Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging:Feasibility and challenges

The integration of 7 Tesla magnetic resonance imaging(7 T MRI)in adult patients has marked a revolutionary stride in radiology.In this article we explore the feasibility of 7 T MRI in paediatric practice,emphasizing its feasibility,applications,challenges,and safety considerations.The heightened resolution and tissue contrast of 7 T MRI offer unprecedented diagnostic accuracy,particularly in neuroimaging.Applications range from neuro-oncology to neonatal brain imaging,showcasing its efficacy in detecting subtle structural abnormalities and providing enhanced insights into neurological conditions.Despite the promise,challenges such as high cost,discomfort,and safety concerns necessitate careful consideration.Research suggests that,with precautions,7 T MRI is feasible in paediatrics,yet ongoing studies and safety assessments are imperative.

Intraoperative cholangio-ultrasonography(IOCUS)during hepatectomy with resection of the biliary confluence:An effective alternative to intraoperative cholangiography

Intraoperative ultrasonography(IOUS)in hepatobiliary surgery is well known as an essential tool for radical and safe hepatectomies,allowing to perform parenchymal sparing surgery and,as consequence,to expand the surgical indications for patients otherwise considered unresectable.Nevertheless,since many years,despite its effectiveness in the study of vascular anatomy of the liver,the gold standard for the assessment of biliary anatomy during surgery is intraoperative cholangiography(IOC),which is used for the validation of preoperative imaging as well as for guiding reconstruction in case of bile duct injury or resection.

Exploring the landscape of minimally invasive pancreatic surgery: Progress, challenges, and future directions

Minimally invasive surgery(MI)has become the standard of care for many surgical procedures aimed at reducing the burden on patients.However,its adoption in pancreatic surgery(PS)has been limited by the pancreas’s unique location and the complexity of the dissection and reconstruction phases.These factors continue to contribute to PS having one of the highest morbidity and mortality rates in general surgery.Despite a rough start,MIPS has gained widespread acceptance in clinical practice recently.Robust evidence supports MI distal pancreatectomy safety,even in oncological cases,indicating its potential superiority over open surgery.However,definitive evidence of MI pancre-aticoduodenectomy(MIPD)feasibility and safety,particularly for malignant lesions,is still lacking.Nonetheless,reports from high-volume centers are emer-ging,suggesting outcomes comparable to those of the open approach.The robotic PS increasing adoption,facilitated by the wider availability of robotic platforms,may further facilitate the transition to MIPD by overcoming the technical con-straints associated with laparoscopy and accelerating the learning curve.Alth-ough the MIPS implementation process cannot be stopped in this evolving world,ensuring patient safety through strict outcome monitoring is critical.Investing in younger surgeons with structured and recognized training programs can promote safe expansion.

From strength to precision: A systematic review exploring the clinical utility of 7-Tesla magnetic resonance imaging in abdominal imaging

BACKGROUND After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging(MRI)have demonstrated the feasibility as well as diagnostic capabilities of liver,kidney,and prostate MRI at 7-Tesla.However,the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks,primarily stemming from heightened artifacts and limitations in Specific Absorption Rate,etc.Furthermore,evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence.AIM To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends,details relevant challenges,and provides a concise set of potential solutions.METHODS This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A PubMed search,utilizing Medical Subject Headings terms such as"7-Tesla"and organ-specific terms,was conducted for articles published between January 1,1985,and July 25,2023.Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs,encompassing various study types(in-vivo/ex-vivo,method development,reviews/meta-analyses).Exclusion criteria involved animal studies and those lacking extractable data.Study selection involved initial identification via title/abstract,followed by a full-text review by two researchers,with discrepancies resolved through discussion.Data extraction covered publication details,study design,population,sample size,7T MRI protocol,image characteristics,endpoints,and conclusions.RESULTS The systematic review included a total of 21 studies.The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate(n=8),followed by the kidney(n=6)and the hepatobiliary system(n=5).Studies on these organs,and in the pancreas,demonstrated clear advantages at 7T.However,small bowel studies showed no significant improvements compared to traditional MRI at 1.5T.The majority of studies evaluated originated from Germany(n=10),followed by the Netherlands(n=5),the United States(n=5),Austria(n=2),the United Kingdom(n=1),and Italy(n=1).CONCLUSION Further increase of abdominal clinical MRI field strength to 7T demonstrated high imaging potential,yet also limitations mainly due to the inhomogeneous radiofrequency(RF)excitation field relative to lower field strengths.Hence,further optimization of dedicated RF coil elements and pulse sequences are expected to better optimize clinical imaging at high magnetic field strength.

Evaluating the role of 7-Tesla magnetic resonance imaging in neurosurgery: Trends in literature since clinical approval

BACKGROUND After approval for clinical use in 2017,early investigations of ultra-high-field abdominal magnetic resonance imaging(MRI)have demonstrated its feasibility as well as diagnostic capabilities in neuroimaging.However,there are no to few systematic reviews covering the entirety of its neurosurgical applications as well as the trends in the literature with regard to the aforementioned application.AIM To assess the impact of 7-Tesla MRI(7T MRI)on neurosurgery,focusing on its applications in diagnosis,treatment planning,and postoperative assessment,and to systematically analyze and identify patterns and trends in the existing literature related to the utilization of 7T MRI in neurosurgical contexts.METHODS A systematic search of PubMed was conducted for studies published between January 1,2017,and December 31,2023,using MeSH terms related to 7T MRI and neurosurgery.The inclusion criteria were:Studies involving patients of all ages,meta-analyses,systematic reviews,and original research.The exclusion criteria were:Pre-prints,studies with insufficient data(e.g.,case reports and letters),non-English publications,and studies involving animal subjects.Data synthesis involved standardized extraction forms,and a narrative synthesis was performed.RESULTS We identified 219 records from PubMed within our defined period,with no duplicates or exclusions before screening.After screening,125 articles were excluded for not meeting inclusion criteria,leaving 94 reports.Of these,2 were irrelevant to neurosurgery and 7 were animal studies,resulting in 85 studies included in our systematic review.Data were categorized by neurosurgical procedures and diseases treated using 7T MRI.We also analyzed publications by country and the number of 7T MRI facilities per country was also presented.Experi-mental studies were classified into comparison and non-comparison studies based on whether 7T MRI was compared to lower field strengths.CONCLUSION 7T MRI holds great potential in improving the characterization and understanding of various neurological and psychiatric conditions that may be neurosurgically treated.These include epilepsy,pituitary adenoma,Parkinson's disease,cerebrovascular diseases,trigeminal neuralgia,traumatic head injury,multiple sclerosis,glioma,and psychiatric disorders.Superiority of 7T MRI over lower field strengths was demonstrated in terms of image quality,lesion detection,and tissue characterization.Findings suggest the need for accelerated global distribution of 7T magnetic resonance systems and increased training for radiologists to ensure safe and effective integration into routine clinical practice.

Structured magnetic resonance imaging and endoanal ultrasound anal fistulas reporting template(SMART):An interdisciplinary Delphi consensus

BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis:Insights into mechanisms,pathophysiology,and treatment options

BACKGROUND Autoimmune gastritis(AIG)is a progressive,chronic,immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor.Gastrointestinal symptoms such as dyspepsia and early satiety are very common,being second in terms of frequency only to anemia,which is the most typical feature of AIG.AIM To address both well-established and more innovative information and knowledge about this challenging disorder.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 10 years.RESULTS A total of 125 records were reviewed and 80 were defined as fulfilling the criteria.CONCLUSION AIG can cause a range of clinical manifestations,including dyspepsia.The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion,gastric motility,hormone signaling,and gut microbiota,among other factors.Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG.While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease,they may not be appropriate for AIG.Prokinetic agents,antidepressant drugs,and non-pharmacological treatments may be of help,even if not adequately evidence-based supported.A multidisciplinary approach for the management of dyspepsia in AIG is recommended,and further research is needed to develop and validate more effective therapies for dyspepsia.

Osteosarcopenia in autoimmune cholestatic liver diseases:Causes,management,and challenges

Primary biliary cholangitis and primary sclerosing cholangitis(PSC)are the most common cholestatic liver diseases(CLD)in adults and are both characterized by an immune pathogenesis.While primary biliary cholangitis is a model autoimmune disease,with over 90%of patients presenting very specific autoantibodies against mitochondrial antigens,PSC is considered an immune mediated disease.Osteoporosis is the most common bone disease in CLD,resulting in frequent fractures and leading to significant morbidity.Further,sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients.The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected.Although timely diagnosis,prevention,and management of osteosarcopenia are crucial to limit the consequences,there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD.International guidelines recommend screening for bone disease at the time of diagnosis of CLD.However,the optimal monitoring strategies and treatments have not been defined yet and vary among centers.We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD,and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.

Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid-and long-term prediction of hepatocellular carcinoma among cirrhotic patients

BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.

Fractal nature of human gastrointestinal system:Exploring a new era

The morphological complexity of cells and tissues,whether normal or pathological,is characterized by two primary attributes:Irregularity and self-similarity across different scales.When an object exhibits self-similarity,its shape remains unchanged as the scales of measurement vary because any part of it resembles the whole.On the other hand,the size and geometric characteristics of an irregular object vary as the resolution increases,revealing more intricate details.Despite numerous attempts,a reliable and accurate method for quantifying the morphological features of gastrointestinal organs,tissues,cells,their dynamic changes,and pathological disorders has not yet been established.However,fractal geometry,which studies shapes and patterns that exhibit self-similarity,holds promise in providing a quantitative measure of the irregularly shaped morphologies and their underlying self-similar temporal behaviors.In this context,we explore the fractal nature of the gastrointestinal system and the potential of fractal geometry as a robust descriptor of its complex forms and functions.Additionally,we examine the practical applications of fractal geometry in clinical gastroenterology and hepatology practice.

Is precision medicine for colorectal liver metastases still a utopia?New perspectives by modern biomarkers,radiomics,and artificial intelligence

The management of patients with liver metastases from colorectal cancer is still debated.Several therapeutic options and treatment strategies are available for an extremely heterogeneous clinical scenario.Adequate prediction of patients’outcomes and of the effectiveness of chemotherapy and loco-regional treatments are crucial to reach a precision medicine approach.This has been an unmet need for a long time,but recent studies have opened new perspectives.New morphological biomarkers have been identified.The dynamic evaluation of the metastases across a time interval,with or without chemotherapy,provided a reliable assessment of the tumor biology.Genetics have been explored and,thanks to their strong association with prognosis,have the potential to drive treatment planning.The liver-tumor interface has been identified as one of the main determinants of tumor progression,and its components,in particular the immune infiltrate,are the focus of major research.Image mining and analyses provided new insights on tumor biology and are expected to have a relevant impact on clinical practice.Artificial intelligence is a further step forward.The present paper depicts the evolution of clinical decision-making for patients affected by colorectal liver metastases,facing modern biomarkers and innovative opportunities that will characterize the evolution of clinical research and practice in the next few years.

Endoscopic ultrasound-guided ablation of solid pancreatic lesions:A systematic review of early outcomes with pooled analysis

BACKGROUND Endoscopic ultrasound-guided radiofrequency ablation(EUS-RFA)is emerging as a complementary therapeutic approach for pancreatic solid masses.However,results of published data are difficult to interpret because of a retrospective design and small sample size.AIM To systematically review data on EUS-RFA for solid lesions and to pool the results of the different experiences in order to provide more consistent evidence in terms of safety and efficacy.METHODS A comprehensive systematic literature search on the main databases was performed to identify articles in which patients with pancreatic solid lesions underwent EUS-RFA.The primary outcomes were procedure-related adverse events(AEs)and mortality.Secondary outcomes were the technical success rate and the effects on primary tumor growth.Statistical analyses were performed using Stata version 14.0.RESULTS In total,14 studies were included,with 120 patients undergoing 153 ablations of 129 solid pancreatic lesions.The STARmed technology was used in seven studies,the Habib system in six studies,and the HybridTherm probe in one study.The pooled technical success rate was 99.0%(I2:25.82%).The pooled overall AE rate was 8.0%(I2:11.46%).Excluding mild AEs,the pooled rates of serious AEs was 1.0%(I2:0%).No mortality related to the procedure was reported.CONCLUSION The present pooled analysis confirms the safety and feasibility of EUS-RFA.

Unusual Case of Bilateral Breast Cancer: A Pure Encapsulated Papillary Breast Tumor of the Right Breast and a Contralateral Invasive Ductal Carcinoma

Background: Intracystic papillary breast cancer is a very rare tumor that occurs most frequently in elderly postmenopausal women. Aim: In this article we presented a case of a 66-year-old woman who underwent excisional biopsy due to a right breast mass. Case presentation: Histological examination revealed the “pure” encapsulated papillary breast carcinoma without coexisting in situ neoplasm and/or invasive carcinoma. This is a rare lesion of the breast that can clinically mimic breast benign mass with only local or regionally aggressive course. Conclusion: In order to avoid misdiagnosis, both the clinician and the breast radiologist should have the possibility of diagnosing this tumor. Intracystic papillary carcinoma of the breast associated with lymph node?metastasis has rarely been reported, but the sentinel lymph node biopsy may be prudent in such cases, despite the non aggressive behavior.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Chemerin is a key player in antimicrobial defense in skin

The skin is the first line of defense to prevent entry of pathogenic bacteria from the environment and their dissemination to internal organs.This crucial function is accomplished mostly by keratinocytes,which serve as a physical barrier and produce antimicrobial peptides.

Parenchymal sparing anatomical liver resections for hepatocellular carcinoma

The rationale of the performance of anatomic resection(AR)of the liver in case of hepatocellular carcinoma(HCC)is the removal of portal pedicle feeding the tumor because of the tumor’s tendency to invade the portal veins(1).This technical approach is expected to be effective from an oncological perspective for a disease such as HCC,which is associated with a high rate of intrahepatic recurrence(2,3).In the eighties,Makuuchi et al.proposed the systematic subsegmentectomy(4)reporting excellent results(5),and later some other authors reported new techniques to identify the portal territory of a given HCC and perform a true AR of the liver(5-7).

Understanding evidence-based clinical practice guidelines for cholelithiasis 2021

Cholelithiasis is characterized by impaired metabolism of bile acids,cholesterol and bilirubin resulting in deposition of gallstones within the gallbladder(1).The article by Fujita et al.outlines the third revision of the evidence-based practice guidelines issued by the Japanese Society of Gastroenterology(JSGE)on cholelithiasis(2).For these current guidelines,52 questions were adopted through discussions among committee members,covering epidemiology,pathogenesis,diagnosis,treatments,complications,and prognostic aspects of cholelithiasis in Japan(2).The strengths of recommendations were determined by voting by committee members after assessing current available literature,patient preferences,and cost-benefit balance(2).Similar to the previous guideline(second revision),consensus among committee members was defined as the acquisition of 70%votes or over(2).

Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases

Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA’s neuroprotective action derives from animal models of Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases.

Liver metastases “siphon” off immunotherapy response

For many different cancers,the advent of immunotherapy(IT)treatments,in particular immune checkpoint inhibitors,aimed at reviving the immune response against cancer cells,has led to a great improvement in terms of clinical benefit.Despite the success of IT,even in advanced metastatic cancers,some patients still fail to respond for reasons yet unclear(1,2).Yu et al.in an issue of Nature Medicine.

The promise of precision medicine:how biomarkers are shaping the future of cholangiocarcinoma treatment

Cholangiocarcinoma(CCA)is the second most frequent primary malignant neoplasm of the hepatobiliary system.Unfortunately,CCA is often diagnosed at an advanced stage,when potentially curative surgical treatments are not recommended.The probability of achieving complete resection in patients who undergo surgery is about 25%(1)and even when complete tumor removal is achieved,the risk of recurrence is greater than 50%.Identification and validation of reliable biomarkers is crucial for the early detection,accurate diagnosis,appropriate staging/prognosis,therapy selection and effective monitoring of patients with biliary tract cancers(BTCs)(Figure 1).Achieving early diagnosis remains a challenge to improve survival and,although many promising biomarkers have been identified(2),to date none have reached clinical practice.