Technique of sentinel node biopsy in breast cancer.
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Axilla↗
Biomedical subjects
B B Kroon
Publications and source records attributed to B B Kroon.
Computed tomography for the detection of neck node metastases in melanoma patients.
AIMS: To assess the value of CT scanning for detection of lymph node metastases in the neck. METHODS: The appearance and site of the metastases was studied, as well as the sensitivity and specificity of CT. RESULTS: Nodal metastases did not always show a high contrast uptake and nodal density therefore cannot be used as a criterion for metastasis. Irregular contrast enhancement was seen in seven of the 21 tumour-positive necks. Frequently, metastases in the parotids, superficial nodes in the neck and in the posterior triangle were seen. The sensitivity and specificity of palpation and CT scanning were 87 and 100%, respectively. CONCLUSIONS: However, because small, clinically occult, melanoma metastases were frequently overlooked on CT, the role of this imaging modality in assessing occult metastases remains limited. Based on recent data from literature it is reasonable to speculate that ultrasound guided fine needle aspiration cytology (FNAC) will prove to be more effective than a non-invasive staging procedure of the neck in melanoma patients.
Adult↗
Identification and biopsy of the sentinel lymph node in breast cancer.
AIMS: To examine the hypothesis that lymphatic dissemination in breast cancer occurs sequentially. METHODS: Thirty patients with clinically localized adenocarcinoma were studied. Patent blue dye was administered into the tumour at the beginning of a modified radical mastectomy or segmental mastectomy with en bloc axillary lymph-node dissection (ALND). In the removed specimen, blue-stained lymphatic channels were dissected from the primary tumour to the first draining lymph node(s) (sentinel node(s)). RESULTS: Identification of a sentinel node (SN) was successful in 26 patients (87%). In 10 patients the SN was tumour-positive. In six of these patients, the SN was the only tumour-positive node. There was no incidence of 'skip' metastasis. CONCLUSIONS: This study confirms the sequential nature of lymphatic dissemination. When confirmed in vivo, these data may lead to a substantial reduction of the need for ALND without compromising survival and regional control and without loss of prognostic and staging information.
Adenocarcinoma↗
Improved staging of breast cancer through lymphatic mapping and sentinel node biopsy.
Sentinel node biopsy is a less invasive technique for staging breast cancer than complete axillary lymph-node dissection and may be as accurate. In the case of a 71-year-old woman with a T1 breast cancer, sentinel node biopsy improved staging. Metastases were discovered in sentinel nodes outside the axilla while the axillary nodes were tumour-free.
Aged↗
Technique of lymphatic mapping and sentinel node biopsy for melanoma.
AIMS: An increasing number of surgeons perform sentinel node biopsy to identify melanoma patients with early lymphatic dissemination who may benefit from regional node dissection or adjuvant therapy. The addition of lymphoscintigraphy and intraoperative gamma-ray detection with a hand-held probe increases the sensitivity of the surgical technique substantially. METHODS: The value of lymphoscintigraphy is discussed. The operative technique of lymphatic mapping and sentinel node biopsy is described, including the use of a vital dye and a gamma-ray probe. CONCLUSIONS: Close to 100% of first-tier lymph nodes can be identified with this combined approach without the unnecessary removal of too many higher-echelon nodes.
Adult↗
Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.
PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.
Adolescent↗
[2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep].
The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.
Biopsy↗
Sentinel-node biopsy in breast cancer.
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Axilla↗
Complications of combined radiotherapy and isolated limb perfusion with tumor necrosis factor alpha +/- interferon gamma and melphalan in patients with irresectable soft tissue tumors.
BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF alpha) +/-interferon gamma (IFN gamma) and melphalan in patients with primarily irresectable soft tissue sarcoma is promising in terms of tumor regression and limb salvage. However, the feasibility of radiotherapy in combination with this treatment modality has not been established. METHODS: Fifteen patients with irresectable soft tissue tumors of the limb underwent ILP with TNF alpha, +/-IFN gamma, and melphalan. Three groups could be distinguished with respect to the role of radiotherapy. In nine patients, the residual tumor could be resected after ILP, and this was followed by radiotherapy with a total dose of 50-70 Gy (2 Gy/day). In one patient with aggressive fibromatosis, ILP was followed by radiotherapy without tumor resection (Group I). In two patients who underwent ILP for recurrent sarcoma, the primary tumor had been treated before by resection and radiotherapy (60 Gy) (Group II). In three patients whose tumors remained irresectable after ILP, radiotherapy was applied later in the course of disease for local palliation (Group III). RESULTS: In Group I, healing of the resection wound was markedly delayed in four patients, with soft tissue necrosis and infection necessitating amputation in two of them. Following completion of radiotherapy, persistent lymphoceles were encountered in two patients. Radiotherapy-induced fibrosis was encountered in five patients, resulting in a mild limb malfunction in two. Three-patients developed mild edema during radiotherapy. Tumor-associated neuropathy was aggravated by ILP in three patients causing severely disabling motor deficits and limb contractures in two of them. In Group II, ILP did not cause any local problem in the heavily irradiated areas. In Group III, pre-existing limb edema was increased after a total palliative dose of 20 Gy in one patient. Another patient, who had been re-operated for arterial thrombosis immediately after ILP, developed occlusion of the brachial artery 4 months after completion of palliative radiotherapy (36 Gy in 6 Gy fractions). CONCLUSIONS: In patients with irresectable soft tissue tumors, multimodality treatment using ILP with TNF alpha +/- IFN gamma and melphalan, tumor resection, and postoperative high-dose radiotherapy is associated with a considerable risk of tissue necrosis and impaired healing. This risk should be weighed against a possible benefit from radiotherapy in local tumor control.
Adult↗
Isolated limb perfusion with high-dose tumor necrosis factor-alpha for locally advanced extremity soft tissue sarcomas.
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Adolescent↗
Localizing the sentinel node in cutaneous melanoma: gamma probe detection versus blue dye.
BACKGROUND: Sentinel node (SN) biopsy can be used to select patients with melanoma for therapeutic lymphadenectomy. We investigated the value of two methods to locate the SN: patent blue dye (PBD) and gamma probe detection of 99mTc-nanocolloid. METHODS: One hundred ten patients with cutaneous melanoma were studied. Lymphoscintigraphy with 99mTc-nanocolloid was performed to determine the position of the SN. Before operation, PBD was injected at the same site as the radiopharmaceutical. When a blue node was identified intraoperatively, its radioactivity level was measured with the probe. In the absence of blue coloration, the probe was used to trace the SN. RESULTS: Scintigrams visualized a total of 219 SNs in 141 basins. Eight SNs were not explored. One SN was not found. The remaining 210 and 27 additional intraoperatively identified SNs were excised. From the total of 237 removed SNs, 200 (84%) were found using PBD only. All 37 nodes that were not found with the PBD were localized with the probe so that the probe combined with PBD identified 99.5% of all SNs. In 23 patients the SN contained tumor. In three patients the SN was false-negative for metastasis. CONCLUSION: The gamma probe together with PBD can identify more SNs (99.5%) than lymphatic mapping with PBD alone (84%).
Adolescent↗
Value of laboratory tests in monitoring acute regional toxicity after isolated limb perfusion.
BACKGROUND: Severe limb toxicity following isolated limb perfusion (ILP) can lead to compartmental compression syndrome and severe rhabdomyolysis, occasionally necessitating amputation of the affected limb. We determined whether laboratory tests for muscle damage and inflammation could predict impending limb toxicity. METHODS: All 184 consecutive ILPs performed in our institute from 1988 to 1994 were included in this study. Creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and white blood cell (WBC) counts were determined on post-ILP days 1-4, 6, 8, and 15. RESULTS: "Late peak" CK patterns, characterised by a peak on or after the 5th post-perfusion day, were strongly associated with severe limb toxicity (p < 0.001). Severe toxicity did develop in 40% of the limbs when CK values exceeded 1000 IU/L on the 2nd to 5th post-ILP day (p < 0.001). There was a correlation between the peak CK and the individual grades of toxicity (r = 0.6, p < 0.001). Serum LDH and ASAT values peaked 2.9 and 3.4 days after the CK peak respectively. Severe limb toxicity was statistically significantly associated with higher WBC counts from the 2nd post-ILP day onwards. CONCLUSIONS: CK values exceeding 1000 IU/L after the 1st and WBC counts increasing after the 2nd post-ILP day could be predictors of impending limb toxicity. These patients should be observed closely for signs of compartmental compression syndrome and severe rhabdomyolysis.
Adult↗
Principles and guidelines for surgeons: management of cutaneous malignant melanoma. European Society of Surgical Oncology Brussels.
This article outlines and discusses the principles of the guidelines for the management of malignant melanoma by surgeons. The guidelines are based, in large part, on the consensus of the Dutch Melanoma Working Party that was revised in 1997. The article reflects internationally accepted treatment principles that have arisen both from critical assessment of existing evidence and data, and from the outcome of randomized studies.
Europe↗
Lymphatic mapping and selective lymphadenectomy for melanoma: not yet standard therapy.
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Humans↗
Carbon dioxide laser for cutaneous melanoma metastases: indications and limitations.
A total of 469 in-transit or satellite lesions were treated by carbon dioxide (CO2) laser vaporization in 15 patients. The treatment was performed mostly on an outpatient basis, under local anaesthesia. The technique was easily mastered and quickly performed. Wound healing and patient acceptance were good. A major drawback, however, proved to be the unexpected high incidence of recurrences at the lasered sites. In our opinion CO2 laser treatment may be considered as a palliative option in patients with a moderate to extensive amount of cutaneous metastases, whose lesions preferably are < 10 mm and in whom local excision is not feasible anymore. For extremity lesions this treatment may have a place after failure of isolated limb perfusion. CO2 laser treatment cannot be considered a first-line option unless the issue of local recurrences is solved.
Aged↗
Rationale for different approaches to combined melphalan and hyperthermia in regional isolated perfusion.
The addition of hyperthermia (HT) to regional isolated perfusion (RIP) with Melphalan theoretically has two advantages. Firstly, heat can selectively kill cells in poorly vascularised areas that are usually not reached by the drug. Secondly, in vitro data have revealed that the effect of Melphalan is enhanced at temperatures 39-45 degrees C. However, for the simultaneous application of Melphalan and HT, as it is given in most institutes, both normal and tumour tissues within the volume are treated with both modalities. It is unclear whether--for the same heat dose--the cytotoxicity of Melphalan is enhanced more in tumour tissue than in normal tissues. As the applied dose of Melphalan in RIP is selected on maximum acceptable toxicity, any enhancement of toxicity is undesired. Indeed, Melphalan application at temperatures > 41 degrees C has resulted in unacceptable toxicity. In most institutes, the hyperthermia dose is reduced in comparison to application as a single-modality treatment, to allow simultaneous combination without unacceptable toxicity. In this review, the rationale for two different approaches is summarised which may make it possible to improve the benefit from the theoretical advantage of the use of HT in RIP. It is meant to stimulate discussion as a possible first step in the design of new treatment protocols.
Animals↗
Topical dinitrochlorobenzene combined with systemic dacarbazine in the treatment of recurrent melanoma.
Fifty-nine selected patients with recurrent melanoma (37 locoregional and 22 locoregional and haematogenic) were treated with a combination of topical dinitrochlorobenzene (DNCB) and systemic dacarbazine (DTIC). The observations were analysed retrospectively. Fifteen patients (25%) (one third with distant spread) experienced a complete response, with a median duration of 10 months (range 3-210 months). Five of these patients, three of them with haematogenic disease, showed prolonged disease-free survival (85, 156, 170, 177 and 210 months). Seven patients (12%) obtained a partial response, and no response was seen in the remaining 37 patients (63%). In the presence of a severe local reaction to topical DNCB application the median survival was 12 months compared with 7 months in cases with a slight or moderate local reaction (P=0.0013). Patients showing a response to the DNCB-DTIC combination had a median survival of 18 months versus 7 months for the non-responders (P<0.0003). In view of the prolonged survival in five patients, this combined treatment schedule yields promising results in the treatment of selected melanoma patients with cutaneous recurrences, whether or not these are associated with other metastases.
Administration, Topical↗
Validation of gamma probe detection of the sentinel node in melanoma.
UNLABELLED: In melanoma, the presence or absence of metastasis in the first lymph node (sentinel node, SN) has a predictive value for the entire lymph node basin. This study explores the efficacy of lymphoscintigraphy with 99mTc-nanocolloid and a gamma-ray detection probe in tracing SNs. METHODS: Sixty patients with clinically localized melanoma were studied. Lymphoscintigraphy was performed after intradermal injection of 60 MBq 99mTc-nanocolloid at the primary tumor site. Scintigraphy included early dynamic images and a body scan 2 hr postinjection. The following day, a gamma detection probe (Neoprobe 1000) was used intraoperatively to trace the still radioactive SNs. The number of counts of the nodes and the surrounding tissues was measured before, during and after excision. Excised nodes and normal tissue samples were measured in a gamma well counter. The uptake of 99mTc-nanocolloid was calculated. RESULTS: Lymphoscintigraphy showed 122 SNs distributed over 73 drainage basins. Use of the probe led to retrieval of all nodes that were searched for. The SN-to-background ratios were high: a median of 36 in vivo (range: 2-722) and a median of 274 ex vivo (range: 6-2,985). Counts in vivo correlated well with counts ex vivo. The mean percentage of the injected dose per SN was 0.69 (range: 0.0013-6.82), versus 0.23 (range 0.0004-2.59) in 23 measured second-echelon nodes (non-SNs). Mean percentage of uptake per gram tissue in SNs was 2.1 (range: 0.003-17.4), in skin 0.01 (range: 0.00-0.22) and in subcutaneous fat 0.0035 (range: 0.00-0.081). CONCLUSION: Average uptake of 99mTc-nanocolloid in SNs is substantially higher than uptake in non-SNs, skin and subcutaneous fat. The resulting high SN-to-background ratios facilitate the intraoperative detection of these nodes using a gamma detection probe.
Adolescent↗