risk increases as the nodule size or nodule count increase were not found to be correct.

MP11-10 RE-REFERRAL RATES IN THE MEDIUM TERM IN PATIENTS WITH A NON-SUSPICIOUS MPMRI WITHIN THE RAPID PATHWAY

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-10 RE-REFERRAL RATES IN THE MEDIUM TERM IN PATIENTS WITH A NON-SUSPICIOUS MPMRI WITHIN THE RAPID PATHWAY Mariana Bertoncelli Tanaka, Uma Walter, David Eldred-Evans, Edward J. Bass, Martin J. Connor, Pallab Sarkar, Feargus Hoskings-Jervis, Heather Bhola-Stewart, Elizabeth Pegers, Laura Powell, Deepa Leelamany, Kathie Wong, Shahzad Ahmad, Henry Tam, Hasan Qazi, Stephen Gordon, David Hrouda, Stuart McCracken, Mathias Winkler, and Hashim U. Ahmed Mariana Bertoncelli TanakaMariana Bertoncelli Tanaka More articles by this author , Uma WalterUma Walter More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Edward J. BassEdward J. Bass More articles by this author , Martin J. ConnorMartin J. Connor More articles by this author , Pallab SarkarPallab Sarkar More articles by this author , Feargus Hoskings-JervisFeargus Hoskings-Jervis More articles by this author , Heather Bhola-StewartHeather Bhola-Stewart More articles by this author , Elizabeth PegersElizabeth Pegers More articles by this author , Laura PowellLaura Powell More articles by this author , Deepa LeelamanyDeepa Leelamany More articles by this author , Kathie WongKathie Wong More articles by this author , Shahzad AhmadShahzad Ahmad More articles by this author , Henry TamHenry Tam More articles by this author , Hasan QaziHasan Qazi More articles by this author , Stephen GordonStephen Gordon More articles by this author , David HroudaDavid Hrouda More articles by this author , Stuart McCrackenStuart McCracken More articles by this author , Mathias WinklerMathias Winkler More articles by this author , and Hashim U. AhmedHashim U. Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Our ‘one-stop’ Rapid Access Prostate Imaging and Diagnosis (RAPID) pathway across five hospitals in our region streamlined our one-stop mpMRI and if required, transperineal prostate biopsies. We report on the re-referral rates of men who had undergone previous investigation on the RAPID pathway. METHODS: Data from consecutive patients on the RAPID pathway (April/2017 to December/2020) was entered into the online RAPID registry. A transperineal targeted and systematic prostate biopsy (TP-Bx) was offered on the same day if the mpMRI score was 4 or 5. A score of 3 required a PSA density ≥ 0.12. The re-referral assessment was checked based on computer assistance. RESULTS: 2869 patients with mean age 66 [IQR 59-72] and mean PSA 7.5 (5.8-11.3) were referred for prostate cancer investigation. In total, 49% [1406/2869] were discharged without a suspicion of cancer. 3% (37/1196) were rereferred by their GP due to ongoing concern for prostate cancer. Mean age was 67 (46-80) and mean PSA 9.5 (1.4-19.5). From those, 13 (35%) required biopsy in addition to MRI. Four (10%) had a histological diagnosis of prostate cancer of Gleason 3+4. CONCLUSIONS: RAPID is a safe pathway in the medium term when discharging men without biopsy following a non-suspicious mpMRI. After 3 years of follow-up, the mpMRI diagnostic pathway has a low re-referral rate and even on the rereferral group, 65% still did not meet criteria for a biopsy. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e181-e181 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mariana Bertoncelli Tanaka More articles by this author Uma Walter More articles by this author David Eldred-Evans More articles by this author Edward J. Bass More articles by this author Martin J. Connor More articles by this author Pallab Sarkar More articles by this author Feargus Hoskings-Jervis More articles by this author Heather Bhola-Stewart More articles by this author Elizabeth Pegers More articles by this author Laura Powell More articles by this author Deepa Leelamany More articles by this author Kathie Wong More articles by this author Shahzad Ahmad More articles by this author Henry Tam More articles by this author Hasan Qazi More articles by this author Stephen Gordon More articles by this author David Hrouda More articles by this author Stuart McCracken More articles by this author Mathias Winkler More articles by this author Hashim U. Ahmed More articles by this author Expand All Advertisement Loading ...

MP35-09 TRANSPERINEAL PROSTATE BIOPSY: THE FIRST ANALYSIS OF THE TRUE PROSTATE MICROBIOME

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia (MP35)1 Sep 2021MP35-09 TRANSPERINEAL PROSTATE BIOPSY: THE FIRST ANALYSIS OF THE TRUE PROSTATE MICROBIOME Clay Martin, Pandya Shashank, Annette Lee, and Michael Schwartz Clay MartinClay Martin More articles by this author , Pandya ShashankPandya Shashank More articles by this author , Annette LeeAnnette Lee More articles by this author , and Michael SchwartzMichael Schwartz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002044.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The human microbiome has become a rapidly evolving field of research with health implications in a variety of organ systems. Despite this growing body of literature, little is understood about the microbiome of the prostate. A major difficulty in prostate microbiome research is the difficulty in uncontaminated sample collection. Prior studies have utilized transrectal biopsy cores or surgical pathology specimens, both of which introduce significant contamination. The shift from transrectal to transperineal prostate biopsy technique provides a novel way of obtaining uncontaminated prostate specimens. This study aims to use transperineal prostate biopsy specimens to provide an initial description of the microbiome of the prostate. METHODS: Adult, biopsy-naive men (age 18 and older) who were undergoing elective transperineal prostate biopsy for medically indicated purposes were collected prospectively for inclusion in the study. Those with prior prostate biopsies or surgery, a history of chronic or acute prostatitis, history of chronic pelvic pain, antibiotics within 30 days of biopsy, catheterization within 60 days of biopsy, history of chronic indwelling or clean intermittent catheterizations were excluded such to represent the native bacteria of the unmanipulated gland. In addition to 12-14 diagnostic biopsies, enrolled patients underwent 2 additional biopsies. These core biopsies, along with skin and urine samples were sent directly for microbiome analysis via Illumina 16S Metagenomic sequencing. RESULTS: Prostate tissue samples, voided urine and perineal skin swabs from 10 patients were sent for analysis. 1 prostate biopsy specimen was excluded for suspected contamination. Evidence of a distinct microbiome within the prostate was discovered. Prominent species included Pseudomonas veronii, Comamonas testosteroni and Achromobacter xylosoxidans groups. Phylogenic diversity and weighted UniFrac analysis suggest a significant difference between biopsy specimens and perineal skin swabs but not a significant difference between the biopsy specimens and voided urine samples. CONCLUSIONS: These findings suggest that there exists a distinct microbiome specific to the human prostate gland, which may be closely related to that of bladder urine. Sterile sampling via transperineal ultrasound-guided prostate biopsy represents a viable method of sample collection for microbiome analysis. Further research is needed to further characterize the microbiome of the prostate and to elucidate the potential implications on human health and disease states. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e630-e630 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Clay Martin More articles by this author Pandya Shashank More articles by this author Annette Lee More articles by this author Michael Schwartz More articles by this author Expand All Advertisement Loading ...

PD56-12 UTILIZATION OF MRI AND GENOMIC TESTS IN MEN WITH LOW-RISK PROSTATE CANCER AND A LIMITED LIFE EXPECTANCY WITHIN A MULTI-INSTITUTIONAL REGIONAL COLLABORATIVE

You have accessJournal of UrologyProstate Cancer: Detection & Screening VI (PD56)1 Sep 2021PD56-12 UTILIZATION OF MRI AND GENOMIC TESTS IN MEN WITH LOW-RISK PROSTATE CANCER AND A LIMITED LIFE EXPECTANCY WITHIN A MULTI-INSTITUTIONAL REGIONAL COLLABORATIVE Laura Kidd, Adrien Bernstein, Kevin Ginsburg, Elizabeth Handorf, Kaynaat Syed, Chintan Mehta, John Danella, Serge Ginzburg, Laurence Belkoff, Adam Reese, Jeffrey Tomaszewski, Eric Singer, Edouard Trabulsi, Bruce Jacobs, Jay Raman, Thomas Guzzo, and Marc Smaldone Laura KiddLaura Kidd More articles by this author , Adrien BernsteinAdrien Bernstein More articles by this author , Kevin GinsburgKevin Ginsburg More articles by this author , Elizabeth HandorfElizabeth Handorf More articles by this author , Kaynaat SyedKaynaat Syed More articles by this author , Chintan MehtaChintan Mehta More articles by this author , John DanellaJohn Danella More articles by this author , Serge GinzburgSerge Ginzburg More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Adam ReeseAdam Reese More articles by this author , Jeffrey TomaszewskiJeffrey Tomaszewski More articles by this author , Eric SingerEric Singer More articles by this author , Edouard TrabulsiEdouard Trabulsi More articles by this author , Bruce JacobsBruce Jacobs More articles by this author , Jay RamanJay Raman More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , and Marc SmaldoneMarc Smaldone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002090.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Watchful waiting (WW) is the recommended management for men with low-risk prostate cancer (LRPC) and limited life expectancy (LLE). As such, the utility of ancillary testing (AT), MRI or genomics, in this population has not been well established. Herein we investigate the use of ancillary testing in a population of LRPC patients with LLE. METHODS: The Pennsylvania Urologic Regional Collaborative database was queried, identifying men with LRPC and LLE (age ≥70 & Charlson Comorbidity Index ≥5). Patients were stratified by receipt of post-diagnostic AT. The primary outcome was the proportion of men who underwent treatment with curative intent (radiation or surgery). AT results were deemed non-reassuring (non-RA; 2.7% probability of prostate cancer mortality for Prolaris, Risk group > low risk for OncotypeDx and Decipher, PIRADS 4 or 5 on mpMRI) or reassuring (RA). Categorical parameters were compared with the Chi-squared test and Fisher's exact test. Non-parametric continuous measures were assessed by the Wilcoxon rank sum test. Multivariable logistic regression models were fit to assess the association of obtaining an ancillary test and management strategy or obtaining additional biopsies. RESULTS: 299 men with LLE were newly diagnosed with LRPC. 155 (53%) underwent ancillary testing with their longitudinal experience plotted in Figure 1. Both groups had similar PSA at diagnosis and volume of disease on diagnostic biopsy. AT patients were more likely to have very low-risk prostate cancer (64.1% vs. 51.1%, p=0.03). There was also significant variability in testing by practice site (0-100% of LRPC patients, p<0.001). MRI was ordered in 80% of AT patients and was non-RA in 41%, while genomic testing was ordered in 35% and was non-RA for 73% of patients. Overall, 43% of men received definitive therapy, with the highest rate in RA patients (55%), and lower rates in non-RA (38%) or no ancillary studies (40%, p<0.001). On multivariable analysis, adjusting for age, disease volume and race, AT was not associated with odds of definitive treatment (OR=1.1, 95% CI 0.7-1.7, p=0.62). Paradoxically, men with RA tests were at increased risk of treatment (OR=3.1, 95% CI: 1.6-6.0 p=0.001). Additionally, men with AT were five-times more likely to receive additional biopsies (OR 5.2, 95% CI: 3.07-8.91 p<0.001). CONCLUSIONS: Ancillary testing occurs frequently in older men with LRPC and does not appear to shape subsequent treatment decisions, potentially increasing the cost and invasiveness of care without adding value. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1008-e1008 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Laura Kidd More articles by this author Adrien Bernstein More articles by this author Kevin Ginsburg More articles by this author Elizabeth Handorf More articles by this author Kaynaat Syed More articles by this author Chintan Mehta More articles by this author John Danella More articles by this author Serge Ginzburg More articles by this author Laurence Belkoff More articles by this author Adam Reese More articles by this author Jeffrey Tomaszewski More articles by this author Eric Singer More articles by this author Edouard Trabulsi More articles by this author Bruce Jacobs More articles by this author Jay Raman More articles by this author Thomas Guzzo More articles by this author Marc Smaldone More articles by this author Expand All Advertisement Loading ...

1772P Demonstration of T cell redirection and immune activation in skin rash following tebentafusp treatment

Tebentafusp (tebe) is an investigational TCR–anti-CD3 bispecific fusion protein that targets gp100 and activates T cells. In a recent phase 3 study, tebe improved overall survival (OS) in metastatic uveal melanoma patients (pts)1. Most pts developed skin rash after dose 1, an expected adverse event since melanocytes also express gp100; however, rash was not an independent predictor of OS benefit2. 12/14 pts developed >1 grade rash within 7 days post 1st dose. Paired skin biopsies from pts with metastatic melanoma (NCT01211262) were collected pre and post the 1st (N=12) or 4th (N=2) dose of tebe. Fixed samples were assessed by hematoxylin and eosin and CD3 immunohistochemistry (IHC). On 5 additional skin biopsies, dual IHC for Melan-A and CD4/8 was performed. RNAlater® samples were analyzed by RNAseq. Differential gene expression, pathway and cell type composition analysis were performed using R software. Biopsies from these pts showed increase in lymphocytic infiltrate, exocytosis of lymphocytes and basal cell vacuolization (p=0.002) along the dermo-epidermal junction (DEJ) and upper dermal perivascular inflammatory infiltrate (p=0.01) post treatment compared to baseline. The DEJ inflammatory infiltrate consisted of CD3+ T cells, which were predominantly CD8+ and localized close to melanocytes. RNAseq identified 1786 differentially expressed genes (threshold: p-adj≤0.05, log2-ratio≥0.75), with enrichment of innate and adaptive pathways, including IFNγ signaling, post treatment compared to baseline (p-adj<10-17). An increase in macrophage and CD8+ T cell genes was accompanied by upregulation of the cytotoxic genes GZMB and PRF1 (p-adj<10-6). Chemokines CXCL9/10/11 and cytokines IL-10/15/32 were overexpressed (p-adj<10-7). Expression of melanocyte markers, PMEL, MLANA and DCT were decreased. Tebe induced rapid recruitment of T cells in the proximity of intraepidermal melanocytes in addition to macrophage activation. Thus tebe-induced skin rash is an on-target effect and may be an important pharmacodynamic tool to better understand the precise molecular and cellular cascades of T cell redirection in the tumor. 1Piperno-Neumann S. AACR 2021 CT002. 2Hassel J. ASCO 2021 #9527.

PD17-06 PSA VELOCITY PREDICTS CLINICAL PROGRESSION IN AFRICAN AMERICAN AND NON-HISPANIC WHITE PATIENTS WITH LOW RISK PROSTATE CANCER UNDERGOING ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (PD17)1 Sep 2021PD17-06 PSA VELOCITY PREDICTS CLINICAL PROGRESSION IN AFRICAN AMERICAN AND NON-HISPANIC WHITE PATIENTS WITH LOW RISK PROSTATE CANCER UNDERGOING ACTIVE SURVEILLANCE Juan Javier-DesLoges, Tyler Nelson, Rishi Deka, Patrick Courtney, Vinit Nalawade, Loren Mell, James Murphy, J. Kellogg Parsons, and Brent Rose Juan Javier-DesLogesJuan Javier-DesLoges More articles by this author , Tyler NelsonTyler Nelson More articles by this author , Rishi DekaRishi Deka More articles by this author , Patrick CourtneyPatrick Courtney More articles by this author , Vinit NalawadeVinit Nalawade More articles by this author , Loren MellLoren Mell More articles by this author , James MurphyJames Murphy More articles by this author , J. Kellogg ParsonsJ. Kellogg Parsons More articles by this author , and Brent RoseBrent Rose More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001999.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. METHODS: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. RESULTS: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p<0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). CONCLUSIONS: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols. Source of Funding: Department of Defense, grant number W81XWH-17-PCRP-PRA (RD and BSR) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e286-e287 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan Javier-DesLoges More articles by this author Tyler Nelson More articles by this author Rishi Deka More articles by this author Patrick Courtney More articles by this author Vinit Nalawade More articles by this author Loren Mell More articles by this author James Murphy More articles by this author J. Kellogg Parsons More articles by this author Brent Rose More articles by this author Expand All Advertisement Loading ...

MP11-07 CLINICAL BENEFIT OF A HIGH CONCORDANCE BETWEEN TRANSPERINEAL TARGETED PLUS SYSTEMATIC MAPPING BIOPSIES AND RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-07 CLINICAL BENEFIT OF A HIGH CONCORDANCE BETWEEN TRANSPERINEAL TARGETED PLUS SYSTEMATIC MAPPING BIOPSIES AND RADICAL PROSTATECTOMY Marian S. Wettstein, Josias B. Grogg, Andres Affentranger, Camille Cruz, Nico C. Grossmann, Thomas Hermanns, Cédric Poyet, and Christian D. Fankhauser Marian S. WettsteinMarian S. Wettstein More articles by this author , Josias B. GroggJosias B. Grogg More articles by this author , Andres AffentrangerAndres Affentranger More articles by this author , Camille CruzCamille Cruz More articles by this author , Nico C. GrossmannNico C. Grossmann More articles by this author , Thomas HermannsThomas Hermanns More articles by this author , Cédric PoyetCédric Poyet More articles by this author , and Christian D. FankhauserChristian D. Fankhauser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Accurate diagnosis in men with suspected prostate cancer (PC) is essential when several alternative treatment options to radical prostatectomy (RP) such as active surveillance, brachytherapy, radiotherapy, and focal treatment are available. The selection of treatment options heavily depends on the accuracy of tissue sampling during prostate biopsy. However, the concordance of ultrasound guided systematic transrectal prostate biopsy (SB) and RP specimens is limited. To improve the diagnostic accuracy of biopsy results, multiparametric MRI (mpMRI) of the prostate followed by transperineal targeted biopsies (TB) using MRI ultrasound scanning fusion with additional systematic mapping biopsies (SMB) is increasingly used to obtain tissue from men with suspected prostate cancer. The aim of our study was to quantify the concordance between mpMRI-TB-SMB and RP in patients undergoing RP for PC. METHODS: Patients undergoing RP for ISUP 2-5 PC in a tertiary referral center were included in this retrospective analysis. Whereas SB included systemic biopsies of 12 predefined regions in the prostate, mpMRI-TB-SMB was performed by taking biopsy cores from 20 predefined regions of the prostate and from MRI-suspicious lesions after fusion. Concordance was descriptively assessed by confusion matrices. RESULTS: We identified a cohort of 873 patients of which 530 (60.7%) underwent SB while 343 (39.3%) received mpMRI-TB-SMB. In men with biopsy proven ISUP 2 PC, upgrade to ISUP 3-5 using mpMRI-TB-SMB compared to SB decreased from 35.2% to 28.2% and downgrade to ISUP 1 decreased from 3.5% to 0%. In men with ISUP 2-3 PC, upgrade to ISUP 4-5 decreased from 14.4% to 5.4% and downgrade to ISUP 1 decreased from 2.7% to 0%. CONCLUSIONS: The improved concordance between mpMRI-TB-SMB and RP compared to SB and RP offers patients more accurate treatment allocation and may improve outcomes. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e180-e180 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marian S. Wettstein More articles by this author Josias B. Grogg More articles by this author Andres Affentranger More articles by this author Camille Cruz More articles by this author Nico C. Grossmann More articles by this author Thomas Hermanns More articles by this author Cédric Poyet More articles by this author Christian D. Fankhauser More articles by this author Expand All Advertisement Loading ...

MP62-01 UNCHANGED NEGATIVE PROSTATE MPMRI DURING ACTIVE SURVEILLANCE. DO WE NEED TO BIOPSY AND FOLLOW-UP?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II (MP62)1 Sep 2021MP62-01 UNCHANGED NEGATIVE PROSTATE MPMRI DURING ACTIVE SURVEILLANCE. DO WE NEED TO BIOPSY AND FOLLOW-UP? Henk Luiting, Antti Rannikko, Chris Bangma, Egbert Boevé, Axel Semjonow, Frédéric Staerman, Karl Tully, Riccardo Valdagni, and Monique Roobol Henk LuitingHenk Luiting More articles by this author , Antti RannikkoAntti Rannikko More articles by this author , Chris BangmaChris Bangma More articles by this author , Egbert BoevéEgbert Boevé More articles by this author , Axel SemjonowAxel Semjonow More articles by this author , Frédéric StaermanFrédéric Staerman More articles by this author , Karl TullyKarl Tully More articles by this author , Riccardo ValdagniRiccardo Valdagni More articles by this author , and Monique RoobolMonique Roobol More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002102.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is ongoing discussion if the negative predictive value of mpMRI during active surveillance (AS) is sufficient to omit prostate biopsies. The next question is, what to do with patients having serial negative MRIs. The AUA guidelines only recommend to perform biopsies within 2 years after diagnosis and do not specify if MRI has a role in preventing unnecessary biopsies during active surveillance. The aim of this study is to add to the current evidence and to evaluate the predictive value of consecutive negative MRIs. METHODS: The PRIAS study is a multicenter prospective study providing an evidence-based recommendation on how to perform AS for patients with low-risk prostate cancer (PCa). The inclusion criteria and recommended follow up schedule are available on www.prias-project.org. All patients with consecutive negative MRIs during AS were included in the current analysis. RESULTS: In total, 180 men had two consecutively negative MRI (negMRI) during AS. The median time between the negMRI was 16 (interquartile range (IQR) 11-25) months. The median PSA at the time of the last negMRI was 6.0 (IQR 4.2-8.6) ng/ml. A total of 68 (38%) men underwent systematic biopsy (SBx) at the last negMRI showing no PCa in 29 patients (43%), PCa grade group (GG) 1 in 35 patients (51%) and PCa GG 2 in 4 patients (6%). Additionally, one patient underwent extraprotocollair PSMA PET/CT targeted prostate biopsies at the time of the last negMRI and was reclassified to PCa GG 3. Follow up data of 158 patients without reclassification at last negMRI who continued AS was available (Figure 1). Median follow up after last negMRI was 21 (IQR 10-34) months. 36 patients underwent additional biopsies of which 10 patients upgraded to GG2 and 3 patients upgraded to GG≥3. All upgrading to GG≥3 was detected by TBx on subsequent MRI. CONCLUSIONS: Patients with repeated negMRI during AS represent a low-risk group, however reclassification to GG2 cannot completely be excluded as, although very rare, reclassification to GG≥3. This questions the need to perform SBx in these patients. Monitoring however, including repeat MRI should continue since progression on the long term cannot be excluded. It is reassuring that all upgrading to GG≥3 was detected on MRI. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1092-e1092 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Henk Luiting More articles by this author Antti Rannikko More articles by this author Chris Bangma More articles by this author Egbert Boevé More articles by this author Axel Semjonow More articles by this author Frédéric Staerman More articles by this author Karl Tully More articles by this author Riccardo Valdagni More articles by this author Monique Roobol More articles by this author Expand All Advertisement Loading ...

CHONDROID LIPOMA AS SOFT TISSUE PSEUDOSARCOMA: LITERATURE REVIEW AND CASE REPORT

Background. Pseudosarcomas of soft tissues can cause diagnostic and treatment challenges. On the one hand, it is difficult to make a nosological diagnosis based on a biopsy specimen of a tumor; on the other hand, it is difficult to determine the most appropriate treatment strategy based on a histological pattern.The purpose of the study was to analyze available literature data and systematize the histological characteristics of the chondroid lipoma and pseudosarcoma.Case description. We present the case of chondroid lipoma in a 57-year-old female patient with atypical clinical symptoms. This case shows the difficulties of differential diagnosis of soft tissue sarcomas. Using a clinical example of chondroid lipoma, a rare soft tissue tumor, and an analysis of literature data, the authors showed the importance of a detailed study of the obtained material, a qualified description of the morphological picture, in those cases when the diagnostic conclusion cannot be unambiguous about the malignancy of the tumor process. Additional biopsy is not always possible to clarify the histotype of the tumor. The presented observation shows the difficulties of differential diagnosis of soft tissue sarcomas. Minimally invasive biopsy provides no a full appreciation of histological structure; therefore, if there is a suspicion for chondroid lipoma, it is necessary to perform total surgical biopsy followed by a morphological study using the immunohistochemical method.

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the presence of noninflamed and/or inflamed regions in IBD patients, up to two biopsies were obtained from IBD patients as compared to a single noninflamed biopsy from non-IBD pediatric control patients. Additional biopsies were obtained and analyzed from 33 of the IBD patients after IBD-directed therapeutic intervention for comparison of pre- and post-treatment proteomes. SuperSILAC was utilized to perform quantitative analysis of homogenized tissues, which were processed by filter-aided sample preparation. Hierarchical clustering and principal component analyses revealed proteomic patterns that distinguished inflamed from noninflamed tissues independent of therapy. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of pre- and post-treatment proteomes from CD patients identified over 100 proteins that are significantly different between patients who responded and those who did not respond to therapy, including creatine kinase B and basigin.