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J Patrick O'Leary

Publications and source records attributed to J Patrick O'Leary.

7 recordsLinked to original sources
PubMed2003

Development of a novel in vitro human tissue-based angiogenesis assay to evaluate the effect of antiangiogenic drugs.

OBJECTIVE: To describe a novel in vitro human tissue-based angiogenic model that can predict an individual tumor's response to antiangiogenic drugs. SUMMARY BACKGROUND DATA: A number of in vitro and in vivo angiogenesis assays exist, but they do not provide potentially useful information for the treatment of an individual patient. Clonogenic assays have been used to evaluate the response of an individual's tumor to antineoplastic agents, but these tumor fragments are cultured in an environment that does not lead to neovessel growth. The authors have previously demonstrated that human vein disks or human tumor xenograft fragments incorporated into a 0.3% fibrin-thrombin clot will develop angiogenic vessel growth from the cut edge of the vessel disk or xenograft fragment. METHODS: Fresh human tumor or normal tissue disks (2 x 1 mm) from fresh surgical specimens were incorporated into fibrin-thrombin clots overlain with nutrient medium containing either 20% fetal bovine serum alone or in combination with Epothilone B, a tubulin inhibitor with antiangiogenic properties. Tissue disks were visually assessed over time to determine the percentage of wells that developed an angiogenic response. Neovessel growth, density, and length were graded at intervals using a semiquantitative visual neovessel growth-rating scheme (angiogenic index, 0-16 scale) devised in the authors' laboratory. RESULTS: Epothilone B treatment at doses of 10-6 mol/L and 10-8 mol/L decreased the number of wells that developed an invasive angiogenic response and limited the development of vessels that invaded the matrix. At these doses, Epothilone B also caused regression of vessels in wells that had been allowed to develop an angiogenic response. Treatment of tumors or normal tissues with Epothilone B at doses less than 10-8 mol/L was ineffective. CONCLUSIONS: Epothilone B may be an effective antiangiogenic agent in a variety of tumor types. The authors speculate that this in vitro model might provide useful information to the clinician on the effect of specific antiangiogenic agents on individual tumors. This may be particularly useful in patients with tumors that, as a group, are unresponsive to treatment with antineoplastic agents.

Angiogenesis Inhibitors↗
PubMed2002

Cytoreductive surgery in patients with advanced-stage carcinoid tumors.

The role of aggressive surgical resections as well as criteria for resectability in patients with advanced carcinoid tumors is not clearly defined. Thirty patients (17 male and 13 female) who were previously diagnosed to have "unresectable carcinoid disease" were treated using a multimodality approach over a period of 2 years. Extensive liver involvement was present in 28 of 30 (93%) of the cases. Small bowel involvement was noted in 22 of 30 (73%), and peritoneal/retroperitoneal/mesenteric invasion was observed in 15 of 30 (50%) of the cases. Three patients had remote metastases (brain, bone, and eye). Twenty of 30 (66%) patients had carcinoid syndrome with severely disabling symptoms. Eight patients (26%) had small bowel obstruction. All patients underwent at least one surgical exploration/intervention. Radiofrequency ablation (RFA) of one or more liver lesions was performed as an adjunct in 22 of 30 (73%) patients. Six patients (20%) had a second surgical procedure. There were 11 complications in eight patients (27%) after the initial operation. Median hospital stay for patients who underwent RFA only, RFA/liver resection, and liver resection with abdominal tumor debulking were 2, 4, 8, and 16 days respectively. Twenty-five of 30 patients (83%) showed symptomatic improvement. Mean pre- and postoperative Karnofsky physical performance scores were 55 and 85 respectively (P < 0.02). Small bowel obstruction was due to adhesions in five patients. All patients with intestinal obstruction had complete relief of their symptoms postoperatively. 5-Hydroxyindolacetic acid levels decreased by 50 per cent in all patients with follow-up determinations available. Aggressive surgical exploration and tumor debulking could be performed with significantly improved symptomatic outcome and relatively minor complications. Longer follow-up is needed for assessment of effect on survival.

Adolescent↗
PubMed2002

Colorectal cancer in patients younger than 40 years of age.

Previous studies have suggested a poor outcome for patients presenting with colorectal cancer under the age of 40 years. This study was conducted to evaluate the outcomes of these patients during a 10-year period at the Medical Center of Louisiana in New Orleans. A retrospective study was designed to review all patients under the age of 40 with a diagnosis of colorectal cancer from January 1990 to December 2000. There were 664 patients presenting with colorectal cancer during the 10-year period; of these 24 presented for surgery under the age of 40. There were 17 male and seven female patients. The median age was 35 years (range 22-39). Eleven (44%) patients had a positive family history of colorectal cancer. Seven lesions were right sided, one transverse, eight left sided, and eight rectal. Histologically 20 lesions were typical adenocarcinomas and four were mucinous. Twelve were stage IV, six stage III, five stage II, and one stage I. Twenty-one patients underwent resection, six with stoma formation; three patients had stoma formation only for a total of nine stomas (38%). The mean operative duration was 3.3 +/- 1.9 hours. The operative mortality was 4 per cent with a complication rate of 17 per cent. The eight rectal cancer patients received preoperative chemoradiation therapy (33%). Twelve (50%) patients with colon cancer received postoperative 5-fluorouracil-based chemotherapy. The mean survival for all patients was 24.7 +/- 23.2 months. Estimated 5-year survival using Kaplan-Meier analysis was 30 per cent. We conclude that colorectal cancer patients less than 40 years of age present at an advanced stage and tend to have a positive family history. In general patients tolerate surgery well, with stoma formation in more than one-third. Long-term survival is as predicted for their advanced stage of presentation. The study highlights the need for early diagnosis in this patient group.

Adenocarcinoma↗