Extensive Biopsy Research Articles

A case of suspected gliomatosis cerebri: diagnostic and therapeutic challenges in a resource-poor setting.

We present a case of a 70-year-old male with gliomatosis cerebri (GC), who initially presented with behavioural changes and amnesia, which progressed to extrapyramidal and cortical dysfunction. Neuroimaging revealed possible extensive cerebral gliomatosis and brain biopsy showed reactive gliosis. Despite treatment with levodopa-carbidopa, the symptoms worsened, and he succumbed after 18 months. This case highlights the challenges in diagnosing and managing GC in a resource-poor setting.

Abstract 1453: Development and evaluation of subcutaneous and orthotopic PC3M metastatic prostate cancer xenograft model in SRG rats for therapeutic assessment

Abstract Introduction: Prostate cancer is the most prevalent cause of cancer deaths in American males after lung cancer. The establishment of clinically relevant prostate cancer models is crucial for advancing our understanding of the disease and evaluating potential therapeutics. Oncology studies in rats provide a secondary species to mice with the advantage of extensive longitudinal blood sampling and tumor biopsies in pharmacodynamics analysis. This in vivo study evaluates the behavior of subcutaneous and orthotopic luciferase (luc) tagged metastatic PC3M-luc cells in immunodeficient SRG rats (Hera Biolabs) for tumor growth kinetics, metastasis, and response to paclitaxel and carboplatin alone and in combination. Methods: PC3M-luc cells were implanted subcutaneously into the right flank or orthotopically into the prostate of SRG rats. Subcutaneous tumor progression and treatment responses were monitored using calipers and bioluminescent imaging (BLI), with the capacity to detect developing metastases prior to necropsy. Orthotopic implants were monitored exclusively using BLI. Tolerability was evaluated based on biweekly changes in body weight, daily observations for signs of tumor- or treatment-related clinical signs, necropsy results, and complete blood count (CBC) and clinical chemistry marker comparisons with immunocompetent CD rats. Results: PC3M-luc prostate carcinoma was successfully established orthotopically and subcutaneously in SRG rats, with similar growth rates and the development of spontaneous metastases to distant organs, modeling metastases observed in prostate cancer patients. Paclitaxel treatment was less tolerated in SRG rats in comparison to nude rats, enhanced toxicity was observed when combined with carboplatin. Comparison of CBC and clinical chemistry blood markers in naïve immunocompetent CD and immunodeficient SRG rats differed mainly in White Blood Cell (WBC) counts that were significantly lower in SRG rats, as expected due to the lack of mature B, T, and NK cells in these animals. Conclusion: The development of orthotopic and subcutaneous PC3M-luc prostate cancer models in rats provides a valuable alternative platform for assessing the effectiveness of established and novel therapies. This rat-based models offers a secondary species for comparison of prostate cancer behavior in mice, successfully mimics the clinical development of metastases, and provides additional insights into disease progression and therapeutic strategies. Future studies will focus on the assessment of tolerability and combination therapy strategies for improved treatment outcomes. Citation Format: Kyle Draheim, Elizabeth Rainbolt, Bincy John, Cara Clouse, Karyn Shinn, Justin Avery, Koh Meng Aw Yong, Chassidy Hall, Patrick Fadden, Anya Avrutskaya. Development and evaluation of subcutaneous and orthotopic PC3M metastatic prostate cancer xenograft model in SRG rats for therapeutic assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1453.

Detecting MRI-Invisible Prostate Cancers Using a Weakly Supervised Deep Learning Model.

MRI is an important tool for accurate detection and targeted biopsy of prostate lesions. However, the imaging appearances of some prostate cancers are similar to those of the surrounding normal tissue on MRI, which are referred to as MRI-invisible prostate cancers (MIPCas). The detection of MIPCas remains challenging and requires extensive systematic biopsy for identification. In this study, we developed a weakly supervised UNet (WSUNet) to detect MIPCas. The study included 777 patients (training set: 600; testing set: 177), all of them underwent comprehensive prostate biopsies using an MRI-ultrasound fusion system. MIPCas were identified in MRI based on the Gleason grade (≥7) from known systematic biopsy results. The WSUNet model underwent validation through systematic biopsy in the testing set with an AUC of 0.764 (95% CI: 0.728-0.798). Furthermore, WSUNet exhibited a statistically significant precision improvement of 91.3% (p < 0.01) over conventional systematic biopsy methods in the testing set. This improvement resulted in a substantial 47.6% (p < 0.01) decrease in unnecessary biopsy needles, while maintaining the same number of positively identified cores as in the original systematic biopsy. In conclusion, the proposed WSUNet could effectively detect MIPCas, thereby reducing unnecessary biopsies.

P217 Rate of undetected dysplasia at colectomy in patients with IBD - What are we missing?

Abstract Background Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia. Methods We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both. Results Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis. In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both. In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well. Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy. Further results are shown in Table 1. Conclusion The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.

Endoscopic transmural resection as an alternative to colorectal surgery after high-risk (non-curative) endoscopic resection.

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal lesions. The full-thickness resection device (FTRD®, Ovesco, Germany) has primarily been used for non-exposed transmural resection of challenging subepithelial or epithelial lesions, where conventional methods may be limited. This technique represents an alternative to surgery in selected patients, and its applications are rapidly expanding. In recent years, eFTR has been described as an alternative to surgery for scars aiming to exclude residual tumors after non-curative endoscopic resection. We present a case of a 41-year-old woman with Lynch syndrome (dMLH1) with rectal adenocarcinoma at the age of 20 underwent anterior resection of the rectum and adjuvant chemoradiotherapy. At the age of 39, during endoscopic surveillance, she presented with a suspicious lesion (Paris 0-Is+IIa, NICE2, JNET2B) measuring 16mm in the hepatic angle, and underwent en bloc endoscopic mucosal resection (EMR). Histopathological analysis revealed a low-grade invasive adenocarcinoma with lymphoid stroma with deep invasion of the submucosa and resection margin involvement (vertical R1). After a multidisciplinary team discussion, complementary surgery was proposed but the patient refused, opting for close endoscopic and imaging surveillance. Two subsequent colonoscopies plus computed tomography (CT) scans showed no signs of macro or microscopic residual or recurrent tumor, even after extensive biopsies of the colonic scar. However, a CT scan 20months post-resection showed a de novo 2cm thickening of the parietal wall in the hepatic angle, consistent with the location of the previous endoscopic resection. Suspecting deep parietal tumor recurrence without superficial endoscopic findings, a transmural endoscopic resection using FTRD® of the EMR scar was performed, whose histology revealed no transparietal tumor recurrence.

Interim Analysis of a Trial Evaluating the Utility of Non-Targeted Biopsies for Colorectal Neoplasia Detection in Inflammatory Bowel Disease

Persons with inflammatory bowel disease (IBD) affecting the colorectum (cIBD) have a 1.5- to 2-fold higher risk of developing colorectal cancer (CRC) relative to age- and sex-matched members of the general population.1 Intensive surveillance colonoscopy is recommended in this population to detect and treat early neoplastic lesions before they evolve to incurable cancers.2 Some societies advocate for widespread non-targeted ("random") biopsies throughout the colorectum to screen for "invisible" neoplastic lesions, in addition to targeted biopsies and/or resection of visible lesions.2 Despite the theoretical value of non-targeted biopsies in this setting, there are no high-quality, controlled data to support this practice. In addition to adding significant time and costs to colonoscopy screening, extensive biopsy sampling may also increase the risk of colorectal bleeding and bowel perforation, particularly in elderly patients and those receiving anticoagulant/antiplatelet therapies. With the widespread adoption of disease-modifying biologic and small molecule therapies,3 mucosal healing as a treatment end point,4 high-definition endoscopes,5 and endoscopy quality standards,6 as well as reports of very low neoplasia yield for non-targeted biopsies (0.1%-0.2% of biopsies),7 many experts have started to question the value of non-targeted biopsies as an adjunct for neoplasia surveillance in persons with cIBD.8 However, a recent large French cohort study reported that non-targeted biopsies still identify up to 20% of all neoplastic foci in persons with cIBD,9 albeit primarily in individuals with other major CRC risk factors.

Colorectal neoplasia surveillance in inflammatory bowel disease

Performing colorectal neoplasia surveillance in persons with inflammatory bowel disease (IBD) that is both clinically effective and cost effective is among the greatest challenges facing endoscopists who care for this population. While heightened colorectal cancer (CRC) risk has long been recognized among persons with IBD, this risk has been declining over time, with recent reports suggesting no more than a 1.5–2-fold higher risk compared to age and sex matched members of the general population. Nonetheless, given that CRC still occurs at a higher rate in this population, current surveillance strategies are inadequate for some persons. Conversely, 80–90% of persons with IBD had no neoplastic lesions identified during colonoscopy surveillance, suggesting that many persons with IBD are unnecessarily exposed to the risks of colonoscopy, with society bearing these excess costs.&#x0D; The purpose of colorectal neoplasia surveillance is to reduce the burden of CRC and CRC-related death in the IBD population. Societal guidelines recommend initiating colorectal neoplasia screening with colonoscopy in all persons with colorectal IBD involving at least the rectosigmoid (or at least 1/3 of the colorectum if accompanied by discontinuous inflammation) at 8–10 years following disease diagnosis and continuing lifelong surveillance every 1–5 years. Major factors influencing surveillance frequency include historical disease severity, extent of colorectal inflammation, chronic post-inflammatory changes, family history of CRC, history of colorectal neoplasm, primary sclerosing cholangitis, prior colonoscopy findings, and adequacy of prior surveillance. All guidelines further recommend targeted sampling or resection of suspicious visible abnormalities, and some societies continue to recommend extensive non-targeted biopsies to detect “invisible” neoplasia, particularly if other adjunctive optical modalities, such as dye-spray chromoendoscopy (DCE) or virtual chromoendoscopy (VCE), are not performed, or if the mucosa is poorly visualized, such as in areas of significant inflammation, post-inflammatory polyposis, or poor bowel preparation. Most societies now advocate for DCE or VCE as primary screening tools for IBD neoplasia surveillance or, at a minimum, as alternative modalities to traditional white light colonoscopy with non-targeted biopsies where resources and expertise exists.&#x0D; However, there are no prospective studies demonstrating a reduction in the incidence of CRC or of death from CRC with current surveillance strategies in persons with IBD. Furthermore, observations from large retrospective studies are also conflicting. A Cochrane analysis of 3 studies in persons with UC did not find a significant mortality benefit for current surveillance strategies. Considering that IBD afflicts many persons at a young age, is rising in prevalence in Canada and globally, and requires intensive lifelong surveillance , the amount of endoscopy resources directed toward IBD surveillance is potentially enormous. Increasing demands on colonoscopy resources from expansion of population-based CRC screening programs and an aging population are likely to challenge the ability to continue to provide intensive surveillance to all persons with IBD. Optimizing delivery of limited colonoscopy resources will thus be essential to maintain effective CRC prevention programs in this population.&#x0D; Current standards for neoplasia surveillance in IBD have been recently updated. Shah and Itzkowitz authored a comprehensive review that includes epidemiology, pathogenesis, and management of colorectal neoplasia, along with a chart that compares surveillance recommendations put forward by multiple societies. The present review will highlight new evidence influencing neoplasia surveillance and provide practical approaches for surveillance and management of neoplastic lesions in the IBD population.

The association between endometrial polyps, chronic endometritis, and IVF outcomes.

Endometrial polyps (EPs) are one of the most common pathologies detected during the examination of the uterine cavity of infertile women. We aimed to demonstrate the relationship between EPs, chronic endometritis (CE) and in vitro fertilization (IVF) outcomes. This retrospective study was performed on 394 hysteroscopically examined infertility cases. We performed polyp resections (PR) and extensive biopsies of the endometrium to demonstrate the association with clinical pregnancy (CP) by IVF. We performed statistical analysis to compare these associations. The incidence of CE was twice as high in the presence of EPs as in the absence of EPs. The associations between EPs and PR were found to be significant for positive CP outcomes. A significant difference in IVF outcome was found between the group with EPs and the group without EPs. All these associations were statistically significant (p < 0.05). We found a frequent association between EPs and CE. The pregnancy rate obtained after IVF was negatively affected by the presence of EPs. Treatment of these pathologies improved IVF outcomes.

Grade Group accuracy is improved by extensive prostate biopsy sampling, but unrelated to prostatectomy specimen sampling or use of immunohistochemistry.

Assessing the accurate Grade Group of a prostate needle biopsy specimen is essential for choosing the adequate therapeutic modality for prostate cancer patients. However, it is well-known that biopsy Grade Group tends to up- or downgrade significantly at radical prostatectomy. We aimed to investigate the correlation between accuracy and biopsy core number, performed immunohistochemical staining (IHC) or prostatectomy specimen sampling, with the latest also being correlated with higher detection rates of adverse pathological features, e.g., positive surgical margins, higher pathological stage or presence of perineural invasion (PnI status). The study cohort consisted of 315 consecutive patients diagnosed with prostate adenocarcinoma via transrectal ultrasound-guided needle biopsy who later underwent radical prostatectomy. We grouped and compared patients based on Grade Group accuracy, presence of IHC on biopsy, margin status, pathological stage, and PnI status. Inter-observer reproducibility was also calculated. Statistical analyzes included ANOVA, Tukey's multiple comparisons post hoc test, Chi-squared test, and Fleiss kappa statistics. Undergraded cases harboured a significantly lower number of biopsy cores (p < 0.05), than accurately graded cases. Using IHC did not affect grading accuracy significantly, nor did the number of slides from prostatectomy specimens. The mean number of slides was virtually identical when margin status, pathological stage and PnI status of prostatectomy specimens were compared. Inter-observer reproducibility at our institute was calculated as fair (overall kappa = 0.29). Grade Group accuracy is significantly improved by obtaining more cores at biopsy but is unrelated to performed IHC. The extent of sampling prostatectomy specimens, however, did not affect accuracy and failed to significantly improve detection of adverse pathological features.

Serum GDF-15 Levels Accurately Differentiate Patients with Primary Mitochondrial Myopathy, Manifesting with Exercise Intolerance and Fatigue, from Patients with Chronic Fatigue Syndrome.

Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more common chronic fatigue syndrome (CFS). Nonetheless, other possibilities must be excluded for the final diagnosis of CFS, with PMM being one of the primary differential diagnoses. For this reason, many patients with CFS undergo extensive studies, including extensive genetic testing and muscle biopsies, to rule out this possibility. This study evaluated the diagnostic performance of growth differentiation factor-15 (GDF-15) as a potential biomarker to distinguish which patient with chronic fatigue has a mitochondrial disorder. We studied 34 adult patients with symptoms of fatigue and exercise intolerance with a definitive diagnosis of PMM (7), CFS (22), or other non-mitochondrial disorders (5). The results indicate that GDF-15 can accurately discriminate between patients with PMM and CFS (AUC = 0.95) and between PMM and patients with fatigue due to other non-mitochondrial disorders (AUC = 0.94). Therefore, GDF-15 emerges as a promising biomarker to select which patients with fatigue should undergo further studies to exclude mitochondrial disease.

What Is the Risk? Epidemiology and Evidence for Surveillance Regimens.

Patients with inflammatory bowel disease (IBD) have increased risk of colorectal cancer (CRC). The risk for CRC is positively correlated to the duration of disease, extent of colonic involvement, and severity of inflammation. After 8 to 10 years of IBD diagnosis, the risk for CRC rises substantially and screening colonoscopy is recommended. Surveillance colonoscopy interval ranges from 1 to 5 years depending on patient and disease-specific risk factors. IBD patients with high risk factors such as having concomitant primary sclerosing cholangitis, moderate-to-severe inflammation, first-degree relative with CRC at early age, or history of invisible dysplasia or high-risk visible dysplasia should undergo surveillance colonoscopy in 1 year. Meanwhile, those with minimal colonic involvement or ≥2 consecutive unremarkable examinations while in continuous remission may consider extending the surveillance interval to 5 years. Advance in colonoscopy technique such as chromoendoscopy using dyes and/or image digital processing (virtual chromoendoscopy) may enhance dysplasia detection and is the preferred method for IBD surveillance. In the era of high-definition colonoscope, the practice of obtaining extensive biopsies throughout the colon remains controversial but is generally recommended to improve the detection rate of invisible dysplasia. Endoscopic surveillance in IBD has been shown to result in earlier detection of CRC and improved prognosis.

Oncologic Outcomes of a Novel Mapping Biopsy Technique Before Surgical Excision in the Management of Extramammary Paget Disease

Objective To analyze oncologic outcomes of patients with extramammary Paget disease (EMPD) undergoing a novel mapping biopsy before tumor excision (WLE). Methods We analyzed 19 consecutive patients with EMPD treated with biopsy and/or surgical excision at Moffitt Cancer Center from 2013 to 2021. Biopsy technique, patient demographics, pathology, and oncologic outcomes were analyzed. Results In total, 19 patients were included in the analysis. Median age at diagnosis was 72. No patients were diagnosed with secondary malignancy during mandatory workup. Of the 17 patients receiving novel mapping biopsy, 8/17 had at least one positive core biopsy site, with a mean of 7% positivity of the total core sites (4/60). Mapping biopsy positive sites helped shape perimeters for wide local excision (WLE) for patients opting for surgical treatment. Although an extensive mapping biopsy was performed, WLE margins were positive in 11/17 patients. Although positive pathologic margins following surgical excision were prominent, only one patient experienced recurrence of EMPD during a median follow-up period of 38 months. Conclusions We have demonstrated a standardized mapping biopsy before surgical excision in the management of EMPD in men. Despite extensive mapping biopsies, positive surgical margin rates are high, and this may reflect the occult nature of the disease process. Close follow-up is warranted in patients regardless of margin status, but those with positive surgical margins may benefit from more aggressive regimens.

Clinico-cytomorphological Spectrum of Calcinosis Cutis.

The deposition of calcium in the skin is known as calcinosis cutis. It can affect any part of the body and can mimic soft tissue or bony lesions clinically. To describe the clinical and cytomorphologic features of calcinosis cutis on fine needle aspiration cytology smears. A total of 17 cases reported as calcinosis cutis on fine needle aspiration cytology were reviewed for the available clinical and cytological details. The cohort included both adult and pediatric patients. Clinically, the lesions appeared as painless swellings of variable sizes. The common sites affected were the scrotum, iliac region, scalp, pinna, neck, axilla, elbow, arm, thigh, and gluteal region. Aspirate was chalky white, paste-like in all the cases. The cytologic evaluation revealed amorphous crystalline deposits of calcium along with histiocytes, lymphocytes, and multinucleated giant cells. Calcinosis cutis has a wide spectrum of clinical presentations. Fine needle aspiration cytology is a minimally invasive approach for diagnosing calcinosis cutis, thus eliminating the need for more extensive biopsy procedures.

Comparative Study on Cancer Yielding Rate Between sextant vs Ten Cores TRUS Biopsy

Background: The standard sextant biopsy protocol misses about 15% of cancer when compared with results obtained from a more extensive biopsy procedure. The number of systematic biopsies has increased over the years, with 10–12 cores currently accepted as the minimum standard. Objectives: To compare the detection rate of carcinoma prostate through standard sextant biopsy and extended 10-core biopsy in Bangladeshi male subjects. Methods: This prospective experimental study was conducted in the Department of Urology of Dhaka Medical College Hospital, Dhaka from January 2007 to May 2008 including a total of 69 male patients aged over 56 years having normal digital rectal examination (DRE) findings with serum PSA level of 4 ng/mL or greater or having abnormal findings on DRE irrespective of serum PSA level. The subjects underwent transrectal ultrasound (TRUS) and biopsies were taken systematically. Biopsy results were interpreted according to different sextant biopsy protocols and also following extended 10-core biopsy protocol. Data collection sheet containing the selected points were filled up. Data were analysed using SPSS version 12. The test statistic used to analyse the data were descriptive statistics and McNemar’s test. The level of significance was set at 0.05 and p &lt;0.005 was considered significant. Result: Out of the total 69 subjects, 29 (42%) were diagnosed to have prostate cancer following biopsy. In the standard mid lobar sextant protocol the cancer detection was lowest (79.3%) while it was highest (89.7%) when lateral zone biopsy was performed. The extended 10-core biopsy regimen had higher cancer detection rate than any of the standard sextant protocols and it was 96.6%. The difference in the cancer detection rates between the two schemes was statistically significant (p &lt;0.001). Conclusion: The sextant biopsy is inadequate in detecting carcinoma prostate and extended 10-core biopsy protocol including the apex, midlobar mid gland, lateral mid gland and lateral base with more extensive sampling of the lateral aspects of the prostate is superior. Bangladesh J. Urol. 2021; 24(2): 214-219

De Novo Diagnosis of Lymphocytic Colitis After SARS-CoV-2 Vaccination

ABSTRACTSARS-CoV-2 mRNA vaccines are safe and effective for most patients. Gastrointestinal complications reported after vaccination have included gastroparesis and inflammatory bowel disease flares. In this study, we present a unique case of lymphocytic colitis that occurred in a healthy middle-aged man after Moderna SARS-CoV-2 mRNA vaccination. This reveals an unexpected complication of a mRNA vaccine that presented as worsening diarrhea after vaccination in a dose-dependent pattern. Caregivers should be aware of lymphocytic colitis as a possible complication of the Moderna vaccine and monitor those patients closely for symptom resolution.

Abstract 1598: Defining the transcriptional complexity of persister cell populations in relapsed small cell lung cancer patient biopsies

Abstract Small cell lung cancer (SCLC) is an aggressive malignancy characterized by robust, however transient, responses to frontline platinum-based therapy that are rapidly followed by refractory relapses. Treatment resistance is a significant concern in SCLC and a major factor regulating resistance is an emergence of unique cellular populations and an increase in intratumoral heterogeneity (ITH). We hypothesize that these emerging populations expressing various resistance-associated pathways, represent multiple, unique drug-resistant persister cell populations that underlie increased ITH and promote therapeutic resistance and, eventually, relapse, despite the initial response to therapy. Persister cells represent a unique population of cancer cells that are resistant to therapeutic pressure. While most persister cells remain arrested under treatment, a rare sub-population exists that can reverse state and re-enter the cell cycle. We performed single cell RNAseq of relapsed, extensive stage SCLC patient paired core biopsies collected 1) following relapse to standard of care (SOC) platinum chemotherapy plus immune checkpoint blockade (ICB) and 2) after six weeks of further therapy. Unlike what we found in platinum-sensitive disease, there is not a meaningful change in ITH score between cancer cells in the first and second biopsy. Presumably, maximum heterogeneity developed along with relapse to SOC treatment. Biopsies represent SCLC across subtypes (SCLC-A/N/P/I) with a modest loss of transcription factor expression following treatment (e.g., 76.8% to 57.9% NEUROD1). Cancer cells were classified as cycling or non-cycling to identify potential persister cell populations in paired patient core biopsies. Molecular subtype marker ASCL1 was reduced in non-cycling cells, but there was no change in NEUROD1 or POU2F3. Cycling cells demonstrate increased expression of NE genes (SYP, INSM1, UCHL1), biomarkers of response (SLFN11 and CDH1), but also genes associated with resistance (EZH2, NFIB). Non-cycling cells exhibit some common resistance mechanisms (e.g., EMT and MYC, AXL, ZFP36L1, and REST overexpression) and increased expression of inflammatory genes (e.g. HLA family) compared to cycling cells, reminiscent of the SCLC-Inflamed (SCLC-I) subtype. These data suggest that non-cycling persister cells may be more sensitive to ICB, AXL and/or AURK inhibition, while cycling cells may be more responsive to platinum chemotherapy, epigenetic modifiers or DNA repair targeted therapies. Clinically, these data underscore the importance of maximizing and maintaining the initial response in platinum-sensitive SCLC tumors, while highlighting the transcriptional complexity underlying SCLC’s profound treatment resistance following SOC and address the major need to develop combination therapies to target these distinct cell populations. Citation Format: C. Allison Stewart, Yuanxin Xi, Runsheng Wang, Michael M. Frumovitz, Jing Wang, Lauren A. Byers, Carl M. Gay. Defining the transcriptional complexity of persister cell populations in relapsed small cell lung cancer patient biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1598.

MP09-09 THE RESULTS OF TRANSPERINEAL VERSUS TRANSRECTAL PROSTATE BIOPSY: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP09-09 THE RESULTS OF TRANSPERINEAL VERSUS TRANSRECTAL PROSTATE BIOPSY: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS Jindong Dai, Jiyu Yang, Xingming Zhang, Pengfei Shen, and Hao Zeng Jindong DaiJindong Dai More articles by this author , Jiyu YangJiyu Yang More articles by this author , Xingming ZhangXingming Zhang More articles by this author , Pengfei ShenPengfei Shen More articles by this author , and Hao ZengHao Zeng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002531.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This updated systematic review was performed to compare the efficacy and complications of transperineal (TP) vs. transrectal (TR) prostate biopsy. METHODS: Systematic research of PUBMED, EMBASE and the Cochrane Library was performed to identify all clinical controlled trials on prostate cancer (PCa) detection rate and complications achieved by TP and TR biopsies. Prostate biopsies included sextant, extensive and saturation biopsy procedures. All patients were assigned to TR group or TP group. Subgroup analysis was performed according to prostate-specific antigen (PSA) levels, prostate volume, prostate anatomical structure, and digital rectal examination (DRE) findings. The Cochrane Collaboration’s RevMan 5.4 software was used for the meta-analysis. RESULTS: A total of sixteen trials, including eight randomized controlled trials (RCTs) and eight case control studies (CCS), met our inclusion criteria. Meta-analysis for RCTs combined with CCS showed that there was no difference in the cancer detection rate between the extensive TR and TP group (risk difference (RD), -0.01; 95% confidence interval (CI), -0.04–0.02; P=0.47). However, the more prostate cancer was detected in TP group with 10≤PSA (RD, 0.03; 95%CI, 0.01-0.05; P=0.009). CONCLUSIONS: In the patients with PSA>10ng/ml, TP has more advantages than TR in cancer detection. Moreover, a significantly lower risk of fever and rectal bleeding was reported for TP prostate biopsy. Source of Funding: 2021YFS0119 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e138 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jindong Dai More articles by this author Jiyu Yang More articles by this author Xingming Zhang More articles by this author Pengfei Shen More articles by this author Hao Zeng More articles by this author Expand All Advertisement PDF DownloadLoading ...

BRAIN UK: Accessing NHS tissue archives for neuroscience research.

The purpose of BRAIN UK (the UK BRain Archive Information Network) is to make the very extensive and comprehensive National Health Service (NHS) Neuropathology archives available to the national and international neuroscience research community. The archives comprise samples of tumours and a wide range of other neurological disorders, not only from the brain but also spinal cord, peripheral nerve, muscle, eye and other organs when relevant. BRAIN UK was founded after the recognition of the importance of this large tissue resource, which was not previously readily accessible for research use. BRAIN UK has successfully engaged the majority of the regional clinical neuroscience centres in the United Kingdom to produce a centralised database of the extensive autopsy and biopsy archive. Together with a simple application process and its broad ethical approval, BRAIN UK offers researchers easy access to most of the national archives of neurological tissues and tumours (http://www.brain-uk.org). The range of tissues available reflects the spectrum of disease in society, including many conditions not covered by disease-specific brain banks, and also allows relatively large numbers of cases of uncommon conditions to be studied. BRAIN UK has supported 141 studies (2010-2020) that have generated 70 publications employing methodology as diverse as morphometrics, genetics, proteomics and methylomics. Tissue samples that would otherwise have been unused have supported valuable neuroscience research. The importance of this unique resource will only increase as molecular techniques applicable to human tissues continue to develop and technical advances permit large-scale high-throughput studies.

CHANNELOPATHIES AND RELATED DISORDERS: EP.225 Autosomal dominant early onset vacuolar myopathy with granular material, without periodic paralysis, associated with c.1583C>A CACNA1S gene mutation

Dominant mutations in CACNA1S gene mainly causes hypokalemic periodic paralysis (PP)(hypoPP). We report a patient with progressive early onset myopathy associated with heterozygous CACNA1S mutation and aim to extend the description of phenotypical spectrum of CACNA1S-related muscle diseases. A 68-year-old man developed progressive proximal weakness from the age of 35 years. He had four siblings including an affected brother. His mother had PP and became wheelchair bound at 55 years. CK level was elevated (<1.5 upper normal value). Electroneuromyography showed axonal sensorimotor polyneuropathy and myogenic potentials. Thigh magnetic resonance imaging showed extensive muscle fatty replacement and muscle biopsy showed atrophic fibers with vacuoles containing granular material. Clinical exome identified the heterozygous c.1583G>A well-known pathogenic variant in CACNA1S. The patient's brother had PP from the age of 27. Neurological examination was normal at the age of 39. Muscle biopsy showed a vacuolar myopathy with granular material. No further medical information was available. The patient died at the age of 72 yrs. Molecular characterisation was not achieved. CACNA1S-HypoPP evolving to fixed myopathy in late adulthood is well described but isolated progressive myopathy was only exceptionally reported and never with an onset <50 years. We hereby report the earliest “myopathy onset” ever described, enlarging the phenotypical spectrum of CACNA1S-related myopathies and suggest considering it even in young adult-onset myopathies, especially when granular vacuoles are present.

PD65-09 ROLE OF PROSTATE HEALTH INDEX TO PREDICT GLEASON SCORE UPGRADING AND HIGH-RISK PROSTATE CANCER IN RADICAL PROSTATECTOMY SPECIMEN

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-09 ROLE OF PROSTATE HEALTH INDEX TO PREDICT GLEASON SCORE UPGRADING AND HIGH-RISK PROSTATE CANCER IN RADICAL PROSTATECTOMY SPECIMEN Hwanik Kim, Jung Kwon Kim, Hakmin Lee, Sangchul Lee, Jong Jin Oh, Seong jin Jeong, Seok-Soo Byun, Sung Kyu Hong, and Changhee Ye Hwanik KimHwanik Kim More articles by this author , Jung Kwon KimJung Kwon Kim More articles by this author , Hakmin LeeHakmin Lee More articles by this author , Sangchul LeeSangchul Lee More articles by this author , Jong Jin OhJong Jin Oh More articles by this author , Seong jin JeongSeong jin Jeong More articles by this author , Seok-Soo ByunSeok-Soo Byun More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , and Changhee YeChanghee Ye More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate health index (PHI) seems to be a simple and inexpensive test for a multivariant approach to prostate cancer (PCa) screening and management. The PHI improves cancer prediction at initial and extended biopsy stages and even the disease recurrence after radical prostatectomy (RP). In this study, we aimed to evaluate the role of PHI in localized PCa and whether they are independent predictors of Gleason score (GS) upgrading at RP specimen in GS 3 + 3 PCa, unfavorable or high risk PCa or adverse pathologic feature in RP specimen. METHODS: 300 patients with prostate specific antigen ≥3ng/mL, PHI and prostate biopsy were retrospectively included in the study. The primary study outcomes are PCa and clinically significant PCa (csPCa) diagnostic rate of PHI, and GS upgrading rate at RP specimen. The secondary outcomes are the comparison between GS upgrading and non-upgrading group, GS upgrading and high-risk PCa (International Society of Urological Pathology Grade Group [ISUP GG] ≥3 or ≥pT3a) predictability of preoperative clinical factors. RESULTS: Overall, 139 (46.3%) and 92 (30.7%) were diagnosed with PCa and csPCa, respectively. GS upgrading rate was 38.8% in total patients with RP. Significant differences were shown in the total prostate volume (p=0.014), the rate of ISUP GG at biopsy (p=0.001), and the proportion of ISUP GG at RP (p=0.016). PHI valued ≥55 (p=0.032) and presence of PIRADS lesion ≥4 (p=0.008) were the significant predictors of GS upgrading in ISUP GG1. In addition, PHI grouping (p=0.016) can predict significantly ISUP GG ≥3 at RP. PHI (p=0.039) can also predict adverse pathologic feature (≥pT3a) in RP specimen. CONCLUSIONS: PHI can predict GS upgrading in combination with PIRADS lesions ≥4 in ISUP GG1. PHI alone can evaluate the possibility of high-risk PCa after surgery as well. Source of Funding: This study was supported by institutional grant (02-2020-021) from the Seoul National University Bundang Hospital Research Fund © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1155-e1156 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hwanik Kim More articles by this author Jung Kwon Kim More articles by this author Hakmin Lee More articles by this author Sangchul Lee More articles by this author Jong Jin Oh More articles by this author Seong jin Jeong More articles by this author Seok-Soo Byun More articles by this author Sung Kyu Hong More articles by this author Changhee Ye More articles by this author Expand All Advertisement Loading ...