Endoscopic Submucosal Dissection in North America: A Large Prospective Multicenter Study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) in Asia has been shown to be superior to endoscopic mucosal resection (EMR) and surgery for the management of selected early gastrointestinal cancers. We aimed to evaluate technical outcomes of ESD in North America. METHODS: We conducted a multicenter prospective study on ESD across 10 centers in the United States and Canada between April 2016 and April 2020. End points included rates of en bloc resection, R0 resection, curative resection, adverse events, factors associated with failed resection, and recurrence post-R0 resection. RESULTS: Six hundred and ninety-two patients (median age, 66 years; 57.8% were men) underwent ESD (median lesion size, 40 mm; interquartile range, 25-52 mm) for lesions in the esophagus (n = 181), stomach (n = 101), duodenum (n = 11), colon (n = 211) and rectum (n = 188). En bloc, R0, and curative resection rates were 91.5%, 84.2%, and 78.3%, respectively. Bleeding and perforation were reported in 2.3% and 2.9% of the cases, respectively. Only 1 patient (0.14%) required surgery for adverse events. On multivariable analysis, severe submucosal fibrosis was associated with failed en bloc, R0, and curative resection and higher risk for adverse events. Overall recurrence was 5.8% (31 of 532) at a mean follow-up of 13.3 months (range, 1-60 months). CONCLUSIONS: In this large multicenter prospective North American experience, we demonstrate that ESD can be performed safely, effectively, and is associated with a low recurrence rate. The technical resection outcomes achieved in this study are in line with the current established consensus quality parameters and further support the implementation of ESD for the treatment of select gastrointestinal neoplasms; ClinicalTrials.gov, Number: NCT02989818.

Effect of endoscopic submucosal dissection on histologic diagnosis in Barrett's esophagus visible neoplasia.

BACKGROUND AND AIMS: Data are limited on the role of endoscopic submucosal dissection (ESD) as a potential diagnostic and staging tool in Barrett's esophagus (BE) neoplasia. We aimed to evaluate the frequency and factors associated with change of histologic diagnosis by ESD compared with pre-ESD histology. METHODS: This was a multicenter, prospective cohort study of patients who underwent ESD for BE visible neoplasia. A change in histologic diagnosis was defined as "upstaged" or "downstaged" if the ESD specimen had a higher or lower degree, respectively, of dysplasia or neoplasia when compared with pre-ESD specimens. RESULTS: Two hundred five patients (median age, 69 years; 81% men) with BE visible neoplasia underwent ESD from 2016 to 2021. Baseline histology was obtained using forceps (n = 182) or EMR (n = 23). ESD changed the histologic diagnosis in 55.1% of cases (113/205), of which 68.1% were upstaged and 31.9% downstaged. The frequency of change in diagnosis after ESD was similar whether baseline histology was obtained using forceps (55.5%) or EMR (52.2%) (P = .83). In aggregate, 23.9% of cases (49/205) were upstaged to invasive cancer on ESD histopathology. On multivariate analysis, lesions in the distal esophagus and gastroesophageal junction (odds ratio, 2.1; 95 confidence interval, 1.1-3.9; P = .02) and prior radiofrequency ablation (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = .02) were predictors of change in histologic diagnosis. CONCLUSIONS: ESD led to a change of diagnosis in more than half of patients with BE visible neoplasia. Selective ESD can serve as a potential diagnostic and staging tool, particularly in those with suspected invasive disease. (Clinical trial registration number: NCT02989818.).

Per-Oral Endoscopic Myotomy for Esophagogastric Junction Outflow Obstruction: A Multicenter Pilot Study.

Esophagogastric junction outflow obstruction (EGJOO) is a rare but increasingly recognized diagnosis as described by The Chicago Classification of Esophageal Motility Disorders version 3.0 (version 3.0).1 On high-resolution manometry (HRM), EGJOO is characterized by increased integrated relaxation pressure (IRP) of the lower esophageal sphincter (LES), yet with some preserved esophageal peristalsis.2-4 Little consensus exists on the preferred therapeutic approach.3 Although conceptually per-oral endoscopic myotomy (POEM) should address the measurable dysfunction in the LES, few data exist to support this.5 Thus, we aimed to evaluate the safety and efficacy of POEM for the treatment of symptomatic EGJOO.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Evaluating learning curves and competence in colorectal EMR among advanced endoscopy fellows: a pilot multicenter prospective trial using cumulative sum analysis.

BACKGROUND AND AIMS: Data on colorectal EMR (C-EMR) training are lacking. We aimed to evaluate C-EMR training among advanced endoscopy fellows (AEFs) by using a standardized assessment tool (STAT). METHODS: This multicenter prospective study used a STAT to grade AEF training in C-EMR during their 12-month fellowship. Cumulative sum analysis was used to establish learning curves and competence for cognitive and technical components of C-EMR and overall performance. Sensitivity analysis was performed by varying failure rates. AEFs completed a self-assessment questionnaire to assess their comfort level with performing C-EMR at the completion of their fellowship. RESULTS: Six AEFs (189 C-EMRs; mean per AEF, 31.5 ± 18.5) were included. Mean polyp size was 24.3 ± 12.6 mm, and mean procedure time was 22.6 ± 16.1 minutes. Learning curve analyses revealed that less than 50% of AEFs achieved competence for key cognitive and technical C-EMR endpoints. All 6 AEFs reported feeling comfortable performing C-EMR independently at the end of their training, although only 2 of them achieved competence in their overall performance. The minimum threshold to achieve competence in these 2 AEFs was 25 C-EMRs. CONCLUSIONS: A relatively low proportion of AEFs achieved competence on key cognitive and technical aspects of C-EMR during their 12-month fellowship. The relatively low number of C-EMRs performed by AEFs may be insufficient to achieve competence, in spite of their self-reported readiness for independent practice. These pilot data serve as an initial framework for competence threshold, and suggest the need for validated tools for formal C-EMR training assessment.

Management of patients after failed peroral endoscopic myotomy: a multicenter study.

BACKGROUND: Although peroral endoscopic myotomy (POEM) is highly effective for the management of achalasia, clinical failures may occur. The optimal management of patients who fail POEM is not well known. This study aimed to compare the outcomes of different management strategies in patients who had failed POEM. METHODS: This was an international multicenter retrospective study at 16 tertiary centers between January 2012 and November 2019. All patients who underwent POEM and experienced persistent or recurrent symptoms (Eckardt score > 3) were included. The primary outcome was to compare the rates of clinical success (Eckardt score ≤ 3) between different management strategies. RESULTS : 99 patients (50 men [50.5 %]; mean age 51.4 [standard deviation (SD) 16.2]) experienced clinical failure during the study period, with a mean (SD) Eckardt score of 5.4 (0.3). A total of 29 patients (32.2 %) were managed conservatively and 70 (71 %) underwent retreatment (repeat POEM 33 [33 %], pneumatic dilation 30 [30 %], and laparoscopic Heller myotomy (LHM) 7 [7.1 %]). During a median follow-up of 10 (interquartile range 3 - 20) months, clinical success was highest in patients who underwent repeat POEM (25 /33 [76 %]; mean [SD] Eckardt score 2.1 [2.1]), followed by pneumatic dilation (18/30 [60 %]; Eckardt score 2.8 [2.3]), and LHM (2/7 [29 %]; Eckardt score 4 [1.8]; P = 0.12). A total of 11 patients in the conservative group (37.9 %; mean Eckardt score 4 [1.8]) achieved clinical success. CONCLUSION : This study comprehensively assessed an international cohort of patients who underwent management of failed POEM. Repeat POEM and pneumatic dilation achieved acceptable clinical success, with excellent safety profiles.

Discrepancy between self-reported and actual colonoscopy polypectomy practices for the removal of small polyps.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP) is associated with higher rates of complete resection compared with cold biopsy forceps (CBF) for the removal of small polyps (4-9 mm). This study aimed to evaluate self-reported polypectomy preferences and actual practice patterns among endoscopists at an academic center and to identify factors associated with the use of CSP for small polyps. METHODS: In phase A, endoscopists completed a survey evaluating preferences for polypectomy techniques. In phase B, we performed a retrospective analysis of all consecutive colonoscopies with polypectomy (January 2016 to September 2018). Uni- and multivariate analysis were performed to identify factors associated with CSP for small polyps. RESULTS: Nineteen of 26 (73%) endoscopists completed the survey (phase A); 3 (15.8%) were interventional endoscopists. Most respondents indicated that they use CSP (89.5%) for small polyps and identified no reasons for choosing CBF over CSP (73.7%). In phase B, we identified 1118 colonoscopies with 2625 polypectomies for polyps ≤9 mm. Most diminutive polyps (≤3 mm) were removed with CBF (819 of 912; 90%). CBF (46.2%) was also preferentially used for removal of small polyps (n = 1713), followed by hot snare polypectomy (27.2%), and CSP (26.6%). On multivariate analysis, interventional endoscopists were associated with a higher likelihood of using CSP for small polyps (odds ratio, 1.38; 95% confidence interval, 1.07-1.79; P = .01). CONCLUSIONS: Significant discrepancy exists between self-reported preferences and actual polypectomy practices. CBF is still preferentially used over CSP for the removal of polyps sized 4-9 mm; further strategies are needed to monitor and implement adequate polypectomy techniques.

Life after per-oral endoscopic myotomy: long-term outcomes of quality of life and their association with Eckardt scores.

BACKGROUND AND AIMS: The clinical efficacy of per-oral endoscopic myotomy (POEM) has been commonly established by reduction in the Eckardt score (<3) after the procedure. However, achalasia can lead to significant impairment in the patient's quality of life that may go beyond the 4 classic achalasia symptoms as measured by the Eckardt score. The aims of our study were to evaluate the effect of POEM on short-term and long-term health-related quality of life (HRQOL) and to assess the association between HRQOL and Eckardt scores. METHODS: Single-center, prospective, cohort study of consecutive POEMs during a 3-year period. Eckardt and HRQOL scores as measured by the short-form survey questionnaire (SF-36) were obtained at baseline and at various intervals after POEM. Comparison of the mean scores was described by using univariate linear regression. The association between Eckardt scores and HRQOL were calculated by using a linear, mixed-model analysis. RESULTS: POEM was performed in 143 consecutive patients (54% male; mean ± standard deviation [SD] age, 56.9 ± 17.9 years). At long-term follow-up (mean 16.4 months, range 12-40), both the HRQOL baseline mental and physical component scores improved significantly from 61.5 ± 2.2 to 71.2 ± 3.6; (P < .021) and from 55.8 ± 2.2 to 63.6 ± 3.3; (P = < .034), respectively. Mixed-model analysis showed a significant association between Eckardt and all HRQOL scores (P < .001). CONCLUSION: POEM improved all dimensions of HRQOL as measured by the SF-36 survey at both short-term and long-term follow-up. A strong association was seen between Eckardt scores and all HRQOL domains. Further studies with the use of disease-specific HRQOL instruments are warranted. (Clinical trial registration number: NCT01832779.).

Efficacy and Safety of Peroral Endoscopic Myotomy for Treatment of Achalasia After Failed Heller Myotomy.

BACKGROUND & AIMS: In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. METHODS: We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non-HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. RESULTS: POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non-HM group (P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non-HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non-HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. CONCLUSIONS: POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups.

Comprehensive Analysis of Adverse Events Associated With Per Oral Endoscopic Myotomy in 1826 Patients: An International Multicenter Study.

OBJECTIVES: The safety of peroral endoscopic myotomy (POEM) is still debated since comprehensive analysis of adverse events (AEs) associated with the procedure in large multicenter cohort studies has not been performed. To study (1) the prevalence of AEs and (2) factors associated with occurrence of AEs in patients undergoing POEM. METHODS: Patients who underwent POEM at 12 tertiary-care centers between 2009 and 2015 were included in this case-control study. Cases were defined by the occurrence of any AE related to the POEM procedure. Control patients were selected for each AE case by matching for age, gender, and disease classification (achalasia type I and II vs. type III/spastic esophageal disorders). RESULTS: A total of 1,826 patients underwent POEM. Overall, 156 AEs occurred in 137 patients (7.5%). A total of 51 (2.8%) inadvertent mucosotomies occurred. Mild, moderate, and severe AEs had a frequency of 116 (6.4%), 31 (1.7%), and 9 (0.5%), respectively. Multivariate analysis demonstrated that sigmoid-type esophagus (odds ratio (OR) 2.28, P=0.05), endoscopist experience <20 cases (OR 1.98, P=0.04), use of a triangular tip knife (OR 3.22, P=0.05), and use of an electrosurgical current different than spray coagulation (OR 3.09, P=0.02) were significantly associated with the occurrence of AEs. CONCLUSIONS: This large study comprehensively assessed the safety of POEM and highly suggests POEM as a relatively safe procedure when performed by experts at tertiary centers with an overall 7.5% prevalence of AEs. Severe AEs are rare. Sigmoid-type esophagus, endoscopist experience, type of knife, and current used can be considered as predictive factors of AE occurrence.

Impact of Endotracheal Intubation on Interventional Endoscopy Unit Efficiency Metrics at a Tertiary Academic Medical Center.

OBJECTIVES: Measures for evaluating interventional endoscopy unit efficiency have not been adequately validated, especially in reference to the involvement of anesthesia services for endoscopy. Primary aim was to compare process measures/metrics of interventional endoscopy unit efficiency between intubated and non-intubated patients. Secondary aim was to assess variables associated with the need for endotracheal intubation. METHODS: The prospectively collected endoscopy unit metrics database at UF Health was reviewed for procedures performed in the interventional endoscopy unit for 6 months. Parameters included hospital-mandated metrics available from the database. RESULTS: A total of 1,421 patients underwent 1,635 interventional endoscopic procedures and 271/1,421 patients (19.1%) were intubated. There was no significant difference between intubated and non-intubated cohorts with respect to age, gender, BMI, ASA Score, Mallampati Score, or the Charlson Comorbidity Index. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were more frequently intubated than those undergoing non-ERCP procedures (41.3 vs. 12.4%, P<0.0001). Inpatients comprised 48.3% of all intubated patients, whereas only 29.2% of non-intubated patients were inpatients (P<0.0001). Most patients (159/271, 58.7%) were intubated per anesthesiologist preference. All process efficiency metrics were significantly prolonged in the intubated compared with the non-intubated patient cohort, except the time interval between successive procedures. Multivariate analysis revealed that patients with an anesthesiologist who had performed a greater number of total endoscopic sedations were less likely to be intubated than patients with an anesthesiologist who had performed fewer total procedures (P=0.0066). CONCLUSIONS: Endotracheal intubation negatively impacts efficiency metrics in an interventional endoscopy unit. Careful assessment for the need for intubation should be emphasized.

Single-Session Endoscopic Ultrasound-Directed Transgastric Intervention for a Fine Needle Biopsy of Pancreatic Head Mass Using Endoscopic Through-the-Scope Suturing in a Patient With Roux-en-Y Gastric Bypass Anatomy.

Endoscopic ultrasound (EUS) is a diagnostic tool used to examine pancreatic lesions. In patients who have undergone Roux-en-Y gastric bypass, lesions of the pancreatic head can be difficult to access because of altered foregut anatomy. To access the excluded stomach for better visualization of the pancreatic head, EUS-directed transgastric intervention can be used in a 2-step fashion. We present an interesting case of a 62-year-old woman who underwent a single-session modified EUS-directed transgastric intervention with a fine needle biopsy of a pancreatic head mass. A novel through-the-scope suturing system, the X-tack system (Apollo Endosurgery, Austin, TX), was used to allow for a successful single-session procedure.

The association between adverse cardiovascular outcomes in celiac disease and the role of inflammation: Retrospective analysis using the national inpatient sample.

Celiac disease (CD) is an immune-mediated disease with patients being prone to a proinflammatory state. With recent studies showing an association between adverse cardiovascular events in patients with CD, we aim to further elucidate this relationship. Furthermore, when risk-stratifying patients with cardiovascular disease (CVD), chronic inflammatory conditions such as CD are not included in these calculations. We conducted a retrospective analysis using the National Inpatient Sample database from 2016 to 2019 to investigate the relationship between CD and adverse cardiovascular events. Our secondary endpoints include examining patient demographics, underlying comorbidities, in-hospital mortality, and cost of hospitalization. In addition, we performed a subgroup analysis in the CD cohort to assess if concomitant iron deficiency anemia increased CVD. Our study aims to examine the association between atherosclerosis and inflammation and aims to be a stepping stone for future long-term randomized controlled trials for the incorporation into atherosclerotic CVD risk score stratification.

CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM).

Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013-2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8-11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.

Detection of SARS-CoV-2 in the gastrointestinal tract among patients with negative nasopharyngeal COVID-19 testing prior to endoscopy.

Background and study aims The clinical significance of SARS-CoV-2 RNA in the stool remains unclear. We aimed to determine whether SARS-CoV-2 is detected via real-time reverse transcriptase polymerase chain reaction (rRT-PCR) in the gastrointestinal tracts of patients scheduled for endoscopy and if the virus obtained from these clinical specimens could be isolated in culture. Patients and methods All patients underwent symptom screening and had negative nasopharyngeal testing for SARS-CoV-2 within 72 hours of their scheduled procedure. Study samples were collected via nasopharyngeal swab, rectal swab, and fluid from the upper gastrointestinal tract and/or colon based on their endoscopic procedure(s). Samples were tested for SARS-CoV-2 via rRT-PCR. SARS-CoV-2 positive specimens were isolated and cultured in Vero-E6 cells. Results 243 patients (mean age 63.1 years;54.3 % men) were enrolled from July 15, 2020 to September 2, 2020. SARS-CoV-2 testing was performed from 242 (99.6 %) nasopharyngeal, 243 (100 %) rectal, 183 (75.3 %) upper gastrointestinal tract and 73 (30 %) colon samples. SARS-CoV-2 RNA was detected in the nasopharynx and gastrointestinal specimens in one patient (0.4 %). After a 14-day incubation period, there was no evidence of virus growth in cells incubated with any of these specimens. Conclusions SARS-CoV-2 was rarely detected in the gastrointestinal tract of patients with negative nasopharyngeal testing prior to endoscopy. No live virus was detected by culture, further highlighting that presence of viral genome on its own is not sufficient proof of infectivity. PCR-based screening provides limited insight into virus infectivity and its results should be interpreted carefully as to avoid unnecessary delays in clinical care or inadvertent risk exposure.

Update on the diagnosis and management of exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) is characterized by inadequate pancreatic enzyme delivery to the small intestine Exocrine pancreatic insufficiency (EPI) is characterized by inadequate pancreatic enzyme delivery to the small intestine, resulting in malabsorption. Clinical manifestations of EPI are often nonspecific and can lead to lack of timely recognition and diagnosis. Central to this clinical dilemma is the lack of highly accurate or specific testing which leads to misdiagnosis and suboptimal treatment. Identification of high-risk patients is key in the diagnosis of EPI and this includes patients with pancreatic parenchyma disorders such as chronic pancreatitis, pancreatic malignancy, cystic fibrosis, and those undergoing pancreatic resection for benign and malignant disease. Less recognized are the number of additional conditions which may also have EPI as a consequence. Owing to an increase in morbidity and impaired quality of life associated with this condition, goals of treatment have been aimed at repleting exocrine enzyme deficiency by oral pancreatic enzyme replacement therapy (PERT). The basis of PERT is to provide activated digestive enzymes to the small bowel during the prandial period, mainly, leading to sufficient absorption of fat and fat-soluble vitamins. The benefits of PERT have been shown to go beyond the improvement in signs and symptoms associated with EPI and include decreasing prevalence of osteopathy and improving survival outcomes in subsets of patients with this condition. However, despite the overall benefits in treatment, the diagnosis and management of EPI are suboptimal. Current literature suggests patients at high risk of developing EPI are not tested and those who are diagnosed are not treated with adequate dosages. In this review, we highlight patients who are at high risk for the development of EPI, analyze consequences and treatment of this disorder, review rationale for enzyme replacement therapy, and examine current evidence for treatment optimization.

Safety and efficacy of endoscopic submucosal dissection for rectal neoplasia: a multicenter North American experience.

Background and aims Rectal lesions traditionally represent the first lesions approached during endoscopic submucosal dissection (ESD) training in the West. We evaluated the safety and efficacy of rectal ESD in North America. Methods This is a multicenter retrospective analysis of rectal ESD between January 2010 and September 2018 in 15 centers. End points included: rates of en bloc resection, R0 resection, adverse events, comparison of pre- and post-ESD histology, and factors associated with failed resection. Results In total, 171 patients (median age 63 years; 56 % men) underwent rectal ESD (median size 43 mm). En bloc resection was achieved in 141 cases (82.5 %; 95 %CI 76.8-88.2), including 24 of 27 (88.9 %) with prior failed endoscopic mucosal resection (EMR). R0 resection rate was 74.9 % (95 %CI 68.4-81.4). Post-ESD bleeding and perforation occurred in 4 (2.3 %) and 7 (4.1 %), respectively. Covert submucosal invasive cancer (SMIC) was identified in 8.6 % of post-ESD specimens. There was one case (1/120; 0.8 %) of recurrence at a median follow-up of 31 weeks; IQR: 19-76 weeks). Older age and higher body mass index (BMI) were predictors of failed R0 resection, whereas submucosal fibrosis was associated with a higher likelihood of both failed en bloc and R0 resection. Conclusion Rectal ESD in North America is safe and is associated with high en bloc and R0 resection rates. The presence of submucosal fibrosis was the main predictor of failed en bloc and R0 resection. ESD can be considered for select rectal lesions, and serves not only to establish a definitive tissue diagnosis but also to provide curative resection for lesions with covert advanced disease.