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Kelly K Hunt

Publications and source records attributed to Kelly K Hunt.

At least 91 records · Page 5Linked to original sources
PubMed2004

Factors predictive of having four or more positive axillary lymph nodes in patients with positive sentinel lymph nodes: implications for selection of radiation fields.

PURPOSE: The optimal design of radiation fields for patients with positive sentinel lymph nodes (SLNs) who do not undergo axillary dissection is unknown. We have previously shown that modified breast tangent fields can include most axillary Level I-II lymph nodes. We have also reported that irradiation of the axillary apex/supraclavicular fossa is indicated for patients with four or more positive axillary lymph nodes. To determine the optimal arrangement for patients with positive SLNs, we studied what factors predicted for having four or more positive lymph nodes. METHODS AND MATERIALS: We reviewed the records of 339 consecutive patients with one to three positive SLNs who underwent complete axillary dissection at our institution between 1995 and 2002. We separately analyzed the outcome for those initially treated with surgery (n = 265) and those receiving neoadjuvant chemotherapy (n = 74). A logistic regression model was used to identify independent factors predictive for four or more positive lymph nodes. RESULTS: A total of 28 of 265 patients in the initial surgery group and 20 of 74 patients in the neoadjuvant group had four or more positive lymph nodes. In the initial surgery group, the independent factors associated with four or more positive lymph nodes were no drainage seen on lymphoscintigraphy (rate, 38%, odds ratio [OR] = 5.4, p = 0.03), more than one positive SLN (rate, 24-42%, OR = 2.9, p = 0.02), and lymphovascular space invasion (LVSI; rate, 25%, OR = 4.8, p = 0.01). Of the 106 patients without any of these factors, only 2 had four or more positive lymph nodes. For the patients treated with neoadjuvant chemotherapy, the independent factors were clinical Stage III (rate, 48%, OR = 3.1, p = 0.03), more than one positive SLN (rate, 37-67%, OR = 4.8, p = 0.03), and LVSI (rate, 62%, OR = 8.1, p = 0.02). Of the 28 patients without any of these factors, only 1 had four or more positive lymph nodes. CONCLUSION: It is reasonable to treat with modified tangents fields that include most axillary Level I-II nodes for patients with one positive SLN who do not undergo axillary dissection if drainage is seen on lymphoscintigraphy and no LVSI is present. This approach is also reasonable for patients treated with neoadjuvant chemotherapy who have Stage II disease, no LVSI, and only one positive SLN. The remaining patients have a greater risk of having four or more positive lymph nodes, and, therefore, the high axilla/supraclavicular fossa should also be included in the radiation fields.

Adult↗
PubMed2004

Prospective evaluation of a novel approach for the use of a quantitative galactose oxidase-Schiff reaction in ductal fluid samples from women with breast carcinoma.

BACKGROUND: The galactose oxidase-Schiff reaction (GOS) yields positive findings in a number of malignant solid tumors. The goals of the current study were to develop a novel technique for quantifying GOS reactivity in nipple aspirate fluid (NAF) samples from women with invasive breast carcinoma and to assess the clinical utility of the technique in this setting. METHODS: Patients with biopsy-proven unilateral invasive breast carcinoma were eligible for study entry. Before definitive surgery, NAF samples were obtained from healthy breast tissue and malignant breast tissue from 23 women with breast carcinoma. Under blind conditions with respect to clinical data, 10 microL NAF samples were applied to a glass fiber membrane and incubated with 100 microL galactose oxidase and 1 mL Schiff reagent. The stain was developed and the color reaction quantitated by measuring hue (shade) and chroma (intensity) using a spectrophotometer. RESULTS: GOS reactivity was quantitated using two color parameters, hue and chroma. Because chroma varies with concentration, this measurement was adjusted for the concentration of NAF in each sample. After adjustment for NAF concentration, chroma was found to be statistically significantly different in the affected breast tissue sample and the healthy contralateral internal control sample (P = 0.001). CONCLUSIONS: A quantitative measure of GOS reactivity based on spectrophotometric measurement of intensity of color has been developed and was found to be significantly different in the affected breast compared with the unaffected breast in the current population of patients with breast carcinoma. The preliminary results support further exploration of this novel quantitative test in patients with breast carcinoma.

Adult↗
PubMed2004

Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience.

PURPOSE: To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. PATIENTS AND METHODS: Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. RESULTS: At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1-2 v T3-4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P =.19). CONCLUSION: Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.

Adult↗
PubMed2004

Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer.

INTRODUCTION: Sentinel lymph node (SLN) biopsy allows identification of the first lymph node into which a primary tumor drains. In breast cancer, identification of tumor cells in the SLNs is a predictor of the tumor's metastatic potential. In the present article, we tested the hypotheses that a positive immune response can occur in tumor-free SLNs and that the activation state of dendritic cells (DCs), the major antigen presenting cells within SLNs, predicts the immune status and metastatic potential of the tumor. METHODS: Fifty paraffin-embedded SLN sections, 25 tumor-free and 25 tumor-containing, from patients with breast cancer were analyzed by immunohistochemistry to determine the immune maturation state of their DCs. In addition, 12 lymph nodes from noncancer-containing breasts were analyzed. Tissues were stained with antibodies against CD3, MHC class II, CD1a, CD83, IL-10, and IL-12. Mature DCs were defined by CD83 expression and immature DCs by CD1a expression. RESULTS: We found a trend toward higher numbers of mature CD83-positive DCs in tumor-free SLNs than in tumor-containing SLNs (P = 0.07). In addition, tumor-free SLNs were more likely to contain cells expressing IL-10 (P = 0.02) and, to a lesser extent, IL-12 (P = 0.12). In contrast, when all SLNs, both tumor-free and tumor-containing, were compared with uninvolved lymph nodes, the numbers of mature and immature DCs were similar. CONCLUSIONS: Our results suggest tumor-free SLNs are immunologically competent and potentially a site of tumor-specific T-cell activation, as evidenced by the presence of greater numbers of mature DCs and cytokine-producing cells in tumor-free SLNs.

Adult↗
PubMed2004

Antitumor activity of IFIX, a novel interferon-inducible HIN-200 gene, in breast cancer.

We identified IFIX as a new member of the hematopoietic interferon (IFN)-inducible nuclear protein with the 200-amino-acid repeat (HIN-200) family. Six different alternatively spliced forms of mRNA are transcribed from the IFIX gene, which are predicted to encode six different isoforms of IFIX proteins (IFIXalpha1, alpha2, beta1, beta2, gamma1, and gamma2). The IFIX proteins are primarily localized in the nucleus. They share a common N-terminal region that contains a predicted pyrin domain and a putative nuclear localization signal. Unlike IFIXalpha and IFIXbeta, IFIXgamma isoforms do not have the 200-amino-acid signature motif. Interestingly, the expression of IFIX was reduced in most human breast tumors and breast cancer cell lines. Expression of IFIXalpha1, the longest isoform of IFIX, in human breast cancer cell lines reduced their anchorage-dependent and -independent growth in vitro and tumorigenicity in nude mice. Moreover, a liposome-mediated IFIXalpha1 gene transfer suppressed the growth of already-formed tumors in a breast cancer xenograft model. IFIXalpha1 appears to suppress the growth of breast cancer cells in a pRB- and p53-independent manner by increasing the expression of the cyclin-dependent kinase inhibitor p21(CIP1), which leads to the reduction of the kinase activity of both Cdk2 and p34(Cdc2). Together, our results show that IFIXalpha1 possesses a tumor-suppressor activity and suggest IFIXalpha1 may be used as a therapeutic agent in cancer treatment.

Alternative Splicing↗
PubMed2004

A prospective evaluation of radiocolloid and immunohistochemical staining in colon carcinoma lymphatic mapping.

BACKGROUND: Although the utility of lymphatic mapping (LM) and sentinel lymph node (SLN) biopsy in patients with melanoma and breast carcinoma has been well documented, this same is not true for patients with colon carcinoma. The authors previously reported a high false-negative rate for SLN biopsy in patients with colon carcinoma using isosulfan blue dye alone. The objective of the current study was to determine whether radiocolloid would increase the sensitivity of LM/SLN biopsy in patients with colon carcinoma. METHODS: The authors performed LM on 57 patients with colon carcinoma using both isosulfan blue dye and radiocolloid. The SLN(s) were identified by either their blue color or by increased radioactivity. The SLNs then underwent both routine histologic sectioning and immunohistochemical (IHC) staining for cytokeratins. RESULTS: An SLN was identified in 56 patients (98%). Radiocolloid was able to identify only 1 additional positive SLN (9%). Overall, it was found that the disease had metastasized to the lymph nodes in 22 patients, even though there was no evidence of disease in the SLN(s) in 11 of those 22 patients on routine histologic sectioning (false-negative rate, 50%; sensitivity, 50%). In five patients, IHC of the SLN was the only indicator of metastatic disease. The inclusion of IHC-positive SLNs in these calculations would decrease the false-negative rate to 17% and would increase the sensitivity of SLN biopsy to 83%. CONCLUSIONS: In the current study, the addition of radiocolloid did not increase the sensitivity of detection of positive SLN(s) compared with the use of isosulfan blue dye alone. IHC of the SLN potentially may increase the sensitivity of LM and reduce the false-negative rate. However, the long-term prognostic significance of IHC in patients with colon carcinoma remains controversial.

Adult↗
PubMed2004

T3 disease at presentation or pathologic involvement of four or more lymph nodes predict for locoregional recurrence in stage II breast cancer treated with neoadjuvant chemotherapy and mastectomy without radiotherapy.

PURPOSE: To help define the clinical and pathologic predictors of locoregional recurrence (LRR) in breast cancer patients treated with neoadjuvant chemotherapy and mastectomy without radiotherapy for early-stage disease. METHODS AND MATERIALS: We retrospectively reviewed the outcomes of all 132 patients with Stage I or II breast cancer treated in prospective institutional trials with neoadjuvant chemotherapy and mastectomy without radiotherapy between 1974 and 2001. The clinical stage (American Joint Committee on Cancer 1988) at diagnosis was I in 5%, IIA in 46%, and IIB in 49% of patients. The median age at diagnosis was 49 years. All patients were treated with either a doxorubicin-based neoadjuvant regimen or single-agent paclitaxel. The total LRR rates were calculated by the Kaplan-Meier method, and comparisons were made with two-sided log-rank tests. The median follow-up was 46 months. RESULTS: The actuarial LRR rate at both 5 and 10 years was 10%. Factors that correlated positively with LRR included clinical Stage T3N0 (p = 0.0057), four or more positive lymph nodes at surgery (p = 0.0001), age < or =40 years at diagnosis (p = 0.0001), and no use of tamoxifen. In the patients who did not receive tamoxifen, estrogen receptor-positive disease correlated positively with LRR (p = 0.0067). The 5-year LRR rate for the 42 patients with clinical Stage T1 or T2 disease and one to three positive lymph nodes at surgery was 5% (only two events). CONCLUSIONS: For patients with clinical Stage II breast cancer, T3 primary disease, four or more positive lymph nodes after chemotherapy, and age < or =40 years old predicted for LRR. For most patients with clinical T1 or T2 disease and one to three positive lymph nodes, the 5-year risk for LRR was low, and the routine inclusion of postmastectomy radiotherapy does not appear to be justified.

Adult↗
PubMed2004

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma.

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

Adolescent↗
PubMed2004

Physician recommendations regarding tamoxifen and patient utilization of tamoxifen after surgery for ductal carcinoma in situ.

BACKGROUND: To date, the impact of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial reported in 1999 on the use of tamoxifen after surgery for ductal carcinoma in situ (DCIS) is unknown. The current study was designed to evaluate the impact of NSABP B-24 on current practices at a comprehensive cancer center. METHODS: The records of 350 consecutive patients with DCIS who were treated at the authors' institution between July 1999 and June 2002 were obtained from a prospective database and analyzed. Whether patients were offered tamoxifen, whether patients accepted tamoxifen, and the associated reasons were recorded along with tamoxifen-related side effects and patient compliance with therapy. Clinical and pathologic factors were evaluated for their impact on recommendations regarding tamoxifen. Differences were assessed by chi-square analysis. RESULTS: Of the 350 patients, 73 were excluded because of evidence of invasive carcinoma on final pathology review. Of the remaining 277 patients, 166 patients (60%) were offered tamoxifen, and 90 patients (54%) chose to take tamoxifen. Of 111 patients who were not offered tamoxifen, 39 patients (35%) had documented explanations, which included bilateral mastectomy (n = 25 patients), medical reasons (n = 10 patients), and already received tamoxifen for other reasons at the time of diagnosis (n = 4 patients). Of 94 patients who received tamoxifen, 20 patients (21%) discontinued use because of side effects or complications. Tamoxifen was more likely to be recommended for women who underwent segmental resection compared with women who underwent total mastectomy (P = 0.002) and for women with smaller pathologic DCIS tumors (P = 0.001). In addition, these two factors were interrelated. CONCLUSIONS: Physicians and patients remain cautious regarding the use of tamoxifen after local treatment for DCIS. The current findings have implications for current trials evaluating aromatase inhibitors and other chemopreventive agents for this disease.

Adult↗
PubMed2004

Potential applicability of balloon catheter-based accelerated partial breast irradiation after conservative surgery for breast carcinoma.

BACKGROUND: Balloon catheter-based accelerated partial breast irradiation (APBI) is an alternative to whole-breast external-beam irradiation during breast-conserving therapy (BCT) for breast carcinoma, but it is limited by the size of the segmental mastectomy cavity. There are scant data on the average or optimal volume of resection (VR) in BCT. The objective of the current study was to evaluate the percentage of patients who would be eligible for balloon catheter-based APBI based on the selection criteria of the American Society of Breast Surgeons and the surgical VR. METHODS: The authors reviewed the medical records of 443 patients with ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCT. Patient treatment and pathologic data were analyzed to assess VR and eligibility for APBI. RESULTS: BCT was performed for 178 patients with DCIS and 267 patients with invasive breast carcinoma. The majority of invasive carcinomas (63.3%) were infiltrating ductal carcinomas. The median overall lumpectomy volume was 67.61 cm3, with no significant difference between DCIS and invasive carcinoma (P>0.05). Although the majority (62.9-82.0%) of patients met the individual selection criteria for APBI, only 27.4% of the cohort was found to be eligible for any type of APBI when the selection criteria were considered together. Based on VR, only approximately one-half of the patients initially eligible for APBI would be candidates for immediate balloon catheter-based APBI using the 70 cm3 balloon device (13.3%). However, with the new, larger 125 cm3 balloon device, approximately three-fourths of patients initially eligible for APBI would be eligible for balloon catheter-based APBI at the time of the initial surgical procedure (20.7%). Although not evaluated in the current study, shrinkage of the lumpectomy cavity with time may increase the number of patients eligible based strictly on VR criteria. Patients with a very large VR (> or =125 cm3) were more likely to have invasive carcinoma (P=0.02; hazard ratio [HR], 7.4) and tumors > or =5 cm on final pathology (P<0.01; HR, 22.0). CONCLUSIONS: Approximately one-fifth to one-fourth of patients presenting for BCT may be eligible for balloon catheter-based APBI according to accepted national guidelines and VR. VR must be considered when selecting patients for balloon catheter-based APBI, because a minority of patients will have a lumpectomy cavity that exceeds the size limit of the current balloon device.

Adult↗
PubMed2004

Treatment and outcome of patients with chest wall recurrence after mastectomy and breast reconstruction.

BACKGROUND: Chest wall recurrence (CWR) in the setting of previous mastectomy and breast reconstruction can pose complex management dilemmas for clinicians. We examined the impact of breast reconstruction on the treatment and outcomes of patients who subsequently developed a CWR. METHODS: Between 1988 and 1998, 155 breast cancer patients with CWR after mastectomy were evaluated at our center. Of these patients, 27 had previously undergone breast reconstruction (immediate in 20; delayed in 7). Clinicopathologic features, treatment decisions, and outcomes were compared between the patients with and without previous breast reconstruction. Nonparametric statistics were used to analyse the data. RESULTS: There were no significant differences between the reconstruction and no-reconstruction groups in time to CWR, size of the CWR, number of nodules, ulceration, erythema, and association of CWR with nodal metastases. In patients with previous breast reconstruction, surgical resection of the CWR and repair of the resulting defect tended to be more complex and was more likely to require chest wall reconstruction by the plastic surgery team rather than simple excision or resection with primary closure (26% [7 of 27] versus 8% [10 of 128], P = 0.013). Risk of a second CWR, risk of distant metastases, median overall survival after CWR, and distant-metastasis-free survival after CWR did not differ significantly between patients with and without previous breast reconstruction. CONCLUSIONS: Breast reconstruction after mastectomy does not influence the clinical presentation or prognosis of women who subsequently develop a CWR. Collaboration with a plastic surgery team may be beneficial in the surgical management of these patients.

Adult↗
PubMed2004

Predicting the node-negative mesorectum after preoperative chemoradiation for locally advanced rectal carcinoma.

Preoperative chemoradiation therapy (CRT) in patients with locally advanced rectal cancer allows for radical surgery with sphincter preservation in many patients. To determine whether patients downsized with preoperative CRT may be potential candidates for local excision, we investigated residual disease patterns after neoadjuvant treatment. A retrospective analysis was carried out of patients with T3 or T4 rectal adenocarcinoma who were treated with neoadjuvant CRT. Clinical and pathologic data were analyzed to (1). determine the response rates to preoperative CRT in the tumor bed and regional nodal basin and (2). identify the incidence of residual disease in the mesorectum in patients downsized to <or=T2. A total of 219 patients met the inclusion criteria. Preoperatively 193 patients (88%) were staged as T3, and 99 patients (47%) had clinical N1 disease. The pathologic complete response rate was 20% (43 of 219 patients). T stage was downsized in 64% of the patients (140 of 219), and 69% (67 of 97) of the patients with clinical N1 disease were rendered node negative. Seventeen percent (21 of 122) of patients downsized to <or=T2 had residual disease in the mesentery. With a median follow-up of 40 months, 182 patients (83%) remain alive and free of disease. Nine patients (4.1%) have had a local recurrence. Although tumor response rates to preoperative CRT within the bowel wall and lymph node basin are similar, one in six patients with pT0-2 tumors will have residual disease in the rectal mesentery and nodes. Despite a substantial reduction in tumor volume with neoadjuvant CRT, local excision should be recommended with caution in patients with locally advanced rectal cancer.

Adenocarcinoma↗
PubMed2004

MDA-7/IL-24 is a unique cytokine--tumor suppressor in the IL-10 family.

The melanoma differentiation associated gene-7 (mda-7) cDNA was isolated by virtue of being induced during melanoma differentiation. Initial gene transfer studies convincingly demonstrated potent antitumor effects of mda-7. Further studies showed that the mechanism of antitumor activity was due to induction of apoptosis. Most striking was the tumor-selective killing by mda-7 gene transfer--normal cells were unaffected by Adenoviral delivery of mda-7 (Ad-mda7). A variety of molecules implicated in apoptosis and intracellular signaling are regulated by Ad-mda7 transduction. Different apoptosis effector proteins are regulated in different tumor types, suggesting that Ad-mda7 may regulate various signaling pathways. mda-7 encodes a secreted protein, MDA-7, which has now been designated as IL-24, and is a novel member of the IL-10 cytokine family. MDA-7/IL-24 protein is actively secreted from cells after mda-7 gene transfer. In human peripheral blood mononuclear cells (PBMC), STAT3 activation by MDA-7/IL-24 is followed by elaboration of secondary Th1 cytokines, demonstrating that MDA-7/IL-24 is a pro-Th1 cytokine. Furthermore, MDA-7/IL-24 is antagonized by the prototypic Th2 cytokine IL-10. MDA-7/IL-24 protein is endogenously expressed in cultured NK and B-cells and is also expressed in dendritic cells in tissues. MDA-7/IL-24 protein is expressed in nevi and melanoma primary tumors, to varying degrees, but is rarely expressed in malignant melanoma or other human tumors evaluated. Indeed, loss of MDA-7/IL-24 protein expression correlates strongly with melanoma tumor invasion and disease progression. The "bystander" effects proposed for MDA-7/IL-24 protein include immune stimulation, antiangiogenesis and receptor-mediated cytotoxicity. Thus, mda-7 is a unique multifunctional cytokine in the IL-10 family and may have potent antitumor utility in a clinical setting.

Cytokines↗
PubMed2004

A report on accrual rates for elderly and minority-ethnicity cancer patients to clinical trials of the American College of Surgeons Oncology Group.

BACKGROUND: Incidence and mortality rates for cancers vary by ethnic background and patient age. Accrual of diverse patient populations to cancer clinical trials is essential in order to ensure that findings related to new management strategies can be generalized. The goal of this study was to evaluate accrual patterns for patients participating in the American College of Surgeons Oncology Group (ACOSOG) cancer protocols. Ethnic diversity among clinical trial investigators may also influence accrual patterns, so the ethnic background of the ACOSOG membership was also evaluated. STUDY DESIGN: Demographics for the patients registered on ACOSOG breast, thoracic, and colorectal clinical trials were evaluated and compared with data on the general population and the cancer population in the United States. Accrual patterns for patients from other reported cancer clinical trials were also presented, and the self-reported ethnic distribution of the ACOSOG membership was analyzed. RESULTS: Distribution of African Americans, Hispanic Americans, and Asian Americans to the ACOSOG breast and colorectal clinical trials was relatively proportionate to the cancer population. African Americans were underrepresented in the thoracic clinical trials, and this disparity was partially offset by data on the proportion of African Americans with stage-eligible lung cancer. Accrual rates for patients age 65 years and older were better than those reported by most other clinical trialists. CONCLUSIONS: Elderly patients are successfully recruited into surgical clinical trials, and this will provide important data for future analyses regarding cancer outcomes in this growing population of cancer patients. Aggressive outreach to minority-ethnicity cancer patients for accrual into clinical trials should continue.

Age Factors↗
PubMed2004

Adverse events associated with the intraoperative injection of isosulfan blue.

STUDY OBJECTIVE: To describe the adverse events associated with the intraoperative injection of isosulfan blue in a large group of patients having a wide range of surgical procedures, and to identify risk factors for these events. DESIGN: Retrospective chart review. SETTING: University-affiliated institution specializing in malignancies PATIENTS: 1835 patients representing a total of 1852 surgical procedures. MEASUREMENTS: Incidence, type, severity, onset time, duration, management, and the presence of potential risk factors for adverse events. Events were considered "major" if potentially life-threatening hypotension occurred. MAIN RESULTS: Adverse events occurred in 28 procedures (1.5%) and 14 of these adverse events (0.75%) were classified as major. The types of events were: skin reactions in 21 patients, hypotension in 14 patients, edema in 1 patients, and unspecified in 1 patient. The time of onset for adverse events was 42.2 +/- 53.9 minutes (median, 17.5; range, 1 to 180 min) after isosulfan blue injection, and was significantly longer for minor reactions compared with major events (p = 0.015). The longest adverse event lasted at least 21 hours. Treatment was successful with usual antiallergy/antianaphylaxis medications. Ten patients received diphenhydramine alone, and four patients received intravenous epinephrine infusions. Factors associated with a significantly increased incidence of adverse events were isosulfan blue injection in the vulvar area (p = 0.000038), and the chronic preoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor-blocking agents (p = 0.043). Trends toward an increased risk of an adverse event were noted with isosulfan blue injection in the breast area (p = 0.19), and having more than one surgical procedure with isosulfan blue (p = 0.14). CONCLUSIONS: Although the most frequent adverse event associated with injection of isosulfan blue was a skin reaction, potentially life-threatening hypotension occurred in 0.75% of all procedures. Anesthesiologists must be aware of the variable onset time and potentially prolonged duration of the adverse events. They should recognize the need for extra vigilance in patients with potential risk factors, and have the usual antiallergy/antianaphylaxis medications available for administration if necessary.

Adolescent↗
PubMed2004

Association between ductal fluid proteomic expression profiles and the presence of lymph node metastases in women with breast cancer.

BACKGROUND: Proteomic analysis of nipple aspiration fluid (NAF) is a noninvasive method for studying the local biologic microenvironment of the breast ducts where carcinoma originates. METHODS: NAF samples from each breast of 23 women with stage I or II unilateral invasive breast carcinoma were collected, and protein expression was analyzed comprehensively by using protein arrays and time-of-flight mass spectrometry. Blinded hierarchical clustering analysis was performed to identify potential associations between protein expression patterns and clinicopathologic factors. RESULTS: After analysis of all spectra, 463 distinct peaks in the mass range of 7 to 30 kD were identified in NAF samples. Blinded hierarchical clustering analysis of protein expression patterns demonstrated a conservation of these patterns between the breasts of individual patients (P=.0003 x 10(-12)). Hierarchical clustering revealed an association between protein expression patterns, and the presence and absolute number of axillary lymph nodes containing metastases (P=.038). CONCLUSIONS: Protein expression patterns are highly conserved between cancerous and noncancerous breasts in women with unilateral invasive breast cancer; unique expression patterns may be associated with extent of disease. High-throughput proteomic methods may reveal biologically relevant proteins involved in carcinogenesis and progression of disease.

Adult↗
PubMed2004

Combination therapy of Ad-mda7 and trastuzumab increases cell death in Her-2/neu-overexpressing breast cancer cells.

BACKGROUND: Overexpression of the tumor suppressor gene melanoma differentiation-associated gene-7 (mda-7) induces apoptosis in many cancer cells, and adenoviral-mediated overexpression of mda-7 downregulates beta-catenin and PI 3-kinase signaling in breast cancer cells. Trastuzumab (Herceptin) improves the efficacy of chemotherapeutics against Her-2/neu-overexpressing breast cancer cells. We sought to evaluate the impact of combination therapy of a recombinant adenovirus vector encoding for human mda-7 (Ad-mda7) and Herceptin on Her-2/neu-overexpressing breast cancer. METHODS: The MCF-7-Her-18 cell line was subjected to treatment with Ad-mda7 with and without Herceptin. Western blot analysis was performed with antibodies to beta-catenin, Akt, and phosphorylated Akt (p-Akt). The same treatment groups were utilized in a nude mouse model in vivo. Treatment was initiated when the tumors reached 100 mm3 in size. RESULTS: In Western blotting, the combination of Ad-mda7 + Herceptin showed decreased levels of beta-catenin, Akt and p-Akt compared with Ad-mda7 or Herceptin alone (P < .05). The in vivo analysis revealed a marked decrease in tumor size with the Ad-mda7 + Herceptin combination (P < .05). CONCLUSIONS: These studies demonstrate the growth inhibitory effect of Ad-mda7 + Herceptin on Her-2/neu-overexpressing breast cancer cells in vitro and in vivo. This combination appears to inhibit the pathways involving beta-catenin and Akt, which play important roles in the growth of breast cancer cells.

Adenoviridae↗