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Kelly M McMasters

Publications and source records attributed to Kelly M McMasters.

89 records · Page 5Linked to original sources
PubMed2002

Update on the use of sentinel node biopsy in patients with melanoma: who and how.

This review highlights the utility of sentinel lymph node biopsy for melanoma. The histopathologic status of the sentinel lymph node is acknowledged as the most powerful indicator of prognosis. Changes by the American Joint Committee for Cancer have not only incorporated the importance of ulceration in cutaneous melanoma, but have focused on the number of metastatic lymph nodes as well as whether the disease is macro- or micrometastatic. Specific technical aspects of the sentinel lymph node procedure are discussed, with emphasis on practical guidelines to minimize incorrect nodal staging.

Clinical Trials as Topic↗
PubMed2002

Sentinel lymph node metastasis in anal melanoma: a case report.

Anal melanoma represents only 1% of all melanomas. Owing to delayed diagnosis and early metastasis, the prognosis is uniformly poor. Sentinel lymph node (SLN) biopsy has become the preferred method of nodal staging method for cutaneous melanoma. The role of SLN biopsy for staging of anal melanoma remains unclear. We report a 39-yr-old Caucasian woman who presented with a history of chronic hemorrhoidal pain. She noted a pedunculated peri-anal mass associated with bleeding. Upon biopsy, the lesion was found to be a 6-mm thick primary anal melanoma. There was no evidence of metastatic disease on preoperative imaging studies. She underwent wide local excision of the peri-anal site of the primary melanoma and intra-operative lymphatic mapping with both isosulfan blue and filtered technetium sulfur colloid. With the guidance a lymphoscintigram, ipsilateral inguinal sentinel lymphadenectomy identified five nodes, all of which were both "hot" and blue. One node was found to have a 1-mm metastatic deposit. Subsequently, the patient was treated with adjuvant radiation therapy to the primary site as well as to the superficial and deep inguinal nodal basins. She also received four cycles of biochemotherapy. SLN biopsy appears feasible for staging the superficial inguinal lymph nodes in patients with anal melanoma. However, the impact of SLN biopsy, early detection of occult metastasis, and adjuvant systemic and radiation therapy on the long-term survival of patients with anal melanoma is uncertain.

Adult↗
PubMed2002

Advances in the treatment of soft-tissue sarcomas.

Over 8000 newly diagnosed cases of sarcoma will occur in the United States this year. The family practitioner will encounter many soft-tissue masses, and the great majority of such masses will be benign. The clinician should maintain a high index of suspicion for lesions 5 cm or larger. Tissue diagnosis as well as accurate staging are important for optimal management. Limb salvage and improved prognosis are possible with the use of multimodality techniques. The goal in the overall management of soft-tissue sarcomas is a curative, yet functional, outcome. Adjuvant brachytherapy may be advantageous for patients who require but who are unable to receive daily external beam radiation. Treatment options, including some with targeted molecular therapies, are in the forefront of ongoing research.

Chemotherapy, Adjuvant↗
PubMed2002

State-of-the-art breast care: Multidisciplinary Breast Conference.

State-of-the-art breast care has become highly sophisticated over the past 20 years. Dialogue among participating breast imagers, pathologists, surgeons, medical oncologists, radiation oncologists, plastic and reconstructive surgeons, as well as genetic counselors, can only complement and enhance the care of the breast cancer patient. In an ongoing effort to offer an open forum to such breast care experts, the Multidisciplinary Breast Conference was launched in December 2000.

Breast Neoplasms↗
PubMedDate not supplied

The effect of lymphatic tumor burden on sentinel lymph node biopsy results.

Increasing tumor burden in the axilla, as determined by the number of positive lymph nodes, adversely affects sentinel lymph node (SLN) identification and false-negative rates. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective, multi-institutional study. All enrolled patients underwent SLN biopsy, followed by complete level I/II axillary dissection. Participating surgeons represent a variety of practice settings, mostly community-based private practice. A total of 229 surgeons enrolled 2206 patients between August 1997 and November 2000. SLN biopsy was performed using blue dye injection alone, radioactive colloid alone, or a combination of the two agents. Two key parameters used to measure SLN biopsy success are the SLN identification rate and SLN false-negative rate. The overall SLN identification and false-negative rates were 92.5% and 8.0%, respectively. With increasing numbers of positive axillary nodes, there was a decreased sentinel node identification rate. There was no difference in the false-negative rate with increasing axillary tumor burden. Increased tumor burden in the axilla (as determined by the mean number of positive nodes) is associated with failure to identify a SLN in some cases, but is not an explanation for false-negative results. Standard axillary dissection should be performed when a SLN cannot be identified.

Axilla↗
PubMedDate not supplied

Palpable breast carcinomas: a hypothesis for clinically relevant lymphatic drainage in sentinel lymph node biopsy.

Previous studies have shown that independent of tumor size, palpable breast tumors have a higher incidence of lymph node metastasis compared with nonpalpable tumors. This study further examines this phenomenon using a large sentinel lymph node (SLN) database. Data from a prospective, institutional review board (IRB)-approved, multi-institutional study from the University of Louisville Breast Cancer Sentinel Lymph Node Study Group was used. From August 1997 through December 2001, 3192 patients with clinical T1 and T2 N0 breast cancer underwent SLN biopsy, most with a combined technique of radioactive colloid and blue dye, followed by level I/II axillary dissection. Patients with palpable tumors tended to be younger (mean age 58 years) compared with nonpalpable tumors (mean age 61 years). The incidence of positive axillary metastasis was significant between palpable and nonpalpable tumors (43% and 23%, respectively), independent of tumor size by logistic regression (p = 0.0001). The SLN identification rate was significantly different between palpable and nonpalpable tumors (95% versus 91%, respectively; p < 0.0001). A unifying theory to explain the phenomenon that palpable tumors, stage for stage, are associated with a higher rate of nodal metastasis is that palpable tumors are, on average, closer to the skin and the rich network of dermal lymphatics. We believe that the dermal lymphatics of the breast represent a clinically relevant metastatic pathway to the axilla.

Age Factors↗
PubMedDate not supplied

Polymerase chain reaction in the staging of solid tumors.

Polymerasechain reaction (PCR) is a molecular biology technique that holds great promise as a way to perform molecular staging of cancer by detecting very early metastatic disease. Significant data suggest that PCR analysis may play an important role in the management of colorectal cancer in the future. However, for PCR staging of breast cancer, progress awaits identification of gene markers that have sufficient sensitivity and specificity. Within the next few years, the results of the Sunbelt Melanoma Trial and other ongoing studies will determine whether PCR evaluation of sentinel lymph nodes and peripheral blood cells has prognostic relevance in melanoma. The future of cancer management will likely revolve around the molecular staging of tumors, and PCR is but one method that may better define subgroups of patients that are appropriate candidates forvarious anticancer therapies.

Biomarkers, Tumor↗
PubMedDate not supplied

Sentinel lymph node biopsy for breast cancer: improvement in results over time.

Many modifications in the technique of sentinel lymph node (SLN) biopsy for breast cancer have taken place since it was first introduced. This analysis was undertaken to determine, in a large multi-institutional study, whether SLN biopsy results have improved over time. Patients with clinical stage T1-2, N0 breast cancer were enrolled in this prospective study between August 1997 and February 2002. SLN biopsy was performed using blue dye and/or radioactive colloid along with completion level I/II axillary dissection in all patients. The majority of subjects included in this study represent the surgeons' initial experience with SLN biopsy for breast cancer. Statistical comparison of the SLN identification (ID) rate and false-negative (FN) rate were performed by chi-squared analysis. A total of 3370 subjects from 300 surgeons were enrolled in the study. Collectively the SLN ID rate, as well as the mean number of SLNs removed per patient has improved, while the FN rate has remained fairly constant over time. The improved ID rate may be related to improved technical details, while the FN rate has not changed significantly. This highlights the ongoing need for surgeons to perform backup axillary dissection during their initial learning phase.

Adult↗
PubMedDate not supplied

Acceptance of sentinel lymph node biopsy of the breast by all general surgeons in kentucky.

Sentinel lymph node biopsy (SLNB) for breast cancer is now performed routinely in many U.S. medical centers. The acceptance of SLNB in the community and in rural medical centers, however, has not been accurately defined. The purpose of this study was to assess how surgeons in Kentucky, a predominantly rural state, have incorporated SLNB into practice. General surgeons in the state of Kentucky were identified by registration with the state medical association. All general surgeons (n=272) in the state were mailed the questionnaire, with 93% (n=252) responding. Overall, 172 defined themselves as rural surgeons. Among the rural surgeons, 87% perform breast cancer operations and 54% perform SLNB. In comparison, 74% of nonrural surgeons perform breast cancer operations and 80% perform SLNB. A majority of nonrural surgeons (73%) have performed SLNB for more than 2 years when compared to rural surgeons (73% versus 37%, respectively; p<0.0001). Planned backup axillary node dissection was stopped by both rural (26%) and community (39%) surgeons after 10 cases (14% rural, 19% nonrural) or 11--20 cases (12% rural, 20% nonrural). Surgeons reported using SLNB for the following diagnoses: invasive cancer (98%), ductal carcinoma in situ (DCIS) (43%), and lobular carcinoma in situ (LCIS) (11%). The majority of surgeons (87%) reported a greater than 90% SLN identification rate. SLNB has become widely accepted by surgeons in both rural and nonrural medical centers in Kentucky. However, there has been considerable variability in the number of training cases surgeons have performed prior to abandoning routine axillary dissection. This indicates a need for continuing educational efforts aimed at quality assurance.

Breast Neoplasms↗
PubMedDate not supplied

E2F-1 gene therapy induces apoptosis and increases chemosensitivity in human pancreatic carcinoma cells.

Pancreatic cancer is often resistant to conventional chemotherapy. In this study, we examined the role of adenovirus-mediated overexpression of E2F-1 in inducing apoptosis and increasing the sensitivity of pancreatic cancer cells to chemotherapeutic agents. MIA PaCa-2 pancreatic head exocrine adenocarcinoma cells (mutant p53) were treated by mock infection or adenoviruses expressing beta-galactosidase or E2F-1 (Ad-E2F-1) alone or in combination with sublethal concentrations of each chemotherapeutic drug. Cell growth and viability were assessed at selected time points. Apoptosis was evaluated by flow cytometry, characteristic changes in cell morphology and poly (ADP-ribose) polymerase (PARP) cleavage. Western blot analysis was used to examine the expression of E2F-1 and Bcl-2 family member proteins and PARP cleavage. Western blot analysis revealed marked overexpression of E2F-1 at a multiplicity of infection (MOI) of 20 and 70. By 3 days after infection, Ad-E2F-1 treatment at an MOI of 70 resulted in approximately a 20-fold reduction in cell growth and 60% reduction in cell viability as compared to mock-infected cells. Cell cycle analysis, PARP cleavage and changes in cell morphology supported apoptosis as the mechanism of cell death in response to E2F-1. In order to test the efficacy of treatment with a combination of gene therapy and chemotherapy, we utilized concentrations of Ad-E2F-1 which reduced viability to 50% in combination with each chemotherapeutic agent. Cotreatment of the cells with E2F-1 virus and roscovitine (ROS) or etoposide resulted in an additive effect on cell growth inhibition and induction of apoptosis. Interestingly, 5-fluorouracil did not cooperate with Ad-E2F-1 in the mediation of tumor death or inhibition of cell growth. Immunoblotting for Bcl-2 family members revealed no significant changes in the expression levels of Bcl-2, Bcl X(L), Bax or Bak following gene or 'chemogene' therapy with E2F-1. However, a Bax cleavage product was noted which was substantially increased by cotreatment with ROS or etoposide. E2F-1 overexpression initiates apoptosis and suppresses growth in pancreatic MIA PaCa-2 cells in vitro. E2F-1-mediated apoptosis was not associated with significant changes in the expression of Bcl-2 family member proteins in these pancreatic cancer cells. ROS and etoposide, when combined with E2F-1 overexpression, induce apoptosis in an additive manner. This chemogene combination may provide a potentially useful therapeutic strategy for advanced pancreatic cancer.

Adenoviruses, Human↗
PubMedDate not supplied

Inhibition of cyclin A kinase activity in E2F-1 chemogene therapy of colon cancer.

Adenoviral-mediated gene transfer of the apoptotic gene E2F-1 has been shown to induce apoptosis in a variety of tumor cells and acts in an additive or cooperative fashion with several specific chemotherapeutic agents to induce tumor cell death. The apoptotic function of E2F-1 is dependent on its ability to bind DNA; cyclin A kinase activity has been shown to negatively regulate the DNA-binding capacity of E2F-1. In the present study, we sought to determine whether cyclin A kinase activity is involved in mediating the interaction between E2F-1 and chemotherapeutic agents in colon cancer cells. Therefore, human colon adenocarcinoma (SW620) cells were treated with an adenovirus expressing E2F-1 (Ad-E2F-1, multiplicity of infection 20). Immediately following infection, a panel of conventional chemotherapeutic agents with varying modes of cytotoxic action were administered at LD(25 )doses. Three days following treatment, viability and growth inhibition were determined by trypan blue exclusion assay. Apoptosis was confirmed using cellular morphology, poly (ADP-ribose) polymerase cleavage, and flow-cytometric analysis. E2F-1 overexpression and cyclin A protein expression were monitored by immunoblot, and cyclin A kinase activity was determined by kinase assay. Vincristine (VIN), camptothecin (CPT), and actinomycin D were found to have a cooperative (>38% over the additive single therapy values) effect on E2F-1-mediated apoptosis. Etoposide, cisplatin (CIS), and 5-fluorouracil (5-FU) showed the least cooperation ( 0.1) compared to Ad-E2F-1 treatment alone. Combination of Ad-LacZ/5-FU and Ad-LacZ/actinomycin D significantly inhibited cyclin A kinase activity compared to Ad-LacZ treatment alone (p < 0.005). No other Ad-LacZ/drug combinations significantly affected cyclin A kinase activity (p > 0.05). In conclusion, combinations of E2F-1 adenovirus and VIN, CPT, or actinomycin D at LD(25 )had significant cooperative effects on colon cancer apoptotic cell death in vitro. Although inhibition of cyclin A kinase activity was observed in most Ad-E2F-1/drug combination treatments compared to Ad-E2F-1 treatment alone, there was no consistent correlation between degree of inhibition of cyclin A kinase activity and the cooperative effect. Nonetheless, inhibition of cyclin A kinase activity may be an important mechanism by which the chemogene therapy effects involving E2F-1 are modulated.

Adenocarcinoma↗
PubMedDate not supplied

Increased mdm-2 expression in a p53-independent manner blocks UV-induced cell cycle arrest and apoptosis in human osteosarcoma cells.

DNA damage results in an increase in P53 levels, which is required to initiate a P53-mediated cell cycle arrest and/or apoptosis. P53 and MDM-2 form a feedback control loop: while P53 can transactivate the MDM-2 gene, high levels of MDM-2 inhibit P53 transactivation as well as promote rapid degradation of P53. In the present study, we investigated the interaction between endogenous MDM-2 and P53 following UV-induced DNA damage in an MDM-2 overexpression cell line. A human osteosarcoma cell line (OsACL, which contains wild-type P53 and overexpresses MDM-2 protein) was used in this study. Here we show that following UV treatment, P53 levels increased in the OsACL cells despite the presence of high-level endogenous MDM-2; however, CAT assays using a P53 reporter system revealed that this P53 was transcriptionally inactive. Although P53 transactivation was inhibited, MDM-2 levels rose markedly following UV irradiation. Northern blot analysis revealed that the increase in MDM-2 protein levels was a result of increased levels of MDM-2 mRNA, possibly due to increased transcription. Cell cycle analysis revealed that OsACL cells were markedly resistant to UV-induced apoptosis. Transfection of OsACL cells with an anti-sense MDM-2 plasmid dowregulated MDM-2 expression and increased UV-induced apoptosis. In conclusion, MDM-2 overexpression can block UV-induced cell cycle arrest and apoptosis by inhibiting P53 transcriptional activity. Furthermore, increased expression of MDM-2 in OsACL cells following UV irradiation appears to be related to P53-independent mechanisms.

Animals↗
PubMedDate not supplied

Subareolar injection of 99mTc facilitates sentinel lymph node identification.

BACKGROUND: Sentinel lymph node (SLN) biopsy with the standard intraparenchymal injection has been accepted as an alternative to routine axillary dissection for patients with breast cancer. However, the identification and false-negative rates with this method can vary widely from surgeon to surgeon. The subareolar location contains a rich lymphatic network and represents a potential site of injection for SLN identification. METHODS: Between August 1, 1999, and December 31, 2000, we performed 159 SLN biopsy procedures on 158 patients with breast cancer. For each patient, 99mTc-labeled sulfur colloid was injected into the subareolar location, and 1% isosulfan blue dye was given as an intraparenchymal injection. RESULTS: In every case, at least one radioactive SLN was identified with the subareolar injection of technetium; a blue SLN was found in 97% of the cases. The blue SLN was also radioactive in 98% of the cases, indicating that the blue dye injected around the tumor and the technetium injected into the subareolar location drained to the same SLN. CONCLUSIONS: Subareolar injection of technetium can improve SLN identification rates for breast cancer. The simplicity and accuracy of this technique may also reduce the variable results reported with the standard intraparenchymal method.

Adult↗
PubMedDate not supplied

Sentinel lymph node biopsy for head and neck melanomas.

BACKGROUND: Sentinel lymph node (SLN) biopsy for head and neck (H&N) melanomas may be more technically challenging compared with other locations because of complex lymphatic drainage patterns. This analysis was performed to compare the results of SLN biopsy for H&N, truncal, and extremity melanomas. METHODS: The Sunbelt Melanoma Trial includes patients aged 18 to 70 with melanomas > or = 1.0 mm thick. Statistical comparison was performed by chi2 or analysis of variance test. RESULTS: A total of 2610 patients were evaluated with a median follow-up of 18 months. The mean number of SLN per nodal basin was 2.8, 2.7, and 2.1 for H&N, truncal, and extremity melanomas, respectively. Median Clark level, Breslow thickness, and percentage of ulceration were similar between the groups. Peri-parotid SLN was identified in 25% of cases; there were no facial nerve injuries. SLN biopsy for H&N melanoma had higher false-negative rates at 1.5% (vs. 0.5% for trunk or extremity) but less histologically positive SLN at 15% (vs. 23.4%, and 19.5%; P <.001) compared with truncal and extremity melanoma. Blue dye was visualized less frequently in SLN of H&N melanoma patients compared with those with trunk or extremity melanomas. CONCLUSIONS: Preoperative lymphoscintigraphy and meticulous intraoperative search for blue/radioactive nodes may improve results in H&N melanomas.

Adolescent↗
PubMedDate not supplied

An evidence-based staging system for cutaneous melanoma.

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.

Databases, Factual↗
PubMedDate not supplied

Alteration of gene expression in melanoma cells following combined treatment with E2F-1 and doxorubicin.

BACKGROUND: The combination of E2F-1 gene therapy and chemotherapy produces a synergistic effect on melanoma cell apoptosis. However, the molecular mechanisms have not been fully elucidated. The purpose of this study was to identify novel genes or pathways that may play key roles in apoptosis when E2F-1 gene therapy is combined with doxorubicin chemotherapy. MATERIALS AND METHODS: SK-MEL-2 melanoma cells were infected with Ad-E2F-1 alone, Ad-E2F-1 plus doxorubicin, or Ad-LacZ plus doxorubicin. After 16 hours of treatment, the total RNA was extracted from these cells and subjected to microarray analysis. Quantitative real-time PCR was performed to confirm the microarray data. RESULTS: Our results showed that the combination treatment of Ad-E2F-1 and doxorubicin affected the expression of cytokines, transcription factors, as well as genes involved in signal transduction, cell cycle regulation and apoptosis. CONCLUSION: Our findings have identified, for the first time, novel molecular targets and pathways that led to apoptosis in melanoma cells when Ad-E2F-1 was combined with doxorubicin. The molecular information provided here will enhance further mechanistic studies.

Adenoviridae↗