Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma.

AIM: The aim of this study was to evaluate the reliability and clinical impact of sentinel node biopsy, including preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with cutaneous melanoma of the head, neck, trunk or extremities. METHODS: Two hundred patients (103 women, 97 men), median age 57 (range 21-86) years with cutaneous melanoma > or =1.0mm Breslow thickness and clinically negative lymph nodes participated in a single institutional prospective study from May 1995 to January 2000. Primary melanoma sites included: 22 head and neck (11%), 67 trunk (34%), 29 upper extremity (14%) and 82 lower extremity (41%). The median Breslow thickness was 2.5 (range 1.0-20.0)mm. Preoperative dynamic and static lymphoscintigraphy, intraoperative blue dye and a gamma detection probe were used. If histological examination with HE or IHC showed metastases, therapeutic lymph node dissection (TLND) was performed. RESULTS: Sentinel node(s) could be identified in 197 patients (99%); 393 sentinel nodes (mean: 2.0 per patient, range 1-7) were removed from 241 basins. Three procedures failed in the head and neck region. In 167 patients, the sentinel nodes were both blue and radioactive (85%); in 26 patients, they were only radioactive (13%) and in four patients only blue (2%). In total, 150 patients had tumour-negative sentinel nodes (76%). During a median follow-up of 47 (range 24-79) months, nodal recurrence in a negative mapped basin was documented in six patients of which isolated recurrence was in two patients and recurrence together with locoregional recurrence in four patients (false negative rate 6/54=11%). Estimated three-year recurrence-free survival in the node-negative patients and node-positive patients was 83 and 66% respectively (P<0.05). The overall survival at three years was 92 and 73% respectively (P<0.05). CONCLUSION: Sentinel node biopsy provides accurate staging and important prognostic information. The final place of sentinel node biopsy is still undefined, and therefore sentinel node biopsy is still considered as an experimental surgical staging procedure.

Sexual functioning after treatment for testicular cancer--review and meta-analysis of 36 empirical studies between 1975-2000.

Literature concerning sexual functioning after treatment for testicular cancer from 1975-2000 is reviewed. After a literature search in Medline and Psylit was conducted, as well as a search for cross-references made, a meta-analysis was performed. To describe sexual functioning, several aspects of the sexual response cycle were used: sexual desire, sexual arousal, erection, and orgasm; ejaculatory function, sexual activity, and sexual satisfaction were used as well. The number of patients included in the studies as well as treatment modalities were taken into account. A total of 36 relevant studies was screened (28 retrospective and 7 prospective studies), concerning 2,786 cases of testicular cancer. Meta-analysis revealed that ejaculatory dysfunction was reported most frequently and was related to surgery in the retroperitoneal area. Erectile dysfunction was related to irradiation, but was reported least frequently. Other sexual functions were not related to treatment modality. Meta-analysis revealed no deterioration of sexual functioning in the course of time, except a decrease in sexual desire and an increase in sexual satisfaction. Retrospective studies reported more sexual dysfunction than did prospective studies. Detailed analysis of separate studies, however, revealed a wide variation in reported sexual morbidity, as well as in assessment methods. Somatic consequences of disease and treatment may reduce ejaculation; however, other aspects of sexual functioning are not clearly related to disease- or treatment-related factors and may instead refer to a psychological vulnerability caused by one's confrontation with a life-threatening, genito-urinary disease, such as testicular cancer.

Sentinel nodes outside lymph node basins in patients with melanoma.

BACKGROUND: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. METHODS: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous melanoma. One day after lymphoscintigraphy, sentinel node biopsy was performed guided by vital blue dye and a gamma ray detection probe. RESULTS: Persisting hot spots outside the regional node basins were seen in 25 patients (6.6 per cent). Several specific drainage patterns were discerned. In five patients, aberrant sentinel nodes were not explored. The hot spot represented a lymphangioma in two patients. Radioactive lymph nodes were identified in the remaining 18 patients (4.7 per cent). Four patients had metastasis in one of these aberrant lymph nodes. CONCLUSION: Sentinel nodes were found outside a lymph node basin in 5 per cent of patients. Particular drainage patterns exist. It is recommended to incorporate such sites in the late scintigraphy images and to pursue aberrant sentinel nodes, as they may be the only sites of metastasis.

Frozen section analysis of sentinel lymph nodes in melanoma patients.

BACKGROUND: The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS: Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS: Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION: The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes.

The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of which one patient was treated with granulocyte-colony stimulating factor. Lymph nodes of nine patients without malignant melanoma were tested and four cell lines of various other tumours. Six of the nine non-melanoma lymph nodes were positive in this assay. The sensitivity was tested in a spike experiment in vitro, using a melanoma cell line. The detection limit was ten melanoma cells per 10(7) peripheral blood lymphocytes.

Giant melanoma of the left thumb.

A 74-year-old female patient is described with a giant melanoma of the left thenar and concomitant bilateral pulmonary metastases. Palliative treatment consisted of a two-staged procedure in order to save the limb from amputation. Firstly, perfusion with gamma-interferon, tumour necrosis factor- alpha and melphalan was carried out, after which the tumour had been reduced to one third of its initial volume. Secondly, excision of the tumour and coverage of the wound with a split skin graft was done. Remarkably, the extent of the multiple pulmonary metastases was temporary and diminished 1 month after perfusion, although no systemic leakage could be determined during the procedure. The management strategy is discussed with emphasis on this indication for limb perfusion.

[Poor prognosis of osteosarcoma of pelvis; 39 years of registration by the Netherlands Commission on Bone Tumors]. / Slechte prognose van bekkenosteosarcoom; 39 jaar registratie door de Nederlandse Commissie voor Beentumoren.

OBJECTIVE: To evaluate the results of treatment in patients with osteosarcoma of the pelvis. DESIGN: Retrospective. PATIENTS AND METHODS: Sixty-five patients with pelvic osteosarcoma registered in the files of the Netherlands Committee on Bone Tumours over 1957-1995 were reviewed. Complete information was obtained on 62 cases: 27 males and 35 females, median age was 31 years (range: 12-83). Distant metastases were present in 11 patients (stage IIIB; 18%), while 50 patients had stage IIB osteosarcoma (81%) and 1 patient stage IB osteosarcoma (2%). The results of treatment and survival were determined. RESULTS: Median survival was 14 months (2-177), the 5-year survival 15%. Distant metastases developed in 27 of 42 (64%) patients with curatively treated stage IIB osteosarcoma, with prolonged metastasis-free survival after chemotherapy treatment (p < 0.0012). Survival in patients with stage IIB pelvic osteosarcoma was better after surgical resection of the primary tumour than after no operation (p < 0.0054); (neo)adjuvant chemotherapy gave no longer survival than surgery alone (p < 0.083). CONCLUSION: The prognosis of pelvic osteosarcoma was poor, despite modern multimodality treatment regimens, including surgical resection and chemotherapy.

Objective and subjective effects of treatment for testicular cancer on sexual function.

OBJECTIVE: To determine whether the treatment of patients with testicular cancer, using cisplatin combined with etoposide and bleomycin (BEP) after orchidectomy in those with disseminated disease, causes changes in sex hormones and penile vascularization, possibly related to sexual dysfunction. PATIENTS AND METHODS: Ten patients treated with BEP were compared with 11 undergoing orchidectomy alone followed by surveillance. Sex hormone levels were analysed and cavernosal artery duplex ultrasonography performed before orchidectomy and at 6 and 12 months afterward. Patients were questioned about their sexual function. After 1 year, a visual erotic stimulation (VES) test was performed to assess penile rigidity. RESULTS: In contrast to the surveillance group, BEP-treated patients had higher follicle-stimulating hormone (4.6 vs 26.5 U/L) and luteinizing hormone (1.4 vs 8.2 U/L) levels, and lower testosterone levels (21.1 vs 14.7 nmol/L) at 6 months than at baseline. At 1 year, most patients had compensated hypergonadotrophic eugonadism, but Leydig cell function had recovered. Changes in cavernosal artery peak flow velocities induced by local injection with papaverine/phentolamine showed no difference between the groups before and 6 months after orchidectomy. Loss of libido and erectile dysfunction were reported more frequently by BEP-treated patients. However, 1 year after treatment, most reported a satisfying sex life and VES resulted in a rigid erection in nearly all patients. The reported erectile dysfunction could not be explained by changes in plasma testosterone levels or diminished blood flow velocities. CONCLUSIONS: After being diagnosed with testicular cancer, sexual morbidity is considerable, but within 1 year some improvement may be expected. BEP induces transient testicular dysfunction but this recovers. Although BEP is related to symptoms of angiopathy, cavernosal blood flow seems to be unaffected. These findings and the normal VES-evoked penile rigidity suggest that sexual dysfunction is more psychological than organically induced by BEP.

Loss of the Y-chromosome in the primary metastasis of a male sex cord stromal tumor: pathogenetic implications.

The first published chromosomal pattern of the retroperitoneal lymph node metastasis of a malignant gonadal stroma cell tumor of the adult testis is presented. Karyotyping showed structural chromosomal abnormalities and loss of the Y-chromosome. This loss was confirmed in primary tumor and metastasis using fluorescence in situ hybridization (FISH). The characteristic chromosomal abnormality of adult testicular germ cell tumors, an i(12p), was not present. The results are compared with other data of testicular and ovarian sex cord stromal tumors. From the comparison of the male tumors, it is concluded that loss of the Y-chromosome might have a pathogenetic significance.

The changing distribution of stage in nonseminomatous testicular germ cell tumours, from 1977 to 1996.

OBJECTIVE: To determine the changes between 1977 and 1996 in the distribution of stages of testicular cancer (TC). PATIENTS AND METHODS: The stage distribution was assessed, using various classifications, i.e. the Royal Marsden (RM), Indiana, European Organization for Research and Treatment of Cancer (EORTC), International Germ Cell Cancer Collaborative Group (IGCCCG) and the Medical Research Council (MRC), in 517 patients with nonseminomatous testicular germ cell tumours (NSTGCTs) diagnosed at a single institution between 1977 and 1996. RESULTS: The number of patients in four consecutive 5-year periods (1977-81, 1982-86, 1987-91, 1992-96) was 119, 141, 141, and 116, respectively. Frequency analyses showed a significant increase of RM stage I, in proportion to stage II-IV, in 1982-86 (55%, odds ratio, OR, 2.54), 1987-91 (53%, OR 2.33) and 1992-96 (61%, OR 3.24) compared to the period 1977-81 (33%). A separate analysis of patients with disseminated disease showed a proportionate significant decrease of RM stage II in 1992-96 (29%, OR 0.43) compared with 1977-81 (49%). There was also a relative decrease of good-prognosis patients with disseminated disease in 1992-96 compared with 1977-81, using analyses of the Indiana (from 56% to 33%, OR 0.39) and EORTC classification (from 78% to 56%, OR 0.36). Analyses of the IGCCCG and MRC classification showed a significant decrease of good-prognosis patients in the 1982-86 compared with the first 5-year period (for IGCCCG, from 54% to 35%, OR 0.46, and for MRC, from 43% to 24%, OR 0.42). CONCLUSION: The stage distribution of NSTGCT over the past two decades has changed. The proportion of stage I patients has increased since the early 1980s, apparently resulting from a shift of low-extent disseminated disease to stage I disease. This finding is relevant in reducing the treatment required in a higher proportion of patients and the subsequent reduction of long-term risk from treatment.

Cytogenetic analysis of a mature teratoma and a yolk sac tumor component of a late relapse of a disseminated testicular nonseminoma.

We report on the cytogenetics of a primary testicular nonseminoma, a residual mature teratoma after remission-induction chemotherapy, and a late relapse after 9 years of follow-up, in one patient. The late relapse was composed of a mature teratoma and a yolk sac tumor component. Cytogenetic comparison of the different tumors shows that progression of primary testicular nonseminoma to residual mature teratoma and to a late-relapse lesion is accompanied by net loss of chromosomes. In addition, our findings may suggest that transformation to viable cancer in a late-relapse lesion is accompanied by further chromosomal losses.

Bilateral testicular germ cell tumours in patients with initial stage I disease: prevalence and prognosis--a single centre's 30 years' experience.

Development of second testicular tumours, i.e. bilateral testicular cancer, is influenced by systemic chemotherapy for the first tumour. The prevalence of bilateral testicular cancer was studied in patients with initial stage I disease, in which no systemic treatment was given after orchidectomy. All stage I testicular cancer patients entered a surveillance study with an intensive follow-up since 1982. We hypothesised that after 1982, bilateral testicular cancer was diagnosed at an earlier stage of disease. The prevalence of bilateral testicular cancer was 4.7% (8/170) in stage I patients treated between 1967 and 1981, and 2.9% (8/275) in stage I patients treated between 1982 and 1997 (P > 0.5 chi 2-test). In the period 1967-1981, 6 patients had stage I second tumours and 2 patients had stage III second tumours. The former 6 patients are alive with no evidence of disease and the 2 patients with metastatic tumours died of disease or treatment. In the period 1982-1977, all 8 patients had stage I second tumours and all are alive with no evidence of disease. The overall prevalence of bilateral testicular cancer in stage I patients was 3.6% and has slightly decreased over the past three decades. Intensive follow-up, improvement of radiodiagnostic computed tomography techniques, availability of serum tumour markers, and patient education have resulted in earlier diagnosis and lower stage of contralateral testicular tumours, contributing to improved prognosis.

Hyperthermic isolated limb perfusion with tumour necrosis factor-alpha and melphalan as palliative limb-saving treatment in patients with locally advanced soft-tissue sarcomas of the extremities with regional or distant metastases. Is it worthwhile?

The management of locally advanced soft-tissue sarcomas (STS) of the extremities in patients who present with regional and/or distant metastases at the time of diagnosis remains an unsolved problem. The recently introduced hyperthermic isolated limb perfusion (HILP) with tumour necrosis factor (TNF)-alpha and melphalan has been shown to be an effective limb-saving treatment modality, but is it feasible to use this approach with palliative intent? Nine patients, five men and four women, mean age 41 (range 21-75) years with locally advanced extremity STS and regional (n = 3) or distant (n = 6) metastases at the time of diagnosis, underwent a palliative HILP with TNF-alpha and melphalan. Resection of the residual tumour mass was performed, if possible, 6-8 weeks after HILP. Treatment-related morbidity, local recurrences and the limb salvage rate were scored during follow-up. The median follow-up period was 9 (range 3-39) months (seven deaths, but six were due to metastatic disease). Treatment-related morbidity was seen after 3 of the 10 perfusions performed (30%) and consisted of superficial wound infections (n = 2), blow out of the external iliac artery followed by an iliac thrombosis (n = 1). Two patients showed local recurrences after HILP followed by resection of the residual tumour mass, and one patient showed local progression after two perfusions without resection. Limb salvage was achieved in 8 patients (89%). Therefore, HILP with TNF-alpha and melphalan for locally advanced extremity STS in patients with disseminated disease is feasible. The local management of locally advanced extremity STS should be the same whether the intent is curative or palliative, as the local control improves the quality of life.

Hyperthermic isolated limb perfusion with tumour necrosis factor and melphalan as treatment of locally advanced or recurrent soft tissue sarcomas of the extremities.

Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents has been used for the local treatment of high-grade soft tissue sarcomas (STS) of the extremities, but in most cases with a disappointing result. Most regimens should certainly not be considered superior to surgery plus radiotherapy. Although the majority of extremity STS can be resected locally, some have a very large size and are in close proximity to bones, nerves or blood vessels. In these cases, amputation is the only means of resecting the tumour. A new combination of drugs used in the set-up of HILP with tumour necrosis factor-alpha and melphalan has emerged as a very promising option for the limb-saving management of locally advanced STS. In recent studies, complete response rates of approximately 30% and partial remission rates of 50% have been achieved, while the overall limb-salvage rate is more than 80%.

Limb salvage surgery for primary bone sarcoma of the lower extremities: long-term consequences of endoprosthetic reconstructions.

BACKGROUND: Adjuvant chemotherapy and endoprosthetic replacement for bone sarcomas of the lower extremity is well established. The specific long-term consequences of these endoprosthetic reconstructions for the patient's affected limb are unknown. METHOD: The oncologic results and the survival of the endoprostheses were reviewed in 32 patients with primary bone sarcoma of the femur or proximal tibia. There were 26 high-grade sarcomas, and 6 low-grade sarcomas. A proximal femoral endoprosthesis was used for reconstruction in 4 patients, a total or push-through femoral endoprosthesis in 11 patients, a distal femoral endoprosthesis in 15 patients, and a proximal tibial endoprosthesis in two patients. RESULTS: Median survival was 10 years (range, 1.1 to 18.9 years) for patients with high-grade sarcoma, and 8.1 years (range, 7.1 to 10 years) for patients with low-grade sarcomas. Distant metastases developed in seven patients (22%), all with stage IIB sarcoma, with concomitant local recurrence in 3 patients (9%). Five-year overall and disease-free survival rates for high-grade sarcomas were 81% and 73%, respectively. The overall endoprosthetic survival rate was 87% at 5 years, 80% at 10 years, and 56% at 15 years. Median follow-up of the original endoprostheses was 8.3 years (range, 0.6 to 18.7 years). Endoprosthesis-related complications occurred in 13 patients (41%); most complications were mechanical failures. The highest complication rate was found in distal femoral replacements (60%); amputation was necessary in both patients treated with a proximal tibial endoprosthesis. Five endoprostheses (16%) were revised. An amputation of the involved limb was performed in four patients (13%): in two patients because of local recurrence and in the other two patients because of infection. For patients alive at follow-up, the median functional Enneking evaluation score was 22 points (range, 12 to 28 points), with the highest functional scores in patients with a distal femoral endoprosthesis, and the lowest functional scores in patients with total or push-through femoral replacements. CONCLUSION: Endoprosthetic reconstructions gave satisfying functional results in most patients after long-term survival. However, the proximal tibial and distal femoral endoprosthesis are particularly at risk for long-term endoprosthetic complications requiring additional surgical procedures.

L-[1-carbon-11]tyrosine imaging of metastatic testicular nonseminoma germ-cell tumors.

UNLABELLED: The aim of this study was to investigate whether PET with L-[1-11C]tyrosine C(TYR) can be used to visualize metastatic disease of nonseminoma testicular germ-cell tumors and to monitor the effect of systemic cisplatinum-based polychemotherapy in a noninvasive fashion to reduce the number of operations in patients with a residual retroperitoneal tumor mass. METHODS: Ten patients with retroperitoneal nonseminoma testicular germ-cell tumors metastases were studied with TYR PET before the start of cisplatinum-based polychemotherapy. A dose of 370 MBq of TYR was injected intravenously, and a 30-min TYR image was acquired 20 min after injection. The standardized uptake value of TYR was calculated in visualized lesions. RESULTS: PET showed increased focal uptake of TYR in the retroperitoneum of 2 patients (20%). In 2 patients with large and inhomogeneous lesions on CT, PET showed decreased TYR uptake at the site of the lesion (20%). In the other 6 patients, the metastatic tumor masses were not depicted (60%). Because of these disappointing results, no posttreatment scans were obtained. Standardized uptake values of the visualized lesions varied from 1.05 to 2.87 for the lesions with increased metabolism and from 0.29 to 0.34 for lesions with decreased metabolism. CONCLUSION: PET with TYR is not suited to visualize the apparently slowly proliferating nonseminoma testicular germ-cell tumors or determine the nature of a residual retroperitoneal mass after chemotherapy.

Isolated limb perfusion in primary and recurrent melanoma: indications and results.

In advanced melanoma of the limbs with in-transit metastasis, melphalan with isolated limb perfusion (M-ILP) produces around 50% complete remissions (CR). The combination of melphalan with tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in isolated limb perfusion (TIM-ILP) gives around 80% CR. A prospective randomised phase II study compared 32 patients who received TIM-ILP with 32 patients who received TM-ILP (without IFNgamma). The overall remission rate (ORR) and the CR rate were superior with TIM-ILP as compared to TM-ILP, 100% vs. 91% and 78% vs. 69% respectively, but the differences are not significant. Given the efficacy of M-ILP on in-transit metastasis, the procedure was tested as an adjunct to surgery in high-risk (Breslow > or = 1.5 mm) primary melanoma of the limbs. Through the combined effort of the melanoma groups of the European Organization for Research and Treatment of Cancer (EORTC), the World Health Organization (WHO), and the North American Perfusion Group, 832 evaluable patients from 16 centres were entered in a phase III study. Median followup is 6.4 years. There was a trend for a longer disease-free interval after M-ILP. The difference is significant if the patients without elective lymph node dissection (ELND) are separately analysed, with a high significance in the 1.5 to 3 mm thickness subgroup. The occurrence of in-transit metastases was reduced from 6.6% to 3.3% by M-ILP. There was, however, no benefit of M-ILP in terms of survival. Prophylactic M-ILP cannot be recommended as a standard adjunct to surgery in high-risk primary limb melanoma. TIM-ILP or TM-ILP is a regional therapy with a very high regional response rate on melanoma in-transit metastasis.

Hyperthermic isolated limb perfusion for the treatment of soft tissue sarcomas.

Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents has been used for the local treatment of high-grade soft tissue sarcomas (STS) of the extremities, but in most cases, with a disappointing result. Most such regimens certainly should not be considered superior to surgery plus radiotherapy. Although the majority of extremity STS can be resected locally, some are very large and are in close proximity to bone, nerve or blood vessels. In these cases, amputation is the only means of resecting the tumour. A new combination of drugs used in the set-up of HILP with tumour necrosis factor-alpha and melphalan has emerged as a very promising option for the limb-saving management of locally advanced STS. In recent studies, complete response rates of approximately 30% and partial remission rates of 50% have been achieved, while the overall limb-salvage rate is more than 80%.