Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

How to do a laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers syndrome.

We demonstrate the technical details of laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers Syndrome. A 'clean sweep' reduces the risk for future recurrences but was previously performed with an open technique. A minimally invasive approach is safe, reduces bowel trauma and has good postoperative outcomes.

Prevalence of endoscopy-related injuries and their impact on clinical practice: a systematic review and meta-analysis.

BACKGROUND: Endoscopy-related musculoskeletal injuries (ERIs) are commonly reported but their exact prevalence and clinical impact remain obscure. We conducted a systematic review and meta-analysis of the current literature aiming to answer these questions. METHODS: The MEDLINE, EMBASE, and SCOPUS databases were searched for studies evaluating ERIs in gastroenterologists and surgeons. The co-primary outcome was the prevalence of ERIs (i.e. carpal tunnel syndrome, de Quervain's tenosynovitis, and hand numbness). The second co-primary outcome was the prevalence of endoscopy-related pain syndromes. RESULTS: 12 studies, including 4563 respondents, were included. The majority of respondents were men (n = 3321; 72.8%) and most were right-handed (86.2%). The career prevalence of carpal tunnel syndrome (pooled from 10 studies) was 5.3% (95%CI 1.5%-8.9%; I 2 = 97.1%), while the prevalence of de Quervain's tenosynovitis (five studies) was 8.5% (95%CI 0.1%-17.0%). The pooled prevalences of thumb pain, neck pain, and back pain were 25.4%, 23.1%, and 19.7%, respectively, but the prevalence varied according to the type of questionnaire used. Only 341/864 respondents (39.5%) had received prior training in ergonomics, while 623/889 respondents (70.1%) expressed a desire for further training in ergonomics. Overall, there is a moderate risk of bias in the present literature. CONCLUSION: ERIs, including carpal tunnel syndrome, de Quervain's tenosynovitis, and endoscopy-related pain, are very common. These injuries can be severe, requiring surgery, and lead to loss of productivity. Most gastroenterologists report an unmet need for training in the proper ergonomics of endoscopy.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience.

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57 %) and had small esophageal varices (87 %). En bloc, R0, and curative resections were achieved in 22 (96 %), 21 (91 %), and 19 (83 %) of patients, respectively. Severe intraprocedural bleeding (n = 1) and delayed bleeding (n = 1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.

Factors Associated With Cardiac Radiation Dose Reduction After Hypofractionated Radiation Therapy for Localized, Left-Sided Breast Cancer in a Large Statewide Quality Consortium.

PURPOSE: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer. METHODS AND MATERIALS: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022. RESULTS: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal. CONCLUSIONS: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage.

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC. METHODS: Patients who underwent ESD revealing T1b EC (squamous or adenocarcinoma) at 10 academic tertiary referral centers in the United States (n = 9) and Brazil (n = 1) were included. Demographic and clinical data were abstracted. ESD using either traction techniques (tunneling, pocket) or traction devices (clip line, traction wire) were classified as ESD with traction (Tr-ESD) and those without were classified as conventional ESD without traction. The primary outcome was a negative VM. Multivariable logistic regression was used to assess associations with negative VMs. RESULTS: A total of 166 patients with pathologically staged T1b EC underwent Tr-ESD (n = 63; 38%) or conventional ESD without traction (n = 103; 62%). Baseline factors were comparable between both groups. On multivariable analysis, Tr-ESD was found to be independently associated with negative VMs (odds ratio, 2.25; 95% confidence interval, 1.06-4.91; P = .037) and R0 resection (odds ratio, 2.83; 95% confidence interval, 1.33-6.23; P = .008). CONCLUSION: Tr-ESD seems to be associated with higher odds of negative VMs than ESD without traction for pathologically staged T1b EC, and future well-conducted prospective studies are warranted to establish the findings of the current study.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Frequency of endoscopic photodocumentation of large colorectal polyps.

BACKGROUND AND AIMS: Colonoscopy quality affects colorectal cancer (CRC) incidence and mortality. The U.S. Multi-Society Task Force on Colorectal Cancer strongly recommends photodocumentation (PD) of lesions ≥10 mm in size (ie, large polyps [LPs]) pre-resection and suggests PD postresection to enhance the quality of colonoscopy. No studies have assessed the frequency of LP PD. We evaluated the frequency of and factors associated with PD of LPs. METHODS: Reports from endoscopists performing ≥50 colonoscopies with LP resection between 2016 and 2021 were reviewed. The frequency of LP PD pre-resection and post-resection and factors associated with PD were collected. A composite score of 2 quality metrics (PD of completeness of examination and bowel preparation quality) was created. Endoscopists were divided into 2 tiers based on the frequency of the score on all included examinations: Tier 1, ≥95% of examinations; and Tier 2, <95% of examinations. Univariate and multivariate analyses were used to assess factors associated with PD. RESULTS: A total of 1322 colonoscopies, 1693 LPs, and 25 endoscopists were included in this study. PD of LPs occurred in 1392 (82%) pre-resection and in 878 (52%) post-resection. Factors associated with pre-resection PD include endoscopist subspecialty (colorectal surgery vs gastroenterology: odds ratio [OR], .12; 95% confidence interval [CI], .04-.42); >1 LP on examination (2 vs 1 LP: OR, .41 [95% CI, .27-.61]; and ≥3 vs 1 LP: OR, .41 [95% CI, .24-.70]), and longer withdrawal time (OR, 1.02; 95% CI, 1.01-1.04). CONCLUSIONS: We provide the first data on PD of LP pre-resection and post-resection, which can inform future benchmarking in this area. The implications of PD on metachronous advanced neoplasia need to be studied.

Ocular and developmental outcomes of a dosing study of bevacizumab for retinopathy of prematurity.

PURPOSE: To report 2-year ocular and developmental outcomes for infants receiving low doses of intravitreal bevacizumab for type 1 retinopathy of prematurity (ROP). METHODS: A total of 120 premature infants (mean birthweight, 687 g; mean gestational age, 24.8 weeks) with type 1 ROP were enrolled in a multicenter, phase 1 dose de-escalation study. One eye per infant received 0.25 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreal bevacizumab; fellow eyes when treated received one dosage level higher. At 2 years, 70 of 120 children (58%) underwent ocular examinations; 51 (43%) were assessed using the Bayley Scale of Infant and Toddler Development. RESULTS: Correlation coefficients for the association of total dosage of bevacizumab with Bayley subscales were -0.20 for cognitive (95% CI, -0.45 to 0.08), -0.15 for motor (95% CI, -0.41 to 0.14), and -0.19 for language (95% CI, -0.44 to 0.10). Fourteen children (21%) had myopia greater than -5.00 D in one or both eyes, 7 (10%) had optic nerve atrophy and/or cupping, 20 (29%) had strabismus, 8 (11%) had manifest nystagmus, and 9 (13%) had amblyopia. CONCLUSIONS: In this study cohort, there was no statistically significant correlation between dosage of bevacizumab and Bayley scores at 2 years. However, the sample size was small and the retention rate relatively low, limiting our conclusions. Rates of high myopia and ocular abnormalities do not differ from those reported after larger bevacizumab doses.

ACG Clinical Guideline: Diagnosis and Management of Gastrointestinal Subepithelial Lesions.

Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better assess this, we conducted a systematic review and meta-analysis. METHODS: MEDLINE, Embase, and Scopus databases were searched for the key words juvenile polyposis syndrome, juvenile polyps, stomach cancer, GC, SMAD4, BMPR1A, hamartomatous polyposis syndrome, hamartomas, and hereditary cancers for studies reporting upper GI manifestations in JPS. The primary outcome was the reported occurrence of GC in JPS. We then compared GC occurrence based on the presence or absence of pathogenic germline variants (PGVs) and in untested patients. RESULTS: Eleven studies including 637 patients were included. The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8-5.2; I2 = 12.3%) at a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC in patients with SMAD4 PGV was 10.1% (95% CI, 3.2-16.8%; I2 = 54.7%). GC was reported in only 1 BMPR1A PGV carrier and was not reported in patients without an identifiable PGV. In patients with prior germline testing, the risk of GC was higher in SMAD4 PGV carriers (odds ratio, 11.6; 95% CI, 4.6-29.4; I2 = 18.3%) compared with patients without SMAD4 PGV. In JPS patients with unknown status of germline testing, pooled occurrence of GC was 7.5% (95% CI, 0-15.5). There was an overall moderate risk of bias in the studies. CONCLUSIONS: GC is highest in SMAD4-associated JPS and was not reported in patients without identifiable PGVs. The value of GC surveillance in BMPR1A PGV carriers and JPS patients without an identifiable PGV is questionable. Germline testing should be performed in all JPS patients to inform GC risk discussion and utility of surveillance.

Endoluminal management of colon perforations during advanced endoscopic procedures.

BACKGROUND: Advanced endoscopic procedures are gaining attraction despite a steep learning curve, need for high dexterity, and potential complications. Colonic perforation is the most concerning adverse event during advanced endoscopic procedures. This study presents our experience on endoluminal management of iatrogenic colonic perforations. METHODS: Patients who underwent advanced endoscopic procedures at a quaternary center from 2016 to 2021 were identified. Patients who had colonic perforations during advanced procedures and treated with endoscopic closure/clipping were included. Retrospective chart review was performed. Figures represent frequency (proportion) or median (interquartile range/range). RESULTS: There were 22 (2.3%) immediate colonic perforations treated with endoscopic clipping out of 964 advanced endoscopic resections. The median age was 64 (interquartile range = 57-71) years and 50% of the patients were female; 16 (73%) resections were proximal to the splenic flexure. Median polyp size was 36 (20-55) mm. Closure was performed with endoscopic clips in 18 (82%) patients, and over-the-scope clips in 4 patients. Median hospital stay was 0.8 (0-4) days, and 13 (59%) patients were discharged the same day; 2 patients were admitted to the emergency department ≤24 hours of procedure. They underwent subsequent laparoscopic suture repair the same day. No one had segmental colon resection, and there were no complications within postoperative 30 days. Pathology revealed 9 (41%) tubular adenomas, 7 (32%) tubulovillous adenomas, 6 (27%) sessile serrated lesions, and no adenocarcinoma. No recurrence was observed with median follow-up of 24 months (range = 0-90 months). CONCLUSION: Endoscopic management is an effective treatment approach for the management of iatrogenic colonic perforations.

An Unusual Case of a Pharyngeal Fistula to the Cervical Spine Causing Osteomyelitis.

SIGNIFICANCE STATEMENT: Pharyngeal fistulas to the cervical spine resulting in vertebral osteomyelitis are a rare, yet clinically important, complication of total laryngectomy performed in conjunction with chemoradiotherapy or radiation therapy. This complication is likely underdiagnosed and can have a high mortality rate. It is very important that clinicians are aware of this complication as early diagnosis and management may improve patient outcomes.

Prevalence and risk factors of barrett's esophagus in lynch syndrome.

Lynch syndrome (LS), the most common hereditary cause of colorectal cancer, predisposes to upper gastrointestinal neoplasia. The prevalence of Barrett's esophagus (BE) is elevated in some hereditary gastrointestinal cancer syndromes but has not been systematically evaluated in LS. We assessed the prevalence of BE, BE-related dysplasia, esophageal adenocarcinoma (EAC), and factors associated with BE in LS. Asymptomatic patients with a germline pathogenic variant (PV) in the DNA mismatch repair (MMR) genes undergoing EGD for LS surveillance were identified from a hereditary colorectal cancer registry. We assessed the prevalence of BE and compared demographic, clinical, and endoscopic factors in LS patients with and without BE by logistic regression analysis. 323 patients were included. 21 patients (6.5%) were diagnosed with BE including 38% of females and 33% without gastroesophageal reflux disease (GERD). Dysplasia was diagnosed in two patients (9.5%) and EAC in one (4.8%) patient. Factors associated with BE included male gender (OR 3.00, 1.21-7.46), age at last LS EGD (OR 1.04, 1.01-1.08), presence of hiatal hernia (OR 20.09, 4.57-88.23), hiatal hernia > 3 cm (OR 11.25, 2.41-51.94), and GERD (OR 3.39, 1.32-8.67). No MMR PV was associated with BE. BE was diagnosed in 1 of 15 patients undergoing EGD surveillance for LS and nearly 10% had dysplasia including one EAC. Risk factors associated with BE in LS are similar to those established for BE in the general population. More studies are needed to evaluate if an association between BE and LS exists.