Adequate Tissue Sampling Research Articles

RBIO-05. IPAX-2: PHASE 1 SAFETY AND DOSE FINDING STUDY OF [131I]IPA PLUS STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) overexpresses the L-type amino transporter (LAT) 1 & 2, which supports internalization of the therapeutic small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine ([131I]IPA) and its companion diagnostic, 18F-FET. Previous studies of [123I]IPA SPECT have shown uptake by >85% of gliomas. Results from a phase 1 trial (IPAX-1) that explored [131I]IPA + radiotherapy in patients with recurrent GBM demonstrated a favorable safety and tolerability profile and promising efficacy. The objective of IPAX-2 (NCT05450744) is to evaluate the safety and tolerability of [131I]IPA in patients newly diagnosed with GBM. METHODS IPAX-2 is a phase 1, multicenter, open-label, single-arm, parallel-group, dose-finding study to evaluate the safety of ascending radioactive dose levels of [131I]IPA + best standard of care in newly diagnosed patients with GBM. Eligible participants (N=12) will be 18-65 years of age with histologically-confirmed intracranial GBM following surgical resection; no prior systemic therapy or radiation for GBM; a Karnofsky Performance Status ≥70; a plan to begin chemoradiation 3-6 weeks after surgical resection with Stupp regimen; adequate organ function; and adequate tissue samples previously archived. Four cohorts will encompass a 3 + 3 dose escalation, with [131I]IPA administered in 2 fractions corresponding to ½ of full dose activity via intravenous infusion (2x3.0 GBq, 2x4 GBq, 2x5 GBq, 2x6 GBq). Dose 1 will be administered prior to external beam radiation therapy (EBRT), and Dose 2 will be administered following completion of EBRT. 18F-FET PET will be used to identify suitable candidates with LAT1/2 overexpression, establish a baseline, and provide quantitative follow-up information. Primary outcome measures are 1) incidence rate treatment-emergent adverse events and 2) safety and tolerability by determining the dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose. DISCLOSURES: Telix Pharmaceuticals is the sponsor of this study.

"Brain Biopsy Revolution: Unveiling the Core Syringe Technique with Clinical Insights"

BackgroundObtaining a definitive pathological diagnosis from brain tissue sampling was challenging due to the small, non-representative sample. This study introduced a novel syringe technique for brain biopsy aimed at enhancing diagnostic accuracy by obtaining core tissue samples that better represent the targeted tissue. MethodsThe ten patients with atypical brain lesions underwent the syringe biopsy. After meticulous preoperative planning with neuronavigation, a minimally invasive approach was used: a 3 cm skin incision and a 14 mm burr hole were created. A modified 3-cc syringe was used to create negative pressure and cannulate the brain tissue. The desired sample size (24 cm³) was obtained by controlling the syringe depth and withdrawal. Medical records were reviewed to assess sample analysis results and any complications. ResultsThe syringe technique successfully yielded adequate tissue samples in 9 out of 10 patients. In one case, the desired tissue could not be retrieved and required a microsurgical approach for removal. In all ten cases, a correct diagnosis was made without significant complications. ConclusionThe preliminary findings suggest that the syringe technique is both safe and effective for obtaining substantial volumes of brain tissue, facilitating accurate pathological evaluation in cases of complex neurological disorders.

Imaging of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) originates in the renal pelvis or ureters and typically affects elderly patients, with its incidence increasing over the past few decades. UTUC is a distinct clinical entity with more aggressive clinical behavior than that of lower tract urothelial carcinoma. Due to the significant challenge of acquiring an adequate tissue sample for biopsy, comprehensive risk stratification is required for treatment planning, including radical nephroureterectomy and kidney-sparing management. Imaging plays an important integrated role in risk assessment along with endoscopy and pathologic examination. Lifelong surveillance is required after treatment due to the high incidence of recurrent and metachronous tumors. Lynch syndrome is a frequently unrecognized genetic disorder associated with UTUC that warrants specific attention in patient management. UTUC may manifest with diverse imaging findings, including filling defects, wall thickening, and mass-forming lesions. CT urography is the preferred modality for diagnosis and staging or restaging of UTUC, with numerous technical variations. Efforts have been made to optimize image quality and radiation exposure. Due to its poor sensitivity for small lesions, use of MR urography is limited to special clinical scenarios (eg, when patients have contraindications to iodinated contrast agents). Fluorine 18 fluorodeoxyglucose PET helps to detect metastatic lesions. Image-guided biopsy may be considered for uncertain lesions. Radiologists need to be familiar with the imaging findings and their differential diagnoses. ©RSNA, 2024 Supplemental material is available for this article.

Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer

Background & AimsRecent advances in molecular profiling enable the identification of potential therapeutic targets for biliary tract cancer (BTC). However, in patients with BTC, molecular profiling is hindered by challenges in obtaining adequate tissue samples. Circulating tumor DNA (ctDNA) may offer an alternative to tissue-based analysis. Here we aimed to assess the concordance between ctDNA and tissue genomic profiling in a large cohort of Asian patients with advanced BTC, and to evaluate the feasibility of liquid biopsy in BTC treatment. MethodsThis study included patients with systemic treatment-naive advanced BTC, treated at CHA Bundang Medical Center between January 2019 and December 2022. We enrolled patients with available baseline tissue-based next-generation sequencing (NGS), and sufficient plasma samples for ctDNA analysis (AlphaLiquid®100 from IMBdx). ResultsAmong 102 enrolled patients, 49.0% had intrahepatic cholangiocarcinoma, 26.5% extrahepatic cholangiocarcinoma, and 24.5% gallbladder cancer. The concordance between intra-patient ctDNA and tumor tissue mutations revealed a sensitivity of 84.8%, and positive predictive value of 79.4%. ctDNA revealed targetable alterations in 34.3% of patients—including FGFR2 fusion, IDH1 mutation, microsatellite instability (MSI)-high, ERBB2 amplification, PIK3CA mutations, BRCA1/2 mutations, and MET amplification. Notably, a novel FGFR2-TNS1 fusion was identified in ctDNA, which was not targeted in the tissue NGS panel. A high maximum somatic variant allele frequency in ctDNA was associated with poor prognosis after gemcitabine/cisplatin-based chemotherapy, in terms of both overall survival (p = 6.9 × 10−6) and progression-free survival (p = 3.8 × 10−7). ConclusionsAmong patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC. Impact and implicationsOur study is the first large-scale investigation of the clinical utility of liquid biopsy, focusing on ctDNA, as an alternative to conventional tumor tissue analysis, among Asian patients with advanced BTC. The results demonstrated acceptable concordance between analysis of ctDNA versus tissue for identifying therapeutic targets and potentially actionable genetic alterations. This indicates that ctDNA analysis can provide critical insights regarding advanced BTC treatment, particularly in cases where it is challenging to obtain or analyze tumor tissue.

Transesophageal ultrasound-guided bronchoscopic Acquire TBNB versus Vizishot2 TBNA needles for neoplastic lesions: A retrospective study

BackgroundLung cancer is often diagnosed at an advanced stage; however, it has shown improved therapeutic efficacy with the introduction of molecularly targeted drugs and immune checkpoint inhibitors, necessitating accurate molecular diagnosis for effective treatment planning. Traditional sampling techniques, including endobronchial ultrasound-guided transbronchial needle aspiration, frequently require multiple biopsies to obtain sufficient tissues for multiplex testing, highlighting the need for more efficient methods. Therefore, we explored the diagnostic utility of endoscopic ultrasound with bronchoscope-guided fine-needle biopsy (EUS-B-FNB) versus fine-needle aspiration (EUS-B-FNA) in patients with lung cancer, focusing on tissue sample collection for molecular testing. The introduction of the Franseen needle in EUS-B-FNB, characterized by three beveled edges, allows for more tissue collection in cylinder form. MethodsWe retrospectively analyzed the data of 97 patients who underwent EUS-B-FNB or EUS-B-FNA at Hakodate Goryoukaku Hospital and evaluated diagnostic yields, safety, and nucleic acid concentrations using collected specimens. ResultsThe diagnostic yields of EUS-B-FNB and EUS-B-FNA were comparable (92.2% vs. 92.3%), with no significant differences in complications. However, EUS-B-FNB provided significantly higher DNA and RNA concentrations (DNA; 41.05 vs. 10.20 ng/mL; P < 0.0001, RNA; 36.80 vs. 11.80 ng/mL; P = 0.0009), essential for comprehensive molecular testing. ConclusionThis study highlights the potential of EUS-B-FNB for enhancing the molecular diagnosis of lung cancer by ensuring adequate tissue sample collection for multiplex testing, paving the way for personalized medicine. This technique is comparable in safety and efficacy to traditional methods while offering a substantial improvement in the quality of molecular diagnostics.

Untethered Microgrippers for Biopsy in the Upper Urinary Tract.

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstratedthat µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental dataand clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.

P-741 Standard IV Cannula Aspiration (SIVCA): A step-by-step video demonstration of the minimally invasive testicular sperm aspiration technique with technical improvements after 4 years of experience

Abstract Study question Is there room for further technical improvements in the Standard IV Cannula Aspiration (SIVCA), for a more efficient testicular issue aspiration and sperm extraction procedure? Summary answer A more efficient SIVCA procedure can be achieved by using a higher flow-rate cannula, less negative pressure aspiration and a Luer Lock syringe. What is known already Standard IV Cannula Aspiration (SIVCA) was introduced in 2022. It showed comparable sperm retrieval rates (SRR) to mTESE (56.2 vs 57.3%; McNemar P = 1.000). But given the novelty of the technique, some technical difficulties were encountered: The 14G cannula frequently kinked during the back and forth motions of aspiration, thus having to be replaced several times during the procedure; and the aspirating syringe often detached from the catheter mid-procedure, due to the absence of a lock mechanism securing it to the flashback chamber of the cannula. Study design, size, duration 224 men were enrolled in this prospective 24 months cohort study conducted at a specialized IVF center. The men had testicular tissue aspiration performed via SIVCA, either for azoospermia or increased seminal sperm DNA fragmentation, in anticipation of their partners’ ovum pick-up for an ICSI cycle. If enough testicular tissue was aspirated, it was examined for sperm. If not more than 0.2 gm of tissue could be aspirated from either testis, the patient underwent mTESE. Participants/materials, setting, methods After general anesthesia, 5cc of Xylocaine (lidocaine HCl) 2% was instilled into each spermatic cord. A standard 14-G 310 ml/min flow-rate IV cannula was introduced into the testis. After withdrawing the needle, a 3cc Luer Lock syringe was secured to the cannula. The plunger was maximally retracted to generate −250 Torr of negative pressure and clamped. Back and forth motions were performed, mapping and aspirating tissues from different regions of each testis at a time. Main results and the role of chance Out of a total of 224 cases, an adequate testicular tissue sample of more than 0.2 gm was successfully aspirated from 218 cases, with a 0.97 probability of success. Mild hematoma and pain were encountered in 5.8% of cases (n = 13/224) and subsided within two to three weeks (Grade I on the Clavien Dindo Scale). In a previous series, 130 cases of SIVCA were performed by fully retracting the plunger of a regular 20cc syringe, generating about −520 Torr of negative pressure, while the syringe was connected - but not secured - to the flashback chamber of a 270ml/min flow-rate cannula. In that series, adequate tissue samples could successfully be aspirated in 122 cases, showing a 0.93 probability of success. By using a higher flow-rate 14G IV cannula (310 ml/min vs 270 ml/min), less negative pressure (−250 Torr vs − 520 Torr) and a Luer Lock syringe; fewer number of cannulas were lost to kinking per procedure and no inconvenient disconnections occurred mid-procedure between the cannula and the aspirating syringe owing to the Luer Lock mechanism; all while maintaining a high success rate of aspiration of sufficient testicular tissue (X2 (1, N = 354) = 2.6156, p = .10582). Limitations, reasons for caution Whenever sclerosis and/or fibrosis of testicular tissue rendered aspiration of adequate amounts of testicular tissue difficult or challenging, we reverted to surgical m-TESE. Ice packs should be applied for at least 48 to 72 hours post-procedure to forestall hematomas. Further blinded randomized control studies with larger datasets are recommended. Wider implications of the findings SIVCA is a safe, efficient and easily reproducible method of testicular sperm aspiration. Its allowance for mapping different regions of the testes in order to extract sufficient amounts of tissues, makes it an ideal initial alternative to surgical m-TESE for testicular tissue aspiration and sperm searching. Trial registration number NCT05247723

Reducing Waiting Times and Admission Periods through Pre-Admission Testing: A Quality Improvement Study on In-Hospital Renal Biopsy.

Background: Admission for renal biopsy is considered the gold standard for diagnosing kidney disease. However, prolonged waiting times for admission can lead to delayed diagnosis. Despite this issue, there are currently no studies demonstrating how to improve the efficiency of renal biopsy procedures. Methods: We initiated a quality improvement project to implement pre-admission testing (PAT) for renal biopsy from 2016 to 2024 (until 15 April). Our evaluation focused on waiting times for admission, length of admission periods, hospitalization expenses, percentage of cases with no renal biopsy performed, incidence of severe bleeding due to renal biopsy, and percentage of cases with adequate tissue samples obtained. Additionally, we highlighted the time periods during the outbreak of SARS-CoV-2. Results: The highest annual case number was observed in time period 1 (168.3/year). Following the outbreak of SARS-CoV-2, there was a notable decrease in case numbers during time period 2 (119.8), which then increased to 143.0 in time period 3 (post-SARS-CoV-2 era). The mean waiting time was 13.72 ± 40.30 days for time period 1 and 10.00 ± 47.80 days for time period 2, without statistical significance. Following the implementation of PAT, patients now only need to wait approximately 0.76 days for admission, representing a significant reduction in waiting time. Subsequently, following the implementation of PAT, the waiting time decreased significantly to 2.09 ± 2.65 days. Additionally, hospitalization expenses per patient significantly decreased from approximately USD 69.62 ± 97.09 to USD 41.66 ± 52.82. The percentage of missed biopsy is significantly low (p < 0.001). Severe bleeding events (indicated as embolization and blood transfusion) were consistent across the three time periods (p = 0.617). Conclusions: The implementation of PAT can improve the pre-admission process for renal biopsy, resulting in decreased waiting times, fewer missed appointments, shorter admission durations, and reduced hospitalization expenses. We propose implementing PAT for outpatient individuals awaiting in-hospital renal biopsy procedures to mitigate delayed diagnosis, reduce pre-admission waiting periods, and streamline admission processes, thereby enhancing overall patient care efficiency.

Neoadjuvant toripalimab plus chemotherapy for resectable stage II-IIIB non-squamous non-small cell lung cancer with EGFR mutations: A multi-center, multi-cohort, exploratory study.

TPS8120 Background: Neoadjuvant immunotherapy has been widely applied in the treatment of resectable stage II-IIIB NSCLC patients without driver gene mutation. However, as for the EGFR-positive patients, the therapeutic effect of neoadjuvant treatment, either TKI or chemotherapy, is far from satisfied and the outcome of neoadjuvant immunotherapy plus chemotherapy in these patients remains an unanswered but crucial question. Herein, we conducted a phase 2 prospective trial (NCT05962021). Methods: This is a multicenter, multi-cohort prospective phase 2 study in the treatment-naïve patients with resectable stage II-IIIB (N2) (AJCC 8th edition) non-squamous NSCLC harboring EGFR mutations (19DEL or L858R). Enrolled patients will be divided into two cohorts according to EGFR status and receive neoadjuvant toripalimab (240mg, q3w) plus platinum-based doublet chemotherapy (pemetrexed 500mg/m2 plus carboplatin AUC 5, q3w) for 3 cycles. Surgery will be performed after completion of neoadjuvant therapy based on the multidisciplinary discussion, while local radiotherapy will be considered if the patient cannot undergo surgery due to disease progression. Key inclusion criteria: non-squamous NSCLC, resectable stage II-IIIB (N2), EGFR mutations (19DEL or L858R), age≥18 years, ECOG PS 0-1 and adequate cardiopulmonary function. Exclusion criteria: prior systemic anticancer treatment, contraindication to immunotherapy, active autoimmune disease. Adequate pre-treatment tissue samples are required for RT-PCR or next-generation sequencing to determine the EGFR mutation status and PD-L1 expression immunohistochemical detection. The primary study endpoint is complete pathological response (pCR) rate, per blinded independent pathologist review. Simon's optimal two-stage design will be used to test the null hypothesis of pCR rate ≤5% and alternative hypothesis of pCR rate ≥15%, and 5 or more pCRs among 56 patients per arm are needed for the primary endpoint to be met. Secondary endpoints include major pathological response (MPR) rate, pCR/MPR rate in different EGFR mutation subgroups (19DEL or L858R) and different PD-L1 expression subgroups (TPS &lt; 1% and ≥ 1%), event-free survival and safety and tolerability. Peripheral blood, stool and tissue samples will be obtained longitudinally at baseline, during perioperation and at follow-ups for exploratory analysis. Clinical trial information: NCT05962021 .

Association of CDX2 expression with clinical, pathologic, and molecular features in MSI-H colorectal cancer.

e15583 Background: Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and are seen in 15% of early stage and 5% of metastatic disease. CRC with the MMR-D/MSI-H phenotype carries unique characteristics that are associated with increase mutational burden. Specifically, loss of CDX2 expression is associated with aggressive carcinomas and correlates with worse disease-free survival in the general population. However, the impact of loss of CDX2 expression in MMR-D/MSI-H phenotype is not well known. In this study, we investigated the association of loss of CDX2 expression with clinical and pathological outcomes. Methods: We retrospectively reviewed 543 patients who were diagnosed with colorectal cancer with pathological findings for the presence of MMR-D/MSI-H phenotype, and who had been seen at UPMC Hillman Cancer Center from 2013-2020. CDX2 expression was evaluated across all patients for the association with various molecular, pathological features and survival. In our investigations of association with loss of CDX2, coded as a binary variable in an H score, we used Mann-Whitney or two-sample (Welch’s) t-test for continuous variables, and Chi-square or Fisher’s exact tests for categorical variables. For RFS and OS, we compared H score groups with log-rank tests at two-sided alpha = 0.05 and plotted respective Kaplan-Meier curves. Results: A total of 99 patients were identified with adequate tissue sample to assess for CDX2 expression and with consistent clinical follow-up from date of diagnosis to present. When examining loss of CDX2 expression and association with pathological factors, we observed a significant association with a higher T4 stage (43% vs 14%; p = 0.008), and high grade tumor (86% vs 22%; p = 1.086 x 10-8 ) as well as presence of PNI (peri-neural invasion) (36% vs 17%; p = 0.030). There was no association observed between CDX2 expression and N stage or location of tumor. When examining loss of CDX2 expression and association with molecular factors, we observed that patients with Lynch syndrome were more likely to preserve CDX2 expression (0% vs 27%; p = 0.001) while patients with BRAF mutation were more likely to present with loss of CDX2 expression. Finally, patients with loss of CDX2 expression had numerically lower median survival (8.2 years vs. 9.3 years) though this did not reach statistical significance (p = 0.120). Conclusions: Overall, loss of CDX2 expression correlates with worse pathological features as it was significantly seen in patients with a diagnosis of CRC at a higher T stage, grade, presence of PNI and presence of BRAF mutation. Although no significant association was observed in terms of survival outcomes due to likely insufficient power, a notable separation of survival curves was noted, which indicates overall lower survival.

Accurate and safe diagnosis and treatment of neoplastic biliary lesions using a novel 9F and 11F digital single-operator cholangioscope.

Background and study aims Digital single-operator cholangioscopy (DSOC) allows the diagnosis of biliary duct disorders and treatment for complicated stones. However, these technologies have limitations such as the size of the probe and working channel, excessive cost, and low image resolution. Recently, a novel DSOC system (eyeMAX, Micro-Tech, Nanjing, China) was developed to address these limitations. We aimed to evaluate the usefulness and safety of a novel 9F and 11F DSOC system in terms of neoplastic diagnostic accuracy based on visual examination, ability to evaluate tumor extension and to achieve complete biliary stone clearance, and procedure-related adverse events (AEs). Patients and methods Data from ≥ 18-year-old patients who underwent DSOC from July 2021 to April 2022 were retrospectively recovered and divided into a diagnostic and a therapeutic cohort. Results A total of 80 patients were included. In the diagnostic cohort (n = 49/80), neovascularity was identified in 26 of 49 patients (46.9%). Biopsy was performed in 65.3% patients with adequate tissue sample obtained in 96.8% of cases. Biopsy confirmed neoplasia in 23 of 32 cases. DSOC visual impression achieved 91.6% sensitivity and 87.5% specificity in diagnosing neoplasms. In the therapeutic cohort (n = 43/80), 26 of 43 patients required lithotripsy alone. Total stone removal was achieved in 71% patients in the first session. Neither early nor late AEs were documented in either the diagnostic or therapeutic cohort. Conclusions The novel DSOC device has excellent diagnostic accuracy in distinguishing neoplastic biliary lesions as well as therapeutic benefits in the context of total stone removal, with no documented AEs.

Histopathological Evaluation of Pouch Neoplasia in IBD and Familial Adenomatous Polyposis.

IPAA is often required for patients with ulcerative colitis or familial adenomatous polyposis after colectomy. This procedure reduces but does not completely eliminate the risk of neoplasia. This study focuses on the histopathology of neoplasia in the ileal pouch, rectal cuff, and anal transition zone. We performed a MEDLINE search for English-language studies published between 1981 and 2022 using the PubMed search engine. The terms "ileal pouch-anal anastomosis," "pouchitis," "pouch dysplasia," "pouch lymphoma," "pouch squamous cell carcinoma," "pouch adenocarcinoma," "pouch neoplasia," "dysplasia of rectal cuff," and "colitis-associated dysplasia" were used. Human studies of neoplasia occurring in the pouch and para-pouch were selected, and the full text was reviewed. Comparisons were made within and across studies, with key concepts selected for inclusion in this article. Neoplasia in the pouch is a rare complication in patients with IPAA. Annual endoscopic surveillance is recommended for familial adenomatous polyposis patients and ulcerative colitis patients with a history of prior dysplasia or carcinoma. In familial adenomatous polyposis, dysplastic polyps of the pouch are visible and readily amenable to endoscopic removal; however, glandular dysplasia in the setting of ulcerative colitis may be invisible on endoscopy. Therefore, random biopsies and adequate tissue sampling of the pouch and rectal cuff are recommended in this setting. The histological diagnosis of IBD-associated dysplasia can be challenging and should be confirmed by at least 1 expert GI pathologist. See video from the symposium.

Comparison of Monopolar Versus Bipolar Repeat Transurethral Resection of Bladder Tumours.

To compare the effects of monopolar and bipolar energy sources on efficacy of both techniques and possible complications in bladder cancer patients undergoing repeat Transurethral resection of bladder tumour (re-TURBT). Descriptive study. Place and Duration of the Study: University of Health Science, Izmir Bozyaka Research and Training Hospital, Turkiye, from 2019 to 2021. Patients undergoing re-TURBT were inducted. Patients with residual tumour at initial TURBT, recurrent bladder cancer and patients with a non-urothelial pathology report in initial TURBT were excluded. The primary outcome was the complication ratio of the TURBT which were obturator reflex, bladder wall perforation, coagulum retention, fever, and TUR syndrome. The secondary outcome was the efficacy of the TURBT procedure, such as complete tumour resection, adequate sampling of deep muscle tissue, and sampling of qualified tissues without any thermal damage. One hundred and twenty-three patients were enrolled; 75 patients in re-M-TURBT group and 48 patients in re-B-TURBT group were analysed. Demographic and tumour characteristics, and complication rates according to the Clavien classification, were similar between the two groups (p = 0.302). The catheterisation time was shorter significantly in the bipolar re-TURBT group (median 4 vs. 3 days, respectively, p = 0.025). Monopolar and Bipolar energy sources are techniques that can be used safely in re-TURBT in terms of both appropriate pathology sampling (adequate muscle tissue sampling, cautery artifact) and complication (obturator reflex, hyponatraemia, haemoglobin decrease, bleeding) rates. Bladder Cancer, Monopolar, Bipolar, TURBT, Obtrator reflex, Complications.

Leksell Frame-Based Stereotactic Biopsy for Infratentorial Tumor : Practical Tips and Considerations.

The Leksell frame-based transcerebellar approach was proposed with the arc support frame attached upside down to the Z coordinate. This study presented practical tips and considerations for obtaining adequate tissue samples for deep-seated cerebellar lesions or lower brainstem lesions specifically those accessible via the cerebellar peduncle. For practical insights, the Leksell coordinate frame G was fixed to prevent the anterior screw implantation within the temporalis muscle, to avoid interference with the magnetic resonance (MR)-adapter, and taking into account the magnetic field of MR in close proximity to the tentorium. After mounting of indicator box, the MR imaging evaluation should cover both the indicator box and the infratentorial region that deviated from it. The coordinates [X, Y, Za, Arc0, Ringa0] obtained from Leksell SurgiPlan® software (Elekta, Stockholm, Sweden) with arc 00 located on the patient's right side were converted to [X, Y, Zb=360-Za, Arc0, Ringb0=Ringa0-1800]. The operation was performed in the prone position under general anesthesia in four patients with deep cerebellar (n=3) and brainstem (n=1) tumors. The biopsy results showed two cases of diffuse large B-cell lymphoma, one metastatic braintumor and one glioblastoma. One patient required frame repositioning as a complication. Drawing upon the methodology outlined in existing literature, we anticipate that imparting supplementary expertise could render the stereotactic biopsy of infratentorial tumors more consistent and manageable for the practitioner, thereby facilitating adequate tissue samples and minimizing patient complications.

PATH-43. INFRATENTORIAL IDH-MUTANT ASTROCYTOMAS REQUIRE HIGH INDEX OF SUSPICION FOR ACCURATE DIAGNOSIS

Abstract BACKGROUND Banan et al (PMID 2776277) recently identified infratentorial IDH-mutant astrocytomas (Inf-IDHmt) as a distinct subtype in which 80% have non-canonical mutations, precluding the use of IDH1 R132H immunohistochemistry (IHC) for diagnosis. They note “molecular testing is critical for detection of these tumors”. Only 47% have ATRX loss by IHC and only 56% have MGMT promotor methylation. Thus, it is critical that neurosurgeons take this into account during surgical planning due to the requirement for adequate tissue sample volume necessary for diagnosis. We review these diagnostic challenges in our recent single institution experience with these tumors. METHODS Database text word searches were conducted for the years 2007-2023 to generate cases, coupled with chart review. RESULTS 7 cases were identified: 3 male and 4 female, ages 27-44. All cases were small stereotactic biopsies. The histological diagnosis was made exceptionally challenging by paucity of tumor cells (especially in grade 2), coupled with the fact that 5 of 7 had non-canonical IDH-mutation and 5 of 7 showed ATRX retention by IHC, necessitating a very high index of suspicion on the part of the pathologist to send for next-generation sequencing (NGS). Due to the rare co-expression of IDH and histone mutations in this subtype, 6 of 7 had H3 K27M IHC conducted; all were negative. Due to small tissue volumes, MGMT promotor methylation testing could only be conducted on 3 of 7 cases; testing was uninformative on these 3. CONCLUSION Preoperative high index of suspicion is required to obtain maximal safe biopsy volumes of tissue for molecular and MGMT methylation testing, which should be conducted on virtually all brainstem and cerebellar biopsies.

Imaging and Management of Fibroepithelial Lesions of the Breast: Radiologic-Pathologic Correlation.

Fibroepithelial lesions (FELs) are among the most common breast masses encountered by breast radiologists and pathologists. They encompass a spectrum of benign and malignant lesions, including fibroadenomas (FAs) and phyllodes tumors (PTs). FAs are typically seen in young premenopausal women, with a peak incidence at 20-30 years of age, and have imaging features of oval circumscribed hypoechoic masses. Although some FA variants are especially sensitive to hormonal influences and can exhibit rapid growth (eg, juvenile FA and lactational adenomas), most simple FAs are slow growing and involute after menopause. PTs can be benign, borderline, or malignant and are more common in older women aged 40-50 years. PTs usually manifest as enlarging palpable masses and are associated with a larger size and sometimes with an irregular shape at imaging compared with FAs. Although FA and FA variants are typically managed conservatively unless large and symptomatic, PTs are surgically excised because of the risk of undersampling at percutaneous biopsy and the malignant potential of borderline and malignant PTs. As a result of the overlap in imaging and histologic appearances, FELs can present a diagnostic challenge for the radiologist and pathologist. Radiologists can facilitate accurate diagnosis by supplying adequate tissue sampling and including critical information for the pathologist at the time of biopsy. Understanding the spectrum of FELs can facilitate and guide appropriate radiologic-pathologic correlation and timely diagnosis and management of PTs. Published under a CC BY 4.0 license. Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Invasive Diagnostic Procedures from Bronchoscopy to Surgical Biopsy-Optimization of Non-Small Cell Lung Cancer Samples for Molecular Testing.

Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients' treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era.

Ultrasound-guided Tru-cut biopsy of pelvic tumors: First reported case series in the Philippines

This paper documents the first reported cases of patients in the country who underwent transvaginal ultrasound-guided Tru-cut biopsy of pelvic tumors in a tertiary level health institution in 2019. Different indications for Tru-cut biopsy were demonstrated highlighting its clinical utility in the diagnosis and management of malignant pelvic tumors. All patients warranted histologic diagnosis for further planning of the most appropriate management. Adequate tissue samples were obtained from all three patients with no procedure-related complications.

Technetium-99m-pyrophosphate imaging-based computed tomography-guided core-needle biopsy of internal oblique muscle in wild-type transthyretin cardiac amyloidosis

Background Technetium-99m-pyrophosphate (99mTc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition. Objective This study aimed to assess the safety and efficacy of 99mTc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits. Methods Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99mTc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022. Results All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99mTc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results. Conclusion In wild-type ATTR-CA, 99mTc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma.

Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may beviewed onstandard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm-1and 2,930 cm-1. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.