Endoscopic submucosal dissection for colorectal lesions: outcomes from a United States experience.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is commonly used in Asia for resection of large non-pedunculated colorectal polyps (LNPCPs) and early (T1) colorectal cancers. It allows for en bloc removal and is often curative. We describe outcomes of colorectal ESD from a United States (US) academic medical center and compare this to international experiences. METHODS: Retrospective review was performed of colonic lesions referred to the University of Chicago Medical Center for ESD from 2012 to 2020. Clinical and procedural data were collected. RESULTS: The study included 78 lesions with mean size of 29.7 mm (range 10-100 mm). The overall en bloc resection rate was 73.1% (n = 57). Between the first and second half of the study, it improved from 61.5 to 84.6% (p = 0.02). Histology showed adenocarcinoma in fifteen lesions (19.2%). Of all neoplastic lesions (n = 68), resection with negative margins (R0) was achieved in 54 cases (79.4%). Adverse events occurred in 9 cases (11.5%), but most (n = 6, 66.7%) were successfully treated endoscopically. Follow-up endoscopy was performed in 46 patients (59.0%) at a mean interval of 6.8 months (SD ± 5.0 months) with two case of recurrent lesion (4.3%). CONCLUSIONS: This study shows successful colorectal ESD outcomes at a US tertiary center. The en bloc resection rate was lower than other cohorts, but a learning curve was demonstrated. The R0 resection, lesion recurrence, and adverse event rates were similar to other non-Asian experiences, but not as favorable as in Asia [Fuccio et al. in Gastrointest Endosc 86:74-86.e17, 2017]. Increased ESD training in the US can help optimize utilization and outcomes.

Rhodopsin p.N78I dominant mutation causing sectorial retinitis pigmentosa in a pedigree with intrafamilial clinical heterogeneity.

OBJECTIVE: The purpose of this study was to determine the molecular basis of retinitis pigmentosa (RP) in a 4 affected sib-family segregating this retinal phenotype. METHODS: Affected sibs underwent complete ophthalmologic examination including funduscopic inspection, electroretinogram, fluorescein angiography, visual field measurement, and optical coherence tomography. Both parents were deceased after their sixties and were reported with no visual handicap. Molecular analysis included direct nucleotide sequencing of the rhodopsin gene (RHO), at chromosome 3q21-q24, in DNA from a total of 4 affected sibs. A total of 200 ethnically matched alleles were included as mutation controls. RESULTS: Sector RP was clinically documented in this family. Wide phenotypic variability was observed with visual acuities ranging from 20/20 to 20/200 and variable funduscopic appearance. Molecular analysis disclosed a c.233A>T mutation at RHO exon 1, predicting a missense p.N78I substitution. CONCLUSIONS: Even though RP can be caused by mutations in a variety of genes, the RHO gene was chosen to be investigated in this RP family since it has been previously associated to sector disease. This case exemplifies the value of guiding RP molecular analysis based on funduscopic features.

Susceptibility to advanced age-related macular degeneration and alleles of complement factor H, complement factor B, complement component 2, complement component 3, and age-related maculopathy susceptibility 2 genes in a Mexican population.

PURPOSE: To investigate the association of age-related macular degeneration (AMD)-high risk alleles of the complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), complement component 3 (C3), and age-related maculopathy susceptibility 2 (ARMS2) genes in a Mexican population for the first time. METHODS: Genotyping was performed for the Y402H variant of CFH, for the L9H, R32Q, and K565E variants of CFB, the E318D variant of C2, the A69S variant of ARMS2, and the R102G variant of C3 in 159 Mexican mestizo patients at advanced stages of AMD, i.e., CARMS (Clinical Age-Related Maculopathy Staging System) grade 4 or 5. The frequency of these variants was also investigated in a group of 152 control subjects without AMD. Genomic DNA was extracted from blood leukocytes, and genotyping was performed using PCR followed by direct sequencing. Allele-specific restriction enzyme digestion was used to detect the R102G polymorphism in C3. RESULTS: There were significant differences in the allelic distribution between the two groups for CFH Y402H (p=1×10(-5)), ARMS A69S (p=4×10(-7)), and CFB R32Q (p=0.01). The odds ratios (95% confidence interval) obtained for the risk alleles of these three variants were 3.8 (2.4-5.9), 3.04 (2.2-4.3), and 2.5 (1.1-5.7), respectively. Haplotype analysis including the two most significantly associated alleles (CFH Y402H and ARMS A69S) indicated that the C-T combination conferred an odds ratio (95% confidence interval) of 6.9 (3.2-14.8). The exposed attributable risk for this particular haplotype was 85.5%. CONCLUSIONS: This is the first case-control investigation of AMD-high risk alleles in a Latino population. Our results support that CFH, ARMS2, and CFB AMD-risk alleles are consistently associated with the disease, even in ethnic groups with a complex admixture of ancestral populations such as Mexican mestizos.