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Journal of Hepatology Dec 2021Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Herein, we aimed to determine what drives...
BACKGROUND & AIMS
Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Herein, we aimed to determine what drives tumor cell evolution by performing single-cell transcriptomic analysis.
METHODS
We analyzed 46 hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) biopsies from 37 patients enrolled in interventional studies at the NIH Clinical Center, with 16 biopsies collected before and after treatment from 7 patients. We developed a novel machine learning-based consensus clustering approach to track cellular states of 57,000 malignant and non-malignant cells including tumor cell transcriptome-based functional clonality analysis. We determined tumor cell relationships using RNA velocity and reverse graph embedding. We also studied longitudinal samples from 4 patients to determine tumor cellular state and its evolution. We validated our findings in bulk transcriptomic data from 488 patients with HCC and 277 patients with iCCA.
RESULTS
Using transcriptomic clusters as a surrogate for functional clonality, we observed an increase in tumor cell state heterogeneity which was tightly linked to patient prognosis. Furthermore, increased functional clonality was accompanied by a polarized immune cell landscape which included an increase in pre-exhausted T cells. We found that SPP1 expression was tightly associated with tumor cell evolution and microenvironmental reprogramming. Finally, we developed a user-friendly online interface as a knowledge base for a single-cell atlas of liver cancer.
CONCLUSIONS
Our study offers insight into the collective behavior of tumor cell communities in liver cancer as well as potential drivers of tumor evolution in response to therapy.
LAY SUMMARY
Intratumor molecular heterogeneity is a key feature of tumorigenesis that is linked to treatment failure and patient prognosis. In this study, we present a single-cell atlas of liver tumors from patients treated with immunotherapy and describe intratumoral cell states and their hierarchical relationship. We suggest osteopontin, encoded by the gene SPP1, as a candidate regulator of tumor evolution in response to treatment.
Topics: Biopsy; Carcinoma, Hepatocellular; Cholangiocarcinoma; Humans; Immunotherapy; Liver Neoplasms; Neoplastic Cells, Circulating
PubMed: 34216724
DOI: 10.1016/j.jhep.2021.06.028 -
Molecular Cancer Mar 2022Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies... (Review)
Review
Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.
Topics: Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Prognosis; Proteomics
PubMed: 35303879
DOI: 10.1186/s12943-022-01543-7 -
Nature Reviews. Clinical Oncology Sep 2022Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate... (Review)
Review
Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate 'biopsies' offer numerous advantages, including the relative ease of obtaining serial samples and overcoming the issues of interpreting one or more small tissue samples that might not reflect the entire tumour burden. To date, the majority of research in the area of liquid biopsies has focused on blood-based biomarkers, predominantly using plasma-derived circulating tumour DNA (ctDNA). However, ctDNA can also be obtained from various non-blood sources and these might offer unique advantages over plasma ctDNA. In this Review, we discuss advances in the analysis of ctDNA from non-blood sources, focusing on urine, cerebrospinal fluid, and pleural or peritoneal fluid, but also consider other sources of ctDNA. We discuss how these alternative sources can have a distinct yet complementary role to that of blood ctDNA analysis and consider various technical aspects of non-blood ctDNA assay development. We also reflect on the settings in which non-blood ctDNA can offer distinct advantages over plasma ctDNA and explore some of the challenges associated with translating these alternative assays from academia into clinical use.
Topics: Biomarkers, Tumor; Biopsy; Circulating Tumor DNA; Humans; Liquid Biopsy
PubMed: 35915225
DOI: 10.1038/s41571-022-00660-y -
Oral Diseases Jun 2019To detail a scoping review on the global and regional relative frequencies of oral mucosal disorders in the children based on both clinical studies and those reported... (Review)
Review
OBJECTIVE
To detail a scoping review on the global and regional relative frequencies of oral mucosal disorders in the children based on both clinical studies and those reported from biopsy records.
MATERIALS AND METHODS
A literature search was completed from 1 January 1990 to 31 December 2018 using PubMed and EMBASE.
RESULTS
Twenty clinical studies (sample size: 85,976) and 34 studies from biopsy services (40,522 biopsies) were included. Clinically, the most frequent conditions were aphthous ulcerations (1.82%), trauma-associated lesions (1.33%) and herpes simplex virus (HSV)-associated lesions (1.33%). Overall, the most commonly biopsied lesions were mucoceles (17.12%), fibrous lesions (9.06%) and pyogenic granuloma (4.87%). By WHO geographic region, the pooled relative frequencies of the most common oral lesions were similar between regions in both clinical and biopsy studies. Across regions, geographic tongue (migratory glossitis), HSV lesions, fissured tongue and trauma-associated ulcers were the most commonly reported paediatric oral mucosal lesions in clinical studies, while mucoceles, fibrous lesions and pyogenic granuloma were the most commonly biopsied lesions.
CONCLUSIONS
The scoping review suggests data from the clinical studies and biopsy records shared similarities in the most commonly observed mucosal lesions in children across regions. In addition, the majority of lesions were benign in nature.
Topics: Biopsy; Child; Congresses as Topic; Humans; Mouth Diseases; Mouth Mucosa; Oral Medicine; Oral Ulcer; Stomatitis, Aphthous
PubMed: 31034120
DOI: 10.1111/odi.13112 -
Clinical Journal of the American... Nov 2019In 2012, the Systemic Lupus International Collaborating Clinics proposed that lupus nephritis, in the presence of positive ANA or anti-dsDNA antibody, is sufficient to...
BACKGROUND AND OBJECTIVES
In 2012, the Systemic Lupus International Collaborating Clinics proposed that lupus nephritis, in the presence of positive ANA or anti-dsDNA antibody, is sufficient to diagnose SLE. However, this "stand-alone" kidney biopsy criterion is problematic because the ISN/RPS classification does not specifically define lupus nephritis. We investigated the combination of pathologic features with optimal sensitivity and specificity for the diagnosis of lupus nephritis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Three hundred consecutive biopsies with lupus nephritis and 560 contemporaneous biopsies with nonlupus glomerulopathies were compared. Lupus nephritis was diagnosed if there was a clinical diagnosis of SLE and kidney biopsy revealed findings compatible with lupus nephritis. The control group consisted of consecutives biopsies showing diverse glomerulopathies from patients without SLE, including IgA nephropathy, membranous glomerulopathy, pauci-immune glomerulonephritis, membranoproliferative glomerulonephritis (excluding C3 GN), and infection-related glomerulonephritis. Sensitivity and specificity of individual pathologic features and combinations of features were computed.
RESULTS
Five characteristic features of lupus nephritis were identified: "full-house" staining by immunofluorescence, intense C1q staining, extraglomerular deposits, combined subendothelial and subepithelial deposits, and endothelial tubuloreticular inclusions, each with sensitivity ranging from 0.68 to 0.80 and specificity from 0.8 to 0.96. The presence of at least two, three, or four of the five criteria had a sensitivity of 0.92, 0.8, and 0.66 for the diagnosis of lupus nephritis, and a specificity of 0.89, 0.95, and 0.98.
CONCLUSIONS
In conclusion, combinations of pathologic features can distinguish lupus nephritis from nonlupus glomerulopathies with high specificity and varying sensitivity. Even with stringent criteria, however, rare examples of nonlupus glomerulopathies may exhibit characteristic features of lupus nephritis.
Topics: Adolescent; Adult; Aged; Biopsy; Female; Humans; Kidney; Lupus Nephritis; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity; Young Adult
PubMed: 31653670
DOI: 10.2215/CJN.01570219 -
Clinical Journal of the American... Nov 2020Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman-Tukey double-arcsine transformations were used to stabilize variance as complications were rare.
RESULTS
A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location.
CONCLUSIONS
Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.
Topics: Blood Transfusion; Hematoma; Hematuria; Hemostasis, Surgical; Hospitalization; Humans; Image-Guided Biopsy; Kidney; Kidney Diseases; Pain; Risk Factors
PubMed: 33060160
DOI: 10.2215/CJN.04710420 -
Indian Journal of Ophthalmology Sep 2020An intraocular biopsy is performed for diagnostic, prognostic and investigational purposes. Biopsies help to confirm or exclude malignancies and differentiate... (Review)
Review
An intraocular biopsy is performed for diagnostic, prognostic and investigational purposes. Biopsies help to confirm or exclude malignancies and differentiate inflammatory from infectious processes. Histopathological analysis is the final verdict in unresponsive uveitis, atypical inflammation, metastases and masquerade syndromes. Advances and refinement of techniques in cytopathology, immunohistochemistry, microbiological and molecular biologic study offer much more than just diagnosis. They provide prognosis based on cell characteristics and are helpful in planning treatment and intervention. Many biopsy procedures have evolved to provide more safety and minimise complications thus improving the quality of specimens or samples available for analysis. The type of biopsy and technique adopted varies based on the clinical suspicion, size and location of lesions. In uveitis, a working diagnosis of intraocular inflammation is made on clinical examination and laboratory investigations and ancillary tests. Malignancy and uveitis is interlinked and masquerade syndromes are among the commonest indications for biopsy and analysis of specimen. The various types of intraocular biopsies include aqueous tap, fine needle aspiration biopsy, vitreous biopsy, iris and ciliary body, and retinochoroidal biopsy. They will be reviewed in this article with respect to current perspective.
Topics: Biopsy; Biopsy, Fine-Needle; Humans; Inflammation; Iris; Prognosis; Uveitis
PubMed: 32823400
DOI: 10.4103/ijo.IJO_1325_20 -
Current Opinion in Gastroenterology May 2020Over the past decade, imaging modalities and serological tests have emerged as important tools in the evaluation of liver diseases, in many cases supplanting the use of... (Review)
Review
PURPOSE OF REVIEW
Over the past decade, imaging modalities and serological tests have emerged as important tools in the evaluation of liver diseases, in many cases supplanting the use of liver biopsy and histological examination. Nonetheless, the accuracy and diagnostic value of these methods may not always be conclusive and the assessment of liver histology often remains the gold standard for diagnostic evaluation. The purpose of this review is to summarize the current role of liver biopsy in contemporary hepatology practice.
RECENT FINDINGS
Technical factors were found to influence the diagnostic value of liver biopsy and histological examination of the liver, including specimen number and size (preferably ≥3 nonfragmented specimens of >20 mm in length), needle diameter (1.6 mm Menghini), number of passes (mean 2.5), imaging-guidance, and operator experience. Liver biopsy was demonstrated to be diagnostically valuable in the evaluation of persistently abnormal liver tests of unclear cause, with histology pointing to a specific diagnosis in 84% of patients. Although coagulation abnormalities continue to be an important concern when performing liver biopsy, their influence on complication risk remains unclear. Implementation of less stringent preprocedural coagulation thresholds decreased preprocedural transfusions without increasing the bleeding rate. Serious complications associated with percutaneous liver-biopsy (PLB) and transjugular liver-biopsy are similar, but pain appears to be more common with PLB.
SUMMARY
Histopathological evaluation continues to be fundamentally important in assessing hepatic disease, and liver histology remains the most accurate approach to assess fibrosis and assign prognosis.
Topics: Biopsy; Diagnosis, Differential; Humans; Liver; Liver Diseases; Liver Function Tests
PubMed: 32097176
DOI: 10.1097/MOG.0000000000000621 -
Current Opinion in Urology Jan 2022Prostate biopsy is a very commonly performed office procedure leading to the diagnosis of the most prevalent solid-organ malignancy in American men. Although the... (Review)
Review
PURPOSE OF REVIEW
Prostate biopsy is a very commonly performed office procedure leading to the diagnosis of the most prevalent solid-organ malignancy in American men. Although the transrectal technique for prostate biopsy remains the gold standard, there is increasing interest in the transperineal approach as it offers a clean, percutaneous approach that significantly decreases the risk for infection. In this review, we discuss emerging developments in transperineal prostate biopsy that may optimize the way biopsies are performed in clinical practice.
RECENT FINDINGS
Similarly, to transrectal biopsy, the transperineal approach also allows for the performance of systematic and MRI-targeted biopsy cores. As transperineal biopsy obviates the translocation of rectal bacteria to the prostate or bloodstream, in contrast to transrectal biopsy, it is feasible to forgo peri-procedural antibiotics in accordance with professional guidelines. This may attenuate antimicrobial resistance that may be associated with augmented prophylaxis. In addition, although transperineal biopsy may be traditionally performed under general anesthesia using a template grid, it may also be performed freehand under local anesthesia or sedation. Avoiding prophylactic antibiotics and general anesthesia as well as reducing infections/hospitalizations for transperineal biopsy scaled nationally will likely result in significant healthcare savings.
SUMMARY
Transperineal biopsy with combined systematic and MRI-targeted cores, offers several advantages over conventional transrectal biopsy. Transperineal biopsy under local anesthesia and without periprocedural antibiotic is emerging as a promising method for prostate cancer diagnosis and surveillance.
Topics: Anti-Bacterial Agents; Biopsy; Humans; Image-Guided Biopsy; Male; Perineum; Prostate; Prostatic Neoplasms; Retrospective Studies
PubMed: 34783715
DOI: 10.1097/MOU.0000000000000947 -
Ugeskrift For Laeger Nov 2022Prostate needle biopsies are an essential step in the diagnostic evaluation of prostate cancer. The conventional ultrasound-guided transrectal needle biopsy entails a... (Review)
Review
Prostate needle biopsies are an essential step in the diagnostic evaluation of prostate cancer. The conventional ultrasound-guided transrectal needle biopsy entails a significant risk of infection, which with increasing antibiotic resistance is thought to increase in the future. This has sparked a renewed interest in transperineal prostate biopsies, as this approach avoids the multiple passages of the rectal mucosa, thus reducing the risk of infection significantly. This review describes the devolvement, technical aspects, and current recommendations of transperineal biopsies.
Topics: Male; Humans; Prostate; Biopsy, Needle; Prostatic Neoplasms; Image-Guided Biopsy; Pelvis
PubMed: 36426834
DOI: No ID Found