Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

High-Risk Features of Esophageal Adenocarcinoma Following Neoadjuvant Chemoradiation: Patients for Whom Surgery Should Not Be Delayed.

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.

Performance and attitudes toward real-time computer-aided polyp detection during colonoscopy in a large tertiary referral center in the United States.

BACKGROUND AND AIMS: Computer-aided detection (CADe) has been shown to improve polyp detection in clinical trials. Limited data exist on the impact, utilization, and attitudes toward artificial intelligence (AI)-assisted colonoscopy in daily clinical practice. We aimed to evaluate the effectiveness of the first U.S. Food and Drug Administration-approved CADe device for polyp detection in the United States and the attitudes toward its implementation. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients undergoing colonoscopy at a tertiary center in the United States before and after a real-time CADe system was made available. The decision to activate the CADe system was at the discretion of the endoscopist. An anonymous survey was circulated among endoscopy physicians and staff at the beginning and conclusion of the study period regarding their attitudes toward AI-assisted colonoscopy. RESULTS: CADe was activated in 52.1% of cases. Compared with historical control subjects, there was no statistically significant difference in adenomas detected per colonoscopy (1.08 vs 1.04, P = .65), even after excluding diagnostic and therapeutic indications and cases where CADe was not activated (1.27 vs 1.17, P = .45). In addition, there was no statistically significant difference in adenoma detection rate (ADR), median procedure, and withdrawal times. Survey results demonstrated mixed attitudes toward AI-assisted colonoscopy, of which main concerns were high number of false-positive signals (82.4%), high level of distraction (58.8%), and impression it prolonged procedure time (47.1%). CONCLUSIONS: CADe did not improve adenoma detection in daily practice among endoscopists with high baseline ADRs. Despite its availability, AI-assisted colonoscopy was only activated in half of the cases, and multiple concerns were raised by staff and endoscopists. Future studies will help elucidate the patients and endoscopists that would benefit most from AI-assisted colonoscopy.

Biliary Drainage in Hilar and Perihilar Cholangiocarcinoma; 25-Year Experience at a Tertiary Cancer Center.

INTRODUCTION: This study analyzes the optimal biliary stenting strategy for palliation in cholangiocarcinoma (CCA). METHODS: This is a retrospective study of patients with CCA who underwent biliary drainage from 1997-2023. A per-patient analysis of percutaneous biliary drainage (PTBD) rates, the median number of ERCPs, overall survival (OS), and a per-procedure analysis of clinical success (CS), stent-specific Adverse Events (AEs), and mean time to reintervention by stent type and laterality (unilateral(u) & bilateral(b)) is presented. RESULTS: A total of 333 patients underwent 1,050 ERCPs; 85% with plastic stents (PS). PTBD was eventually done in 23% of PS patients, 35% of whom had PS removed prior to PTBD. ERCPs with SEMS/uniSEMS use had higher CS (89%/91%) vs PS/uPS (85% both) and PS within SEMS (PS-SEMS)/uPS-SEMS (71%/74%;p=0.013/p=0.054). Compared to PS, SEMS and PS-SEMS were associated with higher stent-specific AEs (OR SEMS 4.85; 3.23-7.27; PS-SEMS 9.99; 5.33-18.71;p<0.001). Straight PS were associated with more stent-specific AEs compared to double-pigtail stents (OR 6.74; 3.95-11.45;p<0.001). More 7 Fr stents were used in cases with balloon dilation (BD, 109 vs. 88 with no BD; p<0.001). BD had 79% CS rate vs 87% without BD (p<0.001). Cases with pus on ERCP and those with BD had a shorter mean time to reintervention. On regression analyses, higher Bismuth class, PS use, and PS-SEMS use were associated with a shorter mean time to repeat ERCP. 52% of patients in the bSEMS arm died from cholangitis (p=0.005). CONCLUSION: The relatively higher clinical success of SEMS is countered by the higher stent-specific complication rate. PS can be removed and may better facilitate PTBD. Within PS types, DPTs may have fewer stent-specific AEs. Cases requiring balloon dilation and with endoscopic evidence of pus may benefit from earlier reintervention.

Endoscopy for the diagnosis and treatment of gastrointestinal bleeding caused by malignancy.

BACKGROUND AND AIM: The diagnosis and treatment of gastrointestinal (GI) bleeding secondary to malignancy can be challenging. Endoscopy is the gold standard to diagnose and treat gastrointestinal bleeding but clinical characteristics and outcomes of patients with malignancy-related bleeding are not well understood. This study aims to look at clinical characteristics, endoscopic findings, safety and clinical outcomes of endoscopic interventions for GI malignancy-related bleeding. METHODS: We retrospectively reviewed outcomes of patients with confirmed GI malignancies who underwent endoscopy for GI bleeding at MD Anderson Cancer Center between 2010 and 2019. Cox hazard analysis was conducted to identify factors associated with survival. RESULTS: A total of 313 patients were included, with median age of 59 years; 74.8% were male. The stomach (30.0%) was the most common tumor location. Active bleeding was evident endoscopically in 47.3% of patients. Most patients (77.3%) did not receive endoscopic treatment. Of the patients who received endoscopic treatment, 57.7% had hemostasis. No endoscopy-related adverse events were recorded. Endoscopic treatment was associated with hemostasis (P < 0.001), but not decreased recurrent bleeding or mortality. Absence of active bleeding on endoscopy, stable hemodynamic status at presentation, lower cancer stage, and surgical intervention were associated with improved survival. CONCLUSIONS: This study indicates that endoscopy is a safe diagnostic tool in this patient population; while endoscopic treatments may help achieve hemostasis, it may not decrease the risk of recurrent bleeding or improve survival.

Advanced Endoscopic Resection Techniques: Endoscopic Submucosal Dissection and Endoscopic Full-Thickness Resection.

Endoscopic resection is first-line therapy in the management of superficial neoplasms throughout the gastrointestinal tract, as well as an increasingly viable therapeutic alternative in the resection of selected small deep lesions throughout the upper and lower gastrointestinal tract. The mainstay of therapy has traditionally been endoscopic snare polypectomy and endoscopic mucosal resection. However, recent innovative advancements in therapeutic endoscopy have provided for the ability to resect large superficial lesions and selected subepithelial lesions in en bloc and margin-negative fashion. In this review, we discuss the current state of the art in advanced endoscopic resection techniques including endoscopic submucosal dissection and endoscopic full-thickness resection.

Efficacy of uncovered colonic stents for extrinsic versus intrinsic malignant large bowel obstruction.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 < .001)]. Subsequent intervention was required more frequently [44% vs 35%; p = .23] and earlier [median 9 vs 132 days; p < .001] in the ECM group. Median overall survival in the ECM group was 92 vs 167 days. Among predictive variables analyzed, the ECM group had a higher frequency of peritoneal metastasis (87% vs 32%; p < .001), multifocal strictures with requirement for multiple stents (20% vs 6%; p = .002), sharp angulated strictures (39% vs 25%; p = .04) , and radiation therapy (21% vs 10%; p = .02). CONCLUSIONS: Colonic SEMS for ECM is associated with lower technical and clinical success with earlier intervention rates compared with ICM. Our findings can be used to better inform patients and referring providers as well as guide new stent design to enhance efficacy in this population.

Development and clinical outcomes of an endoscopic submucosal dissection fellowship program: early united states experience.

BACKGROUND/AIMS: Adoption of endoscopic submucosal dissection (ESD) in the USA is challenging due to limited training opportunities. We describe the development of an ESD fellowship program in the USA and evaluate outcomes of ESD performed during this experience. METHODS: A 1-year ESD fellowship was implemented under close supervision from a recognized ESD expert. The curriculum was tailored to the trainee based on their background and prior endoscopic training. Under the expert's discretion, the trainee started by assisting cases and was gradually allowed to begin performing portions of ESD, with increasing difficulty as determined by technical progress, until complete procedures could be performed. Technical characteristics, outcomes, and adverse events were recorded. RESULTS: A total of 72 consecutive ESD cases were performed during the training period, in which the trainee assisted/observed 19 cases, partially performed 18 cases, and mainly performed 26 cases. Mean lesion diameter was 44.5 mm, with 79.2% colorectal cases. The trainee more frequently performed procedures with lower degree of fibrosis (p = 0.016). En bloc, complete, and curative resection was achieved in 84.7, 81.2, and 76.8% of cases, with no significant differences in resection outcomes or adverse events from trainee involvement. CONCLUSIONS: ESD can be safely and effectively taught within a 1-year advanced endoscopy fellowship. This was possible in the USA, even with limited gastric lesions, due to a progression focusing on easier portions of complex ESD procedures and advancing as technical progress allowed. Importantly, there was no increase in adverse event rate with trainee involvement in complex ESD cases.

Clinical features of pseudocirrhosis in metastatic breast cancer.

PURPOSE: Pseudocirrhosis has been demonstrated to mimic cirrhosis radiographically, but studies evaluating the pathophysiology and clinical features are lacking. To better understand the incidence, risk factors, clinical course, and etiology of pseudocirrhosis, we performed a retrospective analysis of consecutively treated patients with metastatic breast cancer (MBC). METHODS: Of 374 patients treated for MBC from 2006 to 2012, 199 had imaging available for review. One radiologist evaluated computed tomography scans for evidence of pseudocirrhosis. Features of groups with and without pseudocirrhosis were compared by Kaplan-Meier product-limit survival estimates and log-rank tests. Wilcoxon Rank-Sum testing evaluated if patients more heavily treated were more likely to develop pseudocirrhosis. Univariate and multivariate Cox proportional hazard models investigated factors associated with mortality. RESULTS: Pseudocirrhosis developed in 37 of 199 patients (19%). Of the patients with liver metastases, 55% developed pseudocirrhosis. Liver metastases were demonstrated in 100% of patients with pseudocirrhosis. Survival in the subset with liver metastases favored those without pseudocirrhosis, 189 versus 69 months (p = 0.01). The number of systemic regimens received were higher in patients with pseudocirrhosis (p = 0.01). Ascites was demonstrated in 68%, portal hypertension in 11%, and splenomegaly in 8% of patients with pseudocirrhosis. CONCLUSIONS: Pseudocirrhosis does not occur in the absence of liver metastases, can manifest as hepatic decompensation, and appears to be associated with poorer survival amongst patients with hepatic metastases. Higher cumulative exposure to systemic therapy may be causative, instead of the previously held belief of pseudocirrhosis as an adverse effect of a particular systemic agent/class.

Suture pulley countertraction method reduces procedure time and technical demand of endoscopic submucosal dissection among novice endoscopists learning endoscopic submucosal dissection: a prospective randomized ex vivo study.

BACKGROUND AND AIMS: The lack of reliable countertraction in endoscopic submucosal dissection (ESD) contributes to its technical demand and increased procedure time. We aimed to prospectively evaluate the efficacy of the suture pulley countertraction method in endoscopists new to both suturing and ESD. METHODS: Two 30-mm circular lesions were created in an ex vivo porcine stomach model. Endoscopists considered novices for both endoscopic suturing and ESD were randomized to either traditional or suture pulley ESD first and performed ESD using each technique. Procedure time was recorded including time of circumferential incision, suture pulley placement, and submucosal dissection. After completion of each ESD, participants graded the difficulty of the procedure using the National Aeronautical and Space Administration (NASA) Task Load Index. RESULTS: Thirteen participants (8 fellows, 5 attendings) completed the study using both methods. Mean total procedure time was shorter using suture pulley ESD compared with traditional ESD (26.7 ± 7.3 vs 59.4 ± 20.4 minutes, P < .001). The suture pulley required a mean 6.2 ± 2.1 minutes to place. Submucosal dissection time was shorter using suture pulley ESD compared with traditional ESD (8.4 ± 2.9 vs 47.2 ± 16.3 minutes, P < .001). All 7 individual indices and total score on the NASA Task Load Index were significantly improved using the suture pulley ESD method (P < .001). CONCLUSIONS: The suture pulley countertraction method significantly decreases procedure time and technical demand of ESD among endoscopists at all skill levels who are new to ESD. The results of this study have potential implications for ESD training in the United States.

EUS-guided gastroenterostomy versus enteral stent placement for palliation of malignant gastric outlet obstruction.

BACKGROUND: EUS-guided gastroenterostomy (EUS-GE) is a novel procedure for palliation of malignant gastric outlet obstruction (GOO); however, data comparing EUS-GE to enteral stent placement are limited. We aimed to compare clinical outcomes between EUS-GE and enteral stent placement in the palliation of malignant GOO. METHODS: Retrospective analysis of a prospectively collected database on patients who underwent EUS-GE or enteral stent placement for palliation of malignant GOO from 2014 to 2017 was conducted. Primary outcome was the rate of stent failure requiring repeat intervention. Secondary outcomes included technical and clinical success, time to repeat intervention, length of hospital stay, and adverse events. RESULTS: A total of 100 consecutive patients (mean age 65.9 ± 11.9 years, 44.0% female) were identified, of which 78 underwent enteral stent placement, and 22 underwent EUS-GE. Rate of stent failure requiring repeat intervention was higher in the enteral stent group than the EUS-GE group (32.0% vs. 8.3%, p = 0.021). Technical success was achieved in 100% in both groups. Higher initial clinical success was attained in the EUS-GE group than the enteral stent group (95.8% vs. 76.3%, p = 0.042). Mean length of hospital stay following stent placement was similar between groups (p = 0.821). The enteral stent group trended towards increased adverse events (40.2% vs. 20.8%, p = 0.098). Kaplan-Meier analysis showed decreased stent function in the enteral stent group (p = 0.013). CONCLUSION: Compared to enteral stent placement, EUS-GE has a higher rate of initial clinical success and lower rate of stent failure requiring repeat intervention. EUS-GE may be offered for selected patients with malignant GOO in centers with extensive experience.

Predicting outcomes in colorectal endoscopic submucosal dissection: a United States experience.

OBJECTIVE: Endoscopic submucosal dissection (ESD) allows for en bloc resection of superficial gastrointestinal neoplasms; however, US experience has been limited. We aimed to evaluate our clinical outcomes in colorectal ESD. DESIGN: This prospective study included consecutive patients undergoing colorectal ESD at a major US center. Demographics, lesion and technical characteristics, outcomes, adverse events, and pathological diagnoses were recorded. Factors affecting resection outcomes and procedure time were evaluated. RESULTS: 77 patients who underwent colorectal ESD were analyzed. Mean colorectal lesion diameter was 49.4 mm. Mean procedure time was 104.7 min, and 97.4% of patients were discharged home on the same day. En bloc, complete, and curative resection was achieved in 97.4%, 97.4%, and 93.5% of colorectal ESD cases. Microperforation and delayed bleeding rates were 1.3% and 3.9%. On univariable analysis, the presence of tattoo adversely affected en bloc resection (p = 0.002), complete resection (p = 0.002), and curative resection (p = 0.008). Prior EMR attempts adversely affected en bloc resection (p = 0.028), complete resection (p = 0.028), and procedure time (p = 0.008). On multivariable analysis, the presence of tattoo predicted failure to achieve curative resection (OR 0.13; 95% CI 0.02-0.98; p = 0.048). Lesion size > 50 mm (OR 3.89; 95% CI 1.13-13.41; p = 0.031), presence of tattoo (OR 9.38; 95% CI 1.05-83.83; p = 0.045), and prior EMR attempts (OR 7.13; 95% CI 1.76-28.90; p = 0.006) predicted procedure time ≥ 90 min. A scoring system was created to predict prolonged ESD procedure time and was externally validated, with AUC 0.78 (95% CI 0.73-0.83). CONCLUSION: This study demonstrates the effects of multiple risk factors on resection outcomes and procedure time in colorectal ESD. Tattoo placement and attempted EMR should be avoided for lesions being considered for ESD.

Plastic biliary stent patency in patients with locally advanced pancreatic adenocarcinoma receiving downstaging chemotherapy.

BACKGROUND: Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy. OBJECTIVE: To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma. DESIGN: Retrospective, multicenter cohort study. SETTING: Three tertiary academic referral centers. PATIENTS: A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013. INTERVENTIONS: Placement of 10F or larger plastic biliary stents. MAIN OUTCOME MEASUREMENTS: Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates. RESULTS: A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days). LIMITATIONS: Retrospective study. CONCLUSIONS: Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

The changing role of beta-blocker therapy in patients with cirrhosis.

Cirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis.