Value of serum S-100B for prediction of distant relapse and survival in stage III B/C melanoma.

BACKGROUND: The biochemical marker serum S-100B has been proven to reflect the stage of melanoma and to be useful for disease monitoring and prediction of survival, mainly in stage IV disease. For stage III melanoma, limited data are available and its predictive value for relapse is unknown. Serum S-100B was evaluated prospectively for monitoring response and its predictive value for relapse and overall survival in stage IIIB/C melanoma patients. PATIENTS AND METHODS: Treatment consisted of one cycle of neoadjuvant and adjuvant chemo(immuno)therapy, around surgery. S-100B was measured at enrollment and prior to and following surgery. The levels of S-100B in serum were compared to the pattern and intensity of the expression of S-100B in the melanoma tissue. RESULTS: Some patients with normal initial S-100B values (n=18) showed responses (3 complete remission and 2 partial remission), in contrast to patients with elevated S-100B values. Distant relapse within one year was found in 11/23 (48%) patients with increased S-100B versus 2/18 (11%) patients with a normal value (p=0.01). Overall survival was decreased in patients with increased S-100B compared to those with normal S-100B (p=0.02). Correlations between the pattern and intensity of S-100B expression in the tumor specimen and the value of serum the S-100B did not reach statistical significance. CONCLUSION: Serum S-100B is a valuable biomarker for the evaluation of response to treatment and prediction of early distant relapse and survival in stage IIIB/C melanoma. The marginal correlation between serum S-100B values and expression of S-100B in the tumor specimens needs further study.

[Regional lymph nodes at a distance]. / Regionale lymfekliergebieden op afstand.

In 3 patients, two men aged 22 years and 38 years with melanoma, and one woman aged 46 years with breast cancer, local tumour growth recurred following regional lymph node dissection. All three developed metastasis in new distant regional basins, which were once more dissected. The first melanoma patient died from haematogenous metastasis, 2 years after the excision of his primary melanoma. The other melanoma patient was alive, without evidence of disease, 8 years after the treatment of his primary tumour. The breast cancer patient, who underwent contralateral axillary lymph node dissection, was also alive, without evidence of disease, 27 years after the treatment of her primary tumour. Diversion of lymphatic flow as a result of regional lymph node dissection for cancer may lead to metastasis to a distant lymph node basin if tumour growth recurs in the original area. Knowledge of this usually unknown phenomenon is important since metastasis to these new regional basins can still be treated curatively, in the form of another lymph node dissection. These distant lymph node basins must therefore be carefully checked during follow-up monitoring.

Lymphatic mapping and sentinel node biopsy in Merkel's cell carcinoma.

AIM: The purpose of this study was to determine the predictive value of lymphatic mapping with selective lymphadenectomy in patients with Merkel's cell carcinoma. METHODS: Eight patients with biopsy proven Merkel's cell carcinoma underwent sentinel node biopsy. Lymphoscintigraphy was performed the day before surgery following intradermal injection of 74-111MBq of 99mTc-nanocolloid divided into four doses around the biopsy scar. Dynamic and static images were obtained. RESULTS: At least one sentinel node was visualized in all patients. The sentinel node was intra-operatively identified with the aid of a hand-held gamma probe in all cases and patent blue dye in six out of eight cases. During surgery, all sentinel nodes were successfully harvested. Metastatic cell deposits were subsequently identified in three patients (37.5%) and they underwent regional lymphadenectomy. No additional involved lymph nodes were identified. No recurrence has been reported in a median follow-up of 4.6 years (range: 8 months-10 years). CONCLUSIONS: In conclusion, sentinel node biopsy in patients with Merkel's cell carcinoma appears to be a reliable staging technique.

The health-related quality of life of long-term survivors of melanoma treated with isolated limb perfusion.

AIMS: To evaluate the generic and condition-specific health-related quality of life (HRQL) of long-term survivors of extremity melanoma treated with isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 292 patients with melanoma of the limbs underwent ILP in our institution. Of these patients, 59 were alive and disease-free for at least six months prior to study entry. Fifty-one of these 59 patients completed a mailed questionnaire assessing generic HRQL (SF-36), condition-specific HRQL (limb function, cosmetic results, fear of recurrence), and problems regarding work and insurance. An age- and gender-matched, normative sample of the Dutch general population was available for comparison of SF-36 scores. RESULTS: Mean age of patients was 57 years, 90% female, with a median time since ILP of 14 years (range 3-25 years). The SF-36 scores of the patient group were equal to or better than that of the general population, significantly for bodily pain, general health perceptions, and the physical and mental health component scores. Nevertheless, the patients reported a number of specific problems: complaints of limb function were reported by 49-55%, cosmetic problems by 31-38% and fear of local disease recurrence and distant metastases by 77 and 63% of the patients, respectively. Less than 10% of patients reported problems in obtaining a mortgage or life insurance. CONCLUSIONS: The HRQL of long-term survivors of melanoma treated with ILP appears comparable to, and sometimes better than that of healthy peers within the general population. Nevertheless, this survivor group reports a number of specific problems that impact on daily life. Although these findings need to be confirmed with larger, prospective studies, they suggest that rehabilitation should focus on improving limb functionality, and addressing chronic fear of disease recurrence.

Repeat isolated limb perfusion with TNFalpha and melphalan for recurrent limb melanoma after failure of previous perfusion.

AIM: To assess the effectiveness of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) and melphalan for recurrent or persistent melanoma lesions after previous ILP. METHODS: Between 1978 and 2001, 21 patients (mean age 65, range 29-83 years) underwent repeat ILP for recurrent or persistent melanoma after a previous ILP. First ILPs had been performed with melphalan alone in 13 patients and with addition of TNFalpha in eight, for a median of nine lesions (interquartile (IQ) range 2-23 lesions). Repeat ILP was performed with TNFalpha and melphalan in all 21 patients for a median of nine lesions (IQ range 5-25 lesions). Median follow-up after repeat ILP was 18 months (IQ range 6-36 months). RESULTS: Thirteen patients attained a complete response (CR) after repeat ILP compared to 11 of 17 with measurable lesions after the first ILP. Nine patients relapsed after CR. Median limb recurrence-free survival was 13 months. Fourteen patients had mild acute regional toxicity after repeat ILP compared to 18 after the first ILP (n.s.). One patient underwent amputation for critical limb ischemia 10 months following repeat ILP. The limb salvage rate was 95%. Overall median survival was 62 months after CR compared to 13 months for those without CR (P=0.05). CONCLUSION: Repeat ILP with TNFalpha and melphalan is feasible after previous ILP with mild regional toxicity. The CR rate is relatively high and comparable to the first procedure with good limb recurrence-free survival and high limb salvage rate.

The sentinel node biopsy in patients with breast cancer; many controversies remain.

The sentinel node procedure has increasingly been used as a diagnostic tool for staging breast cancer. Although many institutes have embraced this procedure, many issues concerning the indications and the technique itself remain unsolved. In this review, several aspects regarding these controversies are discussed from the perspective of The Netherlands Cancer Institute. These include the definitions used to identify the sentinel node, the indications and contraindications for this procedure and the injection site of the tracer and blue dye. What are the clinical implications of a micro-metastasis in the sentinel node? What is the best treatment for patients with an involved axillary node? Should non-axillary sentinel nodes be pursued, and if so, what are the implications for further management of these patients? Finally, the current TNM system is discussed in perspective of the evolving sentinel node procedure. Although many questions remain to be solved, the regional recurrence rates are low when axillary clearance is omitted because of a tumor-free sentinel node.

Major amputation for intractable extremity melanoma after failure of isolated limb perfusion.

AIM: The aim of this study was to analyse indications and results of amputation for intractable extremity melanoma after failure of isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 451 patients with loco-regional advanced extremity melanoma underwent 505 ILPs. Amputation of the affected extremity had to be carried out for intractable recurrent disease in 11 of these patients. RESULTS: The indications for amputation were uncontrollable pain (n=2), extensive loco-regional tumour progression (n=4), loss of ankle function due to local tumour growth (n=1), and ulcerating and fungating lesions, not responding to other treatments (n=4). Four patients developed stump recurrence after amputation. Ten patients died of melanoma metastases after a median of 11 months (range 2-110 months). Two patients survived more than 5 years after amputation. CONCLUSIONS: Major amputation is rarely indicated for intractable extremity melanoma but long-term survival can be achieved in selected patients.

Alveolar soft part sarcoma. a report of 15 cases.

The aim of this study was to evaluate the presentation, course and treatment outcome of 15 patients with this rare type of sarcoma. The files of the patients were retrospectively analysed. Overall survival was calculated according to the Kaplan-Meier method. There were 15 patients, 8 male and 7 female. The mean age at diagnosis was 29 years for men and 24 years for women. The median survival was 48 months with an overall 5-year survival of 38%. 5 patients had haematogenic metastases at the time of diagnosis. For the remaining 10 patients with localised disease, the median survival was 48 months and the 5-year survival 48%. The median disease-free survival for these patients was 12 months with a 5-year disease free survival of 40%. After the occurrence of haematogenic metastases, patients survived a median period of 8 months (range 0-45 months). 5 patients are still free of disease after a median period of 234 months (12-295 months). Alveolar soft part sarcoma is found especially in young adults. When diagnosed, it is often metastasised with a poor prognosis. However, when radically resected, long-term survival is possible.

Eight false negative sentinel node procedures in breast cancer: what went wrong?

AIMS: The purpose of the study was to evaluate the false negative sentinel node procedures in patients with breast cancer at our institution. METHODS: A total of 606 sentinel node biopsies were performed on 599 clinical N0 breast cancer patients between January 1997 and November 2001. RESULTS: The axillary sentinel node revealed metastasis in 204 (36.1%) of the 565 patients in whom it was identified and was false negative in eight patients. Two false negative results came to light by confirmatory axillary lymph node dissection during the learning phase. Tumour-positive lymph nodes were incidentally found in the axillary tail of the simple mastectomy specimen in two patients. Excision of a firm, non-radioactive, unstained but tumour-positive non-sentinel node occurred in three other patients. One patient developed an axillary recurrence 22 months postoperatively. Presumptive causes were surgical delay, pathological sampling error and tumour blocking. CONCLUSION: Intra-operative palpation of the axilla to identify suspicious lymph nodes is recommended. In a two-day protocol, surgery should be performed first thing in the morning. Seven slices of 50-150-micro m strike an acceptable balance between sensitivity and work load for the pathologist.

Lymphatic mapping with tracer administration into the primary breast cancer.

There is an ongoing debate over the best tracer injection technique in lymphatic mapping for breast cancer. The technique of low tracer volume administration into the primary breast cancer is presented. The reasons that led to this approach are explained as well as its advantages. Excision of radioactivity that remains at the injection site in the breast cancer prevents the gamma ray scatter that may hamper retrieval of a sentinel node. The intralesional injection technique avoids potential injection of tracer fluid across a lymphatic watershed, it enables identification of extra-axillary sentinel nodes and allows probe-guided excision of non-palpable tumours.