Full-thickness chest wall resection for recurrent breast carcinoma: an institutional review and meta-analysis

Locoregional recurrence of breast cancer can occur in up to 30 per cent of patients and has often been considered to indicate a poor prognosis. We reviewed our experience with full-thickness chest wall resection for recurrent breast cancer and conducted a meta-analysis of the English literature to determine patient characteristics and outcomes. Twenty-two women with isolated chest wall recurrence of breast cancer were treated between 1970 and 2000 at our institution. We reviewed their preoperative demographics, operative management and outcome, and combined our results with seven other English language studies. A majority of women (90%) underwent a mastectomy as initial management of their breast cancer. Only 18 per cent of patients had metastatic disease at the time of chest wall resection, and 71 per cent of patients had an R0 resection. The 5-year disease-free survival at City of Hope National Medical Center (COH) was 67 per cent and was 45 per cent for the entire group of 400 patients. The 5-year overall survival was 71 per cent for the COH group and 45 per cent for the entire group. Several studies reported prognostic factors, the most common being a better prognosis in patients with a disease-free interval greater than 24 months. Full-thickness chest wall resection for patients with isolated local recurrence of breast cancer can provide long-term palliation and even cure in some patients.     

The Role of Donor Bone Marrow Infusions in Withdrawal of Immunosuppression in Adult Liver Allotransplantation

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.     

The relationship between activity and ions in patients with metal-on-metal bearing hip prostheses

BACKGROUND: Total hip replacements with metal-on-metal bearings are frequently implanted in young, active patients. The relationship between patient activity and cobalt and chromium ion levels has not been investigated, to our knowledge. METHODS: Seven patients with well-functioning metal-on-metal bearing hip prostheses and one control subject (no implants), all with normal renal function, were monitored during a two-week-long activity protocol. Lower-extremity activity was continuously assessed with use of a computerized, two-dimensional accelerometer. During the first week, the subjects were requested to limit physical activity. The subjects then completed an hour-long treadmill test followed by a week in which they were encouraged to be as physically active as practically possible. Serum levels of cobalt and chromium ions and urine levels of chromium were assessed at ten time-points during these two weeks. RESULTS: Regardless of activity, the serum ion levels for a given patient were essentially constant and no correlation was found between patient activity and serum levels of cobalt or chromium, or urine levels of chromium. A mean increase in activity of 28% during the week of high-intensity activity was associated with a mean decrease of 2.7% in the serum cobalt level and a mean increase of 2.0% in the serum chromium level. During the treadmill test, a mean increase in activity of 1621% was associated with a mean increase of 3.0% in the serum cobalt level and a mean increase of 0.8% in the serum chromium level. These results fall within the variability for the measurement accuracy of these tests. CONCLUSIONS: For these patients, serum cobalt and chromium ion levels were not acutely affected by patient activity. Periodic measurements of serum ion levels could be used to monitor the tribologic (lubrication, friction, and wear) performance of a metal-on-metal bearing without adjusting for patient activity. Additional research is needed into the kinetics of ion production, transport, and excretion.     

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.     

Large cell carcinoma of the lung: a highly aggressive tumor with dismal prognosis

A retrospective review was made of 96 consecutive patients with large cell carcinoma of the lung admitted to Emory University Hospital over 10 years. Only 10 patients were seen with stage I lesions favorable for resection. The remainder were treated primarily with irradiation or chemotherapy. Mean survival for clinical stage I patients was 15.9 months; stage IIIA patients, 7.9 months; stage IIIB patients, 7.1 months; and stage IV patients, 5.8 months. Only 1 patient survived for 5 years. This distinct and highly aggressive form of lung cancer most commonly is seen at an advanced stage and is associated with an unusually dismal prognosis regardless of the method of treatment employed.     

Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration

PURPOSE: Senescent Ccl2(-/-) mice are reported to develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are also found to be associated with AMD. The authors generated Ccl2(-/-)/Cx3cr1(-/-) mice to establish a more characteristic and reproducible AMD model. METHODS: Single Ccl2- and Cx3cr1-deficient mice were crossbred to obtain Ccl2(-/-)/Cx3cr1(-/-) mice. Funduscopy, histopathology, retinal A2E quantification, proteomics, RT-PCR gene expression assay, immunochemistry, and Western blotting were used to examine the retina and to evaluate gene expression within the retinal tissue. RESULTS: By 6 weeks of age, all Ccl2(-/-)/Cx3cr1(-/-) mice developed AMD-like retinal lesions, including drusen, retinal pigment epithelium alteration, and photoreceptor degeneration. Furthermore, choroidal neovascularization occurred in 15% of the mice. These degenerative lesions progressed with age. A2E, a major lipofuscin fluorophore that accumulated during AMD progression, was significantly higher in the Ccl2(-/-)/Cx3cr1(-/-) retina than in the wild-type retina. Complement cofactor was higher in the Ccl2(-/-)/Cx3cr1(-/-) RPE. Proteomics data indicated that four proteins were differentially expressed in Ccl2(-/-)/Cx3cr1(-/-) retina compared with control. One of these proteins, ERp29, an endoplasmic reticulum protein, functions as an escort chaperone and in protein folding. CONCLUSIONS: The authors concluded that Ccl2(-/-)/Cx3cr1(-/-) mice develop a broad spectrum of AMD abnormalities with early onset and high penetrance. These observations implicate certain chemokines and endoplasmic reticulum proteins in AMD pathogenesis. Similar to the mechanism of neurodegeneration caused by dysfunction of endoplasmic reticulum proteins, decreased chaperoning may cause misfolded protein accumulation, leading to drusen formation and retinal degeneration.     

Iron toxicity as a potential factor in AMD

While it has been known for years that iron overload is associated with retinal degeneration in the context of ocular siderosis, intraocular hemorrhage, and the hereditary diseases aceruloplasminemia and pantothenate kinase associated neurodegeneration, recent evidence suggests that age-related macular degeneration (AMD) may also be exacerbated by retinal iron overload. In the retina, iron is necessary for normal cellular function. Iron overload, however, can cause retinal toxicity through the generation of oxygen free radicals. Histopathology of eyes with macular degeneration has shown elevated levels of iron in the retinal pigment epithelium, Bruch membrane, and within drusen, some of which was chelatable in vitro with deferoxamine. In this review, the authors summarize the evidence that iron overload may contribute to AMD pathogenesis. It is hoped that continued investigation of the role of iron and iron associated proteins in the retina will uncover clues to AMD pathogenesis and lead to new preventative or therapeutic options.