It is known that two-thirds of patients who develop clinical metastases following treatment of a primary cutaneous melanoma initially present with locoregional metastases and one-third initially present with distant metastases. However, few reports in the literature give detailed figures on different metastatic pathways in cutaneous melanoma.
The aim of the present study was to perform a detailed analysis of the different metastatic pathways, the time course of the development of metastases and the factors influencing them.
In a series of 3001 patients with primary cutaneous melanoma at first presentation, 466 subsequently developed metastasis and were followed-up over the long term at the University of Tuebingen, Germany between 1976 and 1996. Different pathways of metastatic spread were traced. Associated risk factors for the different pathways were assessed. Differences in survival probabilities were calculated by the Kaplan-Meier method and evaluated by the log-rank test.
In 50.2% of the patients the first metastasis after treatment of the primary tumour developed in the regional lymph nodes. In the remaining half of the patient sample the first metastasis developed in the lymphatic drainage area in front of the regional lymph nodes, as satellite or in-transit metastases (21.7%) or as direct distant metastases (28.1%). Anatomical location, sex and tumour thickness were significant risk factors for the development of metastasis by different pathways. The most important risk factor appeared to be the location of the primary tumour. The median intervals elapsing before the first metastasis differed significantly between the different metastatic pathways. The direct distant metastases became manifest after a median period of 25 months, thus later than the direct regional lymph node metastases (median latency period, 16 months) and the direct satellite and in-transit metastases (median latency period, 17 months). In patients who developed distant metastases the period of development was independent of the metastatic route. The time at which the distant metastases developed was roughly the same (between 24 and 30 months after the detection of the primary tumour), irrespective of whether satellite or in-transit metastases, lymph node metastases or distant metastases were the first to occur.
The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed.
"There are other symptoms evoking a testicular melanoma, such as: absence of elevation of tumor markers, presence of melanospermia , presence of a supraclavicular lymphadenopathy, and personal history of skin primitive melanoma . Life expectancy of patients having a testicular metastis is very low, because of the advanced stage of tumoral spreading . "
"Lymph node metastasis is the most frequent form of first recurrence in patients with cutaneous melanoma if no lymph node surgery was performed at initial diagnosis.1 Regional metastases of melanomas most frequently involve the cervical, axillary or inguinal lymph node basins. "
[Show abstract][Hide abstract] ABSTRACT: Background
The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins.
Patients and Methods
Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive.
A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases.
In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed.
"Tumors of any histological origin can give rise to cutaneous and subcutaneous metastases during disease progression; in particular, around 8%–45% of the patients with malignant cutaneous melanoma develop metastases. Among these patients, 21.7% show satellite and in-transit metastases, 50.2% (regional) lymph node metastases, and 28.1% distant metastases (Meier et al 2002). With the exception of distant metastases, surgery is the most widely used therapeutic option, followed by radiotherapy, isolated limb perfusion, hyperthermia, and, lastly, chemotherapy (Wolf et al 2003). "
[Show abstract][Hide abstract] ABSTRACT: Tumors of any histological origin can give rise to cutaneous and subcutaneous metastases during follow-up. This study aims to evaluate the costs and benefits of electrochemotherapy (ECT) with the Cliniporatortrade mark vs other currently used methods in the control and treatment of cutaneous and subcutaneous advanced neoplasms.
A cost-effectiveness analysis was carried out on ECT using the Cliniporator vs other techniques (radiotherapy, hyperthermia associated with radiotherapy and chemotherapy, interferon-alpha, and isolated limb perfusion) for the control and treatment of cutaneous and subcutaneous neoplasms. The direct health costs were attributed a value according to the Italian National Healthcare System. Resource consumption and clinical outcomes were derived from cost survey data collection and literature review.
ECT is cost-effective with an incremental cost effectiveness ratio (ICER) of euro1,571.53 to achieve a further additional response. Radiotherapy and interferon-alpha are the least effective strategies. A combination of hyperthermia, chemotherapy, radiotherapy, and interferon-alpha treatment are dominated by ECT (more costly and less effective). Isolated limb perfusion is the most effective treatment, but is very costly (euro18,530.47) because of the use of antiblastic drugs (TNFalpha), with an ICER of euro92,717.29.
After sensitivity analysis, the study results confirm the favorable cost-effectiveness ratio of ECT with the Cliniporator and justify its wider use.
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