Medical Sciences
Barrett’s Esophagus
Geospace Research, Inc. is currently developing an imaging ultrasound system to perform non-invasive imaging biopsies on patients with Barrett's esophagus. (See Biomedical Research) In addition, preliminary studies for two new projects have been initiated.
Real-Time Processing of Tumor Margins during Breast Cancer Surgery
Segmental mastectomy, also known as breast-conserving surgery or lumpectomy, is increasingly being used to treat operable breast cancers as opposed to a full mastectomy. Breast-conserving surgery involves excision of the visible tumor, along with a section of the surrounding tissue. In the past, a 2-3 mm surgical margin was thought to be adequate for assessing whether all tumor cells had been excised. The objective was to determine the risk of regional recurrence while promoting a cosmetically acceptable outcome. However, current findings indicate that significantly greater surgical margins are often required for a negative margin determination. During surgery, the tumor tissue and the surrounding margins are intraoperatively evaluated by a pathologist to determine if additional tissue margin must be removed. However, these evaluations, whether by gross inspection, specimen X-rays, frozen-section analysis, or touch-prep cytology, are imperfect and are not nearly as accurate as the more comprehensive post-closure analyses of margin tissue. The latter requires too much time to be performed during surgery. The excised tissue is carefully examined subsequent to closure for carcinoma and/or cancer in situ in the margins. If either is positive or close to the edge of a margin, a second surgery is scheduled within two–three weeks of the first procedure to remove more tissue beyond the original margin. This is done prior to the healing of the excised cavity. Otherwise the site of positive margin must be identified by estimation, which is imprecise and usually results in the removal of a larger volume of tissue than necessary. The long term objective of the proposed research is to reliably determine the presence of carcinoma and/or cancer in situ in the margin at the time of the primary surgery before closure. The immediate goal is to establish the feasibility of imaging breast tumor cells within a larger population of benign cells. It is expected that the ultrasound system's resolution will allow detection of small clusters of cancer cells that are 50 μm in size or smaller. (The nominal cancer cell size is ~20 μm.) The proposed work entails the development of novel imaging systems that take advantage of the high-frequency (50-100 MHz) wideband medical ultrasound technology previously developed by Geospace Research, Inc. F. T. Djuth is the principal investigator of this project.
Detection of Cancer Cell Clusters Distal to the Tumor Site during Breast Conservation Surgery
The objective of the study is to develop a surgical tool to detect breast cancer carcinoma cells that are outside of the immediate region of the excised tumor. This study applies primarily to breast conservation surgery (segmental mastectomy), which is the most common form of breast cancer surgery. All modern prospective, randomized trials have shown that survival following breast-conservation therapy is equivalent to that of mastectomy. After the surgical excision, the open breast cavity is palpated by the surgeon in a search for cancer cells/cell clusters beyond the tumor perimeter. If a positive detection is found during palpation, additional margins are taken from the appropriate incision walls. These cells have a high probability of following a metastatic path to the sentinel lymph nodes and/or local blood vessels. The size of the clusters ranges from 2-10 cells to groupings that are ~1 mm in diameter. The proposed ultrasound probe detects the small cellular clusters that are not amenable to palpitation by the surgeon. A low frequency (7-9 MHz) ultrasound array is mounted across the half-sphere topography of the probe head. The low frequency is required to reduce the attenuation from the large amount of adipose tissue in the cavity. The estimated searchable volume consists of a 5 cm spherical half-shell extending radially beyond the head of the probe. With the proposed technique one can readily distinguish between normal breast cells, which have a nucleus size ~20% of the cell size, and a breast cancer cell that has a nucleus that is ~80-90% of the size of the cell. The incident ultrasound wave scatters primarily off of the cell nucleus. The spacing of nuclei in cell clusters varies in different lesions. Regular nuclear spacing suggests a benign process; irregular spacing is characteristic of a malignancy. These two conditions can readily be differentiated with the diagnostic probe. In addition the distinction between fibroadenoma (most common benign tumor) and ductal carcinoma (most common malignant tumor) is straightforward. Fibroadenoma exhibits stromal fragments (foundation supporting tissues as opposed to essential functional tissue), large antler-like epithelial structures (many hundreds of cells), and honeycomb sheets of hundreds of ductal cells; these properties are very uncommon in ductal, invasive carcinomas. Major criteria for the diagnosis of ductal carcinoma are hypercellularity, loosely cohesive amorphous/tubular clusters containing hundreds of cells, and an extensive range of large nuclear sizes and shapes that include multinucleated cells. Tubular clusters and dense fibrosis (fibroblast proliferation and stroma fragments, referred to as scirrhous carcinoma) are indicative of invasive ductal carcinoma (IDC). Thus, the two most common pathologies should be readily distinguishable with the proposed ultrasound array. IDC and ductal cancer in situ (DCIS) appear to be identical from the viewpoint of cytology. However, cohesiveness is a property of DCIS and tubular structures are absent in the case of DCIS. Both IDC and DCIS can present as a palpable mass or as a non-palpable abnormality. The proposed probe can distinguish between the two. F. T. Djuth is the principal investigator of this project.
When is a Medical Advocate Necessary?
A book is currently being written addressing the issue as to when an advocate is needed for a seriously ill patient. The role of this person is to protect the patient from medical errors that can lead to death. In a real-life story the patient develops a rare and very lethal form of acute leukemia. Over the next 20 months there are many dark days and several life-threatening medical challenges. During this period, the support of two specialist physicians is deemed to be dangerous to the patient’s well-being, and the assistance of these physicians is terminated. The patient does in fact find a path to survival but could never do so without an advocate.
Barrett’s Esophagus
Geospace Research, Inc. is currently developing an imaging ultrasound system to perform non-invasive imaging biopsies on patients with Barrett's esophagus. (See Biomedical Research) In addition, preliminary studies for two new projects have been initiated.
Real-Time Processing of Tumor Margins during Breast Cancer Surgery
Segmental mastectomy, also known as breast-conserving surgery or lumpectomy, is increasingly being used to treat operable breast cancers as opposed to a full mastectomy. Breast-conserving surgery involves excision of the visible tumor, along with a section of the surrounding tissue. In the past, a 2-3 mm surgical margin was thought to be adequate for assessing whether all tumor cells had been excised. The objective was to determine the risk of regional recurrence while promoting a cosmetically acceptable outcome. However, current findings indicate that significantly greater surgical margins are often required for a negative margin determination. During surgery, the tumor tissue and the surrounding margins are intraoperatively evaluated by a pathologist to determine if additional tissue margin must be removed. However, these evaluations, whether by gross inspection, specimen X-rays, frozen-section analysis, or touch-prep cytology, are imperfect and are not nearly as accurate as the more comprehensive post-closure analyses of margin tissue. The latter requires too much time to be performed during surgery. The excised tissue is carefully examined subsequent to closure for carcinoma and/or cancer in situ in the margins. If either is positive or close to the edge of a margin, a second surgery is scheduled within two–three weeks of the first procedure to remove more tissue beyond the original margin. This is done prior to the healing of the excised cavity. Otherwise the site of positive margin must be identified by estimation, which is imprecise and usually results in the removal of a larger volume of tissue than necessary. The long term objective of the proposed research is to reliably determine the presence of carcinoma and/or cancer in situ in the margin at the time of the primary surgery before closure. The immediate goal is to establish the feasibility of imaging breast tumor cells within a larger population of benign cells. It is expected that the ultrasound system's resolution will allow detection of small clusters of cancer cells that are 50 μm in size or smaller. (The nominal cancer cell size is ~20 μm.) The proposed work entails the development of novel imaging systems that take advantage of the high-frequency (50-100 MHz) wideband medical ultrasound technology previously developed by Geospace Research, Inc. F. T. Djuth is the principal investigator of this project.
Detection of Cancer Cell Clusters Distal to the Tumor Site during Breast Conservation Surgery
The objective of the study is to develop a surgical tool to detect breast cancer carcinoma cells that are outside of the immediate region of the excised tumor. This study applies primarily to breast conservation surgery (segmental mastectomy), which is the most common form of breast cancer surgery. All modern prospective, randomized trials have shown that survival following breast-conservation therapy is equivalent to that of mastectomy. After the surgical excision, the open breast cavity is palpated by the surgeon in a search for cancer cells/cell clusters beyond the tumor perimeter. If a positive detection is found during palpation, additional margins are taken from the appropriate incision walls. These cells have a high probability of following a metastatic path to the sentinel lymph nodes and/or local blood vessels. The size of the clusters ranges from 2-10 cells to groupings that are ~1 mm in diameter. The proposed ultrasound probe detects the small cellular clusters that are not amenable to palpitation by the surgeon. A low frequency (7-9 MHz) ultrasound array is mounted across the half-sphere topography of the probe head. The low frequency is required to reduce the attenuation from the large amount of adipose tissue in the cavity. The estimated searchable volume consists of a 5 cm spherical half-shell extending radially beyond the head of the probe. With the proposed technique one can readily distinguish between normal breast cells, which have a nucleus size ~20% of the cell size, and a breast cancer cell that has a nucleus that is ~80-90% of the size of the cell. The incident ultrasound wave scatters primarily off of the cell nucleus. The spacing of nuclei in cell clusters varies in different lesions. Regular nuclear spacing suggests a benign process; irregular spacing is characteristic of a malignancy. These two conditions can readily be differentiated with the diagnostic probe. In addition the distinction between fibroadenoma (most common benign tumor) and ductal carcinoma (most common malignant tumor) is straightforward. Fibroadenoma exhibits stromal fragments (foundation supporting tissues as opposed to essential functional tissue), large antler-like epithelial structures (many hundreds of cells), and honeycomb sheets of hundreds of ductal cells; these properties are very uncommon in ductal, invasive carcinomas. Major criteria for the diagnosis of ductal carcinoma are hypercellularity, loosely cohesive amorphous/tubular clusters containing hundreds of cells, and an extensive range of large nuclear sizes and shapes that include multinucleated cells. Tubular clusters and dense fibrosis (fibroblast proliferation and stroma fragments, referred to as scirrhous carcinoma) are indicative of invasive ductal carcinoma (IDC). Thus, the two most common pathologies should be readily distinguishable with the proposed ultrasound array. IDC and ductal cancer in situ (DCIS) appear to be identical from the viewpoint of cytology. However, cohesiveness is a property of DCIS and tubular structures are absent in the case of DCIS. Both IDC and DCIS can present as a palpable mass or as a non-palpable abnormality. The proposed probe can distinguish between the two. F. T. Djuth is the principal investigator of this project.
When is a Medical Advocate Necessary?
A book is currently being written addressing the issue as to when an advocate is needed for a seriously ill patient. The role of this person is to protect the patient from medical errors that can lead to death. In a real-life story the patient develops a rare and very lethal form of acute leukemia. Over the next 20 months there are many dark days and several life-threatening medical challenges. During this period, the support of two specialist physicians is deemed to be dangerous to the patient’s well-being, and the assistance of these physicians is terminated. The patient does in fact find a path to survival but could never do so without an advocate.