Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers.

BACKGROUND: Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). PATIENTS AND METHODS: Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. RESULTS: A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. CONCLUSIONS: dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.

Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection.

BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision-making related to periprocedural prophylaxis selection and post-procedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a one-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on twenty PEP risk factors and 5 prophylactic interventions (rectal non-steroidal anti-inflammatory drugs [NSAID], aggressive hydration, combined rectal NSAID and aggressive hydration, pancreatic duct [PD] stenting, and combined rectal NSAID and PD stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended post-procedure monitoring.

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.

Intra-operative pyloric BOTOX injection versus pyloric surgery for prevention of delayed gastric emptying after esophagectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after esophagectomy. BOTOX injections and pyloric surgeries (PS), including pyloroplasty (PP) and pyloromyotomy (PM), are performed intraoperatively as prophylaxis against DGE. This study compares the effects of pyloric BOTOX injection and PS for preventing DGE post-esophagectomy. METHODS: We retrospectively reviewed Moffitt's IRB-approved database of 1364 esophagectomies, identifying 475 patients receiving BOTOX or PS during esophageal resection. PS was further divided into PP and PM. Demographics, clinical characteristics, and postoperative outcomes were compared using Chi-Square, Fisher's exact test, Wilcoxon rank-sum, and ANOVA. Propensity-score matching was performed between BOTOX and PP cohorts. RESULTS: 238 patients received BOTOX, 108 received PP, and 129 received PM. Most BOTOX patients underwent fully minimally invasive robotic Ivor-Lewis esophagectomy (81.1% vs 1.7%) while most PS patients underwent hybrid open/Robotic Ivor-Lewis esophagectomy (95.7% vs 13.0%). Anastomotic leak (p = 0.57) and pneumonia (p = 0.75) were comparable between groups. However, PS experienced lower DGE rates (15.9% vs 9.3%; p = 0.04) while BOTOX patients had less postoperative weight loss (9.7 vs 11.45 kg; p = 0.02). After separating PP from PM, leak (p = 0.72) and pneumonia (p = 0.07) rates remained similar. However, PP patients had the lowest DGE incidence (1.9% vs 15.7% vs 15.9%; p = < 0.001) and the highest bile reflux rates (2.8% vs 0% vs 0.4%; p = 0.04). Between matched cohorts of 91 patients, PP had lower DGE rates (18.7% vs 1.1%; p = < 0.001) and less weight loss (9.8 vs 11.4 kg; p = < 0.001). Other complications were comparable (all p > 0.05). BOTOX was consistently associated with shorter LOS compared to PS (all p = < 0.001). CONCLUSION: PP demonstrates lower rates of DGE in unmatched and matched analyses. Compared to BOTOX, PS is linked to reduced DGE rates. While BOTOX is associated with more favorable LOS, this may be attributable to difference in operative approach. PP improves DGE rates after esophagectomy without improving other postoperative complications.

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.

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.

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.

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.

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.).

EUS-guided drainage of postsurgical fluid collections using lumen-apposing metal stents: a multicenter study.

BACKGROUND AND AIMS: Postsurgical fluid collections (PSFCs) are traditionally drained either percutaneously or surgically. Endoscopic drainage offers several advantages compared with either percutaneous or surgical approaches, including avoiding repeat surgery or the need to have a percutaneous drain in place for weeks. There are very little data regarding the use of lumen-apposing metal stents (LAMSs) in the drainage of PSFCs. We aim to study the technical and clinical success and adverse events (AEs) of using LAMSs in the drainage of PSFCs. METHODS: Collaborators from 8 centers retrospectively reviewed their endoscopic databases to find procedures using LAMSs for drainage of PSFCs. Technical success (successful placement of LAMSs into the fluid collection), clinical success (complete resolution of the fluid collection on repeat imaging or endoscopy), and intraprocedure and postprocedure AEs were measured. RESULTS: Forty-seven patients were identified with PSFCs after various surgeries. Thirteen patients had failed previous percutaneous or surgical drainage attempts. Fluid collections averaged 78.6 mm (range, 47-150 mm) in size. The most common site of stent placement was transgastric, followed by rectum and duodenum. Technical success rate was 93.6% and clinical success rate 89.3%. The intraprocedural AE rate was 4.25% and postprocedural AE rate 6.4%. There was 1 death unrelated to the procedure. CONCLUSIONS: The use of LAMSs to drain PSFCs has a high technical and clinical success rate with low AEs. For collections that are favorably located adjacent to the stomach, duodenum, or rectum, LAMS placement is a viable alternative to repeat surgery or percutaneous drainage.

Lactated Ringer's solution in combination with rectal indomethacin for prevention of post-ERCP pancreatitis and readmission: a prospective randomized, double-blinded, placebo-controlled trial.

BACKGROUND AND AIMS: Prospective data have shown the benefit of rectal indomethacin (IND) for preventing post-ERCP pancreatitis (PEP). A recent pilot study demonstrated a lower incidence of PEP after an 8-hour lactated Ringer's solution (LR) infusion. The aim of this study was to evaluate the efficacy of IND with or without bolus LR in patients at high-risk for PEP. METHODS: In this randomized, double-blinded, placebo-controlled trial we assigned patients to standard normal saline solution (NS) + placebo, NS + IND, LR + placebo, or LR + IND. Each liter of fluid infusion was completed within 30 minutes. Patients were determined high-risk based established criterion and excluded if they had pancreatitis, contraindications to IND, or signs of volume overload. Our primary outcome was PEP, defined by standardized criterion. Our secondary outcomes were severe acute pancreatitis, localized adverse events, death, length of stay, and readmission. RESULTS: Our sample consisted of 192 patients (48 per group) who completed follow-up at 24 hours and at 30 days post-ERCP. All patients had at least 1 high-risk criterion for PEP, and 56% had >1. PEP occurred in 3 patients (6%) in the LR + IND versus 10 (21%) in the NS + placebo group (P = .04). Readmission rates were lower in the LR + IND group (1 [2%]) versus the NS + placebo group (6 [13%]; P = .03). No differences were found between the other study groups. There was 1 case of severe pancreatitis (NS + IND) and 1 case of pseudocyst (LR + IND). CONCLUSIONS: In patients at high risk for PEP, LR + IND reduced the incidence of PEP and readmission rates compared with NS + placebo. (Clinical trial registration number: NCT02641561.).

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.

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

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.

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.

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 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.