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Biomedical subjects

D Krag

Publications and source records attributed to D Krag.

15 recordsLinked to original sources

Tactile imaging of breast masses: first clinical report.

HYPOTHESIS: Tactile imaging can accurately document the palpable extent of breast masses. DESIGN: Prospective nonrandomized interventional trial, comparing mass size estimates from preoperative physical examination, ultrasound, and tactile imaging with postoperative measurements of the resected masses. SETTING: A community ambulatory surgical center and a university hospital tertiary care center. PATIENTS: Twenty-three women undergoing surgical excision of breast masses. All subjects had a single, palpable, dominant mass, 0.5 to 3 cm in diameter. INTERVENTION: Prior to surgery, the size of each mass was estimated from tactile imaging using an array of pressure sensors that is stroked over the mass. Size was also estimated by ultrasound and physical examination. Immediately following resection of the mass, it was bisected, and the palpable extent was measured with a caliper. MAIN OUTCOME MEASURE: Maximum mass diameter estimates from ultrasound, physical examination, and tactile imaging, compared with the resected measurement. RESULTS: Tactile imaging estimates were repeatable (7.5% mean SD for multiple estimates of the same mass) and show good agreement with the resected measurements. Mean absolute error was 13%, and linear regression with zero intercept had a slope of 0.94, r(2) = 0.51. Physical examination and ultrasound estimates had respective mean absolute errors of 46% and 34%, regression slopes of 1.27 and 0.89, and r(2) = 0.28 and 0.37. CONCLUSIONS: Tactile imaging can provide accurate and reproducible estimates of the size of breast masses. This capability can enhance cancer surveillance for patients with benign masses (eg, due to scarring or fibrocystic changes) because previous work suggests that reliable detection of a difference in mass size by physical examination requires a 40% change in diameter. In contrast, this study suggests tactile imaging requires only a 15% change (95% confidence interval).

Breast Neoplasms↗

Why perform randomized clinical trials for sentinel node surgery for breast cancer?

Long-term outcome of sentinel node surgery without axillary dissection has not been established. To that extent the therapeutic outcome of sentinel node surgery is unknown. Two important clinical trials are under way that are designed to compare sentinel node surgery without axillary dissection to axillary dissection. In partnership with the University of Vermont, the National Surgical Adjuvant Breast and Bowel Project is conducting a trial that will primarily compare node negative breast cancer cases. The American College of Surgeons Clinical Oncology Group is conducting a trial that randomizes node positive breast cancer patients. The primary endpoints of these clinical trials are survival, long-term regional control, and morbidity. At the conclusion of these trials it will be established within a narrow confidence interval whether sentinel node surgery alone provides the same important therapeutic benefits as axillary surgery but without the morbidity associated with axillary surgery.

Axilla↗

Minimal invasive staging for breast cancer: clinical experience with sentinel lymph node biopsy.

During the 1990s, considerable research and development resulted in reasonably reliable methods to target the set of lymph nodes most likely to contain metastases in patients with breast cancer. The methods of identification of these "sentinel nodes" (SNs) involve injection of a visual-based dye or a radioactive tracer. The tracer/dye enters the lymphatics and labels the SNs so that they can be selectively removed. SNs can be successfully identified in > or =90% of patients. In breast cancer patients with clinically negative lymph nodes, the accuracy of the SNs to predict whether any nodal metastases are present is > or =97%. The false-negative rate, however, ranges from 0% (in smaller series) to 11%. Clinical trials are in progress that will determine the long-term safety and predictive value of SN resection in patients with breast cancer. Successful application of SN surgery should allow elimination of conventional axillary lymphadenectomy in at least 75% of patients with breast cancer. Semin Oncol 28:229-235.

Breast Neoplasms↗

Sentinel lymph node biopsy for the detection of metastases.

Although the concept of the sentinel node has existed for most of the twentieth century, it was only in the last decade that methods were developed which allowed practical application to cancer patients. Sentinel nodes (SN) are a highly variable but limited set of lymph nodes first to receive drainage from any given location. Cancer metastasizes to these nodes before other nodes. Radioactive tracers and blue dyes are used to guide the surgeon to the SNs for resection. Two large clinical trials of SN surgery in breast cancer patients are actively underway in the United States. Until the impact of this very promising technology is confirmed to provide the same staging and prognosis, regional control, and survival as conventional surgery, it is considered an experimental procedure.

Biopsy↗

Nuclear medicine and the surgeon.

Nuclear medicine provides the surgeon with important diagnostic and functional information on specific organs and with therapy for a limited set of diseases. Clinical applications of nuclear medicine are beginning to guide surgeons to specific locations, notably to sentinel lymph nodes in patients with cancer. The role of radionuclide diagnosis in oncology has been covered earlier in this Lancet series, so here is a surgeon's perspective on sentinel node and other oncological applications and on the surgical value of nuclear medicine in non-malignant diseases.

Female↗

The sentinel node in breast cancer--a multicenter validation study.

BACKGROUND: Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. METHODS: We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. "Hot spots" representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. RESULTS: The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status of the axillary nodes was 97 percent (392 of 405); the specificity of the method was 100 percent, the positive predictive value was 100 percent, the negative predictive value was 96 percent (291 of 304), and the sensitivity was 89 percent (101 of 114). The sentinel nodes were outside the axilla in 8 percent of cases and outside of level 1 nodes in 11 percent of cases. Three percent of positive sentinel nodes were in nonaxillary locations. CONCLUSIONS: Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient.

Axilla↗

Nonphosphorylated peptide ligands for the Grb2 Src homology 2 domain.

Critical intracellular signals in normal and malignant cells are transmitted by the adaptor protein Grb2 by means of its Src homology 2 (SH2) domain, which binds to phosphotyrosyl (pTyr) residues generated by the activation of tyrosine kinases. To understand this important control point and to design inhibitors, previous investigations have focused on the molecular mechanisms by which the Grb2 SH2 domain selectively binds pTyr containing peptides. In the current study, we demonstrate that the Grb2 SH2 domain can also bind in a pTyr independent manner. Using phage display, an 11-amino acid cyclic peptide, G1, has been identified that binds to the Grb2 SH2 domain but not the src SH2 domain. Synthetic G1 peptide blocks Grb2 SH2 domain association (IC50 10-25 microM) with a 9-amino acid pTyr-containing peptide derived from the SHC protein (pTyr317). These data and amino acid substitution analysis indicate that G1 interacts in the phosphopeptide binding site. G1 peptide requires a YXN sequence similar to that found in natural pTyr-containing ligands, and phosphorylation of the tyrosine increases G1 inhibitory activity. G1 also requires an internal disulfide bond to maintain the active binding conformation. Since the G1 peptide does not contain pTyr, it defines a new type of SH2 domain binding motif that may advance the design of Grb2 antagonists.

Adaptor Proteins, Signal Transducing↗

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.

Adenocarcinoma↗