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.

Reduce bladder cancer recurrence in patients treated for upper urinary tract urothelial carcinoma: The REBACARE-trial.

BACKGROUND: Following radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy. AIM: To reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy. METHODS: Adult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines. RESULTS: The primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences. CONCLUSIONS: A single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

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.

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.

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.

Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.

PURPOSE: To determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS). PATIENTS AND METHODS: Among 55 patients with 30 primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple). The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP. RESULTS: A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases. Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%). When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease. Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels. CONCLUSION: ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.

To perfuse or not to perfuse? A retrospective comparative study to evaluate the effect of adjuvant isolated regional perfusion in patients with stage I extremity melanoma with a thickness of 1.5 mm or greater.

The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.

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.

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.

[The foreskin and squamous-cell carcinoma of the penis]. / De voorhuid en het plaveiselcelcarcinoom van de penis.

The incidence of penile cancer is low in men who have been circumcised at infancy. It is unknown whether a causative relationship exists between circumcision and the substantially reduced incidence of penile cancer. A normal foreskin has no known aetiological role in the development of penile cancer. A narrow, non-retractable foreskin predisposes the patient to infection and contributes to the development of penile cancer, together with the known risk factors of smoking and human papillomavirus infection. Circumcision represents a complex of social and behavioural factors. Analyses have not taken all of these factors into consideration. It is unlikely that circumcision itself protects against the development of penile cancer.

[Less mutilating treatment of penile carcinoma]. / Minder mutilerende behandeling van het peniscarcinoom.

Four patients with penile carcinoma are described. A 60-year-old man with a T1-tumour underwent penis-conserving laser treatment. Two men, aged 52 and 65 years old, with T2-tumors and clinically node-negative groins underwent penile amputation. Sentinel-node biopsy (SNB) revealed no metastases in the 52-year-old patient. High-resolution ultrasound-guided fine-needle aspiration cytology revealed bilateral metastases in the other patient, who underwent bilateral inguinal lymphadenectomy. In the fourth patient, a 73-year-old man with a T3-tumor, a pathological lymph node was palpated in one groin. Inguinal lymphadenectomy revealed 3 positive nodes and an additional pelvic lymphadenectomy was performed. SNB on the other side was positive and inguinal lymphadenectomy followed. No additional positive nodes were found in the dissection specimen. All patients were alive without evidence of disease 4, 3, 3 and 4 years later, respectively. New developments in the management of penile cancer such as laser treatment, high-resolution ultrasonography and SNB result in a more tailored approach with less morbidity without reducing survival rates.

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.

Results of a double perfusion schedule with melphalan in patients with melanoma of the lower limb.

From 1985 to 1990 43 patients with measurable locally inoperable or recurrent melanoma of the lower limb were treated according to a double perfusion schedule. The dose of melphalan given in the first perfusion was low (6 mg/l; 1 h; normothermic) in order to make it possible to carry out a second perfusion (9 mg/l; 1 h; normothermic) with a planned short interval of 3-4 weeks. The toxicity after the first perfusion was slight; after the second it was higher with a Wieberdink grade III reaction in 15 patients. A clinical complete remission (CR) was seen in 33 patients (77%) and a partial one in 6 patients. 16 of the 33 patients with a CR recurred in the perfused area after 5 months (range 1-29); the others remained limb recurrence-free (7-44+ months). The overall 3-year survival rate is 50%, 19 patients are alive with no evidence of disease. The double perfusion schedule shows a high CR rate, an acceptable toxicity and is technically feasible.

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.

A retrospective comparative study evaluating the results of mild hyperthermic versus controlled normothermic perfusion for recurrent melanoma of the extremities.

The aim of this study was to investigate the role of mild hyperthermia (39-40 degrees C) in isolated cytostatic perfusion for patients with recurrent melanoma of the extremities. A total of 218 patients treated with mild hyperthermic perfusion was compared to 166 patients perfused under controlled normothermic conditions (37-38 degrees C). Only patients whose lesions had been excised before or at the moment of perfusion were eligible for this study. A variety of prognostic factors was controlled for in a Cox proportional hazards analysis. The application of mild hyperthermia did not influence limb recurrence-free interval nor survival (corrected P values 0.46 and 0.18, respectively). In this retrospective comparative study, no benefit for mild hyperthermia in regional isolated perfusion could be identified.

Isolation limb perfusion with tumor necrosis factor alpha and chemotherapy for advanced extremity soft tissue sarcomas.

The unique property of high dose recombinant tumor necrosis factor alpha (rTNF alpha) is to activate and selectively destroy the tumor-associated microvasculature. For the systemic application of rTNF alpha it has been shown that the maximum tolerated dose (MTD) is 10 times less than the effective dose in animals. The main toxicity corresponds to systemic inflammatory response syndrome with a decrease in vascular resistance and hypotension. We found that it is possible to administer rTNF alpha at 10 times the MTD in an isolated limb perfusion (ILP) system with heart-lung machine, for locally advanced extremity soft tissue sarcomas. One hundred forty patients received an ILP with high-dose TNF alpha. In 55 patients treated with the combination of high-dose rTNF alpha + interferon-gamma + melphalan an overall objective response rate of 87% with 36% complete responses was observed; it was 81% and 28%, respectively, in a group treated with TNF alpha and melphalan (n = 85). Angiographic and immunohistological studies showed the selective and early damage of the sarcoma-associated microvasculature preceded by the upregulation of adhesion molecules and intratumoral leak of von Willebrand factor. Tumor invasion by platelets and, in some cases, by polymorphonuclear cells, appeared within hours after the application of rTNFa long before the lysis of the tumor. Thus, ILP with high-dose TNF alpha and chemotherapy seems to act through a dual targeting: TNF hits the tumor associated vasculature, and chemotherapy attacks the tumor cells. Therefore, ILP with TNF is a new option in the management of locally advanced soft tissue sarcoma of the extremities.

Evaluation of mammary lymphoscintigraphy by a single intratumoral injection for sentinel node identification.

UNLABELLED: The aim of this study was to evaluate the findings of mammary lymphoscintigraphy by a single intratumoral injection in 150 patients with breast carcinoma: 100 patients (group A) investigated in the validation phase of the study and 50 (group B) studied after the tracer dose was optimized. METHODS: Immediately after injection of 99mTc-nanocolloid using a 25-gauge needle and a 0.2-mL volume, simultaneous anterior and lateral images were acquired with a dual-head gamma camera during 20 min followed by sequential static anterior and prone lateral breast images after 30 min and after 2 and 4 h. 57Co-assisted skin marking defined the sentinel node location for subsequent gamma probe, blue dye-guided sentinel node biopsy. RESULTS: In group A (mean dose, 61.6 MBq; range, 42-88 MBq) scintigraphy revealed lymph nodes in 83 patients (83%), with an increase in the rate of visualization from 72% for the first 40 patients to 90% for the last 60; patient age (P = 0.01) and administered tracer dose (P = 0.04) were found to be significant factors for visualization, with optimal results obtained from doses higher than 65 MBq. Lymph nodes were visible in 34 patients (41%) during the first 30 min after injection, whereas in 49 patients appearance occurred at 2-4 h. A total of 97 lymphatic basins were visualized (80 axillary, 3 clavicular, 14 internal mammary). In group B (mean dose, 90.8 MBq; range, 68-124 MBq), the visualization rate was 94%, with early lymph node appearance in 27 patients (57%) and a total of 53 basins (45 axillary, 8 internal mammary). In combination with intraoperative blue dye mapping and y probing, the identification rate increased to 90% in group A and 98% in group B. Prone lateral images contributed to identification of intramammary lymph nodes in a total of 14 patients and axillary nodes close to the injection site in 8 other patients. CONCLUSION: Mammary lymphoscintigraphy by single intratumoral injection is a valid method for lymphatic mapping and identification of both axillary and nonaxillary sentinel nodes. Lymph node visualization appears to be improved with higher tracer doses. The compactness of the injection site enables high-quality additional lateral images that can depict intramammary or axillary lymph nodes adjacent to the injection site.

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.