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Artificial intelligence has been rapidly deployed in gastroenterology and endoscopy. The acceleration of deep convolutional neural networks along with hardware development has allowed implementation of artificial intelligence algorithms into real-time endoscopy, particularly colonoscopy. However, artificial intelligence implementation in pancreaticobiliary endoscopy is nascent.Initial studies have been conducted in endoscopic retrograde pancreatography (ERCP), endoscopic ultrasound (EUS), and digital single operator cholangioscopy (DSOC). Machine learning has been implemented in identifying significant landmarks, including the ampulla on ERCP, and the bile duct, pancreas, and portal confluence on EUS. Moreover, artificial intelligence algorithms have been deployed in differentiating pathology including pancreas cancer, autoimmune pancreatitis, pancreatic cystic lesions, and biliary strictures.There have been relatively few studies with limited sample sizes in developing these machine learning algorithms. Despite the early successful demonstration of artificial intelligence in pancreaticobiliary endoscopy, additional research needs to be conducted with larger data sets to improve generalizability and assessed in real-time endoscopy before clinical implementation. However, pancreaticobiliary endoscopy remains a promising avenue of artificial intelligence application with the potential to improve clinical practice and outcomes.

Supplementary Figure from Genome-Wide Catalogue of Chromosomal Aberrations in Barrett's Esophagus and Esophageal Adenocarcinoma: A High-Density Single Nucleotide Polymorphism Array Analysis

PDF file - 1574K, YAP1 and SOX9 expression in EC cell lines.

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PDF file - 1015K, YAP1 Induces SOX9 promoter activity in 293T cells and primer design for SOX9 ChIP-PCR.

PDF file - 127K, SOX9 is elevated in mouse liver tumors with inactivating Hippo pathway mutations.

Cholangiocarcinoma (CCA) is the most common neoplasm of the biliary tract. The biological behavior and prognosis of CCA vary depending on the tumor's location in the biliary tree, dictating a different diagnostic, and treatment approach. Establishing a diagnosis of CCA remains a challenge and up to 20% of biliary strictures can yield indeterminate results, despite extensive evaluation. Endoscopic ultrasound (EUS) has become an effective diagnostic tool, as it provides high-quality images of the bile duct and allows for the sampling of strictures in the same plane of view. In this chapter, we explore the utility of EUS as a diagnostic and staging tool for biliary cancers.

BACKGROUND Pancreatic paragangliomas (PPGL) are rare benign neuroendocrine neoplasms but malignancy can occur. PPGL are often misdiagnosed as pancreatic neuroendocrine tumor or pancreatic adenocarcinoma. CASE SUMMARY We reviewed 47 case reports of PPGL published in PubMed to date. Fifteen patients (15/47) with PPGL underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Only six (6/15) were correctly diagnosed as PPGL. All patients with PPGL underwent surgical resection except three (one patient surgery was aborted because of hypertensive crisis, two patients had metastasis or involvement of major vessels). Our patient remained on close surveillance as she was asymptomatic. CONCLUSION Accurate preoperative diagnosis of PPGL can be safely achieved by EUS-FNA with immunohistochemistry. Multidisciplinary team approach should be considered to bring the optimal results in the management of PPGL.

Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related morbidity and mortality with dismal long term survival after diagnosis. Nearly 85% of pancreatic cancer patients present with advanced disease precluding curative surgical resection. In those who are candidates for surgery, preoperative biliary drainage (PBD) has been developed since the 1960s in order to improve surgical outcomes. While obstructive jaundice in resectable pancreatic cancer has been traditionally treated before surgical resection in all patients, data over the past decade demonstrated increased perioperative complications and morbidity with systematic PBD compared to direct surgery. With new evidence of potential adverse events, the role of routine PBD is being reassessed. Current indications for PBD include cholangitis, delayed surgery, and relief of jaundice in patients planned to receive neoadjuvant therapy (NAT). NAT is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer and a higher proportion of patients with likely require PBD in the future. The evidence for endoscopic retrograde cholangiopancreatography as first line for PBD is robust with supporting data from endoscopic ultrasound assisted biliary drainage. Self-expanding metal stent was shown to be cost-effective in recent studies without increase in morbidity compared to plastic stents in this setting. In this review, we will summarize the current evidence for PBD in patients with pancreatic cancer.

Endoscopic mucosal resection of duodenal polyps (EMR) is a challenging intervention. The aim of this study was to review the patient characteristics, techniques, procedure outcomes, adverse events, and recurrence of duodenal polyps.Patients were included if they had pathologically confirmed non-ampullary duodenal polyps and had received EMR with at least one follow-up EGD for surveillance. Descriptive statistics were employed to report the findings.A total of 65 patients underwent a total of 90 EMRs for duodenal polyps. The mean age was 65.4 years, and 29 of the patients were female. Complete resection of the visible mass was achieved in 96.9% of cases. Endoscopic hemostasis was required in 18.5% of patients. Delayed bleeding occurred in 9%, and delayed perforations requiring surgical intervention occurred in 2.2% of patients with no mortality. Surgery after EMR was needed in 12.7% of cases. Eleven (16.9%) patients had recurrent duodenal adenoma on follow-up EGD.Duodenal polyps can be safely resected and have a notable recurrence rate. This is particularly true for adenomas, warranting post-resection endoscopic surveillance. The appropriate interval for post-resection surveillance of duodenal adenomas should be a focus of future study.

ObjectiveGastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.MethodsExtensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation.ResultsOverexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity.ConclusionsOur preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.

ObjectivePrognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes.DesignWe profiled 40 untreated mEGACs (20 shorter survivors 36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts.ResultsKMT2C alterations were exclusively observed in shorter survivors together with high level of intratumour heterogeneity and complex clonal architectures, whereas the APOBEC mutational signatures were significantly enriched in longer survivors. Notably, the loss of heterozygosity in chromosome 4 (Chr4) was associated with shorter survival and ‘cold’ immune phenotype characterised by decreased B, CD8, natural killer cells and interferon-gamma responses. Unsupervised transcriptomic clustering revealed a shorter survivor subtype with distinct expression features (eg, upregulated druggable targets JAK2, MAP3K13 and MECOM). An integrated model was then built based on clinical variables and the identified molecular determinants, which significantly segregated shorter and longer survivors. All the above features and the integrated model have been validated independently in multiple TCGA cohorts.ConclusionThis study discovered novel molecular features prognosticating overall survival in patients with mEGAC and identified potential novel targets in shorter survivors.

Introduction: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. Methods: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. Results: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0–3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. Conclusion: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients’ general condition rather that age alone.

Previous studies evaluating self-expandable metal stents (SEMS) for management of malignant extrinsic colon obstruction have yielded conflicting results. We evaluated the efficacy of uncovered SEMS for extrinsic colon malignancy (ECM) versus intrinsic colon malignancy (ICM). Retrospective review of all patients referred for colonic SEMS at a tertiary cancer center between 2007 and 2018 was performed. Primary outcome measures were technical success, clinical success, intervention rate, and overall survival. 138 patients with ECM and 119 patients with ICM underwent attempted stent placement. The rectum and/or sigmoid colon was the most common stricture site. Technical success was lower in the ECM group [86% vs 96% (p = .009)]. Clinical success was lower in the ECM group both at 7 days [82% vs 95% (p = .004)] and at 90 days [60% vs 86% (p

ObjectivesSolid tumor metastases to the pancreas are rare, and only limited literature on the topic is available. In this retrospective study, we reviewed 107 cases of solid tumor metastases to the pancreas diagnosed by fine-needle aspiration (FNA) from 2005 to 2019.MethodsInformation including the patients’ clinical histories, radiologic and pathologic findings, treatments, and follow-up were collected.ResultsThe mean age of the patients was 62.4 years. The mean tumor size was 2.64 cm with even distribution throughout the pancreas (head, neck and body, and tail). The most common primary site was the kidney, followed by the lung, skin, and breast and the gynecologic, gastrointestinal, and genitourinary tracts. The most common tumor type was carcinoma, followed by melanoma and sarcoma. In comparison to patients with nonkidney primary cancers, those with primary renal cell carcinoma had a longer median interval between primary diagnosis and metastasis (8.5 vs 4.0 years; P < .01), less often had metastasis outside the pancreas (38% vs 74%; P < .01), and had a significantly longer 5-year survival rate (65.7% vs 24.8%; P < .01).ConclusionsFNA plays a crucial role in diagnosing metastases to the pancreas. Metastases originating from kidney and nonkidney primary tumors have distinct clinicopathologic features and prognoses.

Description The purpose of this American Gastroenterological Association Institute Clinical Practice Update is to describe the indications for screening for pancreas cancer in high-risk individuals. Methods The evidence reviewed in this work is based on reports of pancreas cancer screening studies in high-risk individuals and expert opinion. Best Practice Advice 1 Pancreas cancer screening should be considered in patients determined to be at high risk, including first-degree relatives of patients with pancreas cancer with at least 2 affected genetically related relatives. Best Practice Advice 2 Pancreas cancer screening should be considered in patients with genetic syndromes associated with an increased risk of pancreas cancer, including all patients with Peutz–Jeghers syndrome, hereditary pancreatitis, patients with CDKN2A gene mutation, and patients with 1 or more first-degree relatives with pancreas cancer with Lynch syndrome, and mutations in BRCA1, BRCA2, PALB2, and ATM genes. Best Practice Advice 3 Genetic testing and counseling should be considered for familial pancreas cancer relatives who are eligible for surveillance. A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers. Best Practice Advice 4 Participation in a registry or referral to a pancreas Center of Excellence should be pursued when possible for high-risk patients undergoing pancreas cancer screening. Best Practice Advice 5 Clinicians should not screen average-risk individuals for pancreas cancer. Best Practice Advice 6 Pancreas cancer screening in high-risk individuals should begin at age 50 years, or 10 years younger than the initial age of familial onset. Screening should be initiated at age 40 years in CKDN2A and PRSS1 mutation carriers with hereditary pancreatitis and at age 35 years in the setting of Peutz–Jeghers syndrome. Best Practice Advice 7 Magnetic resonance imaging and endoscopic ultrasonography (EUS) should be used in combination as the preferred screening modalities in individuals undergoing pancreas cancer screening. Best Practice Advice 8 The target detectable pancreatic neoplasms are resectable stage I pancreatic ductal adenocarcinoma and high-risk precursor neoplasms, such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasias. Best Practice Advice 9 Screening intervals of 12 months should be considered when there are no concerning pancreas lesions, with shortened intervals and/or the performance of EUS in 6–12 months directed towards lesions determined to be low risk (by a multidisciplinary team). EUS evaluation should be performed within 3–6 months for indeterminate lesions and within 3 months for high-risk lesions, if surgical resection is not planned. New-onset diabetes in a high-risk individual should lead to additional diagnostic studies or change in surveillance interval. Best Practice Advice 10 Decisions regarding therapy directed towards abnormal findings detected during screening should be made by a dedicated multidisciplinary team together with the high-risk individual and their family. Best Practice Advice 11 Surgical resection should be performed at high-volume centers. Best Practice Advice 12 Clinicians should consider discontinuing pancreas cancer screening in high-risk individuals when they are more likely to die of non-pancreas cancer–related causes due to comorbidity and/or are not candidates for pancreas resection. Best Practice Advice 13 The limitations and potential risks of pancreas cancer screening should be discussed with patients before initiating a screening program.

Hippo/YAP1 signaling is a major regulator of organ size, cancer stemness, and aggressive phenotype. Thus, targeting YAP1 may provide a novel therapeutic strategy for tumors with high YAP1 expression in esophageal cancer (EC). Chromatin immunoprecipitation (ChiP) and quantitative ChiP‐PCR were used to determine the regulation of the chromatin remodeling protein bromodomain‐containing protein 4 (BRD4) on YAP1. The role of the bromodomain and extraterminal motif (BET) inhibitor JQ1, an established BRD4 inhibitor, on inhibition of YAP1 in EC cells was dissected using western blot, immunofluorescence, qPCR, and transient transfection. The antitumor activities of BET inhibitor were further examined by variety of functional assays, cell proliferation (MTS), tumorsphere, and ALDH1+ labeling in vitro and in vivo. Here, we show that BRD4 regulates YAP1 expression and transcription. ChiP assays revealed that BRD4 directly occupies YAP1 promoter and that JQ1 robustly blocks BRD4 binding to the YAP1 promoter. Consequently, JQ1 strongly suppresses constitutive or induced YAP1 expression and transcription in EC cells and YAP1/Tead downstream transcriptional activity. Intriguingly, radiation‐resistant cells that acquire strong cancer stem cell traits and an aggressive phenotype can be effectively suppressed by JQ1 as assessed by cell proliferation, tumorsphere formation, and reduction in the ALDH1+ cells. Moreover, effects of JQ1 are synergistically amplified by the addition of docetaxel in vitro and in vivo. Our results demonstrate that BRD4 is a critical regulator of Hippo/YAP1 signaling and that BRD4 inhibitor JQ1 represents a new class of inhibitor of Hippo/YAP1 signaling, primarily targeting YAP1 high and therapy‐resistant cancer cells enriched with cancer stem cell properties., This study, for the first time, demonstrates that BRD4 is a critical regulator of YAP1 through direct occupancy on its promoter, while JQ1 decreases YAP1 expression and its transcription output (CTGF, SOX9, and Cyr61), suppresses CSC traits, and decreases ALDH1+ cells, indicating targeting YAP1 can be achieved through BET inhibition, which provides a new therapeutic strategy for EC.

PURPOSE Effective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX)-based treatment and imaging-based biomarkers for borderline resectable PDAC. METHODS Eligible patients had treatment-naïve, histology-confirmed PDAC and one or more high-risk features: mesenteric vessel involvement, CA 19-9 level of 500 mg/dL or greater, and indeterminate metastatic lesions. Patients received modified FOLFIRINOX and chemoradiation before anticipated pancreatectomy. Tumors were classified on baseline computed tomography as high delta (well-defined interface with parenchyma) or low delta (ill-defined interface). We designated computed tomography interface response after therapy as type I (remained or became well defined) or type II (became ill defined). The study had 80% power to differentiate a 60% from 40% resection rate (α = .10). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and subgroups were compared using log-rank tests. RESULTS Thirty-three patients initiated therapy; 45% underwent pancreatectomy. The median OS was 24 months (95% CI, 16.2 to 29.6 months). For patients who did and did not undergo pancreatectomy, the median OS was 42 months (95% CI, 17.7 months to not estimable) and 14 months (95% CI, 9.0 to 24.8 months), respectively. Patients with high-delta tumors had lower 3-year PFS (4% v 40%) and 3-year OS rates (20% v 60%) than those with low-delta tumors (both P < .05). Patients with type II interface responses had lower 3-year PFS (0% v 29%) and 3-year OS rates (16% v 47%) than those with type I responses (both P < .001). CONCLUSION Preoperative FOLFIRINOX followed by chemoradiation for high-risk borderline resectable PDAC was associated with a resection rate of 45% and median OS of approximately 2 years. Our imaging-based biomarker validation indicates that personalized treatment may be achieved using these biomarkers at baseline and post-treatment.

We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital.Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016.Among the 309 patients, the median age was 67 years and 56% were men. The most common presenting symptoms were abdominal pain (37%) and jaundice (29%). Concordance between radiographic diagnosis and final pathology was 89%. The mean lesion size was 34.9 mm on computed tomography and 31.5 mm on EUS. There were 197 patients (64%) with localized disease, of whom 115 (58%) had resectable lesions, 61 (31%) had borderline resectable, and 21 (11%) had unresectable lesions (mean CA 19-9 levels 1705 U/mL, 2490 U/mL, and 479 U/mL, respectively). A median of 3 FNA passes were performed to establish a pathologic diagnosis. Two patients (1%) had postprocedural adverse events. Median overall survival was 47 months in those who underwent surgery after EUS and 12 months in those who did not (P0.001).A multidisciplinary approach is employed for management of suspected pancreatic neoplasm at our tertiary cancer center. A combination of cross-sectional imaging and EUS-FNA serves as a highly effective duo in establishing a tissue diagnosis and staging with a low adverse event rate. Counterintuitively, CA 19-9 is not necessarily higher with resectable lesions than with unresectable lesions, indicating the limitation of CA 19-9 as a pancreatic tumor marker.

Summary Esophageal stents are widely used for the palliation of malignant esophageal obstruction. Advances in technology have made esophageal stenting technically feasible and widespread for such obstruction, but complications remain frequent. We present outcomes of a large cohort undergoing esophageal stent placement for malignant esophageal obstruction at a tertiary care cancer center. Patients who underwent placement of esophageal stents for malignancy-related esophageal obstruction between 1 January 2001 and 31 July 2020 were identified. Exclusion criteria included stents placed for benign stricture, fistulae, obstruction of proximal esophagus (proximal to 24 cm from incisors), or post-surgical indications. Patient charts were reviewed for demographics, procedure and stent characteristics, complications, and follow-up. A total of 242 patients underwent stent placement (median age: 64 years, 79.8% male). The majority, 204 (84.3%), had esophageal cancer. During the last two decades, there has been an increasing trend in the number of esophageal stents placed. Though plastic stents were previously used, these are no longer utilized. Complications are frequent and include early complications of pain in 68 (28.1%) and migration in 21 (8.7%) and delayed complications of recurrent symptoms of dysphagia in 46 (19.0%) and migration in 26 (10.7%). Over the study period, there has not been a significant improvement in the rate of complications. During follow-up, 92 (38%) patients required other enteral nutrition modalities after esophageal stent placement. No patient, treatment, or stent characteristics were significantly associated with stent complication or outcome. Esophageal stent placement is an increasingly popular method for palliation of malignant dysphagia. However, complications, particularly pain, migration, and recurrent symptoms of dysphagia are common. Almost 40% of patients may also require other methods of enteral access after esophageal stent placement. Given the high complication rates and suboptimal outcomes, removable stents should be considered as first-line in the case of poor palliative response.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA), especially endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), is the mainstay of tissue acquisition for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using flexible biopsy needles has been used for patients with PDAC in an effort to increase diagnostic yields and biomarker testing. However, the role of EUS-TA in biomarker testing for personalized therapy or precise chemotherapy for PDAC is not well established.PDAC cases with specimens acquired through concurrent EUS-FNA and EUS-FNB were identified retrospectively. Smears were prepared from EUS-FNA sampling, and cell blocks (CBs) were prepared from EUS-FNB sampling. Rapid onsite evaluation was conducted for all cases for diagnostic adequacy. The adequacy for biomarker testing, including next-generation sequencing (NGS) and immunohistochemistry (IHC) assays, was evaluated, and cases with smears and CBs adequate for NGS were processed for targeted NGS.There were 26 PDAC cases concurrently sampled by EUS-FNA and EUS-FNB. EUS-FNA smears for all 26 cases and EUS-FNB CBs for 20 cases (77%) were diagnostic for PDAC. Twenty-one smears (81%) and 11 CBs (42%) were adequate for NGS. Nine cases with both smears and CBs adequate for NGS underwent NGS, which identified clinically significant gene mutation variants, including KRAS, TP53, and SMAD4 mutations.Both EUS-FNA and EUS-FNB can provide optimal material for targeted NGS for PDACs. In PDAC cases subjected to concurrent EUS-FNA and EUS-FNB, EUS-FNA specimens had greater diagnostic yields and more adequate material for NGS than EUS-FNB specimens, whereas EUS-FNB was more suitable for IHC-based biomarker testing.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).

Esophageal cancer (EC) generally consists of squamous cell carcinoma (which arise from squamous epithelium) and adenocarcinoma (which arise from columnar epithelium). Due to the increased recognition of risk factors associated with EC and the development of screening programs, there has been an increase in the diagnosis of early EC. Early EC is amenable to curative therapy by endoscopy, which can be performed by either endoscopic resection or endoscopic ablation. Endoscopic resection consists of either endoscopic mucosal resection (preferred in cases of adenocarcinoma) or endoscopic submucosal dissection (preferred in cases of squamous cell carcinoma). Endoscopic ablation can be performed by either radiofrequency ablation, cryotherapy, argon plasma coagulation or photodynamic therapy, amongst others. Endoscopy can also assist in the management of complications post-esophageal surgery, such as anastomotic leaks and perforations. Finally, there is a growing role for endoscopy to manage end-of-life palliative symptoms, especially dysphagia. The growing use of esophageal stents, debulking therapy and dilation can assist in improving a patient's quality of life. In this review, we examine the multiple roles of endoscopy in the management of patients with EC.

Background and Aims The aim of this study was to examine clinical outcomes and adverse events (AEs) of self-expandable metal stents (SEMSs) in the management of malignant colonic obstruction (MCO). Methods Patients with SEMSs for MCO treated at our institution from 2007 to 2016 were included. Clinical success was defined as successful oral intake after the procedure and technical success as stent deployment across the stricture in the desired location. Results Of 199 patients, the mean age was 58, 54% were men, and 99% had stage IV cancer. MCO etiology was colorectal cancer in 82% and extrinsic compression in 17%. Technical success was achieved in 99.5% and clinical success in 89%. The SEMSs were palliative in 97% and were a bridge to surgery in 4%. MCO occurred in the left side of the colon in 90%, transverse in 4.5%, and ascending colon in 5.5%. SEMSs were placed in curved segments in 30% and straight segments in 70%. Tandem SEMSs were required in 27 patients. Forty-six patients had 48 AEs (24%), including 2% periprocedure, 15% postprocedure, and 83% after 72 hours. Stent-related AEs (n = 25) included persistent obstruction (n = 14), occlusion (n = 10), and failure of expansion (n = 1). Procedural AEs (n = 23) included minor bleeding (n = 2), perforations (n = 4), abdominal pain (n = 12), stent migration (n = 4), and respiratory insufficiency (n = 1). Repeat procedures were performed in 21 of 46 patients. After SEMSs, 48 patients underwent surgery, including resection with primary anastomosis (n = 8), resection with definitive stoma (n = 18), and diverting stoma without resection (n = 19). Mean time to surgery after SEMS placement was 175 days. Postsurgical AEs occurred in those with resections (leak, 2; infection, 2). Of 104 receiving bevacizumab, 22% had AEs, including 1 perforation compared with 3 in the nonbevacizumab group (P = .549). Mean overall survival was 5.6 months. Extrinsic compression and curved strictures were associated with poor clinical success by univariate analysis and etiology (noncolonic with poor outcome) by multivariate analysis. Conclusions SEMSs for MCO has high technical but suboptimal clinical success. Curved strictures and extrinsic compression are associated with poor outcomes. The perforation rate was not higher in the bevacizumab compared with the nonbevacizumab group, although this should be further validated in a larger population.

PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC.PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo.PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.

Background & Aims The purpose of this expert review is to describe the current methodologies available to manage malignant alimentary tract obstructions as well the evidence behind the various methods (including their efficacy and safety), indications, and appropriate timing of interventions. Methods This is not a formal systematic review but is based on a review of the literature to provide best practice advice statements. No formal rating of the quality of evidence or strength of recommendation is carried out. Best Practice Advice 1 For all patients with alimentary tract obstruction, the decision about specific interventions should be made in a multidisciplinary setting including oncologists, surgeons, and endoscopists and take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status. Best Practice Advice 2 For patients who present with esophageal obstruction from esophageal cancer and who are potential candidates for resection or chemoradiation, clinicians should not routinely insert a self-expanding metal stent (SEMS) without multidisciplinary review because of high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates. Best Practice Advice 3 For patients who present with esophageal obstruction from esophageal cancer who are potential candidates for resection and who have concerns of malnutrition, clinicians may consider the use of enteral feeding tubes (via nasogastric or percutaneous route). Clinicians should be aware of the potential risk of abdominal wall tumor seeding as well as making subsequent gastric conduit formation difficult with percutaneous endoscopic gastrostomy placement. Best Practice Advice 4 For patients who present with esophageal obstruction from esophageal cancer who are not candidates for resection, clinicians should consider either SEMS insertion or brachytherapy as sole therapy or in combination. Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives. Best Practice Advice 5 For patients with malignant esophageal obstruction who are undergoing SEMS placement, clinicians should use a fully covered or partially covered SEMS and not an uncovered SEMS, with consideration of a stent-anchoring/fixation method. Best Practice Advice 6 For patients with gastric outlet obstruction who have a life expectancy greater than 2 months, have good functional status, and who are surgically fit, surgical gastrojejunostomy should be considered. Best Practice Advice 7 For patients with gastric outlet obstruction who are undergoing surgical gastrojejunostomy, a laparoscopic approach is favored over an open approach because of lower blood loss and shorter hospital stay. Best Practice Advice 8 For patients with gastric outlet obstruction who are not candidates for gastrojejunostomy (surgical or endoscopic ultrasound-guided), clinicians should consider the insertion of an enteral stent. Best Practice Advice 9 Enteral stents should not be used in patients with multiple luminal obstructions or severely impaired gastric motility because of the limited benefit in these scenarios. Clinicians can consider placement of a venting gastrostomy in these patients. Best Practice Advice 10 Depending on the experience of the endoscopist, endoscopic ultrasound-guided gastrojejunostomy is an acceptable alternative to surgical gastrojejunostomy and enteral stent placement. Clinicians should be aware that there are currently no dedicated Food and Drug Administration–approved devices for endoscopic ultrasound–guided gastrojejunostomy. Best Practice Advice 11 For patients with malignant colonic obstruction who are candidates for resection, insertion of SEMS is a reasonable choice as a “bridge to surgery” to allow for one-stage, elective resection. Best Practice Advice 12 For patients with malignant colonic obstruction who are not candidates for resection, either SEMS placement or a diverting colostomy are reasonable choices depending on the patient’s goals and functional status. Best Practice Advice 13 SEMS is a reasonable option for patients with proximal (or right-sided) malignant obstructions, both as a “bridge to surgery” and in the palliative setting. Best Practice Advice 14 SEMS placement is a reasonable alternative for patients with extracolonic malignancy who are not candidates for surgery, although their placement is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.

Background and Objective: The widespread use of colonoscopy has led to an increasing number of subepithelial lesions (SELs) being detected in the lower gastrointestinal (GI) tract. This study aimed to analyze the utility of EUS and its role in the management of lower GI SELs. Patients and Methods: Records of all patients who were referred for lower EUS evaluation of a SEL at a tertiary center between 2007 and 2018 were retrospectively reviewed after IRB approval. Data collection included patient/lesion characteristics, technical details of procedure, and pathology results. Results: A total of 47 patients underwent EUS examinations for the evaluation of 49 suspected SEL in the lower GI tract (2 patients had 2 SELs each). Out of the 49 suspected lesions, the most frequent location was in the rectum (30/49, 61.2%). EUS showed extraluminal compression in 2 cases (2/49, 4.1%) and intraluminal lesions were identified in 40 cases (40/49, 81.6%). In 7 patients (7/49, 14.3%), no lesion could be identified by EUS. Twenty (20/49, 40.8%) SELs were malignant or had malignant potential. Twenty-six EUS-guided fine-needle aspirations (FNAs) and 14 EUS-core biopsies were performed. EUS-FNA alone was able to correctly diagnose 15/26 (57.7%) of the lower SELs. When EUS-guided fine needle biopsies (FNB) were performed during the same procedure, the final diagnosis was confirmed in 21/26 (80.8%) cases. There was only one procedure-related complication caused by use of narcotics. Conclusion: EUS-guided FNA/FNB are feasible and safe techniques for assessing lower GI SELs and provide valuable information regarding lesion characteristics and their malignant potential with high diagnostic accuracy.