Biomedical subjects

Michelle C Specht

Publications and source records attributed to Michelle C Specht.

8 recordsLinked to original sources

PubMed2006

Breast cancer diagnosis in women < or = 40 versus 50 to 60 years: increasing size and stage disparity compared with older women over time.

BACKGROUND: Women < or = 40 years account for 5% of new breast cancer diagnoses. Although there is increased awareness of genetic and other breast cancer risk factors, it is not clear whether this has resulted in earlier diagnosis in young women. METHODS: A database review identified 8892 women treated for breast cancer from 1980 to 2002. We compared 925 women aged < or = 40 years with 2362 women aged 50 to 60 years. The mean and median tumor size and lymph node status were determined for each group. RESULTS: There were significant differences in tumor size and lymph node status in younger versus older women. From 1980 to the mid 1990s, tumor size and nodal status did not differ. Since the mid 1990s, tumor size has decreased more rapidly for women aged 50 to 60 years than for those < or = 40 years. In 1998 to 2002, the mean tumor size reached a plateau of 1.8 cm in women 50 to 60 years, compared with a plateau of 2.4 cm in women < or = 40 years (P < .001). The median tumor size in 1998 to 2002 was 1.4 cm in women 50 to 60 years compared with 1.9 cm in women < or = 40 years (P < .001). Lymph node status was also significantly different during 1998 to 2002: 23.9% positive in women 50 to 60 years versus 35.2% in women < or = 40 years (P < .001). CONCLUSIONS: Since the 1980s, women aged 50 to 60 years have enjoyed a greater decrease in tumor size and percentage with positive nodes. These data could be the result of ineffective screening of younger women or of more aggressive tumor biology. Further study is required to determine whether more effective identification and screening of young, high-risk women can result in earlier detection.

Adult↗

PubMed2005

Predicting nonsentinel node status after positive sentinel lymph biopsy for breast cancer: clinicians versus nomogram.

BACKGROUND: With increasing frequency, breast cancer patients and clinicians are questioning the need for completion axillary lymph node dissection (ALND) in the setting of a positive sentinel lymph node (SLN). We previously developed a nomogram to estimate the likelihood of residual disease in the axilla after a positive SLN biopsy result. In this study, we compared the predictions of clinical experts with those generated by the nomogram and evaluated the ability of the nomogram to change clinicians' behavior. METHODS: Pathologic features of the primary tumor and SLN metastases of 33 patients who underwent completion ALND were presented to 17 breast cancer specialists. Their predictions for each patient were recorded and compared with results from our nomogram. Subsequently, clinicians were presented with clinical information for eight patients and asked whether they would perform a completion ALND before and after being presented with the nomogram prediction. RESULTS: The predictive model achieved an area under the receiver operating characteristic curve of .72 when applied to the test data set of 33 patients. In comparison, the clinicians as a group were associated with an area under the receiver operating characteristic curve of .54 (P < .01 vs. nomogram). With regard to performing a completion ALND, providing nomogram results did not alter surgical planning. CONCLUSIONS: Our predictive model seemed to substantially outperform clinical experts. Despite this, clinicians were unlikely to change their surgical plan based on nomogram results. It seems that most clinicians can improve their predictive ability by using the nomogram to predict the likelihood of additional non-SLN metastases in a woman with a positive SLN biopsy result.

Adult↗

PubMed2005

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important.

BACKGROUND: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. METHODS: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. RESULTS: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. CONCLUSIONS: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla.

Antineoplastic Agents↗

PubMed2005

Is the clinically positive axilla in breast cancer really a contraindication to sentinel lymph node biopsy?

BACKGROUND: Clinically positive axillary nodes are widely considered a contraindication to sentinel lymph node (SLN) biopsy in breast cancer, yet no data support this mandate. In fact, data from the era of axillary lymph node dissection (ALND) suggest that clinical examination of the axilla is falsely positive in as many as 30% of cases. Here we report the results of SLN biopsy in a selected group of breast cancer patients with palpable axillary nodes classified as either moderately or highly suspicious for metastasis. STUDY DESIGN: Among 2,027 consecutive SLN biopsy procedures performed by two experienced surgeons, clinically suspicious axillary nodes were identified in 106, and categorized as group 1 (asymmetric enlargement of the ipsilateral axillary nodes moderately suspicious for metastasis, n = 62) and group 2 (clinically positive axillary nodes highly suspicious for metastasis, n = 44). RESULTS: Clinical examination of the axilla was inaccurate in 41% of patients (43 of 106) overall, and was falsely positive in 53% of patients (33 of 62) with moderately suspicious nodes and 23% of patients (10 of 44) with highly suspicious nodes. False-positive results were less frequent with larger tumor size (p = 0.002) and higher histologic grade (p = 0.002), but were not associated with age, body mass index, or a previous surgical biopsy. CONCLUSIONS: Clinical axillary examination in breast cancer is subject to false-positive results, and is by itself insufficient justification for axillary lymph node dissection. If other means of preoperative assessment such as palpation- or image-guided fine needle aspiration are negative or indeterminate, then SLN biopsy deserves wider consideration as an alternative to routine axillary lymph node dissection in the clinically node-positive setting.

Adult↗

PubMed2004

Personal health behaviors in women who have undergone risk-reducing mastectomy.

BACKGROUND: Risk-reducing mastectomy (RRM) remains an effective yet controversial modality for the primary prevention of breast cancer. Is the choice of RRM consistent with a generally proactive healthy lifestyle? METHODS: The National Prophylactic Mastectomy Registry is a volunteer database comprised of 460 women who have undergone bilateral RRM. Each patient received a questionnaire drawn from the Centers for Disease Control Behavioral Risk Factor Surveillance System. Their responses were compared with gender-specific national data from the Centers for Disease Control. RESULTS: Women in the RRM group were statistically more likely to engage in risk-reducing personal health behavior including not smoking, exercising, maintaining their health, and taking advantage of screening programs. CONCLUSIONS: Women in the registry who underwent RRM practiced a more "healthy" lifestyle than gender-matched controls. Therefore, the decision to have prophylactic surgery may have been part of a proactive approach toward their overall physical well-being.

Adult↗

PubMed2003

Antisense hTERT inhibits thyroid cancer cell growth.

Activation of telomerase represents an early step in carcinogenesis. Increased telomerase expression in malignant thyroid tumors suggests that inactivation of telomerase may represent a potential chemotherapeutic target. The purpose of this study was to inhibit the protein component of telomerase, hTERT, in a human thyroid cancer cell line in vitro and in vivo using an antisense strategy. A 235-bp fragment of hTERT cDNA was subcloned, and sense and antisense hTERT expression vectors were constructed. These vectors were transfected into a human thyroid carcinoma cell line (FRO). Tumorigenic potential was determined by cellular growth assay, rate of apoptosis, anchorage-independent growth, and tumor growth in a nude mouse model. Significant down-regulation of hTERT expression was seen in the antisense transfected cells, compared with control and those transfected with the sense vector. A decrease in telomerase activity by TRAP assay was observed in the antisense hTERT cells but not in cells transfected with the sense hTERT construct. Inhibition of cell growth was observed after approximately 20 population doublings in the antisense-hTERT clones and was associated with an increase in the rate of apoptosis and a change in cellular morphology. Moreover, anchorage-independent growth was reduced in vitro, and tumor growth rate was diminished in vivo in the antisense hTERT clones. Inhibition of telomerase activity with antisense hTERT in human thyroid cancer cells is achievable and may represent a novel target to inhibit tumor growth.

Apoptosis↗

PubMed2002

Effects of limited work hours on surgical training.

BACKGROUND: Legal mandates to reduce resident work hours have prompted changes in the structure of surgical training programs. Such changes have included modification of on-call schedules and the adoption of "night float" resident coverage. Little is known about the effects of these changes on surgical resident education and perceptions of quality of patient care. STUDY DESIGN: The surgical housestaff and faculty at a single institution completed a 21-point Likert survey. Subjects were asked to compare parameters of resident education, patient care, and resident quality of life before and after institution of a strict 80-hour work week resident training schedule. The number of hours worked per week before and after these changes were reported. American Board of Surgery In-Training Examination (ABSITE) scores were compared for the 2 years before and after implementation of this schedule. Total number of surgical cases performed by graduating chief residents were recorded and compared for the 3 years before and after the schedule changes. RESULTS: Resident work hours reduced significantly after schedule changes were implemented. A majority of surgical residents reported an improvement in quality of life, but residents and faculty perceived changes to have a negative impact on continuity of patient care. Mean ABSITE composite percentile scores significantly improved after the reduction of working hours. ABSITE scores for junior residents improved significantly; no significant differences were noted in scores for senior residents. CONCLUSIONS: Reduction in resident work hours has salutary effects on perception of quality of life and basic education for surgical residents. These benefits may come at the expense of patient care, particularly continuity of care. This study did not directly assess patient outcomes but the perceptions of caregivers suggest that patient care may be compromised. Further research is needed to assess the longterm effects of changes on both residents and patients.

Attitude of Health Personnel↗

PubMed2002

Cyclooxygenase-2 expression in thyroid nodules.

Factors contributing to the development of thyroid neoplasia remain poorly understood. Recent evidence indicates that overexpression of the inducible cyclooxygenase, COX-2, is important in the pathogenesis of epithelial carcinomas. These studies were undertaken to evaluate whether COX-2 is up-regulated in human thyroid neoplasia. Benign (n = 14), and malignant (n = 14) thyroid nodules were analyzed for expression of COX-2 mRNA by quantitative RT-PCR. Immunoblotting and immunohistochemistry were performed on representative samples. Three human thyroid cancer cell lines were similarly analyzed for COX-2 expression. Levels of COX-2 mRNA were significantly increased in thyroid nodule samples compared with adjacent thyroid tissue in the malignant specimens but not in the benign specimens. Additionally, COX-2 mRNA levels were significantly increased in malignant nodule samples compared with benign nodule samples. COX-2 protein expression was higher in 8 of 10 thyroid nodules compared with the adjacent tissue. Immunohistochemical analysis localized expression of COX-2 to the malignant epithelial cells. Immunofluorescence demonstrated COX-2 protein expression in all three thyroid cell lines. Finally, COX-2 expression could be detected by RT-PCR in fine needle aspiration specimens of thyroid nodules. These data indicate that COX-2 is up-regulated in human thyroid cancer, but not in benign thyroid nodules, and suggest that COX-2 expression may serve as a marker of malignancy in thyroid nodules.

Biomarkers, Tumor↗