Objective
Surgical technique for loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC) emphasizes a uniform specimen, but sequelae of specimen fragmentation are not established. We evaluated outcomes between fragmented and unfragmented excisional biopsy specimens.
Materials and Methods
Loop electrosurgical excision procedure and CKCs from January 2010 to October 2013 were reviewed. Intraepithelial lesion grade, fragmentation, margin, and Endocervical curettage status were analyzed. Adenocarcinoma in situ and cancer were excluded. Repeat procedures during the study period were included in follow-up. Loop electrosurgical excision procedures with top hat with no separate fragments were analyzed independently versus those with fragmented LEEP and/or top hat. Indeterminate margin was defined as inconclusive or unevaluable margin, or intraepithelial lesion in unidentifiable margin or fragment. Outcomes involved residual or recurrent disease and repeat procedures for intraepithelial lesion. χ2 was used for statistical analysis.
Results
Fragmented specimens were more likely to have any positive margin (p = .01), multiple positive margins (p < .001), and indeterminate margin (p < .001) than unfragmented specimens. There was no significant difference in rates of positive, insufficient, or high-grade Endocervical curettage (p = .74, 0.54, 0.92). Patients with fragmented specimens were more likely to have high-grade lesion recurrence in the following 3 years (p = .04) versus patients with index unfragmented specimens, though not compared with those with unfragmented LEEP + top-hat cases. Overall rates of repeat LEEP/CKC or hysterectomy for dysplasia were not different (p = .56).
Conclusions
Fragmentation of LEEP and CKC specimens is associated with higher rates of positive margins, recurrent high-grade intraepithelial lesions, and indeterminate margins. These may cause diagnostic uncertainty, require closer follow-up, and increase cost with more visits and studies.
Genetic variation can have important consequences for populations: high population genetic diversity is typically associated with ecological success. Some mechanisms that account for these benefits assume that local social groups with high genetic diversity are more successful than low-diversity groups. At the same time, active decision-making by individuals can influence group genetic diversity. Here, we examine how maternal decisions that determine group genetic diversity influence the viability of Drosophila melanogaster larvae. Our groups contained wild-type larvae, whose genetic diversity we manipulated, and genetically marked ‘tester’ larvae, whose genotype and frequency were identical in all trials. We measured wild-type and tester viability for each group. Surprisingly, the viability of wild-type larvae was neither augmented nor reduced when group genetic diversity was altered. However, the viability of the tester genotype was substantially depressed in large, high-diversity groups. Further, not all high-diversity groups produced this effect: certain combinations of wild-type genotypes were deleterious to tester viability, while other groups of the same diversity—but containing different wild-type genotypes—were not deleterious. These deleterious combinations of wild-type genotypes could not be predicted by observing the performance of the same tester and wild-type genotypes in low-diversity groups. Taken together, these results suggest that nonadditive interactions among genotypes, rather than genetic diversity per se, account for between-group differences in viability in D. melanogaster and that predicting the consequences of genetic diversity at the population level may not be straightforward.
Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer (P=0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for β-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.
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