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N Fenske

Publications and source records attributed to N Fenske.

At least 19 recordsLinked to original sources
PubMed2001

Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement.

Although sentinel lymph node (SLN) biopsy for melanoma has been adopted throughout the United States and abroad as a standard method of determining the pathologic status of the regional lymph nodes, some controversy still exists regarding the validity and utility of this procedure. SLN biopsy is a minimally invasive procedure, performed on an outpatient basis at the time of wide local excision of the melanoma, with little morbidity. Numerous studies have documented the accuracy of this procedure for identifying nodal metastases. There are four major reasons to perform SLN biopsy. First, SLN biopsy improves the accuracy of staging and provides valuable prognostic information for patients and physicians to guide subsequent treatment decisions. Second, SLN biopsy facilitates early therapeutic lymph node dissection for those patients with nodal metastases. Third, SLN biopsy identifies patients who are candidates for adjuvant therapy with interferon alfa-2b. Fourth, SLN biopsy identifies homogeneous patient populations for entry onto clinical trials of novel adjuvant therapy agents. Overall, the benefit of accurate nodal staging obtained by SLN biopsy far outweighs the risks and has important implications for patient management.

Chemotherapy, Adjuvant↗
PubMed1999

Cutaneous lymphatic drainage in patients with grossly involved nodal basins.

BACKGROUND: The development of lymphatic mapping techniques has facilitated the identification of the sentinel lymph node (SLN), the first node in the regional basin into which cutaneous lymphatics flow from a particular skin area. Previous studies have shown that SLN histology reflects the histology of the entire basin, because melanoma metastases progress in an orderly fashion, involving the SLN before higher nodes in the basin become involved with metastatic disease. It is uncertain whether these orderly cutaneous lymphatic flow patterns are maintained in grossly involved basins. Lymphatic mapping was performed in a population of melanoma patients with clinically palpable lymphadenopathy to address this question. We aimed to determine whether the presence of gross nodal disease in the basin alters lymphatic flow into that basin so that lymphatic mapping techniques are not applicable, and, in patients referred with a grossly involved basin, whether preoperative lymphoscintigraphy should be performed to identify other regional basins at risk for metastases. METHODS: Eight patients presented with grossly palpable disease in the regional basin and underwent preoperative lymphoscintigraphy. All patients with palpable disease and all basins indicated by lymphoscintigraphy to be at risk were dissected. Three patients presented with clinically palpable nodes at the time of diagnosis, and five developed nodal disease on clinical follow-up after undergoing initial wide local excision only. A total of 10 basins in the eight patients were dissected. Of these, eight of the basins had grossly palpable regional nodal disease, and the other two basins were identified by preoperative lymphoscintigraphy as being at risk for metastases. The SLN was identified with intraoperative mapping, harvested, and submitted to pathology. Complete therapeutic lymph node dissections were performed following the SLN harvest in the basins with grossly palpable disease. SLN biopsy alone was performed in the two basins that did not have clinically palpable adenopathy but showed cutaneous lymphatic flow from the scintigram. RESULTS: Sixteen SLNs were harvested from these eight basins with grossly palpable disease, and 14 (87.5%) contained tumor. In each case, one of the SLNs was the grossly palpable node, and in six of the basins (75%) it was the only site of melanoma metastases. An additional 190 higher level, non-SLNs were removed, 32 (16.8%) of which contained microscopic foci of metastatic melanoma (P = .015). The null hypothesis that melanoma nodal metastasis is a random event is rejected. Two patients with trunk melanoma primary sites were identified to have other basins at risk for metastatic disease on lymphoscintigraphy. SLN biopsies were performed in these two patients, and one had microscopic nodal disease in the SLN. CONCLUSIONS: These data support the fact that cutaneous lymphatic drainage patterns are maintained in patients with grossly involved basins, thus buttressing the idea that the SLN is the node most likely to develop metastatic disease. Gross disease in the basin does not significantly alter cutaneous lymphatic flow into the regional basin, as the sentinel lymph node identified under these circumstances is the same as with the grossly involved node. Preoperative lymphoscintigraphy in patients who present with grossly involved nodes in one basin may identify other regional basins with micrometastatic disease and deserves further study in this setting.

Adult↗
PubMed1998

Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes.

BACKGROUND: The technique of sentinel lymph node (SLN) biopsy for melanoma provides accurate staging information because the histology of the SLN reflects the histology of the entire basin, particularly when the SLN is negative. METHODS: We combined two mapping techniques, one using vital blue dye and the other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify the SLN in 600 consecutive patients with stage I-II melanoma. The SLNs were examined using conventional histopathology and immunohistochemistry for S-100. RESULTS: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs. Thirty percent of patients with primary melanomas greater than 4.0 mm in thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive. All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm. CONCLUSIONS: The rate of SLN-positive patients increases with increasing thickness of the melanoma. SLN-positive patients with primary lesions less than 1.5 mm in thickness may have disease confined to the SLN, thus rendering higher-level nodes free of disease, and may not require a CLND.

Adolescent↗
PubMed1997

Multiple primary melanomas: implications for screening and follow-up programs for melanoma.

BACKGROUND: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. METHODS: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. RESULTS: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p = 0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p = 0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p = 0.002). CONCLUSIONS: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.

Adult↗
PubMed1997

Lymphatic Mapping for Melanoma: Long-term Results of Regional Nodal Sampling With Radioguided Surgery.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy are new techniques used in the surgical treatment of patients with malignant melanoma. These procedures have the potential to change the surgical treatment of the disease to provide a more rational approach to adjuvant therapy. METHODS: A prospective database of melanoma patients undergoing lymphatic mapping and SLN biopsy was reviewed to identify prognostic factors for overall and disease-free survival in this patient population. RESULTS: Five-year overall and disease-free survival was 92.3% and 79.0%, with a median follow-up of 17 months. The number of histologically positive SLNs was the most powerful predictor of overall and disease-free survival. Patients with no histologically positive SLNs had a five-year overall and disease-free survival of 97.9% and 93.3%, respectively. Tumor ulceration and Clark level greater than or equal to III were the significant prognostic factors for survival. CONCLUSIONS: The use of lymphatic mapping and SLN biopsy effectively stages patients with primary cutaneous melanoma. Additionally, the presence of histologically positive SLNs is the most powerful indicator of overall and disease-free survival for these patients.

Journal Article↗
PubMed1997

Florida's undeclared epidemic: malignant melanoma.

Contrary to the trend of early diagnosis observed in other parts of the world, in Florida melanoma is still being discovered in the more advanced stages. This is characterized by thicker lesions at diagnosis, which are hallmarked by bleeding, itching, ulceration, and increased vertical growth. In a study of 1,626 cutaneous melanoma patients at the H. Lee Moffitt Cancer Center in Florida, three prognostic factors, tumor thickness, Clark level, and presence of ulceration in the primary tumor, have remained relatively constant over an eight-year period (1987-1994). Despite the lack of change in tumor thickness in the last four years, mortality rate is decreasing, possibly due to more effective treatments. Regardless of these apparent improvements in mortality rates, definite progress must be made in the early detection of malignant melanoma through the initiation of statewide programs of lay public and professional education. In addition, it is proposed that the establishment of statewide screening programs of the Caucasian population with skin phenotypes 1 and 2 will also facilitate the early diagnosis of melanoma in the future, improve the outlook for these patients, and begin to address a major public health problem in the state of Florida.

Adolescent↗
PubMed1997

Redefining cutaneous lymphatic flow: the necessity of preoperative lymphoscintigraphy in the management of malignant melanoma.

OBJECTIVE: The purpose of this study is to emphasize the instrumental role of preoperative lymphoscintigraphy in the surgical treatment of patients with malignant melanoma. SUMMARY BACKGROUND DATA: The efficacy of lymphoscintigraphy is reflected in its ability to reveal cutaneous lymphatic drainage to regional nodal basins that are at risk for melanoma metastases but not necessarily discernable to be at risk through standard historical anatomical guidelines or clinical experience. This preoperative lymphatic mapping technique has contributed greatly to the accuracy and efficiency of staging procedures including sentinel node biopsy and elective lymph node dissection. PATIENTS AND METHODS: After informed consent, a selected series of four patients with primary melanomas located in watershed areas of the body (left neck, right mid-abdomen, right scapula, left back) and two patients with extremity melanomas (right distal forearm and left ankle) underwent pre-operative lymphoscintigraphy to identify all basins for metastases. RESULTS: In all of the cases, lymphatic drainage occurred in an unusual and unexpected basin that could not have been predicted clinically and in three of the cases the resected basins contained positive sentinel nodes. If not for the preoperative lymphoscintigraphy, these nodal basins would not have been resected and metastatic disease would have been left behind. In addition, the staging of the melanoma patient would have been inaccurate. CONCLUSION: If the sentinel node biopsy of elective lymph node dissection (ELND) were based on clinical predictions only, nodes equally at risk for metastatic disease would not have been resected and in some cases, nodal basins not at risk for metastases would have been resected unnecessarily. Without lymphoscintigraphy, the validity and efficacy of the ELND or the sentinel node biopsy for nodal staging is greatly compromised. These six case studies illustrate the difficulty of predicating lymphatic drainage from primary sites located on the head and neck, truck and even the extremities and demonstrate the indispensability of preoperative lymphoscintigraphy in the management of malignant melanoma.

Abdomen↗
PubMed1996

Evaluation of new putative tumor markers for melanoma.

BACKGROUND: The early diagnosis of recurrent melanoma can contribute to better outcome if the disease can be surgically resected or if the metastases are responsive to systemic therapies. Lipid-associated sialic acid (LASA-P) and the S-100 protein (S-100) were evaluated as tumor markers for melanoma with the goal of early detection of recurrence. METHODS: Sixty-seven patients were identified who had levels of S-100 and LASA-P drawn during their clinical course. A multivariate regression analysis was performed to determine the significance of the serum markers in relation to other prognostic factors for melanoma. RESULTS: After a median follow-up of 30 months, 58 patients had recurrences, and 49 patients died of disease. LASA-P elevation was not associated with the time to recurrence (p = 0.2176) or survival (p = 0.2507). S-100 positivity was a significant predictor of recurrence (p < 0.0001) and survival (p = 0.0059). The median time to recurrence for S-100-positive and S-100-negative patients was 7.6 and 33.8 months, respectively. The median survival time was 59.2 months for S-100-negative patients and 29.6 months for patients positive for S-100. CONCLUSIONS: Serum S-100 shows significant correlations to both time to recurrence and survival and could be useful in the clinical detection of malignant melanoma.

Adult↗
PubMed1996

Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma.

BACKGROUND: The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES: The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS: To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION: The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS: The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION: The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Adolescent↗
PubMed1996

The tumor biology of melanoma nodal metastases.

Approximately 20 per cent of melanomas greater than 0.76 mm in thickness will metastasize to the regional lymph nodes if treated with wide local excision alone (WLE). Elective lymph node dissection (ELND) is associated with significant morbidity, which includes lymphedema, wound complications, and paresthesias of the extremity. An alternative operative approach uses selective lymphadenectomy with the identification of the sentinel node, defined as the first node in the lymphatic basin that drains the primary cutaneous site. This study consisted of 132 patients with melanomas greater than 0.76 mm. One hundred nine patients (83%) had histologic negative sentinel nodes, and 23 patients (17%) had one or more sentinel nodes positive for disease. In patients with metastatic disease, 30/35 (86%) sentinel nodes were positive, and 25/357 (7%) nonsentinel nodes were positive (P < 0.001). In 18 patients (78%) of the 23 patients with metastatic disease, the sentinel node was the only node positive, strongly suggesting that there is an orderly progression of metastases. Two patients developed metastatic nodal disease after removal of a negative sentinel node (false negative rate = 1.5). The mean follow-up was 1 year. Sentinel node histology reflects the histology of the remainder of the nodes in the lymphatic basin and "skip" metastases, defined as a negative sentinel node but positive nodes higher in the regional chain positive for metastases or an axillary recurrence after a negative sentinel node biopsy, are rare for malignant melanoma. Harvesting the sentinel node in patients with intermediate or greater thickness melanoma will, therefore, identify a subset of patients with metastatic disease who have the most to benefit from a complete node dissection. This surgical approach allows for complete pathological staging and therapeutic management of patients while significantly reducing expense and overall morbidity.

Adolescent↗
PubMed1995

Accurate Nodal Staging of Malignant Melanoma.

The incidence of malignant melanoma is increasing at a faster pace than that of any other cancer in the United States. It is estimated that people born in the year 2000 will have a 1:75 risk of developing melanoma sometime during his or her lifetime. Stimulated by novel lymphatic mapping techniques, the surgical care of the melanoma patient is evolving toward more conservative resections that can provide the same staging information but without the added morbidity of more radical surgeries. This approach promises to yield positive results in the age of health care reform, outcome measurements, and cost:benefit considerations.

Journal Article↗
PubMed1995

The identification and mapping of melanoma regional nodal metastases: minimally invasive surgery for the diagnosis of nodal metastases.

The most controversial part of melanoma surgical care involves the role of elective lymph node dissection (ELND). Whereas proponents cite retrospective studies demonstrating the ability to control regional metastases and more accurate staging, opponents cite the unnecessary morbidity of a complete node dissection for the majority of patients. The technology of sentinel node mapping and selective lymphadenectomy, defined as the identification and removal of the first node into which the primary melanoma drains, may revolutionize melanoma care. If the sentinel node is negative, then theoretically the remainder of the nodes should also be negative (no "skip" metastases), and a complete lymphadenectomy would not be required to control occult nodal disease. The location of the sentinel node may be variable in the lymphatic basin. Ideally, the surgeon needs a map of the position of the sentinel node in reference to the other nodes in the basin in order to do the procedure under local anesthesia with small incisions. In this way, patients are subjected to minimal morbidity and the procedure can be performed as an out-patient. Twenty-nine patients with clinically negative nodes and melanomas greater than 0.76 mm in thickness were judged to be candidates for ELND. Preoperative lymphoscintigraphy in two planes was used to mark the sentinel node, and the patients were taken to the operating room for intraoperative lymphatic mapping and sentinel node biopsy followed by complete dissection.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

The orderly progression of melanoma nodal metastases.

OBJECTIVE: The aim of this study was to determine the order of melanoma nodal metastases. SUMMARY BACKGROUND DATA: Most solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. METHODS: The investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the "sentinel" lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. RESULTS: Forty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008. CONCLUSIONS: The data presented demonstrate that nodal metastases from cutaneous melanoma are not random events. The sentinel lymph nodes in the lymphatic basins can be mapped and identified individually, and they have been shown to contain the first evidence of melanoma metastases. This information can be used to revolutionize melanoma care so that only those patients with evidence of nodal metastatic disease are subjected to the morbidity and expense of a complete node dissection. Because sentinel node histology accurately reflects the histology of the remainder of the lymphatic basin, information gained from the sentinel node biopsy can be used as a prognostic factor for melanoma. These findings demonstrate effective pathologic staging, no decrease in standards of care, and a reduction of morbidity with a less aggressive, rational surgical approach.

Adolescent↗
PubMed1994

Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma.

BACKGROUND: The presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. METHODS: The assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. RESULTS: Eleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene sequence. CONCLUSION: The RT-PCR method is an extremely sensitive, reproducible, and efficient technique for the identification of micrometastases in patients with melanoma and could be widely applicable. If clinical correlation is obtained, staging of the melanoma patient becomes more accurate, and treatment becomes more standardized and rational, because all those patients who have evidence of nodal disease can be identified so that they may benefit from more extensive surgery (formal node dissections) or adjuvant therapies. Based on these results, RT-PCR could be a powerful tool to detect micrometastatic melanoma.

Humans↗
PubMed1992

An anatomical basis for prognosis of malignant melanoma.

Clinical observations during surgery have led us to speculate that an anatomic basis may in fact exist for the poor prognosis associated with malignant melanoma arising in certain recognized "high-risk" areas. In our study we have treated and followed 45 patients with primary malignant melanoma for over 5 years. During the course of treatment, we identified variations in anatomic characteristics at the tumor sites. Criteria were established for high- and low-risk locations by the neurovascular structure encountered. We speculate that these sites that have neurovascular windows provide a readily accessible vascular pathway for the dissemination of malignant cells to deeper visceral structures and may account for the poor prognosis associated with primary lesions in these locations. Thirty patients were classified as being at high risk for developing metastasis, whereas 13 were classified as being at low risk; 2 patients were in a special-risk category. To date, 12 of the 30 patients with "high-risk" melanoma have gone on to develop metastatic disease, which represents 40 percent of that group, whereas none of the patients classified as "low risk" have developed metastases during the same period.

Adult↗
PubMed1989

Polyarthritis associated with cutaneous T cell lymphoma.

This is the first reported synovial biopsy of a patient with concurrent onset of cutaneous T cell lymphoma and polyarthritis. The biopsy revealed a nonspecific chronic inflammatory process. Immunoperoxidase technique using monoclonal antibodies showed a mixture of helper T cells, suppressor T cells and B cells in the synovial infiltrate. Tumor infiltration was not seen. Our findings indicate that the arthritis associated with cutaneous T cell lymphoma is most likely a reactive phenomenon.

Aged↗