Faculty Bibliography

BACKGROUND: The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents. METHODS: To determine whether cenersen merits testing in larger efficacy studies, an exploratory study of cenersen in combination with idarubicin either alone or with 1 of 2 doses of cytarabine was performed in first-salvage AML patients. Patients who either had failed to respond to a single induction course or had responded to induction but relapsed within 12 months were enrolled. Stopping rules based on an expected 14% complete response (CR) rate were applied to each treatment arm. RESULTS: Fifty-three patients were treated, and none of the arms was terminated for lack of activity. Nearly all patients received a single course unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with incomplete platelet recovery). There was a positive trend for a better response rate with increasing intensity of chemotherapy in the patients refractory to front-line treatment compared with those who had relapsed previously. One-third (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high dose antioxidants) during treatment, and none of these responded to treatment. No unique toxicity was attributed to cenersen. CONCLUSION: The results of this study suggested that the combination of cenersen with chemotherapy may have clinical efficacy, and additional studies are warranted to explore its full potential.

ABSTRACT: BACKGROUND: Chondromyxoid fibromas (CMFs) are rare benign chondroid/myxoid matrix-producing tumors that occur in metaphyses of long tubular bones, and very rarely in small bones of hands and feet. Flat bone involvement is even more uncommon. Prior cytogenetic analyses have identified complex abnormalities involving chromosome 6 in the majority of cases. METHODS: A search for CMF over an 8-year period (1999-2006) from the surgical pathology files of our institution yielded 16 cases. Four cases occurred in relatively unusual regions, three from the small bones of distal extremities and one from the rib. The rib lesion wassubmitted forroutinecytogenetic analysis. RESULTS: Radiographic studies revealed that all four lesions were well-defined expansile radiolucent lesions which expanded the bony cortices with lobulated margins, sclerotic rim, septation, and no calcification. Morphologically, all four lesions showed typical features of CMF and had low proliferative index with Ki-67. Cytogenetic analysis on the rib lesion revealed a novel chromosomal translocation, t(1;5)(p13;p13). None of the four patients had a recurrence after a mean duration of follow-up of 24 months. CONCLUSION: CMF originating in unusual locations should be distinguished from chondrosarcomas, especially on small biopsies, and should be included in the differential diagnosis. As previously noted in the literature, the cells can be positive for actin but unlike conventional chondroid neoplasms can be negative for S-100. To our knowledge, this is the first report describing a novel chromosomal translocation, t(1;5)(p13;p13) in CMF

Chondroblastoma (CBL) is a benign neoplasm of bone for which the genomic characteristics remain unclear. We compared the status of allelic losses of CBL with that seen in a set of chondrosarcomas (CS) to determine whether differences in their natural history and behavior are also reflected genetically. Eleven cases of CBL and 10 cases of CS of different grades were included. Tumors were subjected to microdissection and polymerase chain reaction using 17 markers located near genes on chromosomes 5, 9, 11, 13, 17, and 19. The selected chromosomes are known to be involved in several mesenchymal neoplasms. Fluorescence in situ hybridization was also performed on tumors displaying allelic losses, with dual-color probes for 9p, 17p, and 13q. Fractional allelic losses per gene ranged from 18.2% to 63.7% in CBLs and from 28.6% to 66.7% in CSs. Loss of heterozygosity (LOH) of 5q, 9p, 11p, 13q, and 19q occurred in both CBLs and CSs. Loss of heterozygosity of 17p (p53 locus) occurred in 7 of 11 CBLs and in only 1 case of recurrent CS. The pattern of allelic loss was similar in low-grade CSs and CBLs. Loci with LOH in both tumor types suggest possible involvement of the genes p53, RB1, CDKN2/p16, ERC, and XRCC in tumorigenesis. Overall correlation between LOH and fluorescence in situ hybridization results was 90% with 17p13, 80% with 9p, and 60% with 13q. The role of p53 in CBL is uncertain; however, given the benign behavior of this tumor, it is probably unrelated to tumor progression

Historically, an adequate surgical procedure has been the most effective means of treating the majority of primary musculoskeletal sarcomas, and amputation has figured prominently in the surgical armamentarium. 4, 7, 9, 19, 21, 29, 41 The recent evidence that certain chemotherapeutic agents may have significant anti-sarcoma activity 2, 15, 17, 38 and coincident technical advances in irradiation therapy, radiographic localization, and reconstructive surgery have fostered enthusiastic interest in extremity-saving treatments. Almost all such treatments emphasize limb salvage as an alternative to amputation and are usually performed under a protective cloak of adjunctive chemotherapy, irradiation or immunoactive agents. 20, 23, 24, 30, 37, 39 Since neither chemotherapy nor irradiation therapy alone has been shown to assure long-term local control of bulk disease, surgical intervention remains an essential step in the overall management of musculoskeletal sarcomas. 3, 9, 17, 18, 29 Questions concerning the magnitude and timing of the surgical procedure are as unanswered as those relating to the most appropriate use of the adjuncts themselves. Increasingly, the surgeon and his patient are confronted with a bewildering array of therapeutic options, the long-term outcomes of which are unknown.These relatively rare sarcomas increasingly are distributed among a variety of treatment protocols in which multiple parameters differ. This trend necessitates interinstitutional cooperation if sufficient numbers of patients are to be available for the timely evaluation of treatments in clinical use.Such cooperation and even effective interinstitutional communication are seriously hampered by the lack of uniform language, so that meaningful comparison of treatments is currently impossible. Prime factors include the lack of a consistent definition of the surgery performed and a serviceable surgical staging system encompassing bone and soft tissue. Standard terminology will assure that like and unlike treatments are appropriately compared. Although an effective staging system should serve all members of the multidisciplinary team, the biologic behavior of musculoskeletal sarcomas suggests that the most useful staging system will articulate with the surgical procedure

Since vascular tortuosity of stenosis may preclude placement of the intra-aortic balloon, 63 consecutive patients (37 men) having routine Judkins' cardiac catheterization had an aortogram prior to withdrawal of the last catheter. No patient had a history of claudication, palpable aneurysms, pulse deficit, or bruit. No complications occurred. Significant peripheral vascular disease was found in ten patients: three had aortic, one had iliac, and six had femoral stenosis or tortuosity. All were men. The age of patients with peripheral vascular disease was 61.4 +/- 7.7 years, while those without were 56.9 +/- 9.3 years (P = NS). No difficulty was encountered entering the femoral artery in any patient; there was difficulty advancing the catheter in five of ten (50%) patients with peripheral vascular disease and in three of 54 (6%) patients without (P less than 0.002). Fifteen patients without peripheral vascular disease had normal coronary arteries, while none with peripheral vascular disease was normal. In patients with coronary disease, the number of vessels involved was the same in both groups. Peripheral vascular disease that might preclude placement of the intra-aortic balloon occurs in 14% of patients undergoing cardiac catheterization and 18% of patients with coronary artery disease. Aortography may be safely performed and should be considered during routine cardiac catheterization in patients who may require intra-aortic balloon placement.