Adenocarcinomas of the jejunum and ileum: a 25-year experience.

Adenocarcinomas of the jejunum and ileum are rare gastrointestinal malignancies. Because few large published experiences exist, we reviewed patients with jejunal and ileal adenocarcinoma treated at our institution over the last 25 years. Between January 1976 and December 2001, 77 patients had an operation for a jejunal or ileal adenocarcinoma. Records were retrospectively reviewed for patient, tumor, and treatment variables. Factors affecting disease recurrence and patient survival were investigated. Fifty-two of the adenocarcinomas (67%) occurred in the jejunum and 25 occurred in the ileum (33%). Mean patient age was 63 +/- 14 years. Segmental bowel resection was performed in 50 patients (65%) with curative intent. Palliative operative procedures including resection or bypass were performed in 27 patients (35%). One (1%) patient had stage I, 18 (23%) stage II, 19 (25%) stage III, and 39 (51%) stage IV adenocarcinoma at diagnosis. Postoperatively, 12 patients had palliative and 18 adjuvant chemotherapy (n = 30), radiation therapy (n = 1), or combination treatment (n = 7). Median patient survival was 19 months. Sixty-six percent of patients who had a curative operation had a tumor relapse. Tumor stage had a highly significant effect (P < 0.0001) on median survival (72 months for stage I and II, 30 months for stage III, and 9 months for stage IV disease). In multivariate analysis of patients having curative treatment, tumor recurrence (P < 0.0001), stage (P < 0.0002), and weight loss (P < 0.001) were significant negative prognostic indicators. Most patients with adenocarcinoma of the jejunum or ileum present with advanced disease. Tumor stage, disease recurrence, and weight loss predicted patient outcome following a curative operation. Early recognition of these tumors requires a high index of suspicion.

Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors.

BACKGROUND: Malignant phyllodes tumor (MPT) is a rare but aggressive breast malignancy. The aim of this study was to evaluate parameters that influence outcome in patients with MPT. METHODS: Fifty women were diagnosed with MPT of the breast and treated between August 1971 and July 2000. All medical records were reviewed retrospectively. The Cox regression model was used for multivariate analysis. RESULTS: Tumors were classified as borderline (6%), low grade (32%), or high grade (62%). The median patient age was 46 years (range, 14-77 years). The median tumor diameter was 3.5 cm (range, 1.5-18 cm). Twenty-two patients had wide local excision (WLE), and 28 patients had mastectomy. The median follow-up was 91 months (range, 12-360 months). Local recurrence (LR) occurred in 16 patients (32%) an average of 26 months after surgery (median, 17 months; range, 3-72 months). Distant metastasis occurred in 13 patients (26%) at an average of 53.4 months (median, 36 months; range, 4-177 months). Sixteen (32%) patients have died of their disease. LR was significantly increased with stromal overgrowth (P < .0001), large tumor size (P = .0177), and surgical margins <1 cm (P = .0120), but not with WLE (P = .5099). Stromal overgrowth was the only independent variable predictive of systemic metastasis (P < .0001) and patient survival (P < .0001). CONCLUSIONS: Stromal overgrowth in MPT carries a grave prognosis. Close surgical margins and large tumor size, but not type of operation, significantly increased LR. Either WLE with adequate margins or mastectomy is an appropriate treatment for patients with MPT.

Synergistic effects of CTLA-4Ig and sirolimus on orthotopic lung-allograft survival and histology.

BACKGROUND AND AIMS: The combination of CTLA-4Ig with sirolimus can promote indefinite survival in allograft models for which CTLA-4Ig monotherapy is ineffective. We sought to determine whether a limited course of CTLA-4Ig and sirolimus would alter survival of rat orthotopic single-lung transplantations. METHODS: Left lungs of Brown Norway rats were transplanted into four groups of Lewis recipients (n=6 per group): group 1, no treatment; group 2, mCTLA-4Ig (250 microg/day for 4 days); group 3, sirolimus (3 mg/kg per day for 14 days); group 4, combined therapy with sirolimus and mCTLA-4Ig. Graft survival was determined by daily radiologic examination. Histologic grading of rejection and immunohistochemical staining for T and B lymphocytes were carried out at the time of radiologic graft loss. RESULTS: Rejection of lung allografts in group 1 occurred at a median of 6.5 days. Neither sirolimus nor mCTLA-4Ig monotherapy resulted in significant prolongation of graft survival (median 9.5 and 8.0 days, respectively). Graft survival in group 4 was significantly prolonged compared with all other groups (median 29.5 days), and a significant reduction in histologic grade of rejection was observed following combination therapy compared with all other groups. Infiltration by CD8+ve T cells at the time of rejection was proportionately greater than CD4+ve T-cell infiltration for groups 1, 2, and 3 but not for the combined-therapy group. CONCLUSIONS: A brief course of combined mCTLA-4Ig and sirolimus prolongs graft survival, reduces severity of rejection, and attenuates CD8+ve T-cell infiltration of fully major histocompatibility complex mismatched lung allografts.

Endothelial function in pigs transgenic for human complement regulating factor.

BACKGROUND: Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. Experiments were designed to characterize endothelial and smooth muscle function of arteries from pigs transgenic for hCD46. METHODS: Arterial blood from outbred pigs transgenic for hCD46 expression and nontransgenic animals of the same lineage was analyzed for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic endothelial cells were prepared for measurement of mRNA or activity for nitric oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were suspended in organ chambers for measurement of isometric tension. RESULTS: CNP was significantly greater, ACE was similar, and nitric oxide was significantly less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor activity of NOS differed between the groups. Endothelium-dependent relaxations to bradykinin and acetylcholine but not the calcium ionophore were shifted significantly to the left in femoral and pulmonary arteries from hCD46 transgenic pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did not inhibit relaxations in rings from transgenic pigs. CONCLUSIONS: Data suggest that expression of hCD46 on endothelium of pigs selectively augments endothelium-dependent relaxations to bradykinin by increased release of endothelium-derived factors other than nitric oxide. There does not seem to be any change in activity of ACE or NOS with expression of the human protein. Increased relaxations to bradykinin may be beneficial in lowering vascular resistance when transgenic organs are used for xenotransplantation.