Circulating tumor DNA in liquid biopsy: Current diagnostic limitation

With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

Liquid biopsy for gastric cancer:Techniques,applications,and future directions

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

Integrating Transformer and Bidirectional Long Short-Term Memory for Intelligent Breast Cancer Detection from Histopathology Biopsy Images

Breast cancer is a significant threat to the global population,affecting not only women but also a threat to the entire population.With recent advancements in digital pathology,Eosin and hematoxylin images provide enhanced clarity in examiningmicroscopic features of breast tissues based on their staining properties.Early cancer detection facilitates the quickening of the therapeutic process,thereby increasing survival rates.The analysis made by medical professionals,especially pathologists,is time-consuming and challenging,and there arises a need for automated breast cancer detection systems.The upcoming artificial intelligence platforms,especially deep learning models,play an important role in image diagnosis and prediction.Initially,the histopathology biopsy images are taken from standard data sources.Further,the gathered images are given as input to the Multi-Scale Dilated Vision Transformer,where the essential features are acquired.Subsequently,the features are subjected to the Bidirectional Long Short-Term Memory(Bi-LSTM)for classifying the breast cancer disorder.The efficacy of the model is evaluated using divergent metrics.When compared with other methods,the proposed work reveals that it offers impressive results for detection.

Liver biopsy in the post-hepatitis C virus era in Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

Percutaneous ultrasound-guided coaxial core needle biopsy for the diagnosis of multiple splenic lesions: A case report

BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related complications.CASE SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic lesions.Gray-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic ma-sses.Abdominal contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense lesions.Positron emission CT revealed numerous abnormal hyperglycemia foci.These imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring exclusion.To obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried out.The patient did not express any discomfort during the procedure.CONCLUSION Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.

Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions

BACKGROUND The incidence and mortality of lung cancer have increased annually.Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis.Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer.Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years.AIM To investigate the diagnostic value of contrast-enhanced ultrasound(CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions.METHODS We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People’s Hospital.The patients were randomly divided into two groups:The CEUS-guided before lesion puncture group(contrast group)and conventional ultrasound-guided group(control group).Analyze the diagnostic efficacy of the puncture biopsy,impact of tumor size,and number of puncture needles and complications were analyzed and compared between the two groups.RESULTS Accurate pathological results were obtained for 92.83%(220/237)of peripheral lung lesions during the first biopsy,with an accuracy rate of 95.8%(113/118)in the contrast group and 89.9%(107/119)in the control group.The difference in the area under the curve(AUC)between the contrast and the control groups was not statistically significant(0.952 vs 0.902,respectively;P>0.05).However,when the lesion diameter≥5 cm,the diagnostic AUC of the contrast group was higher than that of the control group(0.952 vs 0.902,respectively;P<0.05).In addition,the average number of puncture needles in the contrast group was lower than that in the control group(2.58±0.53 vs 2.90±0.56,respectively;P<0.05).CONCLUSION CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions,especially for lesions with a diameter≥5 cm.Therefore,CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

Core needle biopsy for thyroid nodules assessment-a new horizon?

Ultrasound-guided fine-needle aspiration is the standard for evaluating thyroid nodules with a high safety profile and a relatively low number of non-diagnostic cytological findings.Nevertheless,this diagnostic method traditionally has its weak points.Several diagnostic categories such as BethesdaⅠ,ⅢandⅣare not reliable for thyroid carcinoma risk assessment.Recent advancements in a core needle biopsy made it possible to use this tool as a new method for thyroid nodules evaluation.The main feature of this method is the use of thin needles(18-21G)and guns with an automatic trigger mechanism.The histological material collected with the use of a core needle biopsy is usually superior to cytological.Therefore,the core needle biopsy can be used as a complementary technique to a standard fine needle aspiration in difficult and dubious cases of thyroid neoplasia with uncertain malignant potential.

Exploring kidney biopsy findings in congenital heart diseases:Insights beyond cyanotic nephropathy

BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis(FSGS),however,this has only been demonstrated in case reports and not in observational or clinical trials.AIM To identify baseline and clinical characteristics,as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital.METHODS This is a retrospective observational study conducted at the Nephrology Depart-ment of the National Institute of Cardiology“Ignacio Chávez”.All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study.RESULTS Ten patients with congenital heart disease and kidney biopsy were found.The average age was 29.00 years±15.87 years with pre-biopsy proteinuria of 6193 mg/24 h±6165 mg/24 h.The most common congenital heart disease was Fallot’s tetralogy with 2 cases(20%)and ventricular septal defect with 2(20%)cases.Among the 10 cases,one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found,receiving specific treatment after histopathological diagnosis,delaying the initiation of kidney replacement therapy.Among remaining 8 cases(80%),one case of FSGS with perihilar variety was found,while the other 7 cases were non-specific FSGS.CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy.In 2 out of 10 patients in our study,interventions were performed,and initiation of kidney replacement therapy was delayed.Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.

Phase II Clinical Study of Three-Dimensional Printed Coplanar Template Combined with CT-Guided Percutaneous Core Needle Biopsy of Pulmonary Nodules in Elderly Patients

Background: As the population age structure gradually ages, more and more elderly people were found to have pulmonary nodules during physical examinations. Most elderly people had underlying diseases such as heart, lung, brain and blood vessels and cannot tolerate surgery. Computed tomography (CT)-guided percutaneous core needle biopsy (CNB) was the first choice for pathological diagnosis and subsequent targeted drugs, immune drugs or ablation treatment. CT-guided percutaneous CNB requires clinicians with rich CNB experience to ensure high CNB accuracy, but it was easy to cause complications such as pneumothorax and hemorrhage. Three-dimensional (3D) printing coplanar template (PCT) combined with CT-guided percutaneous pulmonary CNB biopsy has been used in clinical practice, but there was no prospective, randomized controlled study. Methods: Elderly patients with lung nodules admitted to the Department of Oncology of our hospital from January 2019 to January 2023 were selected. A total of 225 elderly patients were screened, and 30 patients were included after screening. They were randomly divided into experimental group (Group A: 30 cases) and control group (Group B: 30 cases). Group A was given 3D-PCT combined with CT-guided percutaneous pulmonary CNB biopsy, Group B underwent CT-guided percutaneous pulmonary CNB. The primary outcome measure of this study was the accuracy of diagnostic CNB, and the secondary outcome measures were CNB time, number of CNB needles, number of pathological tissues and complications. Results: The diagnostic accuracy of group A and group B was 96.67% and 76.67%, respectively (P = 0.026). There were statistical differences between group A and group B in average CNB time (P = 0.001), number of CNB (1 vs more than 1, P = 0.029), and pathological tissue obtained by CNB (3 vs 1, P = 0.040). There was no statistical difference in the incidence of pneumothorax and hemorrhage between the two groups (P > 0.05). Conclusions: 3D-PCT combined with CT-guided percutaneous CNB can improve the puncture accuracy of elderly patients, shorten the puncture time, reduce the number of punctures, and increase the amount of puncture pathological tissue, without increasing pneumothorax and hemorrhage complications. We look forward to verifying this in a phase III randomized controlled clinical study. .

Comparison of Cognitive Registration Transrectal Ultrasound-Guided Targeted Biopsy of Prostate to Systematic 12-Core Biopsy: A Retrospective, Multicentre Study

Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.

Indications for Renal Needle Biopsy and Histological Spectrum of Kidney Disease in Togo

Introduction: The frequent late-stage diagnosis of chronic kidney disease (CKD) constrains the treatment choices for nephrologists. Renal biopsy (RB) is crucial for accurately identifying renal lesions. This key nephrological procedure, however, is invasive and not without potential complications. The purpose of this study was to evaluate the indications, frequency, and histological lesion profiles of renal biopsies in Togo. Materials and Methods: We conducted a descriptive cross-sectional study encompassing all renal biopsies performed in Togo from the inception of nephrology services to the present. Data were compiled from the medical records of the patients. Results: From 2015 to 2023, 68 high-quality renal biopsies were executed in Togo. The patients had an average age of 30.6 years, with a predominance of males (69.1%). The most common indication was nephrotic syndrome, accounting for 66.2% of cases. Histologically, glomerulopathies were predominant, representing 61.8% of lesions, followed by vascular nephropathies (25%) and tubulointerstitial nephropathies (13.2%). The most frequently observed primary glomerulopathy was focal segmental glomerulosclerosis (FSGS). Gross hematuria was the sole complication, occurring in 1.4% of the cases. Conclusion: RB is an evolving practice in Togo. Glomerulopathies are the most commonly observed lesions. The histological categorization of renal lesions is vital for clinicians in their diagnostic reasoning and approach.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Percutaneous ultrasound and endoscopic ultrasound-guided biopsy of solid pancreatic lesions: An analysis of 1074 lesions

Backgrounds:Percutaneous ultrasound(US)and endoscopic ultrasound(EUS)-guided pancreatic biopsies are widely accepted in the diagnosis of pancreatic diseases.Studies comparing the diagnostic performance of US-and EUS-guided pancreatic biopsies are lacking.This study aimed to evaluate and compare the diagnostic yields of US-and EUS-guided pancreatic biopsies and identify the risk factors for inconclusive biopsies.Methods:Of the 1074 solid pancreatic lesions diagnosed from January 2017 to February 2021 in our center,275 underwent EUS-guided fine needle aspiration(EUS-FNA),and 799 underwent US-guided core needle biopsy(US-CNB/FNA).The outcomes were inconclusive pathological biopsy,diagnostic accuracy and the need for repeat biopsy.All of the included factors and diagnostic performances of both USCNB/FNA and EUS-FNA were compared,and the independent predictors for the study outcomes were identified.Results:The diagnostic accuracy was 89.8%for EUS-FNA and 95.2%for US-CNB/FNA(P=0.001).Biopsy under EUS guidance[odds ratio(OR)=1.808,95%confidence interval(CI):1.083-3.019;P=0.024],lesion size<2 cm(OR=2.069,95%CI:1.145-3.737;P=0.016),hypoechoic appearance(OR=0.274,95%CI:0.097-0.775;P=0.015)and non-pancreatic ductal adenocarcinoma carcinoma(PDAC)diagnosis(OR=2.637,95%CI:1.563-4.449;P<0.001)were identified as factors associated with inconclusive pathological biopsy.Hypoechoic appearance(OR=0.236,95%CI:0.064-0.869;P=0.030),lesions in the uncinate process of the pancreas(OR=3.506,95%CI:1.831-6.713;P<0.001)and non-PDAC diagnosis(OR=2.622,95%CI:1.278-5.377;P=0.009)were independent predictors for repeat biopsy.Biopsy under EUS guidance(OR=2.024,95%CI:1.195-3.429;P=0.009),lesions in the uncinate process of the pancreas(OR=1.776,95%CI:1.014-3.108;P=0.044)and hypoechoic appearance(OR=0.127,95%CI:0.047-0.347;P<0.001)were associated with diagnostic accuracy.Conclusions:In conclusion,both percutaneous US-and EUS-guided biopsies of solid pancreatic lesions are safe and effective;though the diagnostic accuracy of EUS-FNA is inferior to US-CNB/FNA.A tailored pancreatic biopsy should be considered a part of the management algorithm for the diagnosis of solid pancreatic disease.

Diagnostic accuracy of cystoscopic biopsy for tumour grade in outpatients with urothelial carcinoma of the bladder and the risk factors of upgrading

Objective:To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour(TURBT)and explore the risk factors of upgrading.Methods:The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed.Comparative analysis of the tumour grade of biopsy and operation specimens was performed.Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading.Logistic regression an-alyses were performed to identify the risk factors of upgrading.Results:For the 205 patients,the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639.The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912,respectively.Univariate and multivariate logistic regression analyses showed that older age,tumour multifocality,high neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and low lymphocyte-to-monocyte ratio(LMR)were significantly associated with upgrading(odds ratio ranging from 0.412 to 4.364).The area under the curve of the different multivariate models was improved from 0.752 to 0.821,and decision curve analysis demonstrated a high net benefit when NLR,LMR,and PLR were added.Conclusion:Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer,especially for outpatients with low-grade bladder cancer.Moreover,older age,tumour multifocality,high NLR,PLR,and low LMR are risk factors of upgrading,and systemic inflammatory markers improve the predictive ability.

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients

Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

Major complications after ultrasound-guided liver biopsy:An annual audit of a Chinese tertiary-care teaching hospital

BACKGROUND As ultrasound-guided percutaneous liver biopsy(PLB)has become a standard and important method in the management of liver disease in our country,a periodical audit of the major complications is needed.AIM To determine the annual incidence of major complications following ultrasoundguided PLB and to identify variables that are significantly associated with an increased risk of major complications.METHODS A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021.The major complication rate and all-cause 30-d mortality rate were determined.Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB.RESULTS In this audit of 1857 liver biopsies,10 cases(0.53%)of major complications occurred following ultrasound-guided PLB.The overall all-cause mortality rate at 30 d after PLB was 0.27%(5 cases).Two cases(0.11%)were attributed to major hemorrhage within 7 d after liver biopsy.Fibrinogen less than 2 g/L[odds ratio(OR):17.226;95%confidence interval(CI):2.647-112.102;P=0.003],post-biopsy hemoglobin level(OR:0.963;95%CI:0.942-0.985;P=0.001),obstructive jaundice(OR:6.698;95%CI:1.133-39.596;P=0.036),application of anticoagulants/antiplatelet medications(OR:24.078;95%CI:1.678-345.495;P=0.019)and age(OR:1.096;95%CI:1.012-1.187;P=0.025)were statistically associated with the incidence of major complications after PLB.CONCLUSION In conclusion,the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely,with a major complication rate within the accepted range.Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Percutaneous transhepatic intraportal biopsy using gastroscope biopsy forceps for diagnosis of a pancreatic neuroendocrine neoplasm:A case report

BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.