Faculty Bibliography

Purpose: Approximately 20-30% of colorectal cancers arise from serrated polyps (SPs). Like adenomas, SPs range in malignant risk from lower (hyperplastic polyps, HPs) to higher (sessile serrated adenomas/polyps, SSA/Ps). Surveillance intervals after colonoscopic polypectomy are predicated in part on the histology of the polyp(s) removed during the index exam. It can be challenging to differentiate SSA/ Ps from HPs because poor orientation of histologic sections can obscure important histologic features of SSA/Ps, such as architectural changes at the crypt bases. We aimed to identify simple interventions to address this limitation. Methods: Two novel tissue handling interventions were included in a "modified protocol" (MP): (1) immediately after polypectomy, polyps were flattened and enclosed in a small envelope; (2) in the pathology laboratory, polyps were cut into sections after processing (dehydration and permeation with paraffin) rather than before. We performed a two-site, prospective, randomized, single-blinded trial comparing this MP with a conventional protocol (CP). SPs located proximal to the splenic flexure and 5-20 mm in diameter were included. We validated a novel orientation score (OS) that quantifies the quality of histologic section orientation. Our blinded GI pathologists used WHO criteria in diagnosing SSA/Ps and HPs. SPs that did not meet either criterion were labeled "Indeterminate." For confirmation of our diagnoses, we also recruited an external GI pathologist who was blinded to the purpose of the study. The number of deeper sections requested was also followed. Results: 375 lesions were enrolled and 264 SPs were identified for analysis. There were no significant differences between the MP and CP groups in terms of procedure, patient, or gross polyp characteristics. The average OS in the MP and CP groups were 3.11 and 1.12, respectively (P<0.0001). A diagnosis of SSA/P was made in 103/ 135 (76.3%) cases in the MP group versus 54/129 (41.9%) cases in the CP group (P<0.0001).!

BACKGROUND: Proximal colorectal cancer may arise from sessile serrated polyps (SSPs), which are often inconspicuous during colonoscopy. The gross morphologic characteristics of SSPs have not been systematically described, and this omission may contribute to colonoscopists overlooking them. OBJECTIVES: To analyze the gross morphologic characteristics of SSPs detected during routine colonoscopy. DESIGN: Retrospective analysis of high-resolution endoscopic video clips depicting SSPs in situ. SETTING: Outpatient gastroenterology practice. PATIENTS: A total of 124 subjects undergoing surveillance or screening colonoscopy after split-dose bowel preparation. INTERVENTIONS: Analysis of 158 SSPs performed by using validated descriptors. MAIN OUTCOME MEASUREMENTS: The prevalence of morphologic characteristics related to polyp shape, color, and texture. RESULTS: A total of 158 SSPs were studied. For 7 visual descriptors, a kappa coefficient of >/= 0.7 was achieved, indicating good to excellent intraobserver agreement. The most prevalent visual descriptors were the presence of a mucous cap (63.9%), rim of debris or bubbles (51.9%), alteration of the contour of a fold (37.3%), and interruption of the underlying mucosal vascular pattern (32.3%). The most common "sentinel signs" were the presence of a mucous cap and alteration of the contour of a mucosal fold (each 24.6%), rim of debris or bubbles (21.7%), and a dome-shaped protuberance (20.3%). When comparing SSPs with adenomatous polyps, the frequencies of 5 of 7 morphologic characteristics and the distribution of sentinel signs differed (P < .01). LIMITATIONS: Single-site, retrospective analysis. CONCLUSIONS: SSPs exhibit distinct, variable morphologic characteristics. Many do not display classic features such as a mucous cap. Enhanced appreciation of these morphologic characteristics may improve SSP detection and thereby colorectal cancer prevention.

BACKGROUND: Recent studies have shown that colonoscopic polyp detection decreases as the workday progresses. This may reflect time-dependent factors such as colonoscopist fatigue and decreased colon cleanliness, which can be addressed through adaptations in colonoscopy practice. OBJECTIVE: To test for time-of-day differences in adenomatous polyp (AP) and sessile serrated polyp (SSP) detection in a practice that uses split-dose bowel preparation and moderated daily colonoscopist procedure loads. DESIGN: Retrospective chart review. SETTING: Community-based, group gastroenterology practice. PATIENTS: This study involved 2439 patients undergoing surveillance or screening colonoscopy. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Detection rate of all premalignant polyps (PMPs), and of APs and SSPs, individually. RESULTS: A total of 1183 PMPs were identified in 1486 eligible patients (mean PMP/colonoscopy = 0.80; PMP detection rate = 47%). In univariate and multivariate analyses, PMP detection as well as detection of APs or SSPs individually did not vary significantly in relation to the hour of the day. In a binary comparison of morning (am) versus afternoon (pm) procedures, the total polyp detection rate was 67% and 66%, respectively. For PMPs, APs, SSPs, and hyperplastic polyps (HPs), the am and pm detection rates were 46% and 47%, 41% and 44%, 8% and 8%, and 27% and 24%, respectively. Bowel preparation quality was independent of time of day and was rated excellent or good in 86% to 87% of cases. LIMITATIONS: Retrospective, nonrandomized study. CONCLUSION: Stable PMP, AP, SSP, and HP detection rates throughout the workday occur under certain practice conditions, including the use of split-dose bowel preparation and/or moderated daily colonoscopist procedure loads.

GOALS: To assess prospectively the bleeding risk attributable to gastroduodenal biopsy in subjects taking antiplatelet medications. BACKGROUND: No prospective data exist regarding the bleeding risk attributable to endoscopic biopsy in patients taking antiplatelet agents. A majority of Western endoscopists withdraw antiplatelet agents before upper endoscopy, despite expert guidelines to the contrary. STUDY: We performed a prospective, single-blind, randomized study in healthy volunteers participating in a larger study regarding the effect of antiplatelet agents on gastroduodenal mucosal healing. Multiple gastroduodenal biopsies were performed during 2 esophagogastroduodenoscopy in subjects dosed with aspirin enteric-coated 81 mg once daily or clopidogrel 75 mg once daily. Data for endoscopic bleeding, clinical bleeding, blood vessel size, and depth of biopsy in histology specimens were collected. RESULTS: Four hundred and five antral biopsies and 225 duodenal biopsies were performed during 90 esophagogastroduodenoscopy in 45 subjects receiving aspirin or clopidogrel. Median maximum blood vessel diameter per biopsy was 31.9 mu (range: 9.2 to 133.8). About 50.8% of biopsy specimens breached the muscularis mucosa. In the clopidogrel group, no bleeding events were noted after 350 biopsies [upper confidence limit (UCL) for probability of bleeding=0.0085]. In the aspirin group, there were no clinical events (UCL=0.0106) and one minor endoscopic bleeding event (UCL=0.0169). CONCLUSIONS: Consistent with expert guidelines, the absolute risk attributable to gastroduodenal biopsy in adults taking antiplatelet agents seems to be low. Half of routine biopsies enter submucosa. The largest blood vessels avulsed during biopsy correspond to midsized and large arterioles and venules.

Fundic gland polyps (FGPs) of the stomach are regarded as hamartomatous or hyperplastic/functional polyps that occur sporadically but at increased frequency in patients with familial adenomatous polyposis syndrome (FAP).There is controversy about the histopathology of FGPs, including occurrence of dysplasia. We, therefore, studied dysplasia in 270 sporadic FGPs from 216 patients and 49 FGPs from 24 patients with FAP. We evaluated dysregulation of epithelial proliferation manifested by loss of the normal inverse topographic distribution of Ki-67 proliferation marker and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) using immunohistochemistry in 27 sporadic FGPs and in 22 FGPs from patients with FAP. Dysplasia in foveolar and surface epithelia occurred in 12 of 49 (25%) FGPs in patients with FAP but in only 3 of 270 (1%) of sporadic FGPs (p < 0.000001). Fourteen of 49 (29%) of FGPs from patients with FAP were indefinite for dysplasia, as contrasted with 8 of 270 (3%) sporadic FGPs (p < 0.00001). The normal inverse topographic distribution of Ki-67 and p21(WAF1/CIP1) was maintained in 20 of 22 (91%) of FGPs negative for dysplasia but was lost in all (8 of 8) FGPs with dysplasia and in 11 of 19 (58%) FGPs that were indefinite for dysplasia (p = 0.00001). The results indicate that dysplasia can occur in foveolar and surface epithelia of FGPs, especially in patients with FAP, and often is preceded by dysregulation of epithelial proliferation when the morphologic abnormalities are indefinite for dysplasia

Isolated nodular pulmonary amyloidosis is a rare condition characterized by localized deposits of immunoglobulin (Ig) light chain amyloid. Nonamyloid nodular light chain deposits in lungs can occur in systemic light chain deposition disease. Both amyloid and nonamyloid light chain deposits have been described at separate sites in the same or different organs but rarely in lungs. We report the clinical, radiologic, and pathologic findings in a drug user infected with the human immunodeficiency virus who had multinodular pulmonary Ig light chain deposits consisting of both amyloid and nonamyloid granular morphologic features. The deposits, closely associated with numerous plasma cells, had a unique histochemical and ultrastructural profile, with intermixed Congo red-positive fibrillar amyloid and Congo red-negative granular nonamyloid components. Immunohistochemical and immunoelectron microscopic studies showed reactivity of both the fibrillar and granular deposits for kappa and lambda light chains but not heavy chains. There was no evidence of restricted clonality of local or bone marrow plasma cells, serum or urine monoclonal protein, or secondary causes of amyloidosis. The amyloid deposits (but not the nonamyloid deposits) were reactive with antibody to amyloid rho component. There was no staining for other types of amyloid, i.e., amyloid A or transthyretin. The relationship between pulmonary amyloidosis, infection with the human immunodeficiency virus, and illicit drug use is unknown. We conclude that the nodular pulmonary light chain deposits with both amyloid and nonamyloid morphologic features are related to local plasma cell proliferation and that the fibrillar and nonfibrillar components most likely result from different conformations of the Ig light chains

A case of a patient with a malignant thymoma who developed an unusual form of colitis is reported. The patient was a previously healthy 20-year-old man who was referred to the Johns Hopkins Medical Institution for biopsy and resection of a mediastinal mass, which proved to be a malignant thymoma. During this hospitalization and subsequently, the patient developed severe chronic diarrhea, the etiology of which remained uncertain after routine work-up, including cultures. Colonoscopic biopsies revealed only minimal inflammation but numerous, prominent apoptotic lesions within crypt epithelium, suggestive of an autoimmune or graft-versus-host-like colitis. The patient, who was immunocompetent and human immunodeficiency virus (HIV) negative, had no known risk factors for graft-versus-host-disease (e.g., no blood transfusions, no transplantation history before diarrheal episodes). Stool cultures for pathogenic bacteria and viruses were negative. The diarrhea and histologic findings eventually improved with steroid therapy yet returned on recurrence of the thymoma. This unusual form of colitis has not been previously reported to be associated with thymoma and is interesting in light of the role the thymus plays in immune regulation