PubMed Health⌕ Search

Biomedical subjects

Edward M Copeland

Publications and source records attributed to Edward M Copeland.

At least 19 recordsLinked to original sources
PubMed2006

Delayed breast cellulitis: an evolving complication of breast conservation.

PURPOSE: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC. METHODS AND MATERIALS: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring >3 months after definitive surgery and >3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcome were analyzed to characterize the natural course of this syndrome. RESULTS: Of the 601 cases, 16%, 52%, and 32% were Stage 0, I, and II, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/seroma, removal of >5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC. CONCLUSION: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended.

Adult↗
PubMed2006

Preoperative radiotherapy alone or combined with chemotherapy followed by transanal excision for rectal adenocarcinoma.

OBJECTIVE: To evaluate the efficacy of preoperative radiotherapy (RT) and chemoradiation (CRT) followed by transanal excision (TAE) for rectal adenocarcinoma. METHODS: Thirty-two patients were treated between July 1988 and April 2004 and followed from 2 to 123 months (median, 27 months). RESULTS: The 3-year outcomes were: locoregional control, 79%; distant metastasis-free survival, 80%; cause-specific survival, 88%; and overall survival, 75%. Outcomes were better for patients with T1-T2 tumors and those who experienced a complete response to preoperative RT or CRT. Two patients (6%) had chronic RT proctitis after treatment. CONCLUSION: A select subset of patients with T2/T3 tumors will experience similar outcomes after preoperative RT or CRT and TAE compared with radical proctectomy. Reliably predictive clinicopathologic features to define this subgroup would best be elicited in the context of large prospective randomized trials, as would the optimal combination and schedule of systemic agents delivered in conjunction with preoperative RT. Patients who experience a complete response (cCR) after preoperative CRT are excellent candidates for TAE; those with less than a cCR have a less-favorable prognosis and are probably better treated with a low anterior resection or abdominal-perineal resection.

Adenocarcinoma↗
PubMed2005

Minimizing local recurrence after breast conserving therapy using intraoperative shaved margins to determine pathologic tumor clearance.

BACKGROUND: This study analyzed survival, locoregional recurrence, and reexcision rates after breast conserving therapy, based on the margin analysis technique used at the University of Florida, which incorporates frozen section analysis of shaved breast tissue from the lumpectomy cavity. STUDY DESIGN: A retrospective review was done of 257 patients who underwent 267 consecutive lumpectomy operations and completed radiation therapy at our institution. Margins in 189 patients were assessed using frozen section analysis of shaved margins from the lumpectomy cavity. RESULTS: Breast conserving therapy was performed for 220 (83%) patients with early breast cancer (T1 and T2 tumors) and 47 (17%) with ductal carcinoma in situ. With a median followup of 5.6 years, the crude locoregional recurrence rates for patients who had margins analyzed intraoperatively by frozen section analysis or margins analyzed by permanent analysis were 1.9% (3 of 157) and 3.1% (2 of 63), respectively, for early breast cancer and 15.6% (5 of 32) and 6.6% (1 of 15) for ductal carcinoma in situ (p=NS). Survival rates were 97% and 78%, at 5 and 10 years, respectively, for the early breast cancer patients, and 98% and 98%, respectively, for ductal carcinoma in situ patients. Permanent intraoperative frozen section analysis reexcision rates were 33.3% (26 of 78) and 5.8% (11 of 189). CONCLUSIONS: Regardless of the technique used for margin analysis, breast conserving therapy led to low locoregional recurrence relative to national figures, pointing to the importance of the technique of radiation therapy at our institution. Reexcision rate was reduced with the use of frozen section analysis.

Adult↗
PubMed2005

Accuracy of intraoperative frozen-section analysis of breast cancer lumpectomy-bed margins.

BACKGROUND: My colleagues and I have been using intraoperative frozen-section analysis (FSA) to evaluate lumpectomy margins in an attempt to reduce the number of additional operations that patients with ductal carcinoma in situ or stage I and II breast cancer would have to endure. We review our experience in breast-conservation therapy (BCT) at the University of Florida (Gainesville) to determine the effectiveness of this approach. STUDY DESIGN: Operative reports, operative logs, and pathology reports were retrospectively reviewed for patients who had BCT from January 2001 to January 2004. Ninety-seven patients (116 operations) were reviewed. RESULTS: Nineteen patients required an additional operation (19.6%). Forty-three patients had positive margins on paraffin-embedded histologic analysis (44.3%). Accuracy of FSA was 84% when evaluated on a per-case basis, and 96% on a per-slide basis. False negatives were identified in 22 patients, affecting the operative pathway of 19 patients (19.6%) and were identified more frequently in cases of ductal carcinoma in situ (p < 0.001). There were no false positives. Additional operative time required for FSA was approximately 13 minutes per case. Eighty-four (86.6%) patients had successful BCT and 13 patients (13.4%) required mastectomy. CONCLUSIONS: Intraoperative analysis of margins using FSA is effective at minimizing the number of additional operations, with 19 patients benefiting from immediate intervention in this study. The authors believe that the number of second operations prevented and the high BCT rates justify performing FSA. Ductal carcinoma in situ is more difficult to identify in FSA. Preoperative discussions with the patient should reflect these findings.

Adenocarcinoma, Mucinous↗
PubMed2004

Expression of VEGF receptors in cocultured neuroblastoma cells.

BACKGROUND: VEGF is best known for its angiogenic properties. We have found that VEGF expression is increased in neuroblastoma cells cocultured with hepatocytes. In addition, we have previously shown that neuroblastoma cells cultured with exogenous VEGF have an increase in the expression of VEGF receptors. Therefore, we hypothesized that the expression of VEGF receptors would be up-regulated in neuroblastoma cells grown in the coculture environment. MATERIALS AND METHODS: Two neuroblastoma cell lines (IMR-32 or SK-N-DZ) are used. These cells are cultured alone and in a coculture system with hepatocytes. Message for VEGF and the VEGF receptors KDR, flt-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2) are measured with RT-PCR. Flt-4, NRP-1, and NRP-2 protein expression is measured with Western blot. RESULTS: The receptors KDR and flt-1 are not detected in either cell line in either control or coculture conditions. Message for VEGF and flt-4 is significantly increased in the cocultured IMR-32 cells, while that for NRP-1 and NRP-2 is unchanged in these cells. VEGF and its receptors are unchanged in cocultured SK-N-DZ cells. CONCLUSIONS: Neuroblastoma cells express specific VEGF receptors that are differentially regulated in the different cell lines. These findings suggest that the heterogeneity of neuroblastomas may limit the utility of targeting VEGF and its receptors as sole treatments for the tumor, and that successful therapies will be dependent upon the specific biology of the tumor.

Blotting, Western↗
PubMed2004

Should decisions on internal mammary lymph node irradiation be based on current lymphoscintigraphy techniques for sentinel lymph node identification?

BACKGROUND: Treatment of internal mammary lymph node (IMN) metastases remains controversial because of the difficulty in predicting involvement, potential treatment-related morbidity, and questionable efficacy. Lymphoscintigraphy with sentinel lymph node biopsy offers a means to identify occult involvement of IMN, allowing appropriate patient selection for IMN treatment. METHODS: The authors retrospectively reviewed 262 lymphoscintigraphies (LS) of 248 patients treated at the University of Florida (Gainesville, FL) between 1998 and 2002. Tumor characteristics were assessed for their value in predicting IMN drainage and their association with IMN radiation. RESULTS: Lymph flow to the IMN was documented with LS in 23 of 262 tumor specimens (9%). Flow to the IMN was not correlated with any of the five factors: tumor location, tumor size, lymphovascular invasion, pathologic lymph node status, and laterality of the involved breast (right vs. left breast). Identification of IMN flow increased from 5.7% to 10.1% with the use of a deep injection technique. IMN radiotherapy was used more frequently in patients with larger tumors (15 of 188 in Tis/T1 vs. 31 of 70 in T2-T4; P<0.0001) and positive lymph nodes (17 of 91 in lymph node-negative patients vs. 28 of 66 in lymph node-positive patients; P<0.0001). In patients with T2N0 tumors (n=32), IMN radiotherapy was used more frequently with medial tumors (5 of 11 [45%]) than with lateral tumors (4 of 21 [19%]). CONCLUSIONS: The incidence of flow to the IMN documented with the current LS technique was low compared with other LS and extended radical mastectomy series. Histopathologic information was obtained for the sentinel IMN when IMN flow was identified on the LS. In the absence of histopathologic information, treatment decisions should continue to be based on clinical factors known to be correlated with occult IMN involvement.

Adult↗
PubMed2004

Breast-conserving therapy (BCT) for early-stage breast cancer.

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2003

Preoperative chemoradiation for locally advanced rectal adenocarcinoma-the University of Florida experience.

To evaluate the efficacy of preoperative radiotherapy alone or combine with chemotherapy. Between 1975 to 1997, 318 patients with locally advanced rectal adenocarcinomas were treated with preoperative radiation therapy. Between 1991 and 1997, approximately 60% of patients received fluorouracil (5-FU)-based adjuvant chemotherapy. Patients treated since 1991 had improved downstaging compared with those treated prior to 1991. Patients treated between 1991 and 1997 were also more likely to undergo a sphincter preserving surgical procedure. Preoperative chemoradiation probably results in improved downstaging and survival compared with preoperative irradiation alone.

Adenocarcinoma↗
PubMed2003

Differential expression of Bcl-2 and Bax may enhance neuroblastoma survival.

BACKGROUND/PURPOSE: Aggressive tumors may alter their expression of Bcl-2 proteins to decrease apoptosis and increase survival. The authors reported previously that neuroblastoma cells have diminished apoptosis when placed in coculture with hepatocytes to stimulate a metastatic environment. It was hypothesized that the expression of proapoptotic (Bax) and prosurvival (Bcl-2 and Mcl-1) proteins would be altered in neuroblastoma cells grown in a cell culture model of metastatic neuroblastoma. METHODS: Human neuroblastoma cells (IMR-32) were grown alone or in coculture with human hepatocytes for 2, 3, or 4 days. Bcl-2, Mcl-1, and Bax mRNA were measured with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Bcl-2, an antiapoptotic protein, was significantly increased in cocultured neuroblastoma cells by day 4. Bax, a proapoptotic protein, was significantly diminished by day 3. No significant change in Mcl-1 occurred in this study. CONCLUSIONS: When neuroblastoma cells placed in coculture, the prosurvival protein, Bcl-2, is upregulated whereas the proapoptotic protein, Bax, is downregulated. The combination of these changes can maximally enhance the survival rate of neuroblastoma cells in coculture. The propensity for neuroblastoma to either metastasize or regress may be associated with its ability to differentially regulate the expression of different members of the Bcl-2 protein family.

Apoptosis↗
PubMed2003

VEGF receptors are differentially expressed by neuroblastoma cells in culture.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) is best known for its angiogenic properties, but its mitogenic capacity may be more important for tumorigenesis. The ability of VEGF to induce specific biologic activities may be dependent on the amount and type of VEGF receptors present. The authors hypothesize that neuroblastoma cells express specific VEGF receptors and that their expression may be altered when the cells are exposed to differing cytokines and culture environments. METHODS: Four groups of human neuroblastoma cells (IMR-32) are studied. (1) Control cells: cultured in standard media. (2) VEGF cells: VEGF added to the media. (3) Tumor necrosis factor alpha (TNF-alpha) cells: TNF-alpha added to the media. (4) Serum starved cells: cultured in serum-depleted media. Reverse transcriptase polymerase chain reaction (RT-PCR) is utilized to measure the VEGF receptors flt-1, KDR/flk-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2). RESULTS: Flt-1 and KDR are not detected in any groups. Flt-4, NRP-1, and NRP-2 are present in the IMR-32 cells, and their expression is significantly increased by the administration of VEGF. Neuroblastoma cells cultured with TNF-alpha or in serum-depleted media have a significant decrease in the expression of these receptors. CONCLUSIONS: The authors show that neuroblastoma cells express specific VEGF receptors that may be altered by mitogenic or apoptotic stimuli. Specifically targeting VEGF and its receptors may be another therapeutic strategy for the treatment of neuroblastoma.

Culture Media, Serum-Free↗
PubMed2003

Antineoplastic therapy in colorectal cancer through proteasome inhibition.

Upregulation of nuclear factor (NF)-kappaB is found in many forms of cancer. Activation of NF-kappaB in cancer cells by chemotherapy or radiation can blunt the ability of this therapy to induce cell death. Proteasome inhibitors stimulate apoptosis in part via prevention of NF-kappaB activation. We sought to determine whether constitutive NF-kappaB activity is present in human colon cancer. In addition we studied whether alterations of NF-kappaB activity with a proteasome inhibitor would prevent colon cancer cell growth and induce apoptosis. We demonstrated constitutive transcriptional activation of NF-kappaB in SW48 and SW116 colon cancer cells by luciferase and electromobility shift assays. This was confirmed by p65 immunostaining. This activity was further induced in the presence of chemotherapy. In colon cancer specimens constitutive activation of NF-kappaB was observed in the majority of tumors. Treatment with the proteasome inhibitor (MG-132) inhibited growth and also stimulated apoptosis of colon cancer cells. We conclude that inhibition of NF-kappaB activation may be a logical therapy for certain cancers. This can be done via specific approaches on molecules necessary for keeping NF-kappaB inactivated in the cytoplasm. Other potentially useful ways to promote apoptosis in cancer cells include the utilization of proteasome inhibitors. Such inhibitors are currently being evaluated in clinical trials.

Animals↗
PubMed2002

Angiosarcoma after breast-conserving therapy: experience with hyperfractionated radiotherapy.

PURPOSE: To report our promising results of hyperfractionated radiotherapy (RT) in conjunction with surgery for angiosarcoma occurring after breast-conserving therapy for early-stage breast cancer. METHODS AND MATERIALS: Since 1997, 3 cases of angiosarcoma after breast-conserving therapy have been managed at the University of Florida. The histologic specimens in each case were reviewed and graded by one of us (J.D.R.). RESULTS: Explosive growth of discolored skin lesions coincident with histologic evidence of angiosarcoma characterized all 3 cases but was preceded by a fairly indolent period (almost 2 years) of atypical vascular hyperplasia in 2 patients. All 3 patients were treated initially with radical surgery for the angiosarcoma, but extensive recurrences were noted within 1 to 2 months of surgery. Because of the extremely rapid growth noted before and after surgery, hyperfractionated RT was used. Two of the patients underwent planned resection after RT, and neither specimen demonstrated any evidence of high-grade angiosarcoma. All 3 patients were alive without any recurrent disease 22, 38, and 39 months after treatment. CONCLUSIONS: Hyperfractionated irradiation appears to be effective treatment for rapidly proliferating angiosarcoma. For previously untreated angiosarcoma, we now recommend hyperfractionated RT followed by surgery to enhance disease control and remove as much reirradiated tissue as possible.

Aged↗
PubMed2002

Caspase 3 expression is altered in a coculture model of neuroblastoma.

BACKGROUND: Previously, we demonstrated that neuroblastoma cells cocultured with hepatocytes are protected from apoptosis, while apoptosis is upregulated in the hepatocytes. The mechanisms responsible for these findings are unknown. We hypothesize that caspase 3, a cysteine protease central to the apoptotic pathway, will be altered in this coculture model that simulates metastatic neuroblastoma. METHODS: Control human neuroblastoma cells and liver cells are plated in standard media. For the study group, a noncontact, coculture system is used. Hepatocytes are plated on cell culture inserts, placed above a growing layer of neuroblastoma cells, and incubated. Activated caspase 3 is measured after 1, 2, 3, or 4 days. RESULTS: Activated caspase 3 levels are significantly decreased in the cocultured neuroblastoma cells on days 2, 3, and 4. Conversely, cocultured hepatocytes have a significant increase in caspase 3 activation at all time periods, with the largest difference seen after 1 day in coculture. CONCLUSIONS: The capacity for neuroblastoma to differentially alter caspase 3 activation may provide a significant survival advantage for the neuroblastoma cells in metastatic environments. Understanding the mechanisms for this altered regulation may lead to improved and better targeted therapy for this malignancy.

Caspase 3↗