Office-based and intraoperative ultrasound enhance surgeon's care of breast disease patients.
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Breast Neoplasms↗
Biomedical subjects
Michael J Edwards
Publications and source records attributed to Michael J Edwards.
The long-term clinical course of patients with cutaneous melanoma.
BACKGROUND: The clinical course of cutaneous melanoma is associated with pathologic and clinical factors, such as thickness, ulceration, and location of tumor and gender of the patient. The authors used a parametric survival model that incorporated a cured fraction of patients to translate these factors into specific estimates of long-term outcome. METHODS: A cohort study was conducted of 5837 patients who were treated for localized cutaneous melanoma between 1978 and 1990 at the Duke Comprehensive Cancer Center. Of these, 495 patients were excluded because the survival status or one or more of the prognostic factors was unknown. Maximum follow-up was 22 years. The primary outcome measures examined were cured fraction (probability of cure), median tumor specific survival (i.e., median time to death from tumor), and the probability of tumor-related survival at fixed intervals after treatment. RESULTS: For an example of a class of patients with a relatively good prognosis, consider women with nonulcerated lesions measuring 0.5 mm thick on an extremity. The probability of cure (+/- standard error) for these patients was estimated at 80.8% +/- 2.0%, and the median tumor specific survival was 10.0 years +/- 0.8 years. This suggests that, in these patients, half of the deaths from melanoma will occur more than 10 years after treatment, barring death from other causes. Conversely, men with ulcerated lesions measuring 8.00 mm thick on the trunk have a relatively poor prognosis. The probability of cure for these patients was 16.8% +/- 2.4%, and the median tumor specific survival was 2.7 years +/- 0.2 years. Despite this poor initial prognosis, the conditional probability of cure increased to 90%; after 15 years of recurrence free survival. CONCLUSIONS: Parametric statistical analysis provides quantitative measures of long-term survival. These measures show that late recurrence-longer than a decade after treatment-is to be expected in a significant portion of patients, although the probability of cure increases with progressively longer recurrence free survival.
Adolescent↗
Optimal use of sentinel lymph node biopsy versus axillary lymph node dissection in patients with breast carcinoma: a decision analysis.
BACKGROUND: There are no data available from randomized controlled trials that compare the efficacy of sentinel lymph node (SLN) biopsy with Level I/II axillary lymph node dissection (ALND) in patients with breast carcinoma. We performed a formal decision analysis to determine whether SLN biopsy is appropriate, compared with ALND, for patients with T1, T2, and T3 tumors and to quantify the relative value of these two procedures in the management of patients with breast carcinoma. METHODS: All clinically relevant outcomes were modeled for both SLN biopsy and ALND. The probabilities of complications and outcomes were derived using data from the University of Louisville Breast Cancer Sentinel Lymph Node Study and from extensive review of previous studies. Utilities were assigned by the authors, incorporating values from the literature whenever possible. RESULTS: The expected utility of SLN biopsy was higher than the expected utility for ALND for T1 and T2 tumors that were 4.0 cm or smaller. There was no clear preference for either procedure with tumors that were larger than 4.0 cm. The T1 and T2 results were robust to sensitivity analysis. CONCLUSIONS: The results of this decision analysis suggest that SLN biopsy is preferred over ALND for patients with breast tumors that are 4.0 cm or smaller. Patients should be aware of the potential for false-negative results in SLN biopsy, but this risk is outweighed by the decreased morbidity associated with the procedure itself.
Axilla↗
Sentinel lymph node biopsy in patients with ductal carcinoma in situ: a proposal.
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Breast Neoplasms↗
Promotion of hepatic ischemia/reperfusion injury by IL-12 is independent of STAT4.
BACKGROUND: We have recently demonstrated a role for interleukin-12 (IL-12) in the induction and development of hepatic ischemia/reperfusion injury. IL-12 mediates its effects through the transcription factor, signal transducer and activator of transcription-4 (STAT4). Therefore, we investigated the response to hepatic ischemia/reperfusion in STAT4-deficient mice. METHODS: Wild-type and STAT4-deficient mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion. In some experiments, IL-12 was neutralized with antibody administered intravenously. RESULTS: Wild-type mice demonstrated rapid activation of STAT4 in liver after ischemia/reperfusion, which mirrored hepatic protein expression of IL-12. Interestingly, STAT4-deficient mice were indistinguishable from wild-type mice in their response to hepatic ischemia reperfusion. No differences were observed in serum levels of tumor necrosis factor alpha (TNF-alpha), liver accumulation of neutrophils, or hepatocellular injury. However, blockade of endogenous IL-12 significantly reduced these parameters in STAT4-knockout mice. CONCLUSIONS: These data demonstrate that IL-12 promotes hepatic inflammation in a manner that is independent of STAT4 and implicate a novel mechanism for the pro-inflammatory effects of IL-12.
Alanine Transaminase↗
Interval sentinel lymph nodes in melanoma.
HYPOTHESIS: For patients with melanoma, interval or in-transit sentinel lymph nodes (SLNs) have the same risk for nodal metastasis as SLN in traditional (ie, cervical, axillary, and inguinal) nodal basins. DESIGN: Prospective clinical trial. SETTING: Multicenter study. PATIENTS: Eligible patients were aged 18 to 70 years with melanomas of at least 1.0-mm Breslow thickness and nodes with clinically negative findings. INTERVENTION: Sentinel lymph node biopsy was guided by preoperative lymphoscintigraphy to identify all SLNs. MAIN OUTCOME MEASURES: We evaluated interval nodal sites, including epitrochlear, popliteal, and subcutaneous or intramuscular nodes outside of traditional basins, for the presence of metastases. RESULTS: The SLNs were identified in 2332 nodal basins from 2000 patients. In 62 patients (3.1%), interval SLNs were identified. We found SLN metastases in 442 (19.5%) of 2270 conventional nodal basins and 13 (21.0%) of 62 interval sites. In 11 (84.6%) of the 13 cases in which we found an interval node that was positive for metastatic disease, it was the only site of nodal metastasis. CONCLUSIONS: Although interval SLNs are identified infrequently, they contain metastatic disease at nearly the same frequency as SLNs in cervical, axillary, and inguinal nodal basins. Positive interval SLNs are likely to be the only site of nodal metastasis. Therefore, detailed preoperative lymphoscintigraphy and meticulous intraoperative search for interval nodes should be performed.
Adult↗
Frequency of nonsentinel lymph node metastasis in melanoma.
BACKGROUND: Completion lymph node dissection (CLND) may not be necessary for some patients because nodal metastasis is rarely detected beyond the sentinel lymph nodes (SLNs). This analysis was performed to determine, among patients with positive SLNs, the rate of nodal metastasis found in nonsentinel nodes (NSNs). METHODS: This analysis includes patients with positive sentinel nodes, detected by hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC), who then underwent CLND. RESULTS: This analysis included 274 patients with at least one positive SLN who underwent CLND of 282 involved regional nodal basins. Of the 282 SLN-positive nodal basins, 45 (16%) were found to have positive NSNs in the CLND specimen. Breslow thickness, Clark level, presence of ulceration, histological subtype, presence of vertical growth phase, evidence of regression, presence of lymphovascular invasion, number of positive SLNs, age, sex, and presence of multiple draining nodal basins were not predictive of positive nodes in the CLND specimen. Patients with SLN metastases detected only by IHC had an equal likelihood of having positive NSNs as those patients with positive SLNs on H&E examination. CONCLUSIONS: No patient population could be identified with minimal risk of non-SLN metastasis. When a positive SLN is identified on either H&E staining or IHC, CLND should be performed routinely.
Adult↗
The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy.
BACKGROUND: It has been suggested that sentinel lymph node (SLN) biopsy for breast cancer may be less accurate after excisional biopsy of the primary tumor compared with core needle biopsy. Furthermore, some have suggested an improved ability to identify the SLN when total mastectomy is performed compared with lumpectomy. This analysis was performed to determine the impact of the type of breast biopsy (needle vs. excisional) or definitive surgical procedure (lumpectomy vs. mastectomy) on the accuracy of SLN biopsy. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible. All patients underwent SLN biopsy and completion level I/II axillary dissection. Statistical comparison was performed by chi(2) analysis. RESULTS: A total of 2206 patients were enrolled in the study. There were no statistically significant differences in SLN identification rate or false-negative rate between patients undergoing excisional versus needle biopsy. The SLN identification and false-negative rates also were not statistically different between patients who had total mastectomy compared with those who had a lumpectomy. CONCLUSIONS: Excisional biopsy does not significantly affect the accuracy of SLN biopsy, nor does the type of definitive surgical procedure.
Adult↗
Frequency of sentinel lymph node metastases in patients with favorable breast cancer histologic subtypes.
BACKGROUND: The need for axillary nodal staging in favorable histologic subtypes of breast cancer is controversial. METHODS: Patients with clinical stage T1-2, N0 breast cancer were enrolled in a prospective, multi-institutional study. All patients underwent sentinel lymph node (SLN) biopsy followed by completion level I/II axillary dissection. RESULTS: SLN were identified in 3,106 of 3,324 patients (93%). Axillary metastases were found in 35% and 40% of patients with infiltrating ductal carcinoma and infiltrating lobular carcinoma, respectively. Among tumor subtypes, positive nodes were found in 17% of patients with pure tubular carcinoma, 7% of patients with papillary cancer, 6% of patients with colloid (mucinous) carcinoma, 21% of patients with medullary carcinoma, and 8% of patients with DCIS with microinvasion. CONCLUSIONS: Patients with favorable breast cancer subtypes have a significant rate of axillary nodal metastasis. Axillary nodal staging remains important in such patients; SLN biopsy is an ideal method to obtain this staging information.
Adenocarcinoma↗
Patterns of early recurrence after sentinel lymph node biopsy for melanoma.
BACKGROUND: Patterns of early recurrence after sentinel lymph node (SLN) biopsy for melanoma was determined from the Sunbelt Melanoma Trial, which includes patients with Breslow thickness > or =1.0 mm and nonpalpable regional lymph nodes. METHODS: SLN were evaluated by routine histology and S-100 protein stain. Overall, there were 1,183 patients with a median follow-up of 16 months. RESULTS: SLN were positive in 233 of 1,183 patients (20%). The recurrence rate was greater among patients with histologically positive SLN than those with negative SLN (15.5% versus 6.0%, respectively, P <0.05). Patients with positive SLN were more likely to have distant metastases (as opposed to locoregional recurrence) than those with negative SLN (67% versus 46%, respectively, P <0.05). By multivariate analysis, SLN status, Breslow thickness, Clark level, and ulceration were significant independent factors associated with early recurrence. Of patients with negative SLN, 14 of 950 (1.5%) experienced metastatic disease in lymph node basins which were staged as negative for tumor by SLN biopsy initially. CONCLUSIONS: Early regional lymph node recurrence was very uncommon after positive SLN biopsy and completion lymphadenectomy. Patients with positive SLN are more likely than those with negative SLN to develop both local/in-transit recurrence and distant metastases within a short follow-up period.
Female↗
Gene deletion of NF-kappa B p50 does not alter the hepatic inflammatory response to ischemia/reperfusion.
BACKGROUND/AIMS: Nuclear factor kappa B (NF-kappa B) is a primary regulator of gene expression and is activated during hepatic ischemia/reperfusion injury. The objective of the present study was to determine whether activation of NF-kappa B is causally related to the induction of the acute inflammatory response induced by hepatic ischemia/reperfusion. METHODS: Wild-type (p50(+/+)) and NF-kappa B p50-deficient (p50(-/-)) mice underwent hepatic ischemia/reperfusion. NF-kappa B activation was determined by electrophoretic mobility shift assay. Hepatic neutrophil accumulation was measured by liver myeloperoxidase content. Hepatocellular injury was assessed by serum level of alanine aminotransferase and liver histology. RESULTS: In p50(+/+) mice, ischemia/reperfusion induced marked activation of NF-kappa B consisting of p50/p65 heterodimers. In contrast, NF-kappa B activation in livers from p50(-/-) mice was abrogated, but p65 was observed in nuclear extracts. Despite amelioration of NF-kappa B activation there was no significant difference between p50(+/+) and p50(-/-) mice in expression of TNF alpha and MIP-2, liver accumulation of neutrophils or hepatocellular injury. CONCLUSIONS: Gene deletion of NF-kappa B p50 does not alter the hepatic inflammatory response to ischemia/reperfusion. Despite abrogation of DNA-binding by the NF-kappa B p50/p65 complex, p65 was still observed in nuclear extracts suggesting that there may be functional redundancy amongst members of the Rel protein family in order to preserve the inflammatory response.
Animals↗
Mechanisms of hypothermic protection against ischemic liver injury in mice.
Hepatic hypothermia can safely prolong the duration of hepatic inflow occlusion during complex liver resectional surgeries. The mechanism(s) by which hypothermia protects against this form of liver ischemia-reperfusion injury are not completely understood. In this study, we sought to determine whether hypothermia protects against ischemia-reperfusion injury by altering the hepatic inflammatory response. Mice undergoing 90 min of partial hepatic ischemia followed by up to 8 h of reperfusion had their body temperatures regulated at 35-37 degrees C (normothermic) or unregulated, in which rectal temperature dropped as low as 25 degrees C by the end of ischemia (hypothermic). Hypothermic mice had less liver injury vs. normothermic mice, as assessed histologically, by serum transaminase levels (89% decrease), and by liver wet-to-dry weight ratios (91% decrease). Neutrophil accumulation was absent in hypothermic mice (99% reduction vs. normothermic mice). Production of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and macrophage inflammatory protein-2 were reduced by up to 92%. Activation of the transcription factor nuclear factor-kappa B was not reduced in hypothermic mice, but activation of c-Jun NH(2)-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 were greatly diminished. These data suggest that hypothermia suppresses the hepatic inflammatory response through selective inhibition of JNK and AP-1.
Animals↗
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↗
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↗
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↗
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↗
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↗
Paget's disease of the male breast: an unusual case of dermal invasion.
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Breast Neoplasms, Male↗