Multilocular thymic cysts-a diagnostic challenge on computed tomography

A recent case report provided a patient scenario,wherein,a 39-year-old male patient presented with occasional palpitations,headache,and fever.Evaluation of tumor markers did not show any abnormal results.Subsequently,a computed tomography(CT)scan was undertaken,and its findings were affirmative of thymic cancer.Finally,the postoperative histopathological assessment of the mass,after its resection,confirmed it as an anterior mediastinal multilocular thymic cyst(MTC),with concurrent acute upper respiratory tract infection and acute myocarditis.Accordingly,this case report advocates the need for a preoperative histopathological examination with CT imaging to minimize the risk of confusing an MTC with a malignant thymic tumor.

Unveiling sinus venosus atrial septal defect and partial anomalous pulmonary venous return in an elderly patient

Sinus venosus defect(SVD) accounts for 4%–11% of all atrial septal defects(ASD) and may present with dyspnea, heart failure(HF), palpitations, or angina.^[1] The malformation typically involves an interatrial communication due to a deficiency in the common wall connecting the right pulmonary veins and the superior vena cava(SVC) and often accompanies anomalous pulmonary venous connection of some or all of the pulmonary veins.

Revolutionizing palliative care:Electrocautery-enhanced lumenapposing metal stents in endoscopic-ultrasound-guided biliary drainage for malignant obstructions

Patients with malignant biliary obstruction,following endoscopic retrograde cholangiopancreatography(ERCP)failure could be referred for endoscopicultrasound-guided biliary drainage through electrocautery-enhanced(ECE)lumen-apposing metal stent(LAMS)placement.However,the efficacy and safety of ECE-LAMS in this scenario have remained debatable due to minimal scientific evidence.The current confirmed 91.0%clinical success,96.7%technical success,7.3%reintervention rate,and 17.5%adverse events,following the treatment of malignant biliary obstruction with ECE-LAMS delivery.Finally,ECE-LAMS proved to be a generalizable strategy for managing biliary obstruction for patients who were excluded from ERCP.

Impact of pre- and peri-operative risk factors on length of stay and hospital readmission following minimally-invasive partial nephrectomy

Objective:We conducted an analysis of the American College of Surgeons National Surgical Quality Improvement Program database for minimally-invasive partial nephrectomy cases reported with the goal to identify pre-and peri-operative variables associated with length of stay(LOS)greater than 3 days and readmission within 30 days.Methods:Records from 2008 to 2018 for“laparoscopy,surgical;partial nephrectomy”for prolonged LOS and readmission cohorts were compiled.Univariate analysis with Chi-square,t-tests,and multivariable logistic regression analysis with odds ratios(ORs),p-values,and 95%confidence intervals assessed statistical associations.Results:Totally,20306 records for LOS greater than 3 days and 15854 for readmission within 30 days were available.Univariate and multivariable analysis exhibited similar results.For LOS greater than 3 days,undergoing non-elective surgery(OR=5.247),transfusion of greater than four units within 72 h prior to surgery(OR=5.072),pre-operative renal failure or dialysis(OR=2.941),and poor pre-operative functional status(OR=2.540)exhibited the strongest statistically significant associations.For hospital readmission within 30 days,loss in body weight greater than 10%in 6 months prior to surgery(OR=2.227)and bleeding disorders(OR=2.081)exhibited strongest statistically significant associations.Conclusion:Multiple pre-and peri-operative risk factors are independently associated with prolonged LOS and hospital readmission within 30 days of surgery using the American College of Surgeons National Surgical Quality Improvement Program data.Recognizing the risks factors that can potentially be improved prior to minimally-invasive partial nephrectomy is crucial to informing patient selection,optimization strategies,and patient education.

Multimodality Medical Image Fusion Based on Pixel Significance with Edge-Preserving Processing for Clinical Applications

Multimodal medical image fusion has attained immense popularity in recent years due to its robust technology for clinical diagnosis.It fuses multiple images into a single image to improve the quality of images by retaining significant information and aiding diagnostic practitioners in diagnosing and treating many diseases.However,recent image fusion techniques have encountered several challenges,including fusion artifacts,algorithm complexity,and high computing costs.To solve these problems,this study presents a novel medical image fusion strategy by combining the benefits of pixel significance with edge-preserving processing to achieve the best fusion performance.First,the method employs a cross-bilateral filter(CBF)that utilizes one image to determine the kernel and the other for filtering,and vice versa,by considering both geometric closeness and the gray-level similarities of neighboring pixels of the images without smoothing edges.The outputs of CBF are then subtracted from the original images to obtain detailed images.It further proposes to use edge-preserving processing that combines linear lowpass filtering with a non-linear technique that enables the selection of relevant regions in detailed images while maintaining structural properties.These regions are selected using morphologically processed linear filter residuals to identify the significant regions with high-amplitude edges and adequate size.The outputs of low-pass filtering are fused with meaningfully restored regions to reconstruct the original shape of the edges.In addition,weight computations are performed using these reconstructed images,and these weights are then fused with the original input images to produce a final fusion result by estimating the strength of horizontal and vertical details.Numerous standard quality evaluation metrics with complementary properties are used for comparison with existing,well-known algorithms objectively to validate the fusion results.Experimental results from the proposed research article exhibit superior performance compared to other competing techniques in the case of both qualitative and quantitative evaluation.In addition,the proposed method advocates less computational complexity and execution time while improving diagnostic computing accuracy.Nevertheless,due to the lower complexity of the fusion algorithm,the efficiency of fusion methods is high in practical applications.The results reveal that the proposed method exceeds the latest state-of-the-art methods in terms of providing detailed information,edge contour,and overall contrast.

Clinical use of donor-derived cell-free DNA in kidney transplantation

Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.

Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors

This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.

Trypsin in pancreatitis:The culprit,a mediator,or epiphenomenon?

Pancreatitis is a common,life-threatening inflammatory disease of the exocrine pancreas.Its pathogenesis remains obscure,and no specific or effective treatment is available.Gallstones and alcohol excess are major etiologies of pancreatitis;in a small portion of patients the disease is hereditary.Pancreatitis is believed to be initiated by injured acinar cells(the main exocrine pancreas cell type),leading to parenchymal necrosis and local and systemic inflammation.The primary function of these cells is to produce,store,and secrete a variety of enzymes that break down all categories of nutrients.Most digestive enzymes,including all proteases,are secreted by acinar cells as inactive proforms(zymogens)and in physiological conditions are only activated when reaching the intestine.The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens.It was proposed that pancreatitis results from proteolytic autodigestion of the gland,mediated by premature/inappropriate trypsinogen activation within acinar cells.The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis,and in human disease.On the basis of these observations,it has been considered the central pathogenic mechanism of pancreatitis-a concept with a century-old history.This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis,particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis;analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its’damaging effects;discusses the gaps in our knowledge,potential therapeutic approaches,and directions for future research.We conclude that trypsin is not the culprit in the disease pathogenesis but,at most,a mediator of some pancreatitis responses.Therefore,the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes,such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.

Prevalence and risk factors associated with metabolic dysfunctionassociated steatohepatitis in patients with Helicobacter pylori infection: A population-based study

BACKGROUND Helicobacter pylori(H.pylori)is associated with the development of gastrointestinal disorders ranging from gastritis to gastric cancer.The evidence of the association between metabolic dysfunction-associated steatohepatitis(MASH)and H.pylori infection in the literature is scarce.Therefore,we aim to evaluate the risk of developing MASH in patients who have had a diagnosis of H.pylori infection independently of any confounding variables.AIM To evaluate the risk of developing MASH in patients who have had a diagnosis of H.pylori infection.METHODS This study used a validated multicenter research database of over 360 hospitals across 26 healthcare systems across the United States from 1999 to 2022.Multivariate regression analysis assessed the risk of developing MASH,adjusting for confounders including H.pylori infection,obesity,type 2 diabetes,hypertension,dyslipidemia,and male gender.A two-sided P value<0.05 was considered as statistically significant,and all statistical analyses were performed using R version 4.0.2(R Foundation for Statistical Computing,Vienna,Austria,2008).RESULTS A total of 79476132 individuals were screened in the database and 69232620 were selected in the final analysis after accounting for inclusion and exclusion criteria.Smokers(14.30%),patients with hyperlipidemia(70.35%),hypertension(73.86%),diabetes mellitus type 2(56.46%),and obese patients(58.15%)were more common in patients with MASH compared to control.Using a multivariate regression analysis,the risk of MASH was increased in diabetics[odds ratio(OR):3.55;95%CI:3.48-3.62],obese(OR:5.93;95%CI:5.81-6.04),males(OR:1.49;95%CI:1.46-1.52),individuals with hyperlipidemia(OR:2.43;95%CI:2.38-2.49)and H.pylori infection(OR:2.51;95%CI:2.31-2.73).CONCLUSION This is the largest population-based study in the United States illustrating an increased prevalence and odds of developing MASH in patients with H.pylori infection after adjusting for risk factors.

A Study on Multivariable Interactions Concerning Radar Cross Section Reduction through Geometric Attributes

This resolution 5 (25−1 factorial) study aimed to ascertain an understanding of the interactions between different geometries on the resulting Radar Cross Section (RCS) of a target. The results of the study are in line with the general understanding of the impact different geometries have on RCS but show that geometries can also influence the variance of measured RCS, and typical attributes that reduce RCS increase the variance of the measured RCS. Notably, an increased angle between the front face of a plate and the direction of the radar signal decreased RCS but increased the variance of the RCS measured.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

Diagnostic approach to patients with acute idiopathic and recurrent pancreatitis,what should be done?

Acute recurrent pancreatitis (ARP) is a common clinical condition that may be difficult to diagnose. Endoscopic ultrasound (EUS) is proposed to be a safe first line test of choice in the majority of patients. When interventions are needed to remove biliary stones, evaluate sphincter of Oddi or pancreas divisum, endoscopic retrograde cholangiopancreatography (ERCP) is recommended. Magnetic resonance cholangiopancreatography (MRCP) can be a suitable alternative from a diagnostic standpoint although may not be widely available. Finally, genetic testing is increasingly used to detect certain mutations that are associated with this diagnosis.

Complex role for the immune system in initiation and progression of pancreatic cancer

The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound sys-temic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma(PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

Exosomes and their role in the micro-/macro-environment： acomprehensive review

The importance of extracellular vesicles(EVs) in cell-cell communication has long been recognized due to their ability to transfer important cellular cargoes such as DNA, mRNA, miRNAs, and proteins to target cells. Compelling evidence supports the role of EVs in the horizontal transfer of cellular material which has the potential to influence normal cellular physiology and promote various disease states. Of the different types of EVs, exosomes have garnered much attention in the past decade due to their abundance in various biological fluids and ability to affect multiple organ systems. The main focus of this review will be on cancer and how cancer-derived exosomes are important mediators of metastasis, angiogenesis, immune modulation, and the tumor macro-/microenvironment. We will also discuss exosomes as potential biomarkers for cancers due to their abundance in biological fluids, ease of uptake, and cellular content. Exosome use in diagnosis, prognosis, and in establishing treatment regimens has enormous potential to revolutionize patient care.

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.

Distinguishing between parenchymal and anastomotic leakage at duct-to-mucosa pancreatic reconstruction in pancreaticoduodenectomy

AIM： To distinguish anastomotic from parenchymal leakage at duct-to-mucosa reconstruction of the pancreatic remnant. METHODS： We reviewed the charts of 68 pancreaticoduodenectomies performed between 5/2000 and 12/2005 with end-to-side duct-to-mucosa pancreatojejunostomy （PJ）. The results of pancreatography, as well as peripancreatic drain volumes, and amylase levels were analyzed. RESULTS： Of 68 pancreatojejunostomies, 48 had no leak by pancreatography and had low-drain amylase （normal）; eight had no pancreatographic leak but had elevated drain amylase （parenchymal leak）; and 12 had pancreatographic leak and elevated drain amylase （anastomotic leak）. Although drain volumes in the parenchymal leak group were significantly elevated at postoperative day （POD） 4, no difference was found at POD 7. Drain amylase level was not significantly different at POD 4. In contrast, at POD 7, the anastomotic-leak group had significantly elevated drain amylase level compared with normal and parenchymalleak groups （14158 ＋ 24083 IU/L vs 89 ＋ 139 IU/L and 1707 ＋ 1515 IU/L, respectively, P = 0.012）. CONCLUSION： For pancreatic remnant reconstruction after pancreaticoduodenectomy, a combination of pancreatogram and peripancreatic drain amylase levels can be used to distinguish between parenchymal and anastomotic leakage at pancreatic remnant reconstruction.

Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans

AIM:To assess the risk of biliary and pancreatic cancers in a large cohort of patients with type 2 diabetes mellitus(DM) .METHODS:Eligibility for this study included patients with type 2 DM(ICD-9 code 250.0) who were discharged from Department of Veteran Affairs hospitals between 1990 and 2000.Non-matched control patients without DM were selected from the same patient treatment files during the same period.Demographic information included age,sex and race.Secondary diagnoses included known risk factors based on their ICD-9 codes.By multivariate logistic regression,the occurrence of biliary and pancreatic cancer was compared between case subjects with DM and controls without DM.RESULTS:A total of 1172496 case and control subjects were analyzed.The mean age for study and control subjects was 65.8 ± 11.3 and 64.8 ± 12.6 years,respectively.The frequency of pancreatic cancer in subjects with DM was increased(0.9%) in comparison to control subjects(0.3%) with an OR of 3.22(95% CI:3.03-3.42) .The incidence of gallbladder andextrahepatic biliary cancers was increased by twofold in diabetic patients when compared to controls.The OR and 95% CI were 2.20(1.56-3.00) and 2.10(1.61-2.53) ,respectively.CONCLUSION:Our study demonstrated that patients with DM have a threefold increased risk for developing pancreatic cancer and a twofold risk for developing biliary cancer.

Software for automated classification of probe-based confocal laser endomicroscopy videos of colorectal polyps

AIM:To support probe-based confocal laser endomi-croscopy (pCLE) diagnosis by designing software for the automated classification of colonic polyps. METHODS:Intravenous fluorescein pCLE imaging of colorectal lesions was performed on patients under-going screening and surveillance colonoscopies, followed by polypectomies. All resected specimens were reviewed by a reference gastrointestinal pathologist blinded to pCLE information. Histopathology was used as the criterion standard for the differentiation between neoplastic and non-neoplastic lesions. The pCLE video sequences, recorded for each polyp, were analyzed off-line by 2 expert endoscopists who were blinded to the endoscopic characteristics and histopathology. These pCLE videos, along with their histopathology diagnosis, were used to train the automated classification software which is a content-based image retrieval technique followed by k-nearest neighbor classification. The performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists was compared with that of automated pCLE software classification. All evaluations were performed using leave-one-patient- out cross-validation to avoid bias. RESULTS:Colorectal lesions (135) were imaged in 71 patients. Based on histopathology, 93 of these 135 lesions were neoplastic and 42 were non-neoplastic. The study found no statistical significance for the difference between the performance of automated pCLE software classification (accuracy 89.6%, sensitivity 92.5%, specificity 83.3%, using leave-one-patient-out cross-validation) and the performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists (accuracy 89.6%, sensitivity 91.4%, specificity 85.7%). There was very low power (< 6%) to detect the observed differences. The 95% confidence intervals for equivalence testing were:-0.073 to 0.073 for accuracy, -0.068 to 0.089 for sensitivity and -0.18 to 0.13 for specificity. The classification software proposed in this study is not a "black box" but an informative tool based on the query by example model that produces, as intermediate results, visually similar annotated videos that are directly interpretable by the endoscopist. CONCLUSION:The proposed software for automated classification of pCLE videos of colonic polyps achieves high performance, comparable to that of off-line diagnosis of pCLE videos established by expert endoscopists.