Biomedical subjects

Marcella M Johnson

Publications and source records attributed to Marcella M Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma.

BACKGROUND: Sentinel lymph node (SLN) status is the most important prognostic factor with respect to the survival of patients with primary cutaneous melanoma. However, lymphatic mapping and SLN biopsies (LM/SLNBs) performed in patients who have had a wide local excision (WLE) may not accurately reflect the pathologic status of the draining lymph node basins. The purpose of this study was to assess the feasibility and accuracy of LM/SLNB in patients who have had a previous WLE. METHODS: A single-institution database was examined to identify patients who had a WLE before LM/SLNB and patients who had a concomitant LM/SLNB. Primary clinicopathologic features (age, tumor thickness, and ulceration), SLN identification rate, SLN pathologic status, and the incidence and sites of recurrences were compared between patients with and without prior WLE. RESULTS: Of the 1395 patients identified, 104 had WLE before LM/SLNB. The mean preoperative WLE radial margin was 1.4 cm (median, 1.0 cm). LM/SLNB was successful in 103 of 104 (99%) patients. Age, tumor thickness, incidence of ulceration, and incidence of SLN positivity in the group with prior WLE were similar to those of the cohort of patients who had concomitant LM/SLNB and WLE (n = 1291). In 97 (93%) of the 104 prior-WLE patients, the surgical defects were closed by either primary closure or skin graft; 7 patients (7%) had rotational flaps. The median follow-up of these 104 patients was 51 months. Among the prior-WLE group, 19 patients (18%) had a positive SLNB; of these 19 patients, 4 (21%) had recurrences (3 distant failures and 1 local and distant failure). There were no lymph node recurrences-in a mapped or unmapped basin-in these 104 patients with a negative or positive SLNB. CONCLUSIONS: SLNs can be successfully identified and accurately reflect the status of the regional lymph node basin in carefully selected melanoma patients with a previous WLE. Prior WLE does not appear to adversely impact the ability to detect lymphatic metastases, although the utility of LM/SLNB in patients who have undergone extensive reconstruction of the primary excision site remains to be defined. Because more extensive surgery may be required to accomplish accurate lymph node staging in patients who have undergone prior WLE-including the possible removal of SLNs from additional lymph node basins and an additional surgical procedure-to minimize morbidity and cost, concomitant WLE and LM/SLNB is strongly preferred whenever possible.

Adolescent↗

PubMed2006

Galectin-3 expression is associated with tumor progression and pattern of sun exposure in melanoma.

PURPOSE: Most studies accept a multistep pathogenic process in melanoma that may include the phases of benign nevi and dysplastic nevi, melanoma, and metastatic melanoma. Dysregulation of cellular proliferation and apoptosis is probably involved in melanoma progression and response to therapy. We have studied the expression of galectin-3, a beta-galactoside-binding protein involved in apoptosis, angiogenesis, and cell proliferation, in a large series of melanocytic lesions, and correlated the expression with clinical and histologic features. EXPERIMENTAL DESIGN: Tissue microarray blocks of 94 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic or nuclear expression of galectin-3. RESULTS: Primary and metastatic melanomas expressed galectin-3 at a significantly higher level than nevi in both cytoplasm and nuclei (P<0.0073). There was a significant association between anatomic source (as indirect indication of level of sun-exposure) and cytoplasmic and nuclear expression. Lymph node and visceral metastases had a higher level of expression than s.c. lesions (P<0.004). Interestingly, there was an almost significant finding of worse survival in those patients with lesions showing higher levels of cytoplasmic than nuclear galectin-3 expression (log-rank test, P=0.06). CONCLUSIONS: Melanocytes accumulate galectin-3 with tumor progression, particularly in the nucleus. The strong association of cytoplasmic and nuclear expression in lesions of sun-exposed areas suggests an involvement of UV light in activation of galectin-3.

Biomarkers, Tumor↗

PubMed2006

Quantitative analysis of melanocytic tissue array reveals inverse correlation between activator protein-2alpha and protease-activated receptor-1 expression during melanoma progression.

The identification of molecular markers of melanoma progression is needed to more accurately stage and identify treatments for patients with malignant melanoma. Previously, we demonstrated that loss of the activator protein-2alpha (AP-2alpha) expression results in overexpression of the protease-activated receptor-1 (PAR-1) in human melanoma cell lines. Here, we used a tissue microarray platform that consisted of 64 melanocytic lesions, including dysplastic nevi (N=21), primary melanoma (N=20), and metastatic melanoma (N=23). We analyzed the expression of AP-2 and PAR-1 simultaneously by immunofluorescent microscopy with an automated quantification laser scanning cytometer. AP-2 was highly expressed in normal cutaneous melanocytes and dysplastic nevi but not in melanoma metastases. We observed a significantly higher number of AP-2-positive cells in the dysplastic nevi (P=0.0013) and primary melanoma (P=0.0023) compared to the metastatic melanoma. In contrast, we observed a significantly higher percentage of PAR-1-positive cells in the metastatic melanoma compared to dysplastic nevi (P=0.0072) and primary melanoma (P=0.0138). Increased expression of PAR-1 in metastatic melanomas contributes to tumor progression by modulating expression of genes, such as IL-8, matrix metalloproteinase-2, vascular endothelial growth factor, platelet-derived growth factor, and integrins. These findings support our hypothesis that loss of AP-2 is a crucial event in the progression of human melanoma and contributes to the acquisition of the metastatic phenotype via upregulation of PAR-1.

Disease Progression↗

PubMed2006

Tumor iNOS predicts poor survival for stage III melanoma patients.

Inducible nitric oxide synthase (iNOS) produces nitric oxide, which has growth promoting activity in melanoma. A preliminary study of tumors from patients with Stage III melanoma who had received neo-adjuvant therapy revealed an association of tumor iNOS expression with shortened survival. The objective of the present study was to determine whether iNOS expression in tumors of newly diagnosed, untreated Stage III patients is predictive of survival. iNOS expression was examined by immunohistochemistry in tumors from 132 patients. The staining was evaluated for percentage of positive cells (Number score) and the intensity of staining (Intensity score). The association of iNOS expression with overall and disease-specific survival was tested in univariate and multivariate Cox proportional hazards regression models that included other known prognostic factors. Results of the univariate analysis demonstrated that the presence of iNOS in a patient's tumor, whether graded on the basis of Number or Intensity score, was associated with a significant increase in the hazard ratio of death from melanoma. These findings were corroborated by median survival data estimated from Kaplan Meier analysis. In the multivariate model including iNOS number or intensity, gender, age, number of lymph nodes, macroscopic disease and in-transit disease, only iNOS expression predicted survival. We conclude that a significant association exists between tumor iNOS expression and shortened survival in untreated Stage III melanoma patients. The ability of iNOS to predict outcomes for these patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility.

Adolescent↗

PubMed2006

Utility of computed tomography and magnetic resonance imaging staging before completion lymphadenectomy in patients with sentinel lymph node-positive melanoma.

PURPOSE: Although melanoma patients with regional nodal metastases are frequently imaged with computed tomography (CT) and magnetic resonance imaging (MRI) scans, the efficacy of routine radiologic staging in asymptomatic patients with microscopic nodal involvement has not been established. To determine the utility of this approach, we analyzed the incidence of synchronous distant metastases (SDM) detected by CT or MRI of the head, chest, and abdomen in a large group of patients with sentinel lymph node (SLN) -positive melanoma. PATIENTS AND METHODS: Positive SLNs were identified in 314 (16.2%) of the 1,934 melanoma patients who underwent sentinel lymphadenectomy at our institution from 1996 to 2003. Within 3 months of sentinel lymphadenectomy, 270 (86.0%) of the 314 SLN-positive patients were radiologically staged. To determine which prognostic factors were associated with SDM, associations between final staging outcomes and clinicopathologic variables, including SLN tumor burden, were analyzed. RESULTS: CT and/or MRI scans identified lesions that were suspicious for SDM in 23 (8.6%) of the 270 patients who underwent staging. In eight of these patients, further diagnostic studies determined that these abnormalities were benign. The remaining 15 suspicious lesions were percutaneously biopsied (10 negative and five positive), yielding a radiologically detectable SDM rate of 1.9%. Detection of SDM was associated with primary tumor thickness (P = .011), ulceration (P = .018), and SLN tumor burden (P = .018). CONCLUSION: These data suggest that the vast majority of asymptomatic patients with a new diagnosis of microscopic SLN-positive melanoma do not harbor radiologically detectable SDM and can proceed to completion lymph node dissection without immediate CT or MRI staging.

Adolescent↗

PubMed2006

Clinical relevance of soluble HLA-I and beta2-microglobulin levels in non-Hodgkin's lymphoma and Hodgkin's disease.

Plasma levels of beta-2 microglobulin (beta2M), a subunit of the human leukocyte antigen-class I (HLA-I) molecule, correlate negatively with outcome in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). We examined the clinical relevance of soluble HLA-I (sHLA-I) levels in NHL and HD. Sera from consecutive NHL (n=65) and HD (n=37) patients were analyzed in a blinded manner. NHL and HD patients had significantly higher levels of sHLA-1 and beta2M than control subjects. In NHL patients, sHLA-I levels correlated with clinical behavior in a fashion similar to that of beta2M. However, multivariate analysis incorporating beta2M, sHLA-I, and international prognostic index (IPI) indicated that NHL patients with elevated (>312.6mug/100mL) sHLA-I levels had significantly shorter survival, independent of IPI score as well as beta2M. In HD patients, beta2M but not sHLA-I levels were associated with clinical behavior. These findings not only establish the role of sHLA-I as an independent tumor marker in NHL that can be used to stratify patients, but also suggest that beta2M and sHLA-I may reflect different biological processes in HD and NHL. Further studies are needed to assess whether the immunomodulatory properties of sHLA-I may be responsible for its divergence from beta2M as an indicator of clinical behavior in HD.

Adolescent↗

PubMed2006

Assessment of the role of sentinel lymph node biopsy for primary cutaneous desmoplastic melanoma.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in the treatment of desmoplastic melanoma (DM) remains undefined. The purpose of this study was to evaluate the use of SLNB for DM. METHODS: In all, 1850 patients with cutaneous melanoma underwent wide local excision and SLNB. Patients with DM were identified and stratified as 'pure' DM or 'mixed' DM (i.e., DM associated with at least one other common histologic subtype). RESULTS: Of the 1850 patients, 65 (3.5%) had DM. Of these, 46 (70.8%) had pure DM and 19 (29.2%) had mixed DM. Patients with pure DM had a median tumor thickness of 3.5 mm and 6.5% were ulcerated. Compared with patients with pure DM, patients with either mixed DM or non-DM (n = 1785) had thinner primary tumors (median, 1.7 mm and 1.5 mm, respectively, each P < 0.001 vs. pure DM) that were more likely to be ulcerated (27.7% and 21.3%, respectively, each P < 0.05 vs. pure DM). Although the incidence of a positive SLN was similar in patients with mixed DM (15.8%) and non-DM (17.5%), patients with pure DM were less likely to have a positive SLN (2.2%) (each P < 0.01 vs. non-DM and mixed DM). At a median follow-up of 2.9 years, no patient with pure DM had recurred. CONCLUSIONS: Despite having thicker primary tumors, patients with pure DM have a lower incidence of positive SLNs compared with patients with non-DM. Whereas the treatment approach for patients with mixed DM should be similar to that of other melanoma patients, patients with pure DM are unlikely to have metastatic disease in regional lymph nodes and SLNB may not be warranted.

Female↗

PubMed2006

The bacteriostatic properties of ear tubes made of absorbable polylactic acid.

OBJECTIVE: Tympanostomy tube placement remains the most common reason children are brought to the operating room. Of the known complications, transient, recurrent, and chronic otorrhea represent the most common and challenging sequelae of tube insertion. This study was performed to determine if the acidic nature of the polymer of lactic acid (PLA), a possible material for the construction of ear tubes, would have bacteriostatic properties. MATERIAL AND METHODS: Experimental PLA tubes and control fluoroplastic tubes were inoculated with a broth of Pseudomonas aeruginosa or Staphylococcus aureus and incubated. Fluid recovered from the tubes was plated and incubated again. Colony counts were recorded at 24 and 48 h. Two separate trials were conducted for each organism. Repeated measures analysis of variance (ANOVA) models were used to assess the effects of the type of tube, the experimental run, and the tube by run interaction on colony counts. RESULTS: In the Pseudomonas experiments, the mean colony count of the PLA tube group (Run 1: 1.0; Run 2: 26.6) was significantly lower than the mean colony count in the fluoroplastic tube group (Run 1: 132.6; Run 2: 122.2; p=0.0150). Similarly, in the S. aureus experiments, the mean colony count of the PLA tube group (Run 1: 88.2; Run 2: 92.6) was significantly lower than the mean colony count in the fluoroplastic tube group (Run 1: 335.0; Run 2: 325.8; p<0.0001). CONCLUSION: PLA has many properties including an apparent bacteriostatic quality, which may make it an attractive material for the construction of tympanostomy tubes.

Absorbable Implants↗

PubMed2006

Cardiac sequelae in Brooklyn after the September 11 terrorist attacks.

BACKGROUND: Terrorism, such as the attacks on the World Trade Center (WTC) on September 11, 2001, result in higher stress-related disorders, especially in those persons in close proximity. HYPOTHESIS: Cardiac events resulting from the September 11, 2001 tragedy have not been detailed near the WTC. METHODS: Patients admitted to the Telemetry and Coronary Care Units at New York Methodist Hospital 4 miles from the WTC 60 days prior to and after the September 11 attacks were analyzed. In all, 1,653 admissions were reviewed: 427 records pre 9/11/2001 and 422, 393, and 411 records in the post-9/11/2001, pre-9/11/2000, and post-9/11/2000 data sets, respectively. Patients were categorized based on diagnosis: acute myocardial infarction (MI), unstable angina (UA), tachyarrhythmia (TA), and others (including syncope and congestive heart failure). RESULTS: There was a significant difference in the proportion of the various cardiac diagnoses post 9/11/01 (p = 0.008 by chi-square analysis). Compared with pre 9/11/2001, there were significantly more patients with acute MI (15.5 vs. 11.2%) and TA (19.9 vs. 13.6%) but fewer with UA (39.6 vs. 47.3%) after the terrorist attacks. The distribution of cardiac events during a similar period of time in 2000 revealed no such pattern. CONCLUSIONS: There was a significant increase in acute MI and TA and a smaller increase in UA after the September 11 attacks. The difference did not appear to be due to temporal variation. It appears that stress likely contributed to an increase in TA by itself or with ischemia, resulting in progression of UA to acute MI.

Aged↗

PubMed2006

Suburethral sling at the time of radical prostatectomy in patients at high risk of postoperative incontinence.

OBJECTIVE: To evaluate the insertion of a urethral sling at the time of radical prostatectomy (RP) in men at high risk of urinary incontinence after RP. PATIENTS AND METHODS: Between 1998 and 2000, 49 of 871 men undergoing RP at The University of Texas M.D. Anderson Cancer Center, were identified as at risk of urinary incontinence after RP, based on their age (>65 years), previous transurethral resection of the prostate, previous radiation therapy, clinical stage, and obesity (body mass index of > or = 30 kg/m2). These 49 men had a suburethral sling inserted at the time of RP, and incontinence after surgery was evaluated using pad counts and patient-completed questionnaires. Retrospectively, incontinence rates and complications in these men were compared with 122 men also at high risk of urinary incontinence after RP who did not have a sling inserted at the time of RP (control group). RESULTS: In all, 29 of 49 men (59%) with a suburethral sling reported using either no pad or one pad per day for urinary leakage at 6 months after RP, compared with 83 of 118 (70%) in the control group. At 12 months after RP, 34 of 46 (74%) men with a suburethral sling reported using no or one pad, compared with 75 of 89 (84%) in the control group. Seventeen (35%) men were treated for urethral stricture in the sling group and 17 (14%) in the control group (P = 0.001). CONCLUSIONS: The urethral sling modification concurrent with RP is feasible, but does not decrease incontinence compared with a similar group of high-risk patients who did not have the sling modification. In addition, the stricture rate in the sling group was unacceptably high. Currently, we do not recommend the use of a urethral sling at the time of RP.

Aged↗

PubMed2005

Automated quantitative analysis of activator protein-2alpha subcellular expression in melanoma tissue microarrays correlates with survival prediction.

The activator protein-2alpha (AP-2) transcription factor plays a key role in regulating expression of genes involved in tumor growth and metastasis of human melanoma. We sought to assess the prognostic significance of AP-2 expression and its role in the transition of nevi to metastatic melanoma. Two cohorts were analyzed. One was a "progression" microarray containing melanoma specimens from M.D. Anderson Cancer Center representing 84 cases and the other was a retrospective cohort from Yale University representing 214 primary melanomas and 293 metastases. Analysis of total AP-2 expression using two quantitative systems [automated quantitative analysis (AQUA) and laser scanning cytometry (LSC)] revealed no correlation with diagnosis group. LSC analysis of the M.D. Anderson Cancer Center array showed that the number of cells expressing nuclear AP-2 was highest in the benign nevi group (11.85%) and significantly decreased in each phase of melanoma progression to 0.39% in the metastatic group. Both LSC and AQUA showed decreased nuclear AP-2 levels and increased cytoplasmic AP-2 that is directly proportional to progression. Neither nuclear nor cytoplasmic expression levels correlated with outcome. Intriguingly, the ratio of cytoplasmic to nuclear AP-2 predicted outcome in the entire population and in the primary tumors alone, demonstrating the power of the ratio to normalize for variations. Furthermore, the AP-2 ratio directly correlated with other clinicopathologic factors, including Breslow depth (R = 0.334, P < 0.001). We show that a high level of AP-2 expression in the cytoplasm relative to the nucleus correlates with poor prognosis and the loss of nuclear AP-2 expression is associated with malignant transformation and progression of melanoma.

Cell Nucleus↗

PubMed2005

Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival.

BACKGROUND: The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE) or chemoembolization (HACE). METHODS: Patients with metastatic neuroendocrine tumors who underwent HAE or HACE were included in this retrospective study. Follow-up imaging studies were compared with baseline imaging to determine the radiologic response. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to assess the prognostic variables that affected response and survival. RESULTS: The study included 69 patients with carcinoid tumors and 54 patients with pancreatic islet cell carcinomas. Patients who had carcinoid tumors had a higher response rate (66.7% vs. 35.2%; P = 0.0001) and had longer PFS (22.7 mos vs. 16.1 mos; P = 0.046) and OS (33.8 mos vs. 23.2 mos; P = 0.012) compared with patients who had islet cell carcinomas. For patients with carcinoid tumors, multivariate analysis identified male gender as the only independent risk factor for poor survival (P = 0.05). Octreotide was predictive marginally for PFS (P = 0.06). Patients who were treated with HAE had a higher response rate than patients who were treated with HACE (P = 0.004). For patients with islet cell carcinoma, an intact primary tumor, > or = 75% liver involvement, and extrahepatic metastases were associated with reduced OS in the univariate analysis; the presence of bone metastases was the only risk factor (P = 0.031) in the multivariate analysis. Patients who were treated with HACE had a prolonged OS (31.5 mos vs. 18.2 mos) and improved response (50% vs. 25%) compared with patients who were treated with HAE, although the differences did not reach statistical significance. CONCLUSIONS: Patients with carcinoid tumors had better outcomes than patients with islet cell carcinomas. The addition of intraarterial chemotherapy to HAE did not improve the outcome of patients with carcinoid tumors, but it seemed to benefit patients with islet cell carcinomas. In patients who had carcinoid tumors, male gender predicted a poor outcome, and a trend toward prolonged PFS was observed in patients who received concomitant octreotide. An intact primary tumor, extensive liver disease, and bone metastases were associated with reduced survival in patients with islet cell carcinomas.

Adult↗

PubMed2005

N-(4-Hydroxyphenyl)retinamide and nitric oxide pro-drugs exhibit apoptotic and anti-invasive effects against bone metastatic breast cancer cells.

Breast cancer most frequently metastasizes to bone causing decreased quality of life and morbidity. Since current treatments are palliative, strategies to prevent bone metastases in breast cancer patients are required. There is substantial evidence indicating that high levels of nitric oxide (NO) suppress tumor growth and metastasis in vivo. We hypothesize that agents that produce high concentrations of NO could prevent the spread of breast cancer to bone. We previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) produces high levels of NO via the induction of NO synthases. NO pro-drugs are designed to produce large amounts of NO without inducing NO synthases but upon metabolism by their intracellular targets. The objective of this study was to determine the effectiveness of 4-HPR and an NO pro-drug, diethylamineNONOate/AM (NONO-AM), in inhibiting the growth and invasiveness of bone metastatic breast cancer cells. Parental MDA-MB-231 breast cancer cells were resistant to 4-HPR-induced apoptosis at clinically relevant doses, whereas 4-HPR-induced apoptosis in a dose-dependent manner in MDA-MB-231/F10 bone metastatic breast cancer cells. Unlike 4-HPR, NONO-AM induced apoptosis in a dose-dependent manner in both parental MDA-MB-231 cells and F10 cells. The bone metastatic F10 cells were more sensitive to the anti-invasive effects of 4-HPR and NONO-AM than were MDA-MB-231 cells. Although suppression of matrix metalloprotease-9 activity may be one mechanism by which 4-HPR decreases the invasion of F10 cells, it does not appear to be the anti-invasion mechanism of NONO-AM. These in vitro results suggest that 4-HPR and NO pro-drugs may be effective chemopreventive agents against bone metastatic breast cancer.

Anticarcinogenic Agents↗

PubMed2005

Angiogenic factors may have a different prognostic role in adult acute lymphoblastic leukemia.

Angiogenesis plays an important role in solid tumors and hematologic malignancies. The prognostic significance of angiogenic factors in adult acute lymphoblastic leukemia (ALL) remains ambiguous. We therefore analyzed the impact of angiogenic factor levels on overall survival of newly diagnosed adult ALL patients. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-1 receptor alpha (IL-1Ralpha), IL-6, IL-8, VEGF receptors VEGFR1 and VEGFR2, and thrombopoietin (TPO) were measured in plasma samples of 95 patients by enzyme-linked immunosorbent assay (ELISA). In a univariate Cox proportional hazards model, higher levels of IL-1Ralpha, IL-8, VEGFR1, and VEGFR2 were predictive of poor survival. In contrast, higher levels of VEGF were predictive of longer survival, and higher levels of bFGF suggested a similar trend (P = .09). The multivariate model simultaneously included VEGF (relative risk [RR] for death, 8.01; P = .001 for levels less than or equal to 19.5 pg/mL), IL-1Ralpha (RR, 5.12; P = .007 for levels greater than 373 pg/mL), and VEGFR2 (RR, 4.01; P = .04 for levels greater than 8222 pg/mL) as independent factors for survival. Of interest is the association of high levels of VEGF with good prognosis and higher levels of VEGF receptors with poor outcome. These data reflect the complexity by which angiogenic factors may affect the clinical behavior of patients with ALL, and this complexity should be considered in any therapeutic strategy incorporating antiangiogenic agents.

Angiogenesis Inducing Agents↗

PubMed2005

Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy.

BACKGROUND: In-transit recurrence is a unique and uncommon pattern of treatment failure in patients with melanoma. Little information exists concerning the incidence, predictors, and natural history of in-transit disease since the introduction of sentinel lymph node biopsy (SLNB). METHODS: Between 1991 and 2001, 1395 patients with primary melanoma underwent SLNB. Univariate and multivariate logistic regression analyses were performed to examine the association among known clinicopathologic factors, in-transit recurrence, and distant metastatic failure after the development of in-transit disease. RESULTS: With a median follow-up of 3.9 years, 241 patients (17.3%) experienced disease recurrence, including 91 (6.6%) who developed in-transit recurrence. Independent predictors of in-transit recurrence included age >50 years, a lower extremity location of the primary tumor, Breslow depth, ulceration, and sentinel lymph node (SLN) status. Of the 69 patients who presented with in-transit disease as the sole site of first recurrence, 39 developed distant disease. By univariate analysis, predictors of distant failure among patients with in-transit disease included SLN status, largest metastatic focus in the SLN >2.5 mm2, subcutaneous location of in-transit disease, in-transit tumor size > or = 2 cm, and a disease-free interval before in-transit recurrence of <12 months. In-transit tumor size remained a significant predictor of distant metastasis by multivariate analysis (odds ratio, 9.69). CONCLUSIONS: The overall incidence of in-transit metastases in patients undergoing SLNB is low and does not seem to have increased since the introduction of the SLNB technique. In-transit recurrence, as well as subsequent distant metastatic failure, can be predicted on the basis of adverse tumor factors and SLN status.

Adolescent↗

PubMed2005

N-(4-Hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells.

Women with germline mutations in the breast cancer susceptibility gene BRCA1 are at an increased risk of developing breast cancer. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been shown to have a clinical chemopreventive activity in patients with premenopausal breast cancer. Since BRCA1 mutations are associated with an early-onset breast cancer, usually before menopause, we hypothesized that 4-HPR may be an effective chemopreventive agent against breast tumors exhibiting BRCA1 mutations. The objective of this study was to determine the effectiveness and mechanisms of action of 4-HPR and its phenylretinamide analogues in BRCA1-mutated breast cancer cells. At clinically relevant doses, 4-HPR induced apoptosis in human (HCC1937) and murine (W0069, W525) BRCA1-mutated breast cancer cells. Among the various phenylretinamides tested, N-(2-carboxyphenyl)retinamide (2-CPR) and 3-CPR significantly inhibited the growth of HCC1937 cells; however, they were not as potent as 4-HPR in this respect. We also determined the mechanisms by which 4-HPR induces apoptosis in BRCA1-mutated breast cancer cells. The extent to which 4-HPR induced apoptosis in BRCA1-mutated cells correlated with the increases in nitric oxide (NO) production and nitric oxide synthase (NOS) II and NOSIII expression. Use of a NOS inhibitor to block NO production suppressed the inhibitory effects of 4-HPR in all cell lines. These in vitro results suggest that 4-HPR may be an effective chemopreventive agent against breast tumors that exhibit BRCA1 mutations because of its ability to induce NO-mediated apoptosis in such tumors.

Apoptosis↗

PubMed2004

Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies.

BACKGROUND: The authors set out to assess the correlation between smoking-related second primary tumor (SPT) development and cigarette smoking habits after diagnosis and definitive treatment in patients with early-stage head and neck squamous cell carcinoma who were enrolled in a placebo-controlled randomized chemoprevention trial of 13-cis-retinoic acid. METHODS: Longitudinal data collected for 10 years after the index diagnosis are presented for 1190 patients. Cox proportional hazards regression models were used to examine the effects of changes in smoking behavior on smoking-related SPT development. RESULTS: One-third of all patients who quit smoking within 12 months before randomization experienced recurrence, compared with 6.9% and 10.4% of all never-smokers and former smokers, respectively. Approximately 16% of all current smokers stopped smoking, and nearly 22% of current smokers developed SPTs, compared with 14.5%, 13.2%, and 8.8% of all recent smokers, former smokers, and never-smokers, respectively. The probability of developing a smoking-related SPT was highest among patients who were current smokers at randomization. These patients, regardless of whether they ceased smoking during follow-up, were nearly three times more likely than patients who had never smoked to develop a smoking-related SPT. In contrast, former smokers and recent quitters who continued to abstain from smoking during follow-up were approximately 1.5 times more likely to develop an SPT compared with patients who had never smoked. CONCLUSIONS: Patients who continue to smoke after the successful treatment of their index head and neck malignancies have a substantially higher risk of developing smoking-related SPTs.

Follow-Up Studies↗

PubMed2004

Use of inferior vena caval filters and survival in patients with malignancy.

BACKGROUND: Inferior vena cava (IVC) filters have proven to be a viable alternative to anticoagulation therapy for the prevention of life-threatening pulmonary emboli (PE) for patients who have contraindications to anticoagulation therapy. The clinical benefit of placing IVC filters in patients with advanced-stage cancer is controversial. The current study reported the authors' experience with IVC filters in patients with cancer. METHODS: Between January 2000 and May 2003, IVC filters were placed in 308 patients with venous thromboembolic (VTE) disease. Of these patients, 267 had solid tumors and 41 had liquid tumors. Outcome was reviewed retrospectively with regards to patient survival as well as procedural and filter-related complications. Patients with solid and liquid tumors were used to generate Kaplan-Meier estimates for survival and the probability of surviving 30, 90, and 365 days was also calculated. The prognostic effect of age, primary malignancy, gender, extent of disease, indication, admission to the intensive care unit, and IVC thrombus on overall survival was also evaluated using univariate and multivariate Cox models for patients with solid tumors. RESULTS: The median survival periods for patients with solid and liquid tumors were 145 days and 207 days, respectively. The probability of survival at 30, 90, and 365 days was 0.81, 0.60, and 0.35, respectively, for patients with solid tumors and 0.85, 0.67, and 0.48, respectively, for patients with liquid tumors. There was no statistically significant difference in survival based on primary malignancy for solid tumors (P = 0.628) or between solid and liquid tumors (P = 0.16). For patients with solid tumors, a statistically significant difference in survival was found by extent of disease (P = 0.002). Patients with solid tumors classified as local disease (n = 15), locally advanced disease (n = 95), and widely metastatic or disseminated disease (n = 153) had a probability of survival at 30 days of 0.93, 0.87, and 0.76, respectively. Compared with patients with local disease, patients with metastatic or disseminated disease were 3.7 times more likely to die (P = 0.013). Patients with a history of deep venous thrombosis (DVT) and hemorrhage were 2 times more likely to die than patients with DVT and no history of hemorrhage (P = 0.0057). Documented complications occurred in 22 of 308 (7.1%) patients and included PE (n = 4), new caval thrombosis (n = 14), retroperitoneal hemorrhage (n = 2), and maldeployed filters (n = 2). CONCLUSIONS: IVC filters were shown to be safe and highly effective in preventing PE-related deaths in patients with cancer with VTE disease. Patients with a history of DVT and bleeding or metastatic/disseminated stage of disease had the lowest survival after IVC filter placement.

Adult↗