Diagnostic Tissue Research Articles

CTIM-34. EFFECTS OF NEOADJUVANT IMMUNE CHECKPOINT INHIBITION ON PEDIATRIC AND ADULT HIGH-GRADE GLIOMAS

Abstract High-grade gliomas (HGG) are lethal tumors with few long-term survivors affecting adult and pediatric patients. Studies investigating immune checkpoint inhibition (ICI) suggest administration of neoadjuvant anti-PD1 blockade (neo-aPD1) enhances local and systemic anti-tumor responses. This data is supported by increased T cell density in the tumor and proportion of cytotoxic T cells in peripheral blood. In a previous randomized clinical trial, neo-aPD1 improved survival in adult with recurrent glioblastoma. In this study, we utilized multiplex immunofluorescence (mIF), and single-cell RNA sequencing (scRNA-seq) to investigate the effects of neoadjuvant ICI on the TME and compare between pediatric and adult populations. Tissue samples from adult patients with recurrent GBM treated with neo-aPD1 (n=22) or adjuvant only therapy (n=5) were obtained from our UCLA off-label neo-PD1 study. Tissue samples were also obtained from pediatric patients with recurrent/progressive HGG treated with neoadjuvant ICI from the ongoing Pediatric Neuro-Oncology Consortium study PNOC19. Samples included diagnostic tissue from two patients and on study surgery tissue from four patients. All tissue samples were subjected to mIF and underwent imaging analysis to assess immune cell infiltration by quantifying lymphoid and myeloid cell densities across the two treatment groups. Our preliminary findings elucidated a trend of higher T cell infiltration in adult neoadjuvant compared to adjuvant-only treated patients (median density 58.11 vs 15.15 T-cells/mm2). Compared to their adult counterparts, neoadjuvant ICI treated pediatric patients had even more robust total T cell infiltration (median density 268.10 vs 58.11 T-cell/mm2, pediatric vs adult respectively). scRNA-seq analysis revealed a greater enrichment of monocytic macrophages in the pediatric population compared to tissue resident microglia in the adults. This early data requires analysis of additional samples to better understand differences in the anti-tumor immune response between adult and pediatric recurrent/progressive HGG patients.

Comparison of diagnostic yields, operative times, and post-operative hemorrhage between twist drill versus burr hole craniotomy approaches for stereotactic needle brain biopsy.

Stereotactic frameless needle brain biopsy is a common neurosurgical procedure performed via twist drill or open burr hole approaches. We aim to compare diagnostic yields and surgical outcomes to delineate the safety and efficacy of both approaches. A retrospective database of all stereotactic needle biopsy procedures performed at a single institution over 30 months was conglomerated. Demographics, medical comorbidities, operative details/complications, immediate post-operative imaging, and pathology were abstracted. Two hundred and twenty-five needle biopsies were identified, of which 165 (73.3%) were open, and 60 (26.7%) were twist drill. Diagnostic pathology yield rates between open (84.8%) and twist drill (93.3%) approaches were similar (p = 0.15), with a median of 4 cores taken in each (p = 0.30). Diagnostic tissue yields with an intra-operative pause for pathology confirmation was 90.4% compared to 79.1% without pause (p = 0.036, OR 2.49). Median operative times for open versus twist drill procedures were 68.0min (IQR 49-83) versus 35.5min (IQR 26-54), respectively (Wilcoxon p < 0.001), which remained significant after controlling for awaiting intraoperative pathology using bivariable linear modeling (p < 0.001). Intraoperative bleeding through the needle cannula was noted in 22 patients (9.8%), including eight twist drill (13.3%) and 14 open needles (8.5%). Of 197 cases (87.6%) with post-operative cranial imaging (CT/MRI), 90 (45.7%) demonstrated some degree of post-operative hemorrhage characterized as superficial (n = 10, 11.1%), deep/intralesional (n = 64, 71.1%) bleeding, or both (n = 16, 17.9%). Bleeding rates between open (46.7%) and twist drill (43.3%) approaches were similar (p = 0.78). Post-operative clinical decline or neurological change was noted in 9 patients (4.0%), including one twist drill (1.7%) and eight open needles (4.8%), among which 7 (78%) had deep blood products identified on post-operative imaging. Stereotactic needle biopsy via twist drill approach has similar diagnostic yield rates, asymptomatic bleeding rates, and post-operative complications with significantly shorter operative time and smaller incision size than conventional open burr hole needle biopsy. Using intra-operative frozen histopathology for presumed sufficient diagnostic tissue may improve final pathologic diagnostic rates regardless of approach technique.

In situ optical feedback in brain tumor biopsy - a multipara-metric analysis

Abstract Introduction Brain tumor needle biopsy interventions are inflicted with non-diagnostic or biased sampling in up to 25% and hemorrhage, including asymptomatic cases, in up to 60%. To identify diagnostic tissue and sites with increased microcirculation, intraoperative optical techniques have been suggested. The aim of this study was to investigate the clinical implications of in situ optical guidance in frameless navigated tumor biopsies. Methods Real-time feedback on protoporphyrin IX (PpIX) fluorescence, microcirculation, and gray-whiteness was given before tissue sampling (272 positions) in 20 patients along 21 trajectories in total. The primary variables of investigation were fluorescence in relation to neuropathological findings and gadolinium (Gd) enhancement, increased cerebral microcirculation in relation to bleeding incidence, number of trajectories, and impact on operation time. Results PpIX fluorescence was detected in Glioblastoma IDH-wildtype CNS WHO grade 4 (n=12), Primary diffuse large B-cell lymphoma (n=3), astrocytoma IDH-mutated CNS WHO grade 4 (n=1) (Ki67 indices ≥15%). For two patients, no PpIX fluorescence or Gd was found, although samples contained tumorous tissue (Ki67 index 6%). Increased microcirculation was found along nine trajectories (34 sites), located in cortical, tumorous, or tentorium regions. Postoperative bleedings (n=10, nine asymptomatic) were related to skull opening or tissue sampling. The present study strengthens the proposed independence from intraoperative neuropathology as PpIX fluorescence is detected. Objective real-time feedback resulted in fewer trajectories compared to previous studies indicating reduced operation time. Conclusions The integrated optical guidance system provides real-time feedback in situ, increasing certainty and precision of diagnostic tissue before sampling during frameless brain tumor biopsies.

Straightforward, Highly Useful, Innovative and Cost-Effective Method with Potential to Improve Personalized Diagnosis: Sectioning of Prostatectomy Specimen with a Single Blade

Abstract Introduction/Objective There is potential for devices with an adjustable base and a single blade to precisely cut parallel slices of a prostatectomy specimen at a set preferred thickness to improve pathology practice by standardizing the tissue for histological review, allowing for precise punch biopsies of the slices for molecular diagnostics for biobanking and personalized therapy. The current standard method of sectioning the prostate involves serially sectioning the prostatectomy specimen by hand with a sharp long knife, leading to uneven sections. Methods/Case Report A device with an adjustable base was developed at a regional Veteran Affairs Medical Center (VAMC) that consists of two sets of multiple, vertically arranged parallel and flat bars measuring 10 cm in height, 1.5 cm in width and 0.3 cm in thickness spaced 0.4 cm from each other, resembling a comb with flat teeth. After inking, orientation, and removal of the seminal vesicles and apex and base margins, the prostatectomy specimen is immobilized between the two combs and sliced in parallel from apex to base to produce parallel consistent prostate slices. The ability to obtain punch biopsies from precise areas of the prostate was reviewed. Results (if a Case Study enter NA) The device results in uniform 4 mm thick oriented smooth specimen slices of good quality with minimal distortion. The device allows for the obtaining of punch biopsies taken at precise locations of the prostate corresponding to specific imaging locations (highly useful for biobanking or obtaining diagnostic tissue for molecular diagnostics for personalized therapy). The adjustable nature of the device and single blade gives the device flexibility in the specimen. Conclusion This device with an adjustable base and single blade allows for safe and precise parallel slicing. This is highly useful obtaining diagnostic standardized tissue, for obtaining biobank specimens and for obtaining material of precise location for molecular studies to guide the personalized therapy of tumors.

Precision Pathology: Unveiling the role of Interval Sectioning Protocol for Optimal Diagnosis in Pancreatic, Ampullary, and Bile Duct Biopsies

Abstract Introduction/Objective Endoscopic techniques offer advanced diagnostics but encounter challenges in obtaining limited pancreaticobiliary biopsies, including ampullary (AMP), EUS-guided pancreatic (PAN), and spy bite biliary (BD) biopsies. Interval sectioning optimizes immunohistochemical stain utility and tissue conservation. This study evaluates interval sectioning protocols’ impact on diagnostic precision and tissue preservation at our institution. Methods/Case Report This analysis examines cases over four months before and after a protocol change, focusing on AMP, BD, and PAN biopsies. Previously, AMP and BD biopsies used three H&amp;E-stained slides, while PAN required two H&amp;E-stained and five unstained slides (USS). The new protocol adopts seven slides with H&amp;E staining on levels 1, 4, and 7, emphasizing consistency. Parameters assessed include diagnosis, turnaround time (TAT), and USS utilization. A 30% USS utilization cutoff justifies upfront interval sectioning. Results (if a Case Study enter NA) A total of 77 cases from the old protocol and 142 from the new protocol were reviewed. No significant difference in TAT between old and new protocols was found (p=0.340). However, PAN TAT notably improved (4848 min vs. 2932 min). Usage rates varied by site: 22.2% (AMP), 33.3% (BD), and 34.4% (PAN). Conclusion USS usage was lowest for AMP cases (22.2%), below the 30% threshold for upfront interval sectioning justification. Eliminating interval sectioning for AMP would save 116 USS in the new protocol. BD and PAN cases warrant upfront interval sectioning, with USS usage rates of 31.5% and 33.7%, respectively. While PAN cases show no cost difference, the new protocol improves specimen visualization, correlates immunohistochemical stains better, and significantly enhances turnaround time.

The Expression of miR-211-5p in Sentinel Lymph Node Metastases of Malignant Melanoma Is a Potential Marker for Poor Prognosis

Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and its potential use as a prognostic biomarker. We performed in situ hybridization for miRNA-211-5p on 109 FFPE melanoma samples from 76 patients, including 31 paired primary tumor/metastasis samples. For validation, we performed in silico analyses of TCGA skin cutaneous melanoma (SKCM) cohort. High miR-211-5p expression was more frequent in primary tumors (70.8%) compared to metastases (39.3%). In metastases, it was associated with a significantly worse overall survival. Data from TCGA SKCM cohort confirmed that high miR-211-5p expression in melanoma metastases, but not primary tumors, is associated with worse overall survival. MiR-211-5p expression in metastases is associated with a shorter survival, emphasizing the potential of miR-211-5p as a risk predictor for a less favorable clinical outcome in metastatic disease. In situ hybridization could be implemented in a routine laboratory workflow and can be performed on diagnostic tissue.

Comprehensive Evaluation of Pulmonary Masses Using Multi-detector CT: Correlating Morphological Features With CT-Guided Histopathological Findings for Enhanced Diagnostic Accuracy.

Lung masses pose a significant diagnostic challenge due to their diverse causes, from benign hamartomas to malignant bronchogenic carcinoma. Multi-detector CT (MDCT) is essential in evaluating these masses, offering detailed morphological insights to help differentiate between benign and malignant lesions. However, a definitive diagnosis often requires histopathological confirmation. CT-guided biopsy is crucial, providing a minimally invasive method to obtain tissue samples and thus guiding clinical management and treatment decisions. The primary objective of this study was to assess the diagnostic accuracy of MDCT in differentiating between benign and malignant lung mass lesions. The study focused on evaluating the characteristic features of lung masses on MDCT that aid in this differentiation, correlating imaging findings with histopathological results from CT-guided biopsies, and determining the overall diagnostic utility of MDCT in thoracic lesions. This hospital-based observational study was conducted over a period of 17 months. The study included 52 patients with thoracic lesions, identified through imaging techniques such as chest radiographs and CT scans. These patients underwent CT-guided biopsy, with tissue samples sent for histopathological examination. Inclusion criteria involved patients with clinically and radiographically diagnosed lung masses, while exclusion criteria included those who did not consent, had contraindications to contrast media, or had conditions such as severe respiratory distress or coagulopathy. The data were analyzed using descriptive statistics, with efficacy measures such as yield and failure rates of CT-guided biopsies and validation measures like sensitivity, specificity, positive predictive value, and negative predictive value for MDCT. The study included 52 patients (50% male, 50% female), aged 16-80, with the most common age group being 51-60 years. Lesions were mainly in the lung parenchyma (65.38%), followed by the mediastinum (15.38%), hilar region (11.54%), and pleura (7.69%). MDCT evaluation classified 84.44% of the lesions as malignant, characterized by irregular contours, inhomogeneous texture, and contrast enhancement, while 15.55% were benign. Histopathology confirmed 42 malignant lesions, with squamous cell carcinoma being the most prevalent. Benign lesions included abscesses, tuberculosis, and pneumonitis. The study achieved a 100% success rate for CT-guided biopsy, with one minor complication (pneumothorax). The diagnostic accuracy of MDCT was notable, with a sensitivity of 100% for detecting malignancies, a specificity of 77.78%, a positive predictive value of 87.50%, and a negative predictive value of 100%, emphasizing its effectiveness in thoracic lesion evaluation. MDCT is a highly effective tool in the evaluation of lung masses, providing critical information that aids in distinguishing between benign and malignant lesions. When combined with CT-guided biopsy, it offers a reliable method for obtaining diagnostic tissue samples, with a high degree of accuracy and a low complication rate. The study underscores the importance of integrating imaging and histopathological findings in the management of thoracic lesions, ultimately enhancing diagnostic precision and informing appropriate clinical interventions.

Frameless Stereotactic Biopsy of Brainstem Tumors Using the Stealth Autoguide: A Technical Note.

In the molecular era of neuro-oncology, it is increasingly necessary to obtain tissue for next-generation sequencing and methylome profile for prognosis and targeted oncological management. Brainstem tumors can be technically challenging to biopsy in the pediatric population. Frame-based and frameless techniques have previously been described and proven to be safe and efficacious in children. Recent cranial robotic guidance platforms have augmented the fluency of frameless stereotactic approaches, but the technical nuances of these procedures in children are not often discussed. We present a technical workflow for frameless stereotactic biopsy of brainstem tumors in children using the Medtronic Stealth Autoguide cranial robotic guidance platform and examine safety and efficacy of this surgical approach. A minimally invasive, frameless, transcerebellar approach is described, including operative steps and workflow. We assessed operative times, diagnostic accuracy and yield, and complication rates. Five patients underwent biopsy with the technique described. The youngest patient in our series was of 2 years. The intended target was achieved on postoperative imaging in all cases, and diagnostic tissue was obtained in all 5 patients. One patient had a clinically insignificant hemorrhage. Frameless stereotactic biopsy of the brainstem can be performed safely, efficiently, and accurately using the Medtronic Stealth Autoguide robotic platform in children as young as 2 years.

Detection of differentially methylated CpGs between tumour and adjacent benign cells in diagnostic prostate cancer samples

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.

NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2-G3 breast cancer.

Breast cancer is one of the more frequently diagnosed cancers leading to death in women, and, like other tumor types, it is heterogeneous in its immunophenotype. It harbors mutations that modify tumor aggressiveness, therapy responses, residual disease, drug resistance, and relapse rates in advanced stages. This study aims to assess the mutational status of G2 and G3 tumors using next-generation sequencing (NGS) on initial tissue biopsies, liquid biopsies, and mastectomy specimens. The histopathological (HP) diagnosis for the 32 selected cases was established via Hematoxylin-Eosin (HE) staining by two observers. For the immunohistochemical (IHC) testing of estrogen receptor (ER), progesterone receptor (PGR) and human epidermal growth factor receptor 2 (HER2), we used the Ventana BenchMark Ultra. Ki67 testing was conducted using Bond-III from Leica. For cases with a score of 2+, gene amplification was assessed by silver-enhanced in situ hybridization (ISH) (SISH; Inform HER2 Dual ISH) on Ventana BenchMark Ultra. NGS analysis was initially performed on biopsies and plasma, and later on mastectomy specimens. After automated deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) extraction, concentrations were measured using the Invitrogen Qubit system. Libraries were created using Oncomine systems, and sequencing and analysis were done with the Ion Torrent system. Most tumors were graded as G3 (19 cases), with Luminal A being the predominant molecular subtype, and a significant number displayed HER2∕HER2-low characteristics (24 out of 32 cases). The NGS assessment showed that phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations were the most frequent across all sample types. A significant limitation was the high number of invalid plasma tests due to pre-analytical handling errors or transport issues. Nonetheless, plasma testing (liquid biopsy) proved useful for monitoring tumor evolution and assessing residual disease.

CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

AbstractMantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins were measured using GeoMx digital spatial profiling in tissue microarrays from 100 diagnostic MCL tissues. Regions of interest were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophages, CD20+ MCL cells, and CD3+ T-cells was performed. To validate protein profiles, 1811 messenger RNAs were measured in CD20+ cells and 2 subsets of T cells. Image analysis was used to extract the phenotype and position of each targeted cell, thereby allowing the exploration of cell frequencies and cellular neighborhoods. Proteomic investigations revealed that CD163+ cells modulate their immune profile depending on their localization and that the immune inhibitory molecules, V-domain immunoglobulin suppressor of T-cell activation and B7 homolog 3, have higher expression in tumor-sparse than in tumor-rich tissue regions and that targeting should be explored. We showed that MCL tissues with more abundant infiltration of CD163+ cells have a higher proteomic and transcriptional expression of key components of the MAPK pathway. Thus, the MAPK pathway may be a feasible therapeutic target in patients with MCL with CD163+ cell infiltration. We further showed the independent and combined prognostic values of CD11c and CD163 beyond established risk factors.

Initial United States experience with Medtronic Stealth Autoguide cranial robotic guidance platform.

Stereotactic techniques play an important role in neurosurgery. The development of a miniaturized cranial robot with an efficient workflow and accurate surgical execution is an important step in a broader application of these techniques. Herein, the authors describe their experience with the Medtronic Stealth Autoguide miniaturized cranial robot. A retrospective review of 75 cases from 2020 to 2022 was performed. The patients who had undergone surgery utilizing the Stealth Autoguide robot were analyzed for surgical indication and accuracy, operative time, and clinical outcome. The outcomes were defined as follows: for stereoelectroencephalography (SEEG), the electrode placement pattern that identified the seizure focus and did not require any revision or additional leads; for biopsy, the percentage of cases in which diagnostic tissue was obtained; and for laser interstitial thermal therapy (LITT), the percentage of cases in which laser fiber placement was adequate for ablation. Surgical complications were defined as any asymptomatic or symptomatic intracerebral hemorrhage, new neurological deficit, or need for electrode, laser fiber, or biopsy needle repositioning or revision. The Stealth Autoguide robot was utilized in 75 on-label cases, including 40 SEEG cases for seizure focus localization, 19 LITT cases, and 16 stereotactic biopsy cases. The mean real target error (RTE) at the entry was 1.48 ± 0.84 mm for biopsy, 1.36 ± 0.89 mm for Visualase laser fiber placement, and 1.24 ± 0.72 mm for SEEG. The mean RTE at the target was 1.56 ± 0.95 mm for biopsy needle placement, 1.42 ± 0.93 mm for Visualase laser fiber placement, and 1.31 ± 0.87 mm for SEEG electrode placement. The surgical time for unilateral SEEG cases took an average 52 minutes (average 6.5 mins/lead, average 8 electrodes). Bilateral SEEG cases took an average 105 minutes (average 7.5 mins/lead, average 14 electrodes). In the SEEG population, there were no revised or unsuccessful seizure localizations. For biopsy, diagnostic tissue was obtained in 100% of cases. For LITT, fiber placement was adequate for ablation in 100% of cases. There were no cases of symptomatic or asymptomatic intracerebral hemorrhage, and no cases required repositioning or replacement of the laser fiber, electrode, or biopsy needle. One patient experienced transient cranial nerve III palsy following laser ablation that resolved in 10 weeks. A failure of communication between the robotic platform and the Stealth Autoguide as a station required the cancellation of 1 procedure. The Medtronic Stealth Autoguide robot system is versatile across biopsy, SEEG, and laser ablation indications. Setup and surgical execution are efficient with a high degree of accuracy and consistency.

The role for endobronchial biopsy in the era of endobronchial ultrasound guided transbronchial needle aspiration for the diagnosis of sarcoidosis: a single center experience.

Endobronchial biopsy (EBBX) has been reported to increase diagnostic yield for pulmonary sarcoidosis. The purpose of this study is to investigate the diagnostic yield for EBBX following endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). We identified a cohort of patients in the University of Minnesota Sarcoidosis Registry who had EBBx and EBUS-TBNA as part of workup for abnormal chest imaging. Data regarding demographics, biopsy approach and technique were recorded. Our cohort included 37 patients (53.24±9.5, Male, 22±0.57; 3.8% were African American). In these patients who had EBBX, EBUS-TBNA was performed in 100% of patients and TBBX was performed in 2 patients (5%). EBBX was positive in 9 patients (24%) and EBUS-TBNA was positive in 34 patients (92%). TBBX was diagnostic in one of two patients. EBBX was the only diagnostic tissue in 3 of the 37 patients (8%). Conclusion: The diagnostic yield of EBBX is lower than previously reported, with only 8% of EBBXs demonstrating granulomatous inflammation. However, instrumentation used for obtaining EBBX as well as the presence of visible lesions does influence the diagnostic yield. Studies with adequate power are needed before implementing changes in clinical practice. When performed alongside EBUS-TBNA, EBBX did not significantly add to the diagnostic yield in sarcoidosis unless visible lesions were observed.

A 22-G or a 25-G Needle: Which One to Use in the Diagnostics of Solid Pancreatic Lesions? A Systematic Review and Meta-Analysis.

With the 12th highest incidence and a common late diagnostic at advanced stages, neoadjuvant therapies for pancreatic cancer are important, but they require a confirmed diagnosis. Being a diagnostic standard, the clarification of the clinical relevance of needle gauges is needed, as larger ones may retrieve more tissue for diagnostics, but may also increase the risk of complications. We performed a meta-analysis to compare the efficiency of the most commonly used 22-G and 25-G needles for EUS guided biopsy in solid pancreatic lesions. The MEDLINE (via PubMed), Embase, Cochrane (CENTRAL), and Scopus databases were searched with "EUS", "needle", "FNA", "pancreas", "prospective", "22G", and "25G" keywords. Mixed effects were assessed in the model, with a mean of 86% and a 95% confidence interval. Fourteen prospective studies that compared the efficiency of 22-G and 25-G biopsy needles in 508 and 524 lesions, respectively, were analyzed, along with 332 specimens biopsied using both needle sizes. The groups did not significantly differ in the outcomes. A low degree of heterogeneity was observed overall, except for specimen adequacy. Moreover, 22-G and 25-G needles have comparable safety and efficacy for focal pancreatic lesion biopsies without a high risk of complications.

Innovative methodology for noninvasive spatial mapping of gold nanoparticle distribution in tissues: potential applications in biomedical imaging and therapy

Gold nanoparticles (AuNPs) have emerged as versatile agents in biomedical applications, particularly for enhancing contrast in tagged biological tissues for tumor imaging and diagnostics due to their strong absorption cross-section. In this study, we present a methodology for quantifying the spatial distribution of AuNPs within superficial tissue volumes. Utilizing silicone tissue phantoms as a background medium and spatial frequency domain imaging (SFDI) to measure the tissues’ optical properties, we constructed a lookup table (LUT) to infer the optical properties of embedded AuNPs with varying spatial concentrations and depths across multiple spatial frequencies. An analytical solution derived from the LUT facilitated the determination of embedded NP concentration in-depth as a function of measured spatial frequency-dependent optical absorption. Notably, SFDI enabled the spatial localization of NPs in three dimensions. These findings lay the foundation for future in vivo studies on mapping NPs and hold significant promise for advancing biomedical imaging techniques.

Prognostic Analysis Combining Histopathological Features and Clinical Information to Predict Colorectal Cancer Survival from Whole-Slide Images.

Colorectal cancer (CRC) is a malignant tumor within the digestive tract with both a high incidence rate and mortality. Early detection and intervention could improve patient clinical outcomes and survival. This study computationally investigates a set of prognostic tissue and cell features from diagnostic tissue slides. With the combination of clinical prognostic variables, the pathological image features could predict the prognosis in CRC patients. Our CRC prognosis prediction pipeline sequentially consisted of three modules: (1) A MultiTissue Net to delineate outlines of different tissue types within the WSI of CRC for further ROI selection by pathologists. (2) Development of three-level quantitative image metrics related to tissue compositions, cell shape, and hidden features from a deep network. (3) Fusion of multi-level features to build a prognostic CRC model for predicting survival for CRC. Experimental results suggest that each group of features has a particular relationship with the prognosis of patients in the independent test set. In the fusion features combination experiment, the accuracy rate of predicting patients' prognosis and survival status is 81.52%, and the AUC value is 0.77. This paper constructs a model that can predict the postoperative survival of patients by using image features and clinical information. Some features were found to be associated with the prognosis and survival of patients.

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Six paediatric patients (median age:16 years, range: 12-17at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

From ownership to custodianship of tumor biopsy tissue in genomic testing: a mixed methods study of patient views.

Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n = 397) completed a questionnaire prior to undergoing MP (n = 356/397). A subset (n = 23) also completed a qualitative interview. Fifty percent of participants believed they and/or relatives should own and control access to diagnostic tissue. Most (65.5%) believed the government should pay for tissue preparation. Qualitative themes included (1) custodianship of diagnostic tissue, (2) changing value of tissue across time and between cultures, (3) equity regarding payment, and (4) cost-benefit considerations in deciding on additional biopsies. Policy and regulation should consider patient perspectives. Extension of publicly funded health care to include tissue retrieval for clinical trials should be considered.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

Evaluation of fine-needle core biopsy specimens for pancreatic ductal adenocarcinoma: Diagnostic utility and helpful histological features.

With the advent of new biopsy devices, fine-needle core biopsy specimens can be obtained from pancreas masses. This study aimed to report the histological spectrum of intrapancreatic adenocarcinoma on fine-needle core biopsy and the accuracy of sampling. We identified 423 SharkCore™ fine-needle core biopsies taken from patients with a high clinical concern for pancreatic adenocarcinoma. For each, we recorded patient age and sex, percentage of diagnostic tissue in each sample and tumour site, size and histological findings. The cases came from 392 patients (193 men, 199 women; mean age 69 years). Median diagnostic tissue amount in the samples was 30%. Common histological findings included desmoplasia (36%), single atypical cells (44%), haphazard glandular growth pattern (68%), nuclear pleomorphism > 4:1 (39%), incomplete gland lumens (18%) and detached atypical epithelial strips (37%). Additional levels were ordered on 143 cases. Final clinical diagnoses associated with the 423 cases were adenocarcinoma (n = 343), pancreatitis (n = 22), intraductal neoplasm or other benign/low-grade process (n = 16) and unknown (n = 42, patients lost to follow-up). Of the adenocarcinoma cases, the diagnosis was established by the evaluated fine-needle core biopsy sample alone in 178, by fine-needle aspiration biopsy alone in 30, by both concurrently in 89 and by subsequent biopsy or resection in 37 cases. Among 68 cases called suspicious on fine-needle core biopsy, 78% ultimately represented adenocarcinoma. Fine-needle core biopsy allows for histological diagnosis of pancreatic adenocarcinoma, using known histological parameters. Common findings include single atypical cells, desmoplasia, haphazard gland growth and nuclear pleomorphism. Cases interpreted as suspicious often represent malignancy.