Metachronous Colorectal Adenomas Occur Close to the Index Lesion.

GOALS: The aim of this study is to assess the spatial relationship between index and metachronous colorectal adenoma location. BACKGROUND: After the complete excision of a human sporadic colorectal adenoma, patients are at elevated risk of developing a further metachronous adenoma. Data regarding the occurrence site of a metachronous colorectal adenoma relative to the index adenoma are scarce. STUDY: Prospectively maintained databases were interrogated to identify all colonoscopies and adenoma excisions performed over a 10-year period at a single university teaching hospital. Data for the colonic segments at which adenoma removal were reported at index and all subsequent colonoscopies were extracted and 2 allied data sets merged. RESULTS: A total of 15,121 colonoscopies and 4759 polyp events were recorded. Four hundred fifty-two patients [296 male, 156 female, median (range) age 75 (32 to 100) y] developed at least 1 metachronous adenoma at follow-up colonoscopy. When single index events only are considered (ie, synchronous adenoma cases excluded), over 61% of metachronous adenomas were recorded in the same or an adjacent colonic segment. When the full span of the colon is considered, metachronous adenomas were more likely to occur in a section of the colon proximal to that of the index adenoma (41%±5%) than the same (39%±5%) or distal segment (20%±5%; P =0.006; 1-way χ 2 test). CONCLUSIONS: A metachronous human sporadic colorectal adenoma is more likely to be found in the same colonic segment to that of the index adenoma or 1 immediately adjacent. These data suggest a shared origin of metachronous adenoma with preceding lesions, supporting the existence of precancerous fields.

Nonelevation of serum CA 19-9 level in a true nonparasitic splenic cyst.

The diagnosis and management of true nonparasitic splenic cysts has markedly changed in recent years. The use of serum CA 19-9 has been increasingly advocated for diagnosis, while the advent of minimally invasive surgery has radically altered surgical management. We present the first case of a true nonparasitic splenic cyst in which serum CA 19-9 was not elevated. Treatment was by laparoscopic cyst decapsulation utilising the endoscopic Ligasure.

Interstitial cell cyclooxygenase-2 expression is associated with increased angiogenesis in human sporadic colorectal adenomas.

Cyclooxygenase (COX)-2 plays an important role in intestinal tumorigenesis and angiogenesis in animal models. In superficial areas of human sporadic colorectal adenomas, COX-2 is expressed predominantly by interstitial macrophages, in close proximity to microvessels. The aim of this study was to investigate the association between microvessel density (MVD) and COX-2 expression in human sporadic colorectal adenomas. Immunohistochemistry and immunofluorescence for CD31 and COX-2 were performed on a well-characterized series of human sporadic colorectal adenomas (n = 37). The mean MVD and COX-2 expression level (scored 0-3) in superficial and deep interstitial cells of adenomas were assessed by two independent observers. Superficial MVD was increased in COX-2-positive adenomas, compared with COX-2-negative adenomas (p = 0.037). There was a significant correlation between superficial MVD and increasing superficial interstitial cell COX-2 expression score (p = 0.048). COX-2-expressing interstitial cells aggregated in areas of high MVD. No relationship was evident between MVD and COX-2 expression in either deep interstitial cells or epithelial cells. Multivariate analysis demonstrated that only adenoma size (p = 0.005) was a significant independent predictor of MVD. COX-2 protein expression by superficial interstitial cells in human sporadic colorectal adenomas is associated with increased angiogenesis. Promotion of angiogenesis may play a role in the pro-tumourigenic activity of COX-2 during growth of human colorectal adenomas.

Analysis of cyclooxygenase expression in human colorectal adenomas.

INTRODUCTION: Evidence from rodent intestinal tumorigenesis models suggests that both cyclooxygenase-1 and cyclooxygenase-2 may play important roles in the development and progression of human sporadic colorectal adenomas. However, previous studies of cyclooxygenase isoform expression in human colorectal adenomas have produced conflicting data. Cyclooxygenase-1 expression has been poorly studied, and cyclooxygenase-2 positivity of adenomas has been variable depending on the detection technique used. It also remains unclear whether villous adenomas express cyclooxygenase-2. METHODS: Cyclooxygenase isoform expression in human sporadic colorectal adenomas was analyzed by reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry. RESULTS: Variable cyclooxygenase-1 expression was detected in all adenomas (n = 9) by both reverse transcription-polymerase chain reaction and Western blot analysis. Cyclooxygenase-2 expression was detected in eight (89 percent) of nine adenomas by reverse transcription-polymerase chain reaction and immunohistochemistry. Cyclooxygenase-2 protein was not detected by Western blot analysis in any adenoma. Cyclooxygenase-2 was expressed by all histopathologic types of adenoma and localized predominantly to superficial interstitial cells, in which it was associated with increased adenoma size. CONCLUSION: Cyclooxygenase-1 is expressed at variable levels by all adenomas. Cyclooxygenase-2 is expressed by the majority of adenomas, including those of the villous type, at levels below the sensitivity of Western blot analysis.

Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells.

In human colorectal adenomas or polyps, cyclooxygenase-2 is expressed predominantly by stromal (or interstitial) macrophages. Therefore, we tested the hypothesis that macrophage cyclooxygenase-2 has paracrine pro-tumorigenic activity using in vitro models of macrophage-epithelial cell interactions. We report that macrophages can promote tumorigenic progression of intestinal epithelial cells (evidenced by decreased cell-cell contact inhibition, increased proliferation and apoptosis, gain of anchorage-independent growth capability, decreased membranous E-cadherin expression, up-regulation of cyclooxygenase-2 expression, down-regulation of transforming growth factor-beta type II receptor expression and resistance to the anti-proliferative activity of transforming growth factor-beta(1)) in a paracrine, cyclooxygenase-2-dependent manner. Pharmacologically relevant concentrations (1-2 microM) of a selective cyclooxygenase-2 inhibitor had no detectable, direct effect on intestinal epithelial cells but inhibited the macrophage-epithelial cell signal mediating tumorigenic progression. Cyclooxygenase-2-mediated stromal-epithelial cell signalling during the early stages of intestinal tumorigenesis provides a novel target for chemoprevention of colorectal cancer (and other gastro-intestinal epithelial malignancies, which arise on a background of chronic inflammation, such as gastric cancer) and may explain the discrepancy between the concentrations of cyclooxygenase inhibitors required to produce anti-neoplastic effects in vitro and in vivo.