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Colonic Neoplasms↗
Biomedical subjects
Joseph Willis
Publications and source records attributed to Joseph Willis.
Distinct inflammatory mechanisms mediate early versus late colitis in mice.
BACKGROUND & AIMS: Progression from the acute to chronic phase of inflammatory bowel disease cannot be easily evaluated in patients and has not been characterized in animal models. We report a longitudinal study investigating changes in the mucosal immune response in an experimental model of colitis. METHODS: Severity of colitis, body mass, stool consistency and blood content, serum amyloid A, and tissue histology were examined in interleukin (IL)-10-deficient mice over 35 weeks. The corresponding production of IL-12, IL-18, interferon gamma, tumor necrosis factor alpha, IL-4, and IL-13 by lamina propria mononuclear cells in the inflamed intestine was measured. Administration of neutralizing antibody to IL-12 at distinct times during disease progression permitted evaluation of its therapeutic potential. RESULTS: The clinical manifestations and intestinal inflammation delineated an early phase of colitis (10-24 weeks), characterized by a progressive increase in disease severity, followed by a late phase (>25 weeks), in which chronic inflammation persisted indefinitely. Lamina propria mononuclear cells from mice with early disease synthesized progressively greater quantities of IL-12 and interferon gamma, whereas production of both cytokines dramatically declined and returned to pre-disease levels in the late phase of colitis. Consistent with this pattern, neutralizing antibody to IL-12 reversed early, but not late, disease. In contrast, IL-4 and IL-13 production increased progressively from pre- to early to late disease. CONCLUSIONS: Colitis that develops in IL-10-deficient mice evolves into 2 distinct phases. IL-12 plays a pivotal role in early colitis, whereas its absence and the synthesis of IL-4 and IL-13 in late disease indicate that other immune mechanisms sustain chronic inflammation.
Acute Disease↗
Visualization of subsurface blood vessels by color Doppler optical coherence tomography in rats: before and after hemostatic therapy.
BACKGROUND: The ability to visualize subsurface blood vessels and measure flow may be useful in certain experimental and clinical settings. METHODS: Color Doppler optical coherence tomography was used to visualize and measure blood flow in subsurface vessels in vivo in a rat skin flap model. Local "hemostatic" interventions (epinephrine or sclerosant injection, heat probe, and laser) were then applied and imaging was repeated. The skin flap was evaluated histologically. RESULTS: Subsurface blood vessels were easily visualized in cross-section, and vessel diameter and bidirectional blood flow velocity were readily measured. Color Doppler optical coherence tomography demonstrated that flow was significantly reduced after epinephrine injection and became undetectable after the other interventions. This correlated with pathologic evidence of vessel damage in all interventions, except for epinephrine injection. Although vessel response was as predicted to most interventions, the response to epinephrine was only temporary, and limited application of heat alone from the heat probe halted flow without visually apparent surface injury. CONCLUSIONS: Color Doppler optical coherence tomography provides high-resolution, cross-sectional flow imaging in subsurface blood vessels. Color Doppler optical coherence tomography is potentially a better technique for the study of existing and new hemostatic intervention in the laboratory. Potential future clinical applications include monitoring of the response to hemostatic modalities.
Animals↗
Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma.
BACKGROUND: EUS-measured reduction in tumor size after neoadjuvant therapy has previously been correlated with downstaging and improved survival in patients with esophageal cancer. The aim of this study was to determine whether tumor changes measured by EUS correspond to pathologically assessed chemoradiotherapy-induced tumor regression. METHODS: Forty-one patients with esophageal cancer treated with combined modality treatment were studied. After initial EUS, patients completed a cisplatin/carboplatinum, 5-fluorouracil, and radiotherapy regimen and underwent repeat EUS before resection. A positive response on EUS was defined as a 50% reduction in maximal tumor cross-sectional area. Chemoradiotherapy-induced tumor regression was assessed in resection specimens by using a previously defined pathologic scoring system based on the extent of tumor proliferation into adjacent fibrosis. RESULTS: Pathologic tumor regression was present in 23, indeterminate in 5, and minimal or absent in 13 patients. EUS measured a positive response in 20 of 23 (87%) patients with CRT-induced tumor regression and a negative response in 10 of 13 (77%) patients with absent tumor regression (p < 0.001). EUS had a positive predictive value of 80% for pathologic tumor regression. CONCLUSIONS: Measurement of tumor size by EUS is a reliable clinical method for assessing pathologic tumor regression before surgery.
Adult↗