Interventional gastroenterology in oncology.

Cancer is one of the foremost health problems worldwide and is among the leading causes of death in the United States. Gastrointestinal tract cancers account for almost one third of the cancer-related mortality globally, making it one of the deadliest groups of cancers. Early diagnosis and prompt management are key to preventing cancer-related morbidity and mortality. With advancements in technology and endoscopic techniques, endoscopy has become the core in diagnosis and management of gastrointestinal tract cancers. In this extensive review, the authors discuss the role endoscopy plays in early detection, diagnosis, and management of esophageal, gastric, colorectal, pancreatic, ampullary, biliary tract, and small intestinal cancers.

Endoscopic Retrograde Appendicitis Therapy: Is it Really a Need of the Hour?

ABSTRACT: Endoscopic retrograde appendicitis therapy (ERAT) has emerged as a promising, non-invasive treatment for acute uncomplicated appendicitis (AUA). ERAT involves cannulation, appendicography, appendiceal stone extraction, appendiceal lumen irrigation, and stent deployment. Recent randomized trials comparing ERAT to laparoscopic appendectomy (LA) have provided promising results in terms of safety and efficacy of ERAT. If the current trajectory of research and development is maintained, ERAT will likely become a strong contender for the standard of care for AUA. Standardized training and credentialing for ERAT, akin to procedures established for endoscopic retrograde cholangiopancreatography, will be pivotal to global adoption of this modality.

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.

The incremental yield of adenoma detection with I-Scan versus high-definition white light colonoscopy-a systematic review and meta-analysis of randomized studies.

INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.

Self-expanding metal stents for the treatment of malignant colon obstruction from extra-colonic malignancy versus intra-colonic malignancy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The relative utility of self-expanding metal stent (SEMS) insertion for malignant colon obstruction (MCO) due to extra-colonic malignancy (ECM) versus intra-colonic malignancy (ICM) is understudied. METHODS: A systematic search was done from inception-April 2021 to identify reports of safety and efficacy of SEMS insertion for the treatment of MCO-ECM versus MCO-ICM. A meta-analysis of proportions, comparative meta-analysis to compute relative risks (RR), and mean differences (MD) was performed. Subgroup analyses and influence analyses were conducted. The certainty in estimates of effect(s) was assessed using the GRADE approach. RESULTS: Eight non-randomized studies were identified; 46% (39-53%) and 63% (59-67%) of patients in the ECM and ICM groups were male. Most obstructions were in the rectosigmoid colon in both ECM and ICM groups. SEMS insertion in MCO-ECM was associated with an increased risk of technical failure compared to MCO-ICM (RR 2.92; 1.13-7.54; Certainty: Very Low). Risk of clinical failure of SEMS was higher in MCO-ECM compared to MCO-ICM (RR 2.88; 1.58-2.52; Certainty: Very Low). The risk of clinical failure remained significant throughout the influence analysis, as well as on subgroup analysis. There was no significant difference in the risk of adverse events or luminal perforation with SEMS insertion among patients with MCO-ECM and MCO-ICM. On influence analysis, removal of one study unveiled a significant increase in the risk of luminal perforation in MCO-ECM (RR 3.22; 1.44-7.19; p = 0.004). CONCLUSION: SEMS for MCO-ECM may have a technical success rate comparable to or questionably worse than MCO-ICM, with low certainty in estimate of effects. SEMS deployment in MCO-ECM carries a higher risk of clinical failure, with a questionably higher risk of luminal perforation.

Cost-effectiveness analysis of optimal diagnostic strategy for patients with symptomatic cholelithiasis with intermediate probability for choledocholithiasis.

BACKGROUND AND AIMS: EUS, MRCP, and intraoperative cholangiogram (IOC) are the recommended diagnostic modalities for patients with intermediate probability for choledocholithiasis (IPC). The relative cost-effectiveness of these modalities in patients with cholelithiasis and IPC is understudied. METHODS: We developed a decision tree for diagnosing IPC (base-case probability, 50%; range, 10%-70%); patients with a positive test were modeled to undergo therapeutic ERCP. The strategies tested were laparoscopic cholecystectomy with IOC (LC-IOC), MRCP, single-session EUS + ERCP, and separate-session EUS + ERCP. Costs and probabilities were extracted from the published literature. Effectiveness was assessed by assigning utility scores to health states, average proportion of true-positive diagnosis of IPC, and the mean length of stay (LOS) per strategy. Cost-effectiveness was assessed by extrapolating a net-monetary benefit (NMB) and average cost per true-positive diagnosis. RESULTS: LC-IOC was the most cost-effective strategy to diagnose IPC (base-case probability of 50%) among patients with cholelithiasis in health state-based effectiveness analysis (NMB of $34,612), diagnostic test accuracy-based effectiveness analysis (average cost of $13,260 per true-positive diagnosis), and LOS-based effectiveness analysis (mean LOS of 4.13) compared with strategies 2 (MRCP), 3 (single-session EUS + ERCP), and 4 (separate-session EUS + ERCP). These findings were robust on deterministic and probabilistic sensitivity analyses. CONCLUSIONS: For patients with cholelithiasis with IPC, LC-IOC is a cost-effective approach that should limit preoperative testing and may shorten hospital LOS. Our findings may be used to design institutional and organizational management protocols.

Advancing flexible endoscopy to natural orifice transluminal endoscopic surgery.

PURPOSE OF REVIEW: This review is an update on the recent advancements and clinical applications of flexible endoscopy in the context of natural orifice translumenal endoscopic surgery (NOTES). We focus on recent developments in gastrointestinal luminal and transluminal NOTES. RECENT FINDINGS: NOTES has evolved from a hybrid approach utilizing a laparoscopic assistant to pure NOTES without laparoscopic assistance. Current experimental and clinical studies focus on the implementation of new minimally invasive approaches as well as on the training in the use of these procedures. In recent years, flexible endoscopic-NOTES and endoluminal surgery have increasingly reported favorable results in preclinical and experimental settings using flexible endoscopic cholecystectomy, cholecystolithotomy, and appendectomy. Additionally, flexible endoscopic lymphadenectomy and thyroidectomy are among the new interventions that are opening new frontiers for endoscopists to explore. SUMMARY: Flexible endoscopy has paved way to new frontiers for endoscopists and surgeons. As the armamentarium of interventional endoscopy increases and the ability of endoscopists to perform advanced interventions safely fosters an inevitable step forward that will involve the integration of new technology with innovative thinking.

Immune-checkpoint inhibitors induced diarrhea and colitis: a review of incidence, pathogenesis and management.

PURPOSE OF REVIEW: Diarrhea and colitis are among the most commonly encountered immune-mediated adverse events among patients receiving antiprogrammed cell death protein/ligand-1 (PD-1/L1) as well as anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies. With growing indications and widespread use of immune checkpoint inhibitors, it is imperative to summarize the current body of evidence concerning the incidence, pathogenesis, risk factors, diagnostic challenges, and treatment options currently available for the management of immune-mediated diarrhea and colitis. Additionally, with emerging evidence analyzing the resumption of immune checkpoint inhibitors, it is pivotal to summarize our current understanding and future challenges. RECENT FINDINGS: Immune-mediated diarrhea and colitis can potentially be a viable surrogate marker for improved survival as it is validated further in large-scale studies. Early endoscopic evaluation can aid in the identification of patients at risk of developing steroid refractory immune-mediated colitis, and hence can be chosen to receive early add-on therapy with infliximab, vedolizumab or fecal microbiota transplantation, an emerging treatment option for immune-mediated diarrhea and colitis. Resuming immune checkpoint inhibitors carries a manageable risk of recurrent diarrhea and colitis, with most cases being mild and effectively managed with immunosuppressive therapy. SUMMARY: As our understanding of immune-mediated diarrhea and colitis grows, it is likely that this clinicopathologic entity will represent more than just an adverse event. With a growing number of treatment options, the management algorithms for immune-mediated diarrhea/colitis are likely to evolve in the future.

Neutropenic Enterocolitis: Clinical Features and Outcomes.

BACKGROUND: Patients undergoing chemotherapy are at risk for mucosal injury and neutropenia, which facilitate colonic mucosal invasion by the bowel flora and subsequent neutropenic enterocolitis, which has a poor prognosis. OBJECTIVE: This study aimed to assess the clinical features and outcomes of neutropenic enterocolitis in patients at a comprehensive cancer center. DESIGN: This is a retrospective cohort study. SETTING: The study was conducted at the University of Texas MD Anderson Cancer Center. PATIENTS: Neutropenic enterocolitis was defined by the presence of an absolute neutrophil count <1000/mm, compatible abdominal symptoms, and either mucosal thickening on abdominal imaging or mucosal injury on colon biopsy. Patients who had been diagnosed between 2010 and 2018 were included. MAIN OUTCOMES: Complication and survival rates were analyzed using logistic regression and Cox regression analyses, respectively. RESULTS: Of the 49,244 patients who had neutropenia during the study period, 134 (2.7%) were included. The median time from neutropenia onset to neutropenic enterocolitis was 2 days (interquartile range, 1-10 days). Neutropenic enterocolitis symptoms lasted for a median of 11 days (interquartile range, 6-22 days). Most patients received antibiotics (88%) and granulocyte colony-stimulating factor (68%). Complications included sepsis (11%), colonic perforation (2%), pneumatosis intestinalis (2%), and abscess formation (2%). The risks associated with complications included immunosuppressive therapy use within 1 month before neutropenic enterocolitis onset (OR, 3.92; 95% CI, 1.04-14.76) and delayed imaging (OR, 1.10; 95% CI, 1.03-1.17). Older age, severe neutropenia, prolonged neutropenia before and after neutropenic enterocolitis diagnosis, and other concomitant systemic infections were associated with lower survival rates. LIMITATIONS: The performance of this study at a single center and its retrospective nature are limitations of the study. CONCLUSION: The prompt diagnosis and management of neutropenic enterocolitis are critical to prevent complications. The use of granulocyte colony-stimulating factor can be beneficial to shorten the duration of neutropenia. See Video Abstract at http://links.lww.com/DCR/B116. ENTEROCOLITIS NEUTROPÉNICA: CARACTERÍSTICAS CLÍNICAS Y RESULTADOS: Los pacientes sometidos a quimioterapia, están en riesgo de lesión de la mucosa y neutropenia, lo que facilita la invasión de la mucosa colónica por la flora intestinal y la subsecuente enterocolitis neutropénica, con un mal pronóstico.Evaluar las características clínicas y los resultados de la enterocolitis neutropénica de pacientes en un centro integral de cáncer.Estudio de cohorte retrospectivo.El estudio se realizó en el MD Anderson Cancer Center de la Universidad de Texas.Se definió la enterocolitis neutropénica, como la presencia de un recuento absoluto de neutrófilos <1000 / mm3, con síntomas compatibles abdominales y engrosamiento de la mucosa en imagen abdominal o lesión de la mucosa en biopsia de colon. Se incluyeron pacientes diagnosticados entre 2010 y 2018.Se analizaron las tasas de complicaciones y supervivencia mediante análisis de regresión logística y regresión de Cox.De 49,244 pacientes que tuvieron neutropenia durante el período de estudio, 134 (2.7%) fueron incluidos. La media del tiempo desde el inicio de la neutropenia hasta la enterocolitis neutropénica, fue de 2 días (RIC, 1-10 días). Los síntomas de enterocolitis neutropénica duraron una media de 11 días (RIC, 6-22 días). La mayoría de los pacientes recibieron antibióticos (88%) y factor estimulante de colonias de granulocitos (68%). Las complicaciones incluyeron sepsis (11%), perforación colónica (2%), neumatosis intestinal (2%) y formación de abscesos (2%). Los riesgos asociados con las complicaciones incluyeron, uso de terapia inmunosupresora dentro de 1 mes antes del inicio de la enterocolitis neutropénica (razón de probabilidades 3.92; intervalo de confianza del 95% 1.04-14.76) y demora en la obtención de imágenes (razón de probabilidades 1.10; intervalo de confianza del 95% 1.03-1.17), edad avanzada, neutropenia grave, neutropenia prolongada antes y después del diagnóstico de enterocolitis neutropénica y de otras infecciones sistémicas concomitantes, se asociaron con bajas tasas de supervivencia.Centro único y estudio retrospectivo.El rápidodiagnóstico y manejo de la enterocolitis neutropénica, es crítico para prevenir complicaciones. El uso del factor estimulante de colonias de granulocitos puede ser beneficioso para acortar la duración de la neutropenia. Consulte Video Resumen en http://links.lww.com/DCR/B116.

Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma.

BACKGROUND: Gastrointestinal (GI) immune-related adverse events (irAEs) commonly limit immune checkpoint inhibitors' (ICIs) treatment, which is very effective for metastatic melanoma. The independent impact of GI-irAEs on patients' survival is not well studied. We aimed to assess the impact of GI-irAEs on survival rates of patients with metastatic melanoma using multivariate model. METHODS: This is a retrospective study of patients with metastatic melanoma who developed GI-irAEs from 1/2010 through 4/2018. A number of randomized patients who did not have GI-irAEs were included as controls. Kaplan-Meier curves and log-rank test were used to estimate unadjusted survival durations. The Cox proportional hazards model was used to evaluate survival predictors; irAEs were included as time-dependent variables. RESULTS: A total of 346 patients were included, 173 patients had GI-irAEs; 124 (72%) received immunosuppression. In multivariate Cox regression, ECOG 2-3 (HR 2.57, 95%CI 1.44-4.57; P < 0.01), LDH ≥ 618 IU/L (HR 2.20, 95% CI 1.47-3.29; P < 0.01), stage M1c (HR 2.21, 95% CI 1.35-3.60; P < 0.01) were associated with worse OS rates. Any grade GI-irAEs (HR 0.53, 95% CI 0.36-0.78; P < 0.01) was associated with improved OS rates. Immunosuppressive treatment did not affect OS (P = 0.15). High-grade diarrhea was associated with improved OS (P = 0.04). Patients who developed GI-irAEs had longer PFS durations on Cox model (HR 0.56, 95% CI 0.41-0.76; P < 0.01). CONCLUSION: GI-irAEs are associated with improved OS and PFS in patients with metastatic melanoma. Furthermore, higher grades of diarrhea are associated with even better patients' OS rates.

Safety and efficacy of metal stents for malignant colonic obstruction in patients treated with bevacizumab.

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.

Cerebral Radiation Necrosis: Incidence, Pathogenesis, Diagnostic Challenges, and Future Opportunities.

PURPOSE OF REVIEW: Cerebral radiation necrosis (CRN) is a major dose-limiting adverse event of radiotherapy. The incidence rate of RN varies with the radiotherapy modality, total dose, dose fractionation, and the nature of the lesion being targeted. In addition to these known and controllable features, there is a stochastic component to the occurrence of CRN-the genetic profile of the host or the lesion and their role in the development of CRN. RECENT FINDINGS: Recent studies provide some insight into the genetic mechanisms underlying radiation-induced brain injury. In addition to these incompletely understood host factors, the diagnostic criteria for CRN using structural and functional imaging are also not clear, though multiple structural and functional imaging modalities exist, a combination of which may prove to be the ideal diagnostic imaging approach. As the utilization of novel molecular therapies and immunotherapy increases, the incidence of CNR is expected to increase and its diagnosis will become more challenging. Tissue biopsies can be insensitive and suffer from sampling biases and procedural risks. Liquid biopsies represent a promising, accurate, and non-invasive diagnostic strategy, though this modality is currently in its infancy. A better understanding of the pathogenesis of CRN will expand and optimize the diagnosis and management of CRN by better utilizing existing treatment options including bevacizumab, pentoxifylline, hyperbaric oxygen therapy, and laser interstitial thermal therapy.

Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.

Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.