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S Pendas

Publications and source records attributed to S Pendas.

10 recordsLinked to original sources

Clinical patterns of metastasis.

In human solid cancer, lymph node status is the most important indicator for clinical outcome. Recent developments in the sentinel lymph node concept and technology have resulted in a more precise way of examining micrometastasis in the sentinel lymph node and the role of lymphovascular system in the facilitation of cancer metastasis. Different patterns of metastasis are described with respect to different types of solid cancer. Expect perhaps for papillary carcinoma and sarcoma, the overwhelming evidence is that solid cancer progresses in an orderly progression from the primary site to the regional lymph node or the sentinel lymph node in the majority of cases with subsequent dissemination to the systemic sites. The basic mechanisms of cancer metastasis through the lymphovascular system form the basis of rational therapy against cancer. Beyond the clinical patterns of metastasis, it is imperative to understand the biology of metastasis and to characterize patterns of metastasis perhaps due to heterogeneous clones based on their molecular signatures.

Animals↗

Controversial topics in breast lymphatic mapping.

As a result of increased accuracy of staging and decreased patient morbidity, lymphatic mapping and sentinel lymph node (SLN) biopsy for breast cancer has enjoyed a rapid acceptance into clinical practice. Despite the use of lymphatic mapping techniques to obtain nodal staging information, many controversies remain. We have attempted to highlight the major controversies in this report.

Breast Neoplasms↗

Lymphatic mapping in breast cancer.

The most accurate predictor of survival in breast cancer is the presence or absence of lymph node metastases. Lymphatic mapping with sentinel node biopsy is a new technique that provides more accurate nodal staging compared with routine histology for women with breast cancer, but without the morbidity of a complete lymph node dissection. Sentinel lymph node (SLN) biopsy is a more conservative approach to the axilla that requires close collaboration from the surgical team, nuclear medicine, and pathology. National trials are investigating the clinical relevance of the upstaging that occurs with a more intense examination of the SLN. As is the case with breast preservation as a viable alternative to mastectomy for the definitive treatment of the primary node, selective lymphadenectomy has the ability to decrease morbidity without compromising patient care.

Breast Neoplasms↗

Sentinel node biopsy and cytokeratin staining for the accurate staging of 478 breast cancer patients.

Sentinel lymph node (SLN) mapping is an effective and accurate method of sampling the axillary nodal basin for metastatic disease. The SLN is the first node to receive afferent lymphatic drainage from the primary tumor. Lymphatic mapping and SLN biopsy have allowed pathologists to perform a more detailed examination of the SLN(s) and, therefore, provide more accurate staging of the regional lymphatic basin. Recently, more sensitive assays have been developed to increase the detection rate of micrometastatic to the axillary lymph nodes. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN detects micrometastatic disease, which is frequently missed on routine hematoxylin and eosin (H&E) histology. Therefore, lymphatic mapping combined with CK IHC staining of the SLN provides more accurate staging of the regional lymph nodes in patients with breast cancer. At Moffitt Cancer Center, 478 patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by intraoperative imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed malignant by sectioning the block, staining with H&E and finding cells with malignant cytology. Lymphatic mapping and CK IHC staining of the SLNs was successfully performed in 478 newly diagnosed breast cancer patients. Twenty-eight patients had unsuccessful lymphatic mapping for an overall failure rate of 5.5 per cent. A total of 134 (28%) patients had positive nodes (N1) detected. Ninety-three of these patients had both H&E and CK-positive lymph nodes, and an additional 41 patients had only CK-positive SLN(s). A total of 385 patients had H&E-negative SLNs, but only 344 patients had negative SLN(s) defined as both H&E and CK negative. Therefore, 41 (10.6%) of the 385 H&E-negative patients were upstaged, because of the detection of malignant cells by cytokeratin IHC staining of the SLN. Microstaging of SLNs with CK has shifted 10.6 per cent of our patient population from stage I to stage II disease. Undetected micrometastatic disease to the regional lymph nodes may account for the significant proportion of stage I breast cancer treatment failures. Furthermore, the ability to accurately stage the axilla by using lymphatic mapping techniques, SLN biopsy, and more sensitive assays may help identify a subgroup of truly node-negative patients with invasive breast cancer who can avoid the morbidity associated with a complete axillary dissection or systemic chemotherapy. Finally, those patients found to have micrometastatic disease to the regional lymph nodes can be treated appropriately in a more selective fashion.

Axilla↗

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.

OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. METHODS: Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.

Biopsy↗

Local recurrence of breast cancer after cytological evaluation of lumpectomy margins.

Successful breast conservation therapy with optimal cosmesis requires adequate tumor excision and negative tumor margins. Therefore, more sensitive techniques are being developed to identify lumpectomy margins intraoperatively with greater accuracy. Unidentified microscopic disease is seemingly responsible for a local recurrence rate of up to 25 per cent 3 to 5 years after lumpectomy and radiotherapy for breast cancer patients. As a result, Moffitt Cancer Center has routinely used an intraoperative touch preparation cytology (TPC) protocol to evaluate the entire resected surface of all lumpectomies. In addition, resection margins were also evaluated by gross examination and by standard histology. In rare instances frozen sections were used to evaluate tumor margins. In this study 701 consecutive lumpectomy specimens were evaluated by TPC during the period of 9 years with a mean follow-up of 3.5 years. Local cancer recurrence was 2.7 per cent (mean recurrence, 2.53 years), in women whose lumpectomy margins were evaluated by TPC. Of interest, a local recurrence rate of 14.6 per cent was observed in patients who had referral lumpectomies evaluated by conventional histopathology. This study suggests that accurate margin assessment with TPC plays an important role in the control of local recurrence after breast conservation therapy. Therefore, we conclude the routine use of intraoperative TPC provides rapid, reliable, topographically accurate identification of residual microscopic disease at lumpectomy margins.

Biopsy↗

Lymphatic mapping in the treatment of breast cancer.

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested sentinel lymph nodes are evaluated more thoroughly by detailed pathologic examination using serial sectioning, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. This allows for the detection of smaller tumor volumes and leads to more accurate staging. Lymphatic mapping has a 68% to 98% success rate in identifying the sentinel lymph node. The false-negative rate (defined as a negative sentinel lymph node while a higher node or nodes in the axilla are positive) is between 0% and 2%. The morbidity associated with this procedure is minimal. We believe that lymphatic mapping and sentinel lymph node biopsy will ultimately lead to more conservative treatment of patients with breast cancer. This article describes the historical background and technical aspects of the procedure. This is followed by updated, prospectively collected outcomes data from 466 consecutive breast cancer patients who underwent lymphatic mapping at the H. Lee Moffitt Cancer Center, as well as an up-to-date review of the literature.

Biopsy↗

Sentinel node biopsy in ductal carcinoma in situ patients.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes. METHODS: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes. RESULTS: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five node-positive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS. CONCLUSIONS: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.

Axilla↗

Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC. METHODS: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination. RESULTS: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged. CONCLUSION: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.

Biopsy, Needle↗