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D S Reintgen

Publications and source records attributed to D S Reintgen.

At least 37 records · Page 2Linked to original sources

Clinical relevance of molecular staging for melanoma: comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma.

OBJECTIVE: To determine the clinical significance of a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of micrometastatic melanoma cells in sentinel lymph nodes (SLNs). SUMMARY BACKGROUND DATA: Routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease. The authors have previously shown that an RT-PCR assay designed to detect melanocyte-specific expression of the tyrosinase gene could be used to define a population of patients at higher risk for both recurrence and death compared with routine hematoxylin and eosin (H&E) histology. In this study, the authors used the tyrosinase RT-PCR assay in a patient population examined by a more detailed histologic analysis, including S-100 immunohistochemistry. METHODS: Patients underwent lymphatic mapping and SLN biopsy. SLN specimens were bivalved, and half of each specimen was serially sectioned and examined by routine H&E histology and S-100 immunohistochemistry. The other half of each specimen was analyzed by a nested RT-PCR assay. RESULTS: Hematoxylin and eosin histology detected metastatic disease in 36 (16%) of the 233 patients tested. S-100 immunohistochemistry detected micrometastatic disease in another 16 patients, and 114 (63%) of 181 patients with histology-negative nodes had positive findings on RT-PCR. There were significant differences between PCR-positive and PCR-negative patient groups in Breslow thickness, Clark level, and the presence of ulceration of the primary tumor, factors that have been shown to correlate with recurrence and survival. CONCLUSIONS: These results suggest that RT-PCR can increase the sensitivity of detection of metastatic melanoma cells in SLNs over the current standard methods, including H&E histology and S-100 immunohistochemistry. Further long-term follow-up is needed to detect actual differences in recurrence and overall survival.

Adult↗

Lymphatic mapping and sentinel lymph node biopsy in patients with breast cancer.

The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to the SLN. In addition to reviewing the literature, this chapter describes our lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute with 1147 breast cancer patients. Our results, in addition to a meta-analysis of data from 12 institutions comprising an additional 1842 patients undergoing complete axillary dissection, demonstrate that SLN biopsy is an accurate method of axillary staging. Although the results from small series may exaggerate the probability of false negative results, the risk of nodal disease based on tumor size and other risk factors should be evaluated when considering the results of SLN sampling.

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The progression of melanoma nodal metastasis is dependent on tumor thickness of the primary lesion.

BACKGROUND: Recent results of several clinical trials using the technique of intraoperative lymphatic mapping and sentinel lymph node (SLN) biopsy confirm the validity of the concept of there being an order to the progression of melanoma nodal metastases. This report reviews the H. Lee Moffitt Cancer Center experience with this procedure, one of the largest series described to date. These data demonstrate that the involvement of the SLNs, as well as higher-echelon nodes, is directly proportional to the melanoma tumor thickness, as measured by the method of Breslow. METHODS: The investigators at the H. Lee Moffitt Cancer Center retrospectively reviewed their experience using lymphatic mapping and SLN biopsies in the treatment of malignant melanoma. All eligible patients with primary malignant melanomas underwent preoperative and intraoperative mapping of the lymphatic drainage of their primary sites, along with SLN biopsies. All patients with positive SLNs underwent complete regional basin nodal dissection. For 20 consecutive patients with one positive SLN, all of the nodes from the complete lymphadenectomy were serially sectioned and examined by S-100 immunohistochemical analysis, to detect additional metastatic disease. RESULTS: Six hundred ninety-three patients consented to undergo lymphatic mapping and SLN biopsy. The SLNs were successfully identified and collected for 688 patients, yielding a 99% success rate. One hundred patients (14.52%) showed evidence of nodal metastasis. The rates of SLN involvement for primary tumors with thicknesses of <0.76 mm, 0.76-1.0 mm, 1.0-1.5 mm, 1.5-4.0 mm, and >4.0 mm were 0%, 5.3%, 8%, 19%, and 29%, respectively. Eighty-one patients underwent complete lymph node dissection after observation of a positive SLN, and only six patients with positive SLNs demonstrated metastatic disease beyond the SLN (7.4%). The tumor thicknesses for these six patients ranged from 2.8 to 6.0 mm. No patient with a tumor thickness of <2.8 mm was found to have evidence of metastatic disease beyond the SLN in complete lymph node dissection. All 20 patients with a positive SLN for whom all of the regional nodes were serially sectioned and examined by S-100 immunohistochemical analysis failed to show additional positive nodes. CONCLUSIONS: These results suggest that regional lymph node involvement may be dependent on the thickness of the primary tumor. As the primary tumor thickness increases, so does the likelihood of involvement of SLNs and higher regional nodes in the basin beyond the positive SLNs.

Adult↗

Implementation of new surgical technology: outcome measures for lymphatic mapping of breast carcinoma.

BACKGROUND: Recent advances in technology and the subsequent development of minimally invasive surgical techniques have heralded a new era in the surgical treatment of breast cancer. The dilemma of how to train surgeons in new technologies requires teaching, certification, and outcomes reporting in a non-threatening and non-economically damaging manner. This study examines 700 cases of lymphatic mapping and sentinel lymph node (SLN) biopsy for breast cancer and documents surgeon-specific and institution-specific learning curves. METHODS: Seven hundred cases of lymphatic mapping and SLN biopsy were examined. All procedures were performed using a combination of vital blue dye and radiolabeled sulfur colloid. Learning curves were generated for each surgeon as a plot of failure rate versus number of cases. RESULTS: Examination of the learning curves in this study demonstrates similar characteristics. Following a high initial failure rate, there is a rapid decrease after the first twenty cases. The learning curve, representing the mean of the five surgeons' experience, indicates that 23 cases and 53 cases are required to achieve success rates of 90% and 95%, respectively. CONCLUSIONS: The initial reports regarding lymphatic mapping combined with this experience of 700 cases confirm the presence of a significant learning curve. Although this procedure may have an inherent failure rate, it is important to identify those factors that are under the control of the surgeon and, therefore, subject to improvement. We believe that these data provide surgeons performing lymphatic mapping and SLN biopsy with a new paradigm for assessing their skill and adequacy of training.

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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↗

The role of sentinel lymph node biopsy in breast cancer.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy are new techniques that accurately provide crucial staging information while inflicting far less morbidity than complete axillary dissection. As these techniques continue to gain acceptance, issues such as adequacy of training, certification, and outcomes measures become increasingly important. The purpose of this paper is to report the initial lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute and to provide a detailed description of the technical aspects of lymphatic mapping. STUDY DESIGN: From April 1994 to April 1998, 700 patients with newly diagnosed breast cancers underwent an IRB-approved prospective trial of lymphatic mapping using a combination of Lymphazurin (USSC, Norwalk, CT) blue dye and filtered technetium 99m-labeled sulfur-colloid. Failure of the procedure was defined as the inability to detect an SLN by either radiocolloid uptake within a lymph node by the gamma probe or the inability to visualize blue staining of a lymph node. Learning curves were then generated as the failure rate versus serial number of patients for each of the 5 surgeons involved in this study. RESULTS: The SLN was identified in 665 of 700 patients (95.0%). A total of 1,348 SLNs were successfully removed, of which 238 (17.7%) were positive for metastatic disease in 176 of 665 patients (26.5%). In patients who underwent a complete axillary dissection after SLN biopsy, SLNs were identified in 173 of 186 patients (93.0%). Of the 173 patients, 53 patients (30.6%) had positive SLNs and 120 patients (69.4%) had negative SLNs. In the 120 patients with negative SLNs, one patient was found to have disease on complete dissection, for a false-negative rate of 0.83% (95% CI: 0.02%, 4.6%). A learning curve representing the mean of the 5 surgeons' experience indicates that on average 23 patients are required by an individual surgeon to achieve a 90% +/- 4.5% success rate and 53 patients are required to achieve a 95% +/- 2.3% success rate (p = 0.05). CONCLUSIONS: These data validate lymphatic mapping and SLN biopsy as indispensable tools in the surgical treatment of breast cancer. With adequate multidisciplinary training, these techniques can be readily implemented at institutions treating breast cancer.

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Lymphatic mapping for melanomas of the upper extremity.

Over a period of 4 years, 127 consecutive patients with upper extremity melanomas were identified from a prospectively accrued database. A protocol consisting of preoperative lymphoscintigraphy and intraoperative lymphatic mapping and with a vital blue dye and radiocolloid was used; the protocol had a 98% success rate of identifying the sentinel lymph node (SLN). Preoperative lymphoscintigraphy identified unpredictable cutaneous lymphatic flow in 15 (12%) of the patients. These discordant areas would not have been included in classic regional node dissection and possible sites of metastatic disease would not have been identified. Metastatic disease was identified within the SLNs in 12 (9%) of the patients. Of the 12 patients with a positive SLN, 2 (17%) were found on complete node dissection to have metastatic disease in higher nodes in the regional basin. The SLN was the only site of disease in 10 of these 12 patients with documented metastases in the regional basin. Patients with a negative SLN biopsy can be spared the morbidity and expense of a complete lymph node dissection.

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Pathologic examination of the sentinel lymph node in malignant melanoma.

Sentinel lymphadenectomy is gaining increasing popularity in the staging and treatment of patients with melanoma at risk for metastases. As a result, pathologists are encountering these specimens more frequently in their daily practice. The pathologic status of the sentinel lymph node is pivotal to the patient's care because it provides staging information that dictates the need for further therapy, and therefore detailed pathologic assessment is warranted. A standard pathology protocol to handle these nodes has been developed at our institution and involves complete submission of all tissue with routine use of immunohistochemical staining for S-100 protein. By using this protocol, 838 sentinel lymph nodes from 357 patients have been examined, and metastases were found in 16% of patients. Although the metastasis was clearly seen on sections stained with hematoxylin and eosin in 55% of the positive patients, the immunostain showed metastatic disease not appreciable on initial hematoxylin and eosin screening in an additional 28 lymph nodes (45% of node-positive patients). Intraoperative touch preparation cytology may be used as an adjunct technique in sentinel lymph nodes grossly suspicious for metastatic disease. This technique has been performed on 23 sentinel lymph nodes, with no false positives and an overall sensitivity of 62%. The thorough pathologic evaluation of sentinel lymph nodes in patients with malignant melanoma requires complete submission of all tissue, routine use of immunohistochemistry, and touch preparation cytology in selected cases.

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Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity.

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.

Adolescent↗

Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients.

PURPOSE: To compare the effect of pathologic sentinel lymph node (SLN) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS: We reviewed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN pathologic status on disease-free and disease-specific survival. RESULTS: In the 580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN was positive by conventional histology in 85 patients (15%) but negative in 495 patients (85%). SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses. Although tumor thickness and ulceration influenced survival in SLN-negative patients, they provided no additional prognostic information in SLN-positive patients. CONCLUSION: Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for recurrence. The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials.

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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↗

Historical perspectives and future applications.

Lymphatic Mapping and sentinel lymph node biopsy are developing into a new field of minimally invasive surgery. These procedures were brought about by the necessity to better stage patients while minimalizing morbidity. Their application is reaching several aspects of surgery and becoming a major foundation in the armamentarium of the general surgeon.

Animals↗

Radioguided surgery for melanoma.

The advent of lymphatic mapping and sentinel lymph node biopsy provides an effective and less morbid procedure for staging patients with malignant melanoma. There is considerable variation on this technique. This article describes the technique that was developed and is currently in application at the H. Lee Moffitt Cancer Center and Research Institute. Understanding all the steps and paying close attention to all details are important to ensure successful mapping.

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