PubMed · 12383663
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Marc J Gollub. 2002-09-28. Virtual colonoscopy.. https://doi.org/10.1016/s0140-6736(02)11121-4
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CONTEXT: The current literature is unclear about the association between distal hyperplastic polyps and synchronous neoplasia (adenomatous polyps and cancer) in the proximal colon. OBJECTIVE: To estimate the prevalence of proximal neoplasia associated with distal hyperplastic polyps. DATA SOURCES: Database searches (medline and embase from 1966 to 2001) and manual search of the bibliographies of included and excluded studies, case reports, editorials, review articles, and textbooks of Gastroenterology. STUDY SELECTION: Studies describing the prevalence of proximal neoplasia in persons with distal hyperplastic polyps. DATA EXTRACTION: Demographics, clinical variables, study design, and prevalence of proximal neoplasia associated with various distal colorectal findings. DATA SYNTHESIS: Of 18 included studies, 12 involved asymptomatic individuals in which the pooled absolute risk of any proximal neoplasia associated with distal hyperplastic polyps was 25% (95% confidence interval [95% CI], 21% to 29%). In 4 studies where colonoscopy was performed irrespective of distal findings, the absolute risk was 21% (95% CI, 14% to 28%). The relative risk of finding any proximal neoplasia in persons with distal hyperplastic polyps was 1.3 (95% CI, 0.9 to 1.8) compared to those with no distal polyps. Among 6 studies of patients with symptoms or risk factors for neoplasia, the absolute risk of proximal neoplasia was 35% (95% CI, 32% to 39%) in persons with distal hyperplastic polyps. In 2 studies of screening colonoscopy, advanced proximal neoplasia (cancer, or a polyp with villous histology or severe dysplasia, or a tubular adenoma >/=1 cm) was present in 4% to 5% of persons with distal hyperplastic polyps, which was 1.5 to 2.6 times greater than in those with no distal polyps. CONCLUSIONS: In asymptomatic persons, a distal hyperplastic polyp is associated with a 21% to 25% risk for any proximal neoplasia and a 4% to 5% risk of advanced proximal neoplasia, and may justify examination of the proximal colon. Further study is needed to determine the risk of advanced proximal neoplasia associated with size and number of distal hyperplastic polyps.
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The interferon-inducible, double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays key roles in regulation of cell growth and differentiation, and has been postulated as a tumor suppressor. Downstream effectors of PKR include the translation initiation factor, eIF2alpha, and the transcription factor, NF-kappaB. We found elevated levels of PKR protein, dsRNA-dependent PKR autophosphorylation activity, and phosphorylated eIF2alpha in melanoma cells compared to nontransformed melanocytes in culture. Treatment with interferon-alpha2b further induced PKR expression and activity. Immunohistochemical analysis of primary melanomas demonstrated minimal PKR immunoreactivity, but melanoma lymph node metastases expressed a high level of PKR protein. Furthermore, analysis of colon cancer specimens revealed that transformation from normal mucosa to adenomas and carcinomas was coincident with an increase in PKR expression. These data do not support the concept of PKR as a classic tumor suppressor but instead suggest that PKR upregulation occurs at defined steps in cancer progression, probably as a cellular response to neoplasia.