Sporadic non-ampullary duodenal adenomas (SNADAs), although uncommon, pose clinical challenges. Because SNADAs have malignant potential, endoscopic or surgical resection is generally recommended. EMR ...is increasingly used for resection of SNADAs, but large-scale data on natural history after EMR are scarce. In this study, we aimed to evaluate the clinical outcome of EMR for SNADAs and the natural history after EMR from a large, single-operator experience with dedicated follow-up.
We performed a retrospective review of patients with SNADAs who were referred for endoscopic therapy from May 2007 to May 2016. Patient demographics, lesion characteristics, and procedural technical data were collected. The outcomes studied were complete endoscopic resection, major adverse events, and recurrence.
A total of 162 patients were referred for endoscopic therapy, and 142 (88%) (median age 67 years, interquartile range IQR 57-73 years, 42% male) underwent a total of 166 EMRs with the use of a submucosal injection and thermal snare resection technique. In per-patient analysis, the median size of SNADAs was 20 mm (IQR 15-30) in diameter. Complete mucosal resection was achieved in 130 of 142 patients (92%). Local or residual recurrences were observed in 23% of patients (median time until recurrence 277 days IQR 196-591) and were treated endoscopically. No metachronous recurrences were found within a median follow-up of 363 days. In per-procedure analysis, en bloc resection was achieved in 88 (53%). EMR-related bleeding occurred in 18 (11%) EMRs, and all cases were successfully managed with supportive and/or endoscopic measures. No perforations occurred. Increasing size of adenomas was associated with recurrence (P < .001). No association with recurrence was noted with endoscopic or histologic features. Increasing size of resected specimens (P < .001) was associated with an increased risk of bleeding.
EMR of most SNADAs can be performed safely and effectively. Increasing size of adenomas was associated with recurrence and bleeding after EMR. No association with recurrence was noted with endoscopic or histologic features. Focal recurrence can be managed with additional endoscopic therapy. Metachronous lesions do not occur. The findings inform directed management and surveillance.
To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS ...studies.
Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I
higher-stage). Overall survival was determined using the Kaplan-Meier method.
Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio 95% CI; 0.13 0.03 to 0.50,
= .003).
Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.
Background Flat and sessile lesions are being identified more frequently because of increased awareness, improved endoscopic skills, and enhanced imaging. The defiant polyp (DP) is a lesion ...identified at colonoscopy that defies resection by the standard snare polypectomy technique. Increasingly, the DP undergoes photodocumentation and tissue sampling, and the patient is referred for an attempt at curative colonoscopic resection. Objective To evaluate the current nature of the DPs and outcomes of their endoscopic resection. Design Retrospective study. Setting Tertiary referral center. Patients and Interventions Patients with colorectal polyps not amenable to standard snare polypectomy were referred to a single endoscopist at a tertiary center for an attempt at curative endoscopic resection. The indication DP was applied prospectively, as defined previously, beginning in June 2007. An electronic endoscopy report database was searched for this indication from June 2007 to October 2009 for a single endoscopist at an endoscopy referral center. Data pertaining to patient age and sex, polyp site and histopathology, resection technique, use of adjunctive ablation, adverse events, and residual/recurrent neoplasia at follow-up were culled. Submucosal injection of varying quantities of normal saline solution tinted with methylene blue dye was used for endoscopic resection. Standard and mini-snares were used with pure coagulation current. Main Outcome Measurements Complete resection, complications, recurrence. Results This study included 274 patients (50.4% women, age 65 standard deviation 12 years) with a total of 315 DPs who were referred for attempted endoscopic resection. The majority of DPs were located in the right side of the colon (226; 72%). The mean size was estimated at 23 mm (range 8-100 mm; standard deviation 13). In 29 DPs (10%), surgery was required because endoscopic resection was deemed unsuitable because of the unfavorable appearance (n = 3), the location (n = 9), or the inability to lift (n = 10) or because of submucosal invasion on post-EMR histopathology (n = 7). Complete endoscopic eradication (R0) was achieved in a single session in 286 DPs (91%). En bloc resection was performed in 153 polyps (53.5%) and piecemeal resection in 132 (46%). Histopathology revealed 178 tubular adenomas (56.5%), 62 serrated adenomas (20%), 27 tubulovillous adenomas (9%), 10 hyperplastic polyps (3%), and 14 adenocarcinomas (4.5%). Adjunctive ablation of focal residual neoplastic tissue was applied in 69 DPs (24%) to achieve R0. Procedure-related adverse events were recorded in 29 of 249 patients (11.6%). Acute bleeding occurred in 9 patients (1 required hospitalization and repeat endoscopy). There was 1 microperforation managed with clip closure and antibiotics. Delayed bleeding (1-6 days post-procedure) was observed in 18 patients (7.2%), of whom 8 required hospitalization and 4 colonoscopy for hemostasis. Among the patients who underwent follow-up surveillance colonoscopy (135 of 258 patients), residual/recurrent neoplastic tissue at the site of the previous EMR was identified in 36 (27%). Residual/recurrent neoplasia was successfully eradicated with further endoscopic resection or ablation. Limitations A retrospective design. Conclusions DPs consist predominantly of sessile and flat adenomas including serrated adenomas. Most DPs can be successfully eradicated at dedicated therapeutic colonoscopy by using adjunctive resection and ablation techniques. The R0 rate is high and the adverse event rate is low. A relatively high rate of local residual/recurrent neoplasia at the resection site underscores the importance of follow-up colonoscopy.
The Unexpected Perpetrator: A Story of Indigestion Dhawan, Ishita; Palchaudhuri, Sonali; Ginsberg, Gregory G.
Gastroenterology,
January 2021, 2021-Jan, 2021-01-00, 20210101, Letnik:
160, Številka:
1
Journal Article
Background and Aim
Tumor genotyping may allow for improved prognostication and targeted therapy for pancreatic ductal adenocarcinoma (PDAC). We aimed to compare endoscopic ultrasonography (EUS) with ...fine needle aspiration (FNA) to fine needle biopsy (FNB) for obtaining sufficient tissue for genomic analysis and theranostic potential.
Methods
A retrospective cohort study of patients that underwent EUS‐FNA or EUS‐FNB with either positive or suspicious cytology for PDAC between March 2016 and December 2017. Demographic, procedural, and cytology data were recorded. Genetic alterations were recorded, and Kaplan–Meier survival curves were calculated.
Results
The study included 167 patients: 145 patients had FNA and 22 patients underwent FNB. Overall, 117 samples (70.1%) were sufficient for targeted next‐generation sequencing. FNB resulted in a higher proportion of patients with sufficient samples compared with FNA (90.9% vs 66.9%; P = 0.02). In multivariable modeling, only FNB (odds ratio 4.95, 95% confidence interval 1.11–22.05, P = 0.04) was associated with sufficient sampling for genomic testing. FNB was more likely to obtain sufficient tissue from tumors ≤ 3 cm (100% vs 68.4%, P = 0.017) and tumors located in the head/neck of the pancreas (100% vs 63.1%, P = 0.03) compared with FNA. The most commonly identified alterations were in KRAS (88%), TP53 (68%), and SMAD4 (16%).
Conclusions
Endoscopic ultrasonography can reliably obtain sufficient tissue from PDAC for targeted genomic sequencing for prognostication and theranostics. FNB should be considered when tumor genotyping is requested, especially for tumors ≤ 3 cm or tumors located in the head/neck of the pancreas.
BACKGROUND:Alirocumab, an antibody that blocks PCSK9 (proprotein convertase subtilisin/kexin type 9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY ...OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). In this study, higher baseline levels of low-density lipoprotein cholesterol (LDL-C) predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. We performed post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independent of baseline LDL-C and other known risk factors, who might derive greater benefit from alirocumab treatment.
METHODS:ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18 924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death of CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6 579 025 genetic variants was evaluated in 11 953 patients with available DNA samples. Analysis of MACE risk was performed in placebo-treated patients, whereas treatment benefit analysis was performed in all patients.
RESULTS:The incidence of MACE in the placebo group was related to PRS for CAD17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (≤90th percentile; P<0.001); this PRS relationship was not explained by baseline LDL-C or other established risk factors. Both the absolute and relative reduction of MACE by alirocumab compared with placebo was greater in high versus low PRS patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6.0% and 1.5%, respectively, and a relative risk reduction by alirocumab of 37% in the high PRS group (hazard ratio, 0.63 95% CI, 0.46–0.86; P=0.004) versus a 13% reduction in the low PRS group (hazard ratio, 0.87 95% CI, 0.78–0.98; P=0.022; interaction P=0.04).
CONCLUSIONS:A high PRS for CAD is associated with elevated risk for recurrent MACE after acute coronary syndrome and a larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.
IMPORTANCE: Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 ...and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes. OBJECTIVE: To test whether apabetalone significantly reduces major adverse cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019. INTERVENTIONS: Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke. RESULTS: Among 2425 patients who were randomized (mean age, 62 years; 618 women 25.6%), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 95% CI, 0.65-1.04; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 9.4% vs 69 5.7%) for reasons including elevations of liver enzyme levels (35 2.9% vs 11 0.9%). CONCLUSIONS AND RELEVANCE: Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02586155
Summary
Background
Helicobacter pylori infection is the most important risk factor for non‐proximal gastric adenocarcinoma, yet some posit it is protective against oesophageal adenocarcinoma and ...proximal gastric cancers.
Aims
To evaluate the incidence of and risk factors for future oesophageal and proximal gastric cancers, utilizing the largest North American cohort of patients with previously identified H pylori. Also to identify whether treatment and eradication of H pylori alter future oesophageal and proximal gastric cancer risk.
Methods
Retrospective cohort study within the Veterans Administration of 36 803 patients (median age 60.4 years; 91.8% male) with confirmed H pylori between 01 January 1994 and 31 December 2018. Primary outcome was diagnosis of future oesophageal and proximal gastric cancers. A time to event with competing risk analysis was performed, evaluating patient factors and whether the patient received H pylori treatment. Secondary analysis of those treated evaluated whether confirmed eradication was associated with cancer.
Results
The cumulative incidence of oesophageal and proximal gastric cancers 5, 10 and 15 years after H pylori detection was 0.145%, 0.26% and 0.34%. Risk of future oesophageal or proximal gastric cancer was similar amongst whites (reference), African Americans (SHR 0.87, 95%CI 0.57‐1.43) and American Indians (SHR 1.31, 95%CI 0.18‐9.60) but substantially reduced in those of Asian (no cases amongst 213 H pylori positive) or native Hawaiian origin (no cases amongst 295 H pylori positive) (P < .001). Increasing age (SHR 1.17 per 5 years, 95% CI: 1.09‐1.25, P < 0.001) and smoking (SHR 2.06, 95% CI: 1.33‐3.18, P = 0.001) were associated with oesophageal and proximal gastric cancers. Neither treatment of H pylori nor eradication status were associated with cancer (P > 0.20).
Conclusions
In the largest study of US patients with H pylori, we demonstrate that rates of oesophageal and proximal gastric cancers after treatment of H pylori are low. Older age, and smoking are associated with future cancer, whilst Asian or Native Hawaiian race are protective. H pylori treatment and eradication are not associated with future cancer.
Foreign body ingestions (FoBIs) are a common cause for medical attention. However, trends and patterns of adult FoBIs as well as associations with clinical comorbidities and behavioral attributes ...have not been elucidated beyond single institutional experiences.
We utilized survey data from the National Electronic Injury Surveillance System to examine fundamental characteristics of adult FoBIs involving consumer products between 2000 and 2017 across the United States. Data regarding the circumstances of FoBIs were abstracted from narrative data. Relationships among time, intent, demographics, and behavioral attributes were assessed using regression analyses, accounting for survey structure.
Adult FoBIs have increased in incidence over the past 2 decades from 3 to 5.3 per 100,000 persons. Examination of consumer products revealed that jewelry (15.4%), nails (7.2%), and toothpicks (6.9%) were the most commonly ingested products. The most common products ingested varied over time, and the number of unique consumer product categories ingested increased from 103 to 143 in the time period studied. Intentional ingestions accounted for 14% of adult FoBIs and frequently involved plastic bagging (13.6%), batteries (13%), nails (10.1%), and desk supplies (6.8%). Adjusted regression analyses demonstrated that compared with accidental FoBIs, intentional FoBIs have increased over time. Intentional FoBIs were more frequently associated with younger age, substance abuse, police custody, and mental and cognitive illnesses relative to accidental FoBIs.
Our results indicate that adult FoBIs are an increasing burden of disease in the United States with social, psychiatric, and behavioral contributors to this trend.
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