Approaches to improving breast cancer diagnosis using a high resolution,breast specific gamma camera

Mammography remains the gold standard in breast cancer detection, although there remains a challenge for improvement in sensitivity of breast cancer detection and diagnosis. Although mammography is the most frequently utilized examination to screen for breast cancer, which has resulted in a reduction of breast cancer mortality, still some cancers are unable to be visualized on mammographic images. Mammography films are interpreted using an anatomic approach. A new approach to breast cancer diagnosis utilizes a breast specific gamma camera to measure radiotracer uptake of abnormal tissue in the breast in patients with an abnormal mammogram or palpble mass using technetium sestamibi. Images are taken using the same positioning techniques as mammography for comparison of both types of images. Multi-Institutional trials using a traditional gamma camera demonstrated potential for this approach. However, the inability of traditional gamma camera intrinsic resolution and non-optinuized breast imaging limited scintimammography. Therefore, a breast specific, high resolution gamma camera was developed to overcome these limitations.Results of clinical studies evaluating BSGI are promising and are increasingly being used. Additionally, means for minimally invasive imaging-guided acquisition of tissue are being developed so that biopsies will be avaibles for areas of interest based on radiotracer uptake.Breast specific gamma camera nuclear imaging of the breast is a developing and increasingly utilized approach to improving breast cancer detection and diagnosis.     

Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging

ABSTRACT: BACKGROUND: It is not clear if sentinel lymph node (SLN) mapping can improve outcomes in patients with colorectal cancers. The purpose of this study was to determine the prognostic values of ex vivo sentinel lymph node (SLN) mapping and immunohistochemical (IHC) detection of SLN micrometastasis in colorectal cancers. METHODS: Colorectal cancer specimens were obtained during radical resections and the SLN was identified by injecting a 1% isosulfan blue solution submucosally and circumferentially around the tumor within 30 min after surgery. The first node to stain blue was defined as the SLN. SLNs negative by hematoxylin and eosin (HE) staining were further examined for micrometastasis using cytokeratin IHC. RESULTS: A total of 54 patients between 25 and 82 years of age were enrolled, including 32 males and 22 females. More than 70% of patients were T3 or above, about 86% of patients were stage II or III, and approximately 90% of patients had lesions grade II or above. Sentinel lymph nodes were detected in all 54 patients. There were 32 patients in whom no lymph node micrometastasis were detected by HE staining and 22 patients with positive lymph nodes micrometastasis detected by HE staining in non-SLNs. In contrast only 7 SLNs stained positive with HE. Using HE examination as the standard, the sensitivity, non-detection rate, and accuracy rate of SLN micrometastasis detection were 31.8% (7/22), 68.2% (15/22), and 72.2%, respectively. Micrometastasis were identified by ICH in 4 of the 32 patients with HE-negative stained lymph nodes, resulting in an upstaging rate 12.5% (4/32). The 4 patients who were upstaged consisted of 2 stage I patients and 2 stage II patients who were upstaged to stage III. Those without lymph node metastasis by HE staining who were upstaged by IHC detection of micrometastasis had a significantly poorer disease-free survival (p = 0.001) and overall survival (p = 0.004). CONCLUSION: Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging, and may become a factor affecting prognosis and guiding treatment.     

Sentinel node biopsy in breast cancer using infrared laser system first experience with PDE camera

Background

Sentinel node biopsy (SNB) is a gold standard in staging of early breast cancer. Nowadays, routine mapping of lymphatic tract is based on two tracers: human albumin with radioactive technetium, with or without blue dye. Recent years have seen a search for new tracers to examine sentinel node as well as lymphatic network. One of them is indocyanine green (ICG) visible in infrared light.

Aim

The aim of this study is to evaluate clinical usage of ICG in comparison with standard tracer, i.e. nanocoll, in SNB of breast cancer patients.

Materials and methods

In the 1st Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, 13 female breast cancer patients have benn operated since September 2010. All these patients had sentinel node biopsy with nanocoll (human albumin with radioactive technetium), and with indocyanine green. The feasibility of this new method was assessed in comparison with the standard nanocoll.

Results

A lymphatic network between the place of injection of ICG and sentinel node was seen in infrared light. An area where a sentinel node was possibly located was confirmed by gamma probe. Sensitivity of this method was 100%.

Conclusion

SNB using ICG is a new, promising diagnostics technique. This procedure is not without drawbacks; nevertheless it opens new horizons in lymphatic network diagnostics.     

Promising techniques for breast cancer detection,diagnosis, and staging using non-ionizing radiation imaging techniques

Traditional imaging for the diagnosis and staging of breast cancer has relied on the tissue morphology of cancers in the background of normal patterns of fibroglandular breast tissue. X-ray mammography and ultrasound have been the primary modalities for the diagnosis and the work-up of breast cancer. New modalities have been validated including magnetic resonance imaging (MRI) and positron emission tomography (PET). New pulse sequences in MRI combined with contrast enhancement kinetic perfusion curves have greatly enhanced detection of mammographically occult cancers. New modalities on the horizon include optical imaging, exploiting again the differential perfusion properties of cancers in a background of normal glandular tissue. Even more specificity can be ach eved with the addition of ductal or intravenous introduction of optical probes specific to tumor associated antigens such as the HER-2/neu receptor in aggressive breast cancers. Quantum dots and other fluorescent dyes coupled to peptides or other probes will greatly enhance our ability to detect cancers earlier and without ionizing radiation.     

Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery

Extra-abdominal desmoid tumours are slow-growing, histologically benign tumours of fibroblastic origin with variable biologic behaviour. They are locally aggressive and invasive to surrounding anatomic structures. Magnetic resonance imaging is the modality of choice for the diagnosis and the evaluation of the tumours. Current management of desmoids involves a multidisciplinary approach. Wide margin surgical resection remains the main treatment modality for local control of the tumour. Amputation should not be the initial treatment, and function-preserving procedures should be the primary treatment goal. Adjuvant radiation therapy is recommended both for primary and recurrent lesions. Chemotherapy may be used for recurrent or unresectable disease. Overall local recurrence rates vary and depend on patient's age, tumour location and margins at resection.     

Lymphoscintigraphy and triangulated body marking for morbidity reduction during sentinel node biopsy in breast cancer

Current trends in patient care include the desire for minimizing invasiveness of procedures and interventions. This aim is reflected in the increasing utilization of sentinel lymph node biopsy, which results in a lower level of morbidity in breast cancer staging, in comparison to extensive conventional axillary dissection. Optimized lymphoscintigraphy with triangulated body marking is a clinical option that can further reduce morbidity, more than when a hand held gamma probe alone is utilized. Unfortunately it is often either overlooked or not fully understood, and thus not utilized. This results in the unnecessary loss of an opportunity to further reduce morbidity.Optimized lymphoscintigraphy and triangulated body marking provides a detailed 3 dimensional map of the number and location of the sentinel nodes, available before the first incision is made. The number, location, relevance based on time/sequence of appearance of the nodes, all can influence 1) where the incision is made, 2) how extensive the dissection is, and 3) how many nodes are removed. In addition, complex patterns can arise from injections. These include prominent lymphatic channels, pseudo-sentinel nodes, echelon and reverse echelon nodes and even contamination, which are much more difficult to access with the probe only. With the detailed information provided by optimized lymphoscintigraphy and triangulated body marking, the surgeon can approach the axilla in a more enlightened fashion, in contrast to when the less informed probe only method is used. This allows for better planning, resulting in the best cosmetic effect and less trauma to the tissues, further reducing morbidity while maintaining adequate sampling of the sentinel node(s).     

Sentinel node detection and radioguided occult lesion localization in breast cancer

Sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 breast cancer patients and represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. In our Institute, Radioguided Occult Lesion Localization is the standard method to locate non-palpable breast lesions and the gamma probes is very effective in assisting intra-operative localization and removal, as in sentinel node biopsy. The rapid spread of sentinel lymph node biopsy has led to its use in clinical settings previously considered contraindications to sentinel lymph node biopsy.In this contest, we evaluated in a large group of patients possible factors affecting sentinel node detection and the reliability of sentinel lymph node biopsy carried out after large excisional breast biopsy. Our data confirm that a previous breast surgery does not prohibit efficient sentinel lymph node localization and sentinel lymph node biopsy can correctly stage the axialla in these patients.     

Skin and fat necrosis of the breast following methylene blue dye injection for sentinel node biopsy in a patient with breast cancer

Sentinel lymph node biopsy (SLNB) is a simple technique that uses subdermal or peri-tumoral injection of vital blue dye and/or radioactive isotope to identify the first lymph node(s) draining the primary tumor. It has been shown to accurately predict axillary node status in patients with clinically node negative breast cancer. The SLNB is emerging as a new standard of care in patients with early breast cancer. However, the use of methylene blue (MB) dye can be associated with a number of local complications due to its tissue reactive properties. We report a rare case of skin and fat necrosis followed by a dry gangrene of the skin in a female patient with breast cancer who underwent SLNB localization using peri-tumoral injection of MB dye in another institution. This case and literature review suggest that the use of MB dye for SLNB identification should be avoided and replaced with alternative types of blue dye such as Patent Blue V preferably in conjunction with a radioactive isotope tracer.     

Molecular subtype classification is a determinant of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph nodes

Background

Previous studies suggested that the molecular subtypes were strongly associated with sentinel lymph node (SLN) status. The purpose of this study was to determine whether molecular subtype classification was associated with non-sentinel lymph nodes (NSLN) metastasis in patients with a positive SLN.

Methodology and Principal Findings

Between January 2001 and March 2011, a total of 130 patients with a positive SLN were recruited. All these patients underwent a complete axillary lymph node dissection. The univariate and multivariate analyses of NSLN metastasis were performed. In univariate and multivariate analyses, large tumor size, macrometastasis and high tumor grade were all significant risk factors of NSLN metastasis in patients with a positive SLN. In univariate analysis, luminal B subgroup showed higher rate of NSLN metastasis than other subgroup (P = 0.027). When other variables were adjusted in multivariate analysis, the molecular subtype classification was a determinant of NSLN metastasis. Relative to triple negative subgroup, both luminal A (P = 0.047) and luminal B (P = 0.010) subgroups showed a higher risk of NSLN metastasis. Otherwise, HER2 over-expression subgroup did not have a higher risk than triple negative subgroup (P = 0.183). The area under the curve (AUC) value was 0.8095 for the Cambridge model. When molecular subtype classification was added to the Cambridge model, the AUC value was 0.8475.

Conclusions

Except for other factors, molecular subtype classification was a determinant of NSLN metastasis in patients with a positive SLN. The predictive accuracy of mathematical models including molecular subtype should be determined in the future.     

Activity estimation and biokinetic analysis of 99mTc-DMSA in renal infant patients using a gamma camera

Biokinetic data from the administration of radiopharmaceuticals is essential in nuclear medicine dosimetry. It has particular significance in children, as their metabolism is very different from adults. Biokinetic models for paediatric patients could therefore need to be adapted to better reflect their absorption, retention and excretion functions, when compared to adults. Obtaining quality in vivo infant or paediatric biokinetic data is then essential to improve the available reference models, which in turn can lead to the optimization of paediatric procedures and protocols in clinical practice.This study analyses the biokinetic behaviour of ^99mTc-dimercaptosuccinic acid (DMSA), in 8 infants aged 4 months to 2 years old, through an imaging study using a gamma camera, and compares the obtained values with those obtained with the reference ICRP biokinetic model. The in vivo data was treated using an adapted methodology from the MIRD 16 pamphlet. Activity curves for the liver, the kidney and the whole body, were built, and new effective absorption, retention and excretion half-lives were estimated, and compared with the reference biokinetic parameters of ICRP 128. The obtained residence time in the kidneys of 2.56 h, has a deviation of 30.8% to the ICRP 128 value of 3.70 h. The obtained maximum uptake in the kidneys was of 0.22/A₀, which compares to the value of 0.31/A₀ for ICRP.The obtained biokinetic parameters were used to estimate the absorbed dose. The obtained dose values are smaller than the reference ICRP 128 ones by 32.1% in the kidneys, and 18.4% in the liver.     

Image and flow cytometric analysis of DNA content in breast cancer. Relation to estrogen receptor content and lymph node involvement

A comparative flow-cytometric and image-cytometric study was performed on 166 human breast cancers. Parallel measurements of 67 cases showed a good correlation between the DNA indices measured with each of the techniques. However, minor ploidy abnormalities were detected with flow cytometry. Only with this technique about 70% of the tumors appeared to be aneuploid. DNA profiles obtained with image cytometry frequently contained DNA values above the modal G2 value of the tumor. At least part of these broadly scattered DNA profiles resulted from multiploid tumors, as was found with flow cytometry. The mean percentage of cells with DNA contents exceeding the modal G0G1 value in image-cytometric DNA profiles (non- G0G1 cells) appeared to be highest in aneuploid lymph-node-positive (N+) tumors and lowest in near-diploid lymph-node-negative (N-) tumors. Near-diploid tumors were more frequently (70%) estrogen receptor positive (ER+) than were aneuploid tumors (50%), whereas highly aneuploid tumors with low or negative ER contents tended to be N+. Tumors with a high percentage of non- G0G1 cells value were predominantly estrogen-receptor negative (ER-).     

Molecular type and maximal metastasis diameter influence risk of axillary recurrence in breast cancer patients after positive sentinel lymph node biopsy

BackgroundBreast cancer patients with positive sentinel lymph node biopsy (SLNB) may be spared axillary lymph node dissection (ALND) in favour of irradiation. The aim of the study was to estimate local control probability in the axilla (axLCP).Materials and methodsWe identified 1832 invasive breast cancer patients who had undergone SLNB at our centre. We measured maximal metastasis diameter (SLDmax) in the sentinel lymph nodes and lymph node metastasis volume (VALN) from ALND in 246 patients with one or two positive SLNs. We calculated axLCP after irradiation and systemic treatment for different molecular types.ResultsVALN values are higher for high grade tumours and larger metastases in SLNs (> 5 mm). It is smaller in luminal A tumours. axLCP is high, nearly 100%, in all molecular types in radiation sensitive tumours (SF2 Gy = 0.45), except luminal B. Expected axLCP is relatively low (67%) in luminal B radiation sensitive tumours with no chemotherapy and nearly 100% with chemotherapy.ConclusionVALN values differ among molecular tumour types. They depend on SLNDmax and tumour grade. New prognostic factors are needed for selected luminal B breast cancer patients (i.e. high grade tumours, large metastases in SLNs) after positive SLNB intended to be spared ALND and chemotherapy.