Reproducibility of lymphoscintigraphy for lymphatic mapping in cutaneous melanoma.

UNLABELLED: One of the indications for lymphoscintigraphy in patients with melanoma is to determine the lymphatic drainage pattern and position of the first draining lymph node--the sentinel node. Metastasis in the sentinel node indicates the need for therapeutic lymph node dissection. The purpose of the present study was to examine the reproducibility of lymphoscintigraphy in assessing the location and number of sentinel nodes. METHODS: Twenty-five patients with clinically localized melanoma were investigated. The same investigator performed two scintigraphic studies with a 2-4 wk interval in each patient, in an identical manner. A 60-MBq dose of 99mTc-nanocolloid was injected intradermally at the primary tumor site. The lymph flow was studied dynamically, complemented by lateral/oblique views. The images were evaluated by a panel of three observers. RESULTS: The sentinel node was visualized within 20 min in all patients. A difference in number of sentinel nodes depicted on the first and second study was noted in three patients (12%). The melanoma was situated on the head (two patients) and arm (one patient) in these patients. Otherwise, the images were identical for number and location of nodes. CONCLUSIONS: Reproducibility of lymphoscintigraphy with 99mTc-nanocolloid was high in this study. However, some sentinel nodes may be missed in lymphoscintigraphy for melanoma.

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.

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.

Results of regional isolated perfusion for locally inoperable melanoma of the limbs.

In the period 1978-1990, 49 patients with locally inoperable melanoma of the limbs were treated with regional isolated perfusion according to four different perfusion schedules. Perfusion resulted in a complete remission in 28 patients (57%), with a median duration of 10 (1-55+) months, and a partial remission in 10 (21%), with a median duration of 3 (1-9) months. In patients treated with a double (normothermic or sequential hyperthermic) perfusion schedule the complete remission rate was higher. Regional lymph node involvement reduced the chance of achieving complete remission. Twelve patients with complete remission (43%) showed a relapse in the perfused area. The corresponding 3-year limb recurrence-free interval was 46%. This interval was mainly influenced by the number of lesions at the moment of perfusion. Three of the patients who failed to respond eventually required amputation of the affected limb. The median follow-up of the surviving patients was 23 (5-142) months. At the time of analysis 23 patients were still alive, 12 of whom had no evidence of disease. Patients with complete remission had a slightly, though statistically not significant better 3-year survival rate than patients without complete remission (49% vs 33%). Regional isolated perfusion halted progression in all of these 49 patients and resulted in a complete remission for 57%. It is, therefore, an important modality in the management of patients with locally inoperable melanoma and provides a valuable alternative to amputation.

[Nothing gained from the determinations of plasma lactate levels in the evaluation of a patient with acute abdomen]. / Geen meerwaarde van bepaling lactaatplasmaconcentratie bij de beoordeling van een patiënt met een acute buik.

OBJECTIVE: To establish the diagnostic value of laboratory tests, especially the plasma lactate concentration, for determination of the indication for acute surgery in patients with an acute abdomen. DESIGN: Cross-sectional study. SETTING: Kennemer Gasthuis, location Elisabeth Gasthuis, Haarlem, the Netherlands. METHOD: The study group consisted of all 200 successive patients presenting at the emergency room with acute abdomen from June 1993 to December 1994 (19 months). Patients with suspected acute appendicitis were excluded. The diagnosis and indication for surgery if any were based on case history, physical examination, radiological examination if performed and standard laboratory tests: ESR, leukocyte count, haemoglobin, creatinine and amylase. The first matter considered was to what extent the indication for acute operation based on these clinical criteria was in agreement with the diagnosis at discharge. The next question studied was what would be the extra value of the plasma lactate concentration which, although determined, had not been reported to the clinician. Statistical analysis was performed using the two-sample Student t test and the chi 2 test. A p-value of < 0.05 was regarded as statistically significant. RESULTS: Fifty-four patients were operated within 24 hours for good reasons, six were incorrectly not operated within 24 hours, 128 correctly received conservative treatment and 12 were correctly treated conservatively and subsequently underwent operation after longer than 24 hours. Diagnostics based on the clinical criteria had a sensitivity of 90%. The mean plasma lactate concentration, temperature and ESR were statistically significant more often increased in the operated patients than in those treated conservatively. The sensitivities of these determinations were 75%, 67% and 40% (all: p < 0.05). The lactate concentration was increased in 50% of the patients who in retrospect had incorrectly not been subjected to acute surgery. CONCLUSION: Neither determination of the plasma lactate concentration nor the results of the separate standard laboratory tests in acute abdomen patients resulted in a better sensitivity for the determination of an indication for acute surgery than clinical examination combined with standard laboratory tests and, if desired, supplementary radiology.

[Identification of the sentinel node in patients with breast carcinoma]. / Identificatie van de schildwachtklier bij patiënten met mammacarcinoom.

OBJECTIVE: To investigate the hypothesis that lymphatic metastasis of breast cancer progresses in a sequential fashion, and whether the first lymph node on a direct drainage pathway (first-echelon node, sentinel node) can be identified in a mastectomy specimen. DESIGN: Descriptive analysis. SETTING: The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Amsterdam, the Netherlands. METHODS: In 22 patients with clinically localized breast cancer and five with breast cancer and axillary lymphadenopathy, patent blue dye was administered preoperatively into the primary tumor. After mastectomy and axillary lymph node dissection, blue stained lymphatic channels were dissected down to the first draining lymph nodes. These sentinel nodes were removed from the specimen and examined separately for presence of metastatic disease. RESULTS: In 2/5 patients with palpable axillary metastases and in one patient with a tumour in the medial upper quadrant, no sentinel node was found. A total of 35 first-echelon nodes was identified in the 22 patients without palpable lymphadenopathy, on average 1.6 nodes per patient (range: 1-4). In 10 of these patients, metastatic tumour was found in the sentinel nodes. In 6 of these 10 patients, no metastatic disease was detected in the remaining axillary nodes. Metastasis was never found in the other axillary nodes if the sentinel node was disease-free. CONCLUSIONS: Dissemination of breast cancer to the axillary nodes appears to occur in a sequential fashion. Patent blue dye drains from the tumour in the breast to the axillary lymph nodes in mammary cancer patients. These blue nodes can be identified in the surgical specimen.

The role of alpha 4 beta 1 integrin in cell motility and fibronectin matrix assembly.

The alpha 4 beta 1 integrin has been suggested to play important roles in embryogenesis and pathogenesis of many diseases which involve both cell adhesion and cell migration. Previous studies using anti-alpha 4 beta 1 antibodies and fibronectin (Fn) fragments have suggested that alpha 4 beta 1 integrins may be involved in cell motility on Fn and vascular cell adhesion molecule-1 (VCAM-1). However, the cells used in these studies also express other Fn integrin receptors including alpha 5 beta 1 integrin, which is known to function in cell motility on Fn. To test whether alpha 4 beta 1 integrins mediate cell motility on Fn and VCAM-1 in the absence of alpha 5 beta 1 integrin, we expressed human alpha 4 integrin in a Chinese hamster ovary (CHO) cell line that is deficient in alpha 5 beta 1 integrin (CHO B2). The parental alpha 5 deficient CHO B2 cells were unable to adhere, spread or migrate on Fn, nor could they assemble a fibrillar Fn matrix. Expression of alpha 4 beta 1 integrin in the CHO B2 cells enabled the cells to adhere, spread and migrate on Fn and on VCAM-1 but not to assemble a fibrillar Fn matrix. The cellular processes mediated by the interaction of alpha 4 beta 1 with Fn or VCAM-1 were inhibited by the CS1 peptide derived from the major alpha 4 beta 1 binding site on Fn. These findings demonstrate that alpha 4 beta 1 integrins not only function as cell adhesion receptors but also as cell motility receptors for Fn and VCAM-1 independent of alpha 5 beta 1. Moreover, they reveal important functional differences between Fn binding integrins. The alpha 4-positive, alpha 5-negative CHO cells described in this report will be useful tools in studying the mechanism of molecular signalling during integrin mediated cellular processes.

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%).

Sentinel node biopsy for melanoma in the head and neck region.

BACKGROUND: Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region. METHODS: Thirty consecutive patients with clinically localized cutaneous melanoma in the head and neck region were included. Sentinel node biopsy was performed with blue dye and a gamma probe after preoperative lymphoscintigraphy. Average follow-up was 23 months (range, 1-48). RESULTS: In 27 of 30 patients, a sentinel node was identified (90%). Only 53% of sentinel nodes were both blue and radioactive. A sentinel node was tumor-positive in 8 patients. The sentinel node was false-negative in two cases. Sensitivity of the procedure was 80% (8 of 10). CONCLUSIONS: Sentinel node biopsy in the head and neck region is a technically demanding procedure. Although it may help determine whether a neck dissection is necessary in certain patients, further investigation is required before this technique can be recommended for the standard management of cutaneous head and neck melanoma.