Rationale for Hepatitis C Virus Treatment During Hematopoietic Stem Cell Transplant in the Era of Novel Direct-Acting Antivirals.

BACKGROUND AND AIMS: Untreated hepatitis C (HCV) infection in patients undergoing hematopoietic stem cell transplantation (HSCT) can lead to worse outcomes. Traditionally, HSCT patients infected with HCV would wait until after immune reconstitution to receive HCV therapy, as the oncologic urgency of transplant would not allow time for a full preceding treatment course of HCV therapy. However, in the era of newer direct-acting antivirals (DAAs), we propose that concomitant treatment of HCV while undergoing HSCT is safe and feasible, while keeping in mind potential drug-drug interactions. METHODS: A literature review was performed to summarize the available data on the impact of HCV on patients undergoing HSCT. Drug-drug interactions for DAA's and pertinent HSCT drugs were evaluated using Lexicomp online® and http://hep-druginteractions.org . RESULTS: During HSCT, HCV appears to be a conditional risk factor for sinusoidal obstruction syndrome and a potential risk factor for graft versus host disease, both of which are associated with increased mortality. HCV reactivation and exacerbation may impact the use of chemotherapeutics, but available studies haven't shown impact specifically on HSCT. Limited case reports exist but demonstrate safe and effective use DAAs during HSCT. These, along with a drug-drug interaction review demonstrate agents such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are promising DAAs for use in HSCT. CONCLUSION: HCV infection may worsen outcomes for patients undergoing HSCT. Concomitant treatment of HCV during HSCT using newer DAAs appears feasible and may improve patient morbidity and mortality, however large-scale studies are needed to further support this practice.

Pancreatic Cyst Size Measurement on Magnetic Resonance Imaging Compared to Pathology.

BACKGROUND: While multiple cyst features are evaluated for stratifying pancreatic intraductal papillary mucinous neoplasms (IPMN), cyst size is an important factor that can influence treatment strategies. When magnetic resonance imaging (MRI) is used to evaluate IPMNs, no universally accepted sequence provides optimal size measurements. T2-weighted coronal/axial have been suggested as primary measurement sequences; however, it remains unknown how well these and maximum all-sequence diameter measurements correlate with pathology size. This study aims to compare agreement and bias between IPMN long-axis measurements on seven commonly obtained MRI sequences with pathologic size measurements. METHODS: This retrospective cohort included surgically resected IPMN cases with preoperative MRI exams. Long-axis diameter tumor measurements and the presence of worrisome features and/orhigh-risk stigmata were noted on all seven MRI sequences. MRI size and pathology agreement and MRI inter-observer agreement involved concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC), respectively. The presence of worrisome features and high-risk stigmata were compared to the tumor grade using kappa analysis. The Bland-Altman analysis assessed the systematic bias between MRI-size and pathology. RESULTS: In 52 patients (age 68 ± 13 years, 22 males), MRI sequences produced mean long-axis tumor measurements from 2.45-2.65 cm. The maximum MRI lesion size had a strong agreement with pathology (CCC = 0.82 (95% CI: 0.71-0.89)). The maximum IPMN size was typically observed on the axial T1 arterial post-contrast and MRCP coronal series and overestimated size versus pathology with bias +0.34 cm. The radiologist interobserver agreement reached ICCs 0.74 to 0.91 on the MRI sequences. CONCLUSION: The maximum MRI IPMN size strongly correlated with but tended to overestimate the length compared to the pathology, potentially related to formalin tissue shrinkage during tissue processing.

Improving Pancreatic Cyst Management: Artificial Intelligence-Powered Prediction of Advanced Neoplasms through Endoscopic Ultrasound-Guided Confocal Endomicroscopy.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Molecular mechanism of the miR-7/BCL2L1/P53 signaling axis regulating the progression of hepatocellular carcinoma.

Background: To investigate the roles of miR-7 and its potential mechanisms in hepatocellular carcinoma (HCC). Methods: The functions of miR-7 were identified and measured by MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide], colony formation, transwell, and flow cytometry assays. A luciferase assay was applied to verify the direct binding of miR-7 on BCL2L1 3'untranslated region (3'UTR). An in vitro experiment was then used to investigate the biological effects of miR-7 and BCL2L1. A co-immunoprecipitation (COIP) assay was used to detect the protein interaction between BCL2L1 and P53. Results: We found that miR-7 overexpression suppressed cell proliferation, migration, and invasion in HCC. BCL2L1 was also demonstrated as a direct target gene of miR-7. This study showed that BCL2L1 could partially rescue the inhibitory effect of miR-7 on the proliferation, migration, and invasion of HCC cells. Our research showed that miR-7 could inhibit the epithelial-mesenchymal transition (EMT) pathway by regulating BCL2L1. We also further confirmed that miR-7 inhibits the proliferation, migration, and invasion of Hep3B and Huh7 cells by targeting BCL2L1. Furthermore, we observed that the BCL2L1 protein interacts with the P53 protein and BCL2L1 affects the development of liver cancer through P53. We also found that BCL2L1 could promote the invasion and migration of liver cancer cells through P53 inhibition. BCL2L1 also inhibited the expression of Caspase 3/7 in hepatoma cells by inhibiting the expression of P53. Conclusions: Our study demonstrated that miR-7/BCL2L1/P53 may serve as a regulatory molecular axis for HCC treatment. Our results suggest that miR-7/BCL2L1/P53 may have predictive value and represent a new treatment strategy for liver cancer.

Effect of Delayed Endoscopy Protocol on Timing and Safety of Endoscopy for Foreign Body Ingestion and Esophageal Food Impaction.

BACKGROUND AND AIMS: Endoscopic procedures for foreign body ingestion (FBI) and esophageal food impactions (EFI) performed during on-call hours are associated with increased stress, risk, and cost. We implemented a Foreign Body Algorithm (FBA) designed to delay all but the most urgent endoscopy for EFI and FBI until regular working hours. METHODS: Using endoscopy records from multiple academic and community hospitals within a large integrated health system in the United states, we identified esophagogastroduodenoscopy (EGD) performed for food impactions and foreign body ingestions occurring between May 2011 and February 2021. RESULTS: We identified 479 EGDs performed for FBI and EFI. The introduction of the FBA was associated with a shorter length of stay (LOS) for overall cases (0.35 vs. 0.8 d P <0.001), day cases (0.16 vs. 1.0 d P <0.001), and night cases (0.40 vs. 0.6 d P =0.03). The introduction of the FBA did not change the rate of overall adverse events (AE) or night AE. AE from the entire cohort was rare (3%; 16 total). Of the AE, most were sedation related. The introduction of the FBA did not affect the overall rate of night cases or AE, but the rate of after-hours endoscopy for intentional ingestions decreased from 17.2% to 3.1% ( P =0.01). CONCLUSION: This is one of the largest studies of esophageal impactions and foreign bodies in adults in the United States, and the first to examine the effects of a protocol designed to avoid after-hours endoscopy. These results suggest that postponing after-hours EGD until the daytime is not associated with adverse safety outcomes or increased LOS.

A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment.

Background: The family of coiled-coil domain-containing (CCDC) proteins participates in a wide range of physiological functions and plays a pivotal role in governing the invasion and metastasis of malignant tumor cells. Nonetheless, the precise mechanism governing the interaction among the immune microenvironment, hypoxia pathway, and proliferation in hepatocellular carcinoma (HCC) remains elusive. In this study, our objective was to identify the prognostic significance of CCDC family genes in HCC. Methods: We conducted an analysis of RNA-seq data from HCC patients sourced from The Cancer Genome Atlas (TCGA) database. Our analysis involved comparing the expression profiles of 168 CCDC family genes between tumor and normal tissues to identify differentially expressed genes (DEGs). The prognostic value of these genes was verified using overall survival (OS) data from TCGA-LIHC patients, employing Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Subsequently, we constructed a prognostic signature known as the CCDC score and validated it using additional datasets (ICGC-LIRI-JP and GSE14520). Additionally, we performed functional enrichment analysis and conducted an assessment of the tumor immune microenvironment (TIME). Results: We identified 34 DEGs of the CCDC family. Among them, six DEGs (CCDC6/22/51/59/132/134) were upregulated and associated with poor prognosis. Higher CCDC score was an independent predictor of poor OS in TCGA-HCC patients (P<0.001, HR =2.37), which was validated in the ICGC-LIRI-JP (P=0.021, HR =2.15) and GSE14520 (P=0.002, HR =2.23) datasets. Functional enrichment analysis showed that hypoxia pathway genes were enriched in the high CCDC score group. Furthermore, immune microenvironment analysis demonstrated that high CCDC score was associated with a suppressed TIME caused by the extrinsic immune escape. Conclusions: The CCDC score, derived from six CCDC genes, exhibits remarkable expression levels in liver cancer and holds promise as an independent prognostic indicator. Our bioinformatics analysis revealed a high CCDC score is strongly associated with activation of the hypoxia pathway and an immunosuppressive tumor microenvironment in HCC. This profound finding may serve as a cornerstone for innovative targeted drug therapies and pave the way for further investigations into the underlying mechanisms of CCDC-related carcinogenesis in liver cancer.

Glycolysis-related gene dihydrolipoamide acetyltransferase promotes poor prognosis in hepatocellular carcinoma through the Wnt/ß-catenin and PI3K/Akt signaling pathways.

Background: Recent research suggests that dihydrolipoamide acetyltransferase (DLAT), which is a copper-induced cell death-related gene, is involved in multiple biological events in tumors. This study sought to investigate the relationship between DLAT and hepatocellular carcinoma (HCC). Methods: In the Cancer Genome Atlas (TCGA) database, we first identified the differentially expressed gene (i.e., DLAT), then confirmed DLAT expression, and found a link between it and the prognosis of HCC patients. An internal validation nomogram was built based on a multivariate Cox regression analysis. Data from the Tumor Immune Estimation Resource (TIMER) database was used to examine the association between DLT and immunological cells. A gene set enrichment analysis (GSEA) was conducted to investigate the probable mechanism of action. Finally, in vitro cytological research was conducted to further examin the involvement of DLAT in HCC-related unfavorable biological events. Results: The database screenings showed that DLAT was a differentially expressed molecule; that is, DLAT was more highly expressed in the cancer tissues than normal tissues. TCGA results and Kaplan-Meier-plotter data sets showed that HCC patients with reduced DLAT expression had greater disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI). The prediction model had a concordance index of 0.659 (0.614-0.704), which indicates high accuracy. According to the TIMER database, tumor cells in the HCC microenvironment may be able to bypass the immune system due to the expression of DLAT. The in vitro cytological tests showed that DLAT knockdown significantly decreased the proliferation and invasion of the HCC cells. It also inhibited the activity of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/ß-catenin signaling pathways. Conclusions: Decreased DLAT expression significantly prolongs the OS, PFI, and DSS of HCC patients. DLAT may be employed as a new predictive biomarker for HCC, and may be linked to the immune system in HCC patients. The tumor microenvironment (TME) may have a significant effect on the ability of tumor cells to evade the immune system. The PI3K/Akt and Wnt/ß-catenin signaling pathways may affect the prognosis of HCC by interfering with DLAT. Given these findings, HCC may be an ideal target for the development of anti-cancer therapies.

Multilevel stenting of malignant colonic obstructions from multilevel breast cancer colonic metastasis.

Video 1A video depicting the enclosed case, procedure, and discussion.

Endoscopic full-thickness resection of well-differentiated T2 neuroendocrine tumors in the duodenal bulb: a case series.

Background and Aims: Endoscopic therapies have moved to the forefront in the removal of small, well-differentiated duodenal neuroendocrine tumors (NETs). Classic procedures used to address small tumors, especially those less than 1 cm in diameter, are banding without resection, ligation endoscopic mucosal resection, or endoscopic submucosal dissection. Endoscopic full-thickness resection (EFTR) is a procedure developed recently that allows for sealing off of the tissue surrounding the tumor before full-thickness removal. Although surgical resection is typically recommended for NETs measuring 2 cm and larger, this may not always be possible given patients' ages or comorbidities. We present the cases of 3 patients with well-differentiated NETs of the duodenal bulb measuring greater than 2 cm who were poor candidates for surgery and were thus offered EFTR for excision of their tumors. Methods: Three patients with well-differentiated, stage II NETs of the duodenal bulb underwent chromoendoscopy and narrow-band imaging, EUS, prophylactic dilation of the upper esophageal sphincter and pylorus, and EFTR using an over-the-scope clip system. Results: In each case, there was no residual mass seen on endoscopy, Ga-68 Dotatate positron emission tomography-CT imaging, or biopsy up to 1 year after the procedure. Two of the 3 cases had normal chromogranin A levels at all follow-up points, and the third case had chromogranin A levels that trended down to a near-normal level of 145 ng/mL. Conclusions: Three patients with NETs of the duodenal bulb who were poor surgical candidates underwent successful EFTR using a full-thickness resection device. At 1-year follow-up, they have no evidence of disease recurrence on imaging and pathology after EFTR.

Intracystic Glucose and Carcinoembryonic Antigen in Differentiating Histologically Confirmed Pancreatic Mucinous Neoplastic Cysts.

INTRODUCTION: Differentiating mucinous neoplastic pancreatic cysts (MNPC) from cysts without malignant potential can be challenging. Guidelines recommend using fluid carcinoembryonic antigen (CEA) to differentiate MNPC; however, its sensitivity and specificity vary widely. Intracystic glucose concentration has shown promise in differentiating MNPC, but data are limited to frozen specimens and cohorts of patients without histologic diagnoses. This study aimed to compare glucose and CEA concentrations in differentiating MNPC using fresh fluid obtained from cysts with confirmatory histologic diagnoses. METHODS: This multicenter cohort study consisted of patients undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cysts during January 2013-May 2020. Patients were included if the cyst exhibited a histologic diagnosis and if both CEA and glucose were analyzed from fresh fluid. Receiver operating curve (ROC) characteristics were analyzed, and various diagnostic parameters were compared. RESULTS: Ninety-three patients, of whom 59 presented with MNPC, met the eligibility criteria. The area under the receiver operating curve (AUROC) was 0.96 for glucose and 0.81 for CEA (difference 0.145, P = 0.003). A CEA concentration of ≥192 ng/mL had sensitivity of 62.7% and specificity of 88.2% in differentiating MNPC, whereas glucose concentration of ≤25 mg/dL had sensitivity and specificity of 88.1% and 91.2%, respectively. DISCUSSION: Intracystic glucose is superior to CEA concentration for differentiating MNPC when analyzed from freshly obtained fluid of cysts with histologic diagnoses. The advantage of glucose is augmented by its low cost and ease of implementation, and therefore, its widespread adoption should come without barriers. Glucose has supplanted CEA as the best fluid biomarker in differentiating MNPC.

A nationwide analysis of pancreatic cancer trial enrollment reveals disparities and participation problems.

BACKGROUND: Our research group recently surveyed the clinical trial landscape in pancreatic adenocarcinoma and identified 430 active trials. These represent an opportunity to expand treatment options for patients with pancreatic adenocarcinoma. Our primary objective was to detail clinical trial participation among patients with pancreatic adenocarcinoma. Our secondary objective was to evaluate survival. METHODS: We queried the National Cancer Database (2004-2016) for patients with pancreatic adenocarcinoma. Patients were stratified by trial participation: clinical trial or non-trial. Multivariable logistic regression was used to identify variables associated with trial participation. The Kaplan-Meier method and multivariable Cox hazards regression were used to analyze survival. RESULTS: In total, 261,483 patients were included: 1,110 (0.4%) were enrolled in a clinical trial. A total of 57 Black patients participated in a clinical trial (0.19% of Black patients). This was lower compared to White patients (n = 955, 0.49% of White patients, P < .001). After adjusting for demographic and clinical factors, Black patients were less likely to be enrolled in a clinical trial (odds ratio = 0.387, P < .001). Patients treated at nonacademic medical centers were less likely to be in a clinical trial. Trial participation was associated with an increased median survival relative to non-trial patients (stage IV: 9.0 vs 3.8 months, P < .001), and this association remained on multivariable regression (hazard ratio = 0.779, P < .001). CONCLUSION: Fewer than 1% of patients with pancreatic adenocarcinoma participated in a clinical trial. There are racial and sociodemographic disparities in clinical trial enrollment. An association was observed between clinical trial participants and prolonged survival.

Association between radicular low back pain and constipation: a retrospective cohort study using a real-world national database.

INTRODUCTION: Previous observational studies have reported an association between lumbosacral radiculopathy (LSR), a form of low back pain (LBP) with nerve root involvement, and constipation. However, it is unclear whether this association is due to confounding variables such as comorbidities and medications. OBJECTIVES: This study explores the possible association between LSR and constipation, with the hypothesis that adults with LSR have increased odds of developing constipation compared with those with nonradicular LBP. METHODS: Adults aged 18 to 49 years with incident LSR and nonradicular LBP were identified from a national 70 million patient electronic health records network (TriNetX). Propensity score matching (PSM) was used to control for covariates and determine the odds ratio (OR) of constipation over a 1-year follow-up. Lumbar stenosis, cauda equina syndrome, and inflammatory bowel diseases were excluded. RESULTS: After PSM, 503,062 patients were in each cohort. Before PSM, the likelihood of constipation was identical between cohorts (LSR 10.8% vs 10.9%; OR [confidence interval] = 0.99 [0.98-1.0], P = 0.251). This association was unchanged after PSM (LSR 10.8% vs 11.1%; OR [confidence interval] = 0.98 [0.97-0.99]; P = 0.003). CONCLUSIONS: The study hypothesis can be refuted given that the OR approximated the null in a large propensity-matched sample. Patients with LSR have equivalent odds of constipation compared with those with nonradicular LBP, suggesting that LSR is not a direct cause of constipation. The similar risk of constipation between cohorts could be explained by factors common to LBP in general, such as pain severity, physical inactivity, and constipating medications.

Identification of Novel Therapeutic Molecular Targets in Inflammatory Bowel Disease by Using Genetic Databases.

PURPOSE: Utilization of genetic databases to identify genes involved in ulcerative colitis (UC), Crohn's disease (CD), and their extra-intestinal manifestations. METHODS: Protein coding genes involved in ulcerative colitis (3783 genes), Crohn's disease (3980 genes), uveitis (1043 genes), arthritis (5583 genes), primary sclerosing cholangitis (PSC) (1313 genes), and pyoderma gangrenosum (119 genes) were categorized using four genetic databases. These include Genecards: The Human Gene Database (www.genecards.org), DisGeNET (https://www.disgenet.org/), The Comparative Toxicogenomics Database (http://ctdbase.org/) and the Universal Protein Resource (https://www.uniprot.org/). NDex, Network Data Exchange (http://www.ndexbio.org/), was then utilized for mapping a unique signal pathway from the identified shared genes involved in the above disease processes. RESULTS: We have detected a unique array of 20 genes with the highest probability of overlay in UC, CD, uveitis, arthritis, pyoderma gangrenosum, and PSC. Figure 1 represents the interactome of these 20 protein coding genes. Of note, unique immune modulators in different disease processes are also noted. Interleukin-25 (IL-25) and monensin-resistant homolog 2 (MON-2) are only noted in UC, CD, pyoderma gangrenosum, and arthritis. Arachidonate 5-lipoxygenase (ALOX5) is involved in UC, CD, and arthritis. SLCO1B3 is exclusively involved with pyoderma gangrenosum, UC, and CD. As expected, TNF involvement is noted in CD, UC, PSC, and arthritis. Table 1 depicts the detailed result. CONCLUSION: Our work has identified a distinctive set of genes involved in IBD and its associated extra-intestinal disease processes. These genes play crucial roles in mechanisms of immune response, inflammation, and apoptosis and further our understanding of this complex disease process. We postulate that these genes play a critical role at intersecting pathways involved in inflammatory bowel disease, and these novel molecules, their upstream and downstream effectors, are potential targets for future therapeutic agents.

The Role of EUS in Liver Biopsy.

PURPOSE OF REVIEW: EUS-guided liver biopsy (EUS-LB) is being used with increased frequency to perform parenchymal liver biopsy. Evolution of the technique can now achieve excellent liver tissue cores. This review covers important developments in this procedure. RECENT FINDINGS: Clinical studies have recently demonstrated that the 19G EUS core biopsy needle is superior to non-core needles for liver tissue acquisition. In addition, wet suction provides more robust tissue samples than dry suction. Heparin priming of the needle (instead of saline) can prevent blood clogging within the needle lumen. A 1-hour recovery time after the EUS-LB is sufficient in almost all cases. The EUS-LB can deliver bilobar biopsies, which can decrease sampling error. Patients who need a liver biopsy in addition to an endoscopy or EUS are best served by the EUS-LB, as the combination procedure saves time and cost. The EUS-LB is a safe and effective means for procuring good liver core biopsies. Incremental improvements in technique have increased quality of the resulting specimen. Future directions of this technique are discussed.

Endoscopic ultrasound-guided biopsy in chronic liver disease: a randomized comparison of 19-G FNA and 22-G FNB needles.

Background and study aims Endoscopic ultrasound-guided liver biopsy uses a 19-gauge (G) needle for parenchymal liver biopsies. We evaluated tissue yields with a 22G fine-needle biopsy (FNB) versus 19G FNA fine-needle aspirate (FNA) device. Patients and methods Biopsies were obtained from 20 patients using the 19G FNA and 22G FNB randomizing each in a cross-over fashion with a blinded outcome assessor. Tissue adequacy for histologic evaluation was the primary outcome, or the proportion of specimens obtaining pathologic diagnosis (portal structures ≥ 5 or length of the longest piece ≥ 15 mm). Additional secondary outcomes included portal and centrilobular inflammation/fibrosis, length of the longest piece, aggregate specimen length, and small (< 5 mm), medium (5 - 8 mm) and large (> 8 mm) fragments. Results were compared in a per needle basis. Patients with cirrhosis were excluded. Results Eighty biopsies (40 each 19G FNA and 22G FNB) were obtained. Tissue adequacy was greater for the 19G FNA (88 %) versus 22G FNB (68 %), ( P  = 0.03). There was no difference in total portal structures for the 19G FNA (7.4) and 22G FNB (6.1), ( P  = 0.28). There was no difference in pre-processing outcomes. After processing, length of the longest piece was higher for the 19G FNA (9.1 mm) versus 22G FNB (6.6 mm), ( P  = 0.02). More total post-processing small fragments 29.9 versus 20.7, ( P  = 0.01) and fewer large fragments 1.0 versus 0.4 for the 22G FNB ( P  = 0.01) were detected. Conclusions Tissue adequacy was higher for the 19G FNA versus 22G FNB needle. The 22G FNB needle produced samples more prone to fragmentation during specimen processing.

A prospective pilot comparison of wet and dry heparinized suction for EUS-guided liver biopsy (with videos).

BACKGROUND AND AIMS: As EUS-guided liver biopsy sampling (EUS-LB) becomes more widely used, further studies have investigated ways to improve tissue yields. Use of a heparin-primed needle may lead to less clotting of blood within the needle, improve tissue recovery, and decrease fragmentation. The purpose of this study was to prospectively evaluate wet suction using a heparin-primed needle for EUS-LB. METHODS: This was a prospective crossover study evaluating wet suction for EUS-LB in parenchymal liver disease. The primary outcome was specimen adequacy, defined by an aggregate specimen length ≥15 mm and ≥5 complete portal tracts (CPTs). Secondary outcomes included number of CPTs, length of the longest piece, aggregate specimen length, and number of small (≤4 mm), medium (5-8 mm), and large (≥9 mm) fragments. Adverse events were tracked at 7 and 30 days. RESULTS: One hundred twenty biopsy specimens were collected from 40 participants (3 specimens per patient). Specimen adequacy occurred in 39 wet heparin (98%), 37 dry heparin (93%), and 30 dry needle biopsy samples (80%; 95% confidence interval [CI], .14-.18; P = .01). There was no difference between dry needle techniques. Length of the longest piece was 8.9 mm for wet heparin and 5.8 mm for dry techniques (95% CI, .33-1.53; P = .003). Aggregate specimen length was 49.2 mm for wet heparin and 23.9 mm for dry heparin (95% CI, -46.34 to 44.94; P = .003). Mean CPT count was 7.0 for wet heparin versus 4.0 for dry (95% CI, .74-6.26; P = .01). There were more medium (2.0 vs 1.0; 95% CI, .06-1.24; P = .03) and large (1.0 versus 0.0; 95% CI, .33-1.53; P = .003) fragments with wet suction with no difference in small fragments between groups. CONCLUSIONS: The use of wet suction EUS-LB demonstrated improved tissue adequacy compared with dry needle techniques. (Clinical trial registration number: NCT03103997.).