ABSTRACT
OPINION STATEMENT: The sessile serrated polyp (SSP), also known as sessile serrated adenoma, is the evil twin among the colorectal cancer precursors. As will be described, these lesions have multiple aliases (serrated adenoma, serrated polyp, or serrated lesion among others), they hang out in a bad neighborhood (the poorly prepped right colon), they hide behind a mask of mucus, they are difficult for witnesses (pathologists) to identify, they are difficult for police (endoscopists) to find, they are difficult to permanently remove from the society (high incomplete resection rate), they can be impulsive (progress rapidly to colorectal cancer (CRC)), and enforcers (gastroenterologists) do not know how best to control them (uncertain surveillance recommendations). There is no wonder that there is a need to understand these lesions well, learn how best to prevent the colonic mucosa from going down this errant path or, if that fails, detect these deviants and eradicate them from the colonic society. These lesions should be on endoscopists' most wanted list.
ABSTRACT
The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR). In the present study, we set out to determine whether pretransplant HLA-DSAs correlate with clinically significant ACR in the first 90 days after transplantation and, if so, to determine their predictive values. Class I HLA-DSAs and class II HLA-DSAs were determined by single-antigen bead flow cytometry for 113 consecutive adult transplants. A statistical analysis was performed for data from 109 consecutive patients with graft survival greater than or equal to 90 days. All patients who developed biochemical graft dysfunction underwent liver biopsy for hematoxylin-eosin and complement component 4d staining. Cox proportional hazards models and associated hazard ratios revealed a significant association of pretransplant HLA-DSAs with clinically significant ACR: this association started with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard ratio = 2.7, P < 0.01) and class II (hazard ratio = 6.0, P < 0.01). Pretransplant HLA-DSAs were associated with an increased risk of ACR: P < 0.01 for class I (42% versus 18%), P < 0.001 for class II (37% versus 7%), and P < 0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an MFI ≥ 1000 had the best positive predictive value for clinically significant ACR at 46%, whereas class I or II HLA-DSAs with an MFI ≥ 300 had the best negative predictive value at 97.1%. Although our study was based on consecutive patients, it was limited by the relatively low number of single-center subjects. In conclusion, the present study indicates that pretransplant HLA-DSAs, even at low levels of allosensitization, correlate with the risk of clinically significant ACR. Our findings suggest that anti-human leukocyte antigen antibodies could serve as donor-specific markers of immunoreactivity to the liver graft.
