Use of an ultrasound imaging device within the applicator to evaluate placement and support treatment planning for breast brachytherapy and intraoperative radiation therapy.

PURPOSE: We evaluated the use of ultrasound imaging within a brachytherapy applicator as a method for applicator positioning, evaluation, and treatment planning in a series of in vitro, cadaver, and human studies. METHODS AND MATERIALS: We evaluated the performance of a prototype system comprising a small ultrasound imaging catheter inserted within the lumen of a balloon brachytherapy catheter. We tested the device in an ultrasound phantom, in human breast tissue, and in an endoscopic ultrasound catheter in cadaveric breast tissue. We evaluated the visualization of adjacent tissue to consider future development of a similar system for use in brachytherapy and intraoperative radiation therapy. RESULTS: Based on the ultrasound images obtained in an ultrasound phantom, cadaveric breast, and human participants, we observed that an ultrasound imaging catheter placed within the lumen of a brachytherapy applicator can effectively image adjacent tissue, ribs, and air voids, with appropriate quality to support clinical use. We observed high correlation in clinically useful information detected on ultrasound and comparative CT, with ultrasound spatial resolution near 1 mm (spatially variant). CONCLUSIONS: The findings from our pilot work suggest that real-time ultrasound imaging, operated from within the applicator, is a promising technique for image guidance and treatment planning during brachytherapy and intraoperative radiation therapy. Further expansion of this technology for clinical use will require development of a cohesive system of components to suit specific clinical applications.

Factors correlating with lymph node metastases in patients with T1 breast cancer.

BACKGROUND: Identification of reliable predictors of axillary metastases (ALNM) may be useful in selecting appropriate management for patients with T1-size breast cancer. This study was undertaken to determine the degree of correlation between ALNM and several variables, including age, race, menopausal status, palpability, tumor size, positive margin on initial excision, histology, grade, lymphatic invasion (LI), estrogen receptor status (ER), progesterone receptor status, S-phase, and ploidy. METHODS: Data from 1416 patients with T1 breast cancers treated at Columbia-Presbyterian Medical Center between 1989 and 1998 was reviewed. Patients with multifocal tumors were excluded. RESULTS: Mean patient age was 57.5 years (SD = 12.0); 65% of the patients were postmenopausal. One hundred thirty-one patients with Tla (< or =0.5 cm), 435 with T1b (0.6-1.0 cm), and 850 patients with T1c (1.1-2.0 cm) lesions were studied. The overall rate of ALNM was 23%. AM was identified in 11% of T1a, 15% of T1b, and 29% of T1c patients. Statistically significant factors from univariate analysis were age, palpability, skin changes, tumor size, LI, histology, grade, ER status, and positive margin on initial excision. CONCLUSIONS: Axillary staging by either sentinel lymph node biopsy or level I/II axillary dissection is indicated for most T1 breast cancer patients. Omission of axillary staging can be considered for highly selected patients with T1a cancers.

Occult breast cancer and axillary mass.

Occult breast cancer presenting with axillary metastases is an unusual presentation and can be a diagnostic and therapeutic challenge. A comprehensive work-up, including mammogram, sonogram, magnetic resonance imaging, and even pathologic examination of the mastectomy specimen may not disclose the primary tumor in up to one third of patients. Traditionally, occult breast cancer is treated with total mastectomy and axillary dissection, but accumulating data suggest that primary breast irradiation following axillary dissection may provide an equivalent survival with the advantage of breast conservation. Occult breast cancer patients are eligible for adjuvant chemotherapy and radiation as stage II/ III node-positive patients would be treated. Overall, the prognosis for occult breast cancer is equivalent to or slightly better than staged counterparts with detectable primary breast tumors.

Management of axillary lymph nodes in breast cancer: a national patterns of care study of 17,151 patients.

OBJECTIVE: To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. SUMMARY BACKGROUND DATA: Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. METHODS: A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. RESULTS: A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86% vs. 97%), patients with clinical T1 a tumors (81% vs. 93%), grade I histology (90% vs. 95%), and patients with favorable tumor types (88% vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10% vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with > or = 10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. CONCLUSIONS: Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse.

Accuracy of AJCC staging for breast cancer patients undergoing re-excision for positive margins. American Joint Committee on Cancer.

BACKGROUND: The current AJCC protocol for breast cancer staging does not include additional tumor found at the time of re-excision in the calculation of tumor size. We hypothesize that the AJCC protocol may result in understaging and undertreatment of breast cancer patients who have additional tumor found at re-excision. METHODS: In a retrospective chart review of breast cancer patients, patients with tumor present at re-excision for positive margins were placed in group 1 (n=72); patients with no tumor present at re-excision, or who underwent a single, negative margin procedure were placed in group 2 (n=147). RESULTS: Patients in group 1 had a higher risk of nodal metastases when compared to patients in group 2. Mean tumor size did not differ significantly between the subgroups. Positive re-excision was strongly associated with lymph node metastases on multivariate analysis after correction for age, grade, stage, and lymphatic invasion (odds ratio=3.13, 95% CI=1.58 6.18, P=.0011). CONCLUSIONS: Current AJCC guidelines may result in undertreatment of breast cancer patients with positive re-excisions. The presence of additional tumor at the time of re-excision should be considered when determining the need for systemic therapy, and may be relevant in determining T stage.

Breast-conserving surgery in the neoadjuvant setting.

The use of neoadjuvant chemotherapy for the treatment of patients with operable breast cancer remains controversial. Neoadjuvant chemotherapy is highly effective in achieving significant tumor regression. However, the primary goal of improved survival has yet to be clearly demonstrated. The largest prospective trial with adequate follow-up to report 5-year disease-free survival data demonstrated no significant difference between patients treated with neoadjuvant chemotherapy followed by locoregional treatment and locoregional treatment followed by adjuvant chemotherapy. Survival data from the National Surgical Adjuvant Breast and Bowel Project B-18 trial are not yet available. The potential impact on the breast conservation rate for patients with early operable breast cancer is small, and careful follow-up of the long-term risk of local recurrence for patients with neoadjuvant therapy induced downstaging followed by BCT is not yet available. At this time, neoadjuvant chemotherapy for the treatment of patients with operable breast cancer should be considered investigational.

Transgenic technology: an overview of approaches useful in surgical research.

Advances in transgenic science have created powerful tools for the investigation of both genetic and protein regulatory systems. Recently, transgenic animals have been utilized in several vascular and transplantation research laboratories. The ability to specifically mutate genes important in oncologic and cardiovascular research is leading to a greater understanding of the role of gene and protein regulatory systems in cancer and cardiovascular disease. The expanding use of transgenic animals will undoubtedly increase our insight into complex problems in surgical research. This review briefly describes the various techniques utilized to create transgenic animals including: transgene design, gene-transfer utilizing transfection, microinjection and retroviral infection, as well as the use of embryonic stem cells, and methods for screening transgenic offspring.

Cystic neoplasms of the pancreas. A clinicopathologic study, including DNA flow cytometry.

OBJECTIVE: To review the classification, clinical behavior, and appropriate therapy for cystic neoplasms of the pancreas. We examined patient demographics, clinical parameters, preoperative imaging modalities, histologic findings, and tumor DNA content to determine which best predict outcome. DESIGN: Case series and survey of pathologic specimens. SETTING: Tertiary care center. PATIENTS: Twenty-two patients with cystic neoplasms of the pancreas treated at affiliates of Northwestern University Medical School, Chicago, Ill. MAIN OUTCOME MEASURES: Predictive value of preoperative testing, tumor DNA content, patient survival. RESULTS: In 20 patients undergoing computed tomographic scan, the tumor was visualized in every case. All other imaging studies evaluated were less likely to demonstrate the lesion. Eight of 10 patients with serous cystadenomas were alive with no evidence of disease at the time of this report; one patient was alive with local recurrence, and a second patient had died of unrelated causes. All patients with mucinous cystadenomas were alive with no evidence of disease. Three of seven patients with cystadenocarcinomas had aneuploid, high S-phase tumors, and one had a diploid, high S-phase tumor; all four died (mean survival, 4.8 months). Two patients with cystadenocarcinomas had diploid, low S-phase tumors; both were long-term survivors but died of their disease at 8.6 and 9.3 years. CONCLUSIONS: (1) Computed tomographic scan is the most valuable diagnostic imaging study for preoperative evaluation of these patients. (2) Precise preoperative determination of tumor type is not possible. (3) DNA flow cytometry may help identify patients with aggressive tumors who may benefit from adjuvant chemoradiation.

Pluripotent embryonic stem cells from the rat are capable of producing chimeras.

Embryonic stem cells have been enormously important in the production of targeted mutations in mice used in the study of gene function and biological aspects of disease states. The use of these cells for mouse studies is now wide-spread but the production of animals from similar cell lines derived from other species has not been previously reported. We demonstrate here the derivation of diploid rat embryonic stem cells (RESC-01). RESC-01 cells are SSEA-1 and alkaline phosphatase positive, grow best on primary rat embryonic fibroblasts, and can differentiate extensively in vivo. RESC-01 cells form cystic embryoid bodies capable of rhythmic contractions. Rat blastocysts injected with RESC-01 cells form chimeras. The results indicate that the successful in vitro propagation and chimera production with embryonic stem cells is not limited to the mouse. The long-term culture of rat ES cells will provide an important resource for the study of normal physiology and disease models where rat is the species of choice.