Wm Molenaar

Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: a single-center 10-year experience

PURPOSEnA wait-and-see policy for patients with stage I nonseminomatous testicular germ cell tumors (NSTGCT) was evaluated in a prospective study. The frequency and time of recurrence, detection of recurrence, and presence of unfavorable prognostic factors were investigated.nnnPATIENTS AND METHODSnDuring the period 1982 to 1992, 154 patients with stage I NSTGCT (median age, 29 years) underwent orchidectomy and were monitored at follow-up evaluation with physical examinations, alfafetoprotein (AFP) and beta-human choriogonadotropin (hCG) levels, chest x-rays (CXR), and computed tomographic (CT) scans of the abdomen and chest. Multivariate logistic regression analyses were performed to identify prognostic factors.nnnRESULTSnDuring a median follow-up period of 7 years (range, 2 to 12), recurrence was found in 42 patients (27.3%). All cases of recurrence were detected within 2 years, 90% in the first year after orchidectomy. In 29 patients (69.0%), recurrence was detected in the abdominal lymph nodes. Nine patients (21.4%) had metastases in the retroperitoneum and mediastinum and/or lungs, and four patients (9.6%) had metastases only in the mediastinum or lungs. The majority of recurrences (97.6%) were detected by tumor markers and CT scans. Recurrence was related to the presence of vascular invasion, embryonal carcinoma (E), elevated preoperative hCG level, and absence of mature teratoma (M). Only vascular invasion was an independent risk factor. After polychemotherapy treatment for recurrence, the survival rate for the total group was 98.7%.nnnCONCLUSIONnThe wait-and-see policy is a reliable method for follow-up monitoring of patients with stage I NSTGCT. Even in patients with unfavorable prognostic factors, it is justified to await the possible appearance of metastases. For the future, it is recommended that CXR be omitted from the schedule, and it might be feasible to discontinue follow-up evaluations after 5 years.

Aneurysmal bone cysts treated by curettage cryotherapy and bone grafting

We treated 26 patients with 27 aneurysmal bone cysts by curettage and cryotherapy and evaluated local tumour control, complications and functional outcome. The mean follow-up time was 47 months (19 to 154). There was local recurrence in one patient. Two patients developed deep wound infections and one had a postoperative fracture. We compared our results with previous reports in which several different methods of treatment had been used and concluded that curettage with adjuvant cryotherapy had similar results to those of marginal resection, and that no major bony reconstruction was required. We recommend the use of cryotherapy as an adjuvant to the surgical treatment of aneurysmal bone cysts. It provides local tumour control. Combination with bone grafting achieved consolidation of the lesion in all our patients.

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

AbstractBackground: 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 patients affected limb are unknown.nMethod: 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.nResults: 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.nConclusion: 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.

Angiographic response of locally advanced soft-tissue sarcoma following hyperthermic isolated limb perfusion with tumor necrosis factor

AbstractBackground: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and melphalan is associated with a dramatic anti-tumor effect in which the neo-vascularization of the tumor is supposed to be the major target. The aim of the present study was to correlate the angiographic findings with the pathological response in patients undergoing HILP for locally advanced soft-tissue sarcoma.nPatients and Methods: Twenty-five patients, 14 male and 11 female, mean age 47 years (range 18–80) were studied. Angiographies were performed before and a median period of 7 weeks (range 4–14 weeks) after HILP. Eight weeks after perfusion, the residual tumor mass was resected and pathologically examined. The changes in tumor vascularization after treatment were scored and compared with the pathological response.nResults: All baseline angiograms showed a hypervascular tumor. After HILP, a normal angiography result (NA) was observed in 18 patients (72%) and an abnormal angiography result (AA) was observed in seven patients (28%). All patients with an NA showed a pathologically complete response (pCR) or a pathological partial response with >90% necrosis of the tumor. Of seven patients with an AA, pathological examination showed a pCR in one patient, 10–50% viable tumor volume in four patients, and no pathological response after perfusion in two patients. A good correlation was seen between angiographic and pathological classification (p<0.001).nConclusion: An angiography performed after hyperthermic isolated limb perfusion with TNF-α and melphalan provides a good indication, regardless of whether a good pathological response is expected.

Epidemiological aspects of soft tissue sarcomas (STS) - Consequences for the design of clinical STS trials

The purpose of the study was to gain insight into epidemiological aspects of soft tissue sarcomas (STS), based on the population-based cancer registry of the Comprehensive Cancer Center North-Netherlands (CCCN), and to provide data for the development of future STS clinical trials. 456 primary STS (Kaposi, urogenital and gastro-intestinal STS excluded), registered from 1989 to 1995 by the cancer registration of the Comprehensive Cancer Center North-Netherlands (CCCN), were analysed. The annual, age-adjusted, STS incidence was 3.6 per 100,000. Incidence increased with age. Half of the patients were over the age of 65 years. Malignant fibrous histiocytomas and liposarcomas were most frequently encountered. At presentation, nodal involvement was rare (3-8%). Distant metastases were more frequently encountered (9-14%), and appeared to be related to tumour size and site. Above 70 years of age, 16% of patients received no treatment at all, especially for metastatic disease.

Cytologic "differentiation" in childhood rhabdomyosarcomas following polychemotherapy.

The effectiveness of polychemotherapy in young patients with rhabdomyosarcomas has been well established. The morphologic alterations in the tumor tissue, however, have not been widely reported. Therefore, in a group of 15 patients from 1 to 24 years of age, specimens of tumor tissue obtained before and after polychemotherapeutic treatment were compared. No morphologic changes, other than fibrosis and necrosis, occurred in patients who initially had virtually undifferentiated tumors. When moderately or well-differentiated areas were present in the initial specimens, these areas showed proportionate increases in the follow-up specimens. Moreover, the cellular characteristics of round rhabdomyoblasts and strap cells with or without cross-striations became more distinct after treatment. However, cell types that were not present in the initial specimens were never found in follow-up specimens. It was concluded that the major role of polychemotherapy is the selective destruction of undifferentiated tumor cells; further differentiated cells are stimulated either directly or indirectly to reach their maximal inherent differentiation levels, but it does not appear that transitions from one cell type to the other occur.

Epithelioid sarcoma or malignant rhabdoid tumor of soft tissue? Epithelioid immunophenotype and rhabdoid karyotype

Two children and one young adult with extremity sarcomas demonstrating an aggressive clinical behavior are described. Histologically, all three tumors displayed features compatible with a deep-seated epithelioid sarcoma or with a malignant rhabdoid tumor of soft tissue. Immunohistologically, both vimentin and epithelial antigens were demonstrated; however, no desmin was detectable. In all three cases, the DNA profile was diploid. In one case, a trisomy of chromosome 2 was found in the tumor cells, a phenomenon also observed in embryonal rhabdomyosarcomas. It is concluded that, although the immunohistologic findings support the epithelioid character of the tumors, this chromosomal finding suggests a relationship with rhabdomyosarcomas and justifies the designation of rhabdoid.

Histology and DNA contents of a secondary malignancy arising in a mature residual lesion six years after chemotherapy for a disseminated nonseminomatous testicular tumor

The current report describes a secondary malignancy developing in a retroperitoneal mature residual lesion 6 years after chemotherapeutic treatment of a disseminated nonseminomatous testicular tumor. The histologically malignant component was not present in the primary tumor and consisted of polygonal and fusiform cells with focal tubular formations, resembling primitive neuroectodermal tissue. Immuno‐ peroxidase staining for alpha‐fetoprotein and the beta‐subunit of human chorionic gonadotropin remained negative, whereas focal positivity for S100 protein was observed. Neuron specific enolase positivity was equivocal. The DNA contents of both the mature components in the primary and the metastatic retro‐ peritoneal tumor and in the various malignant components of the primary tumor, were in the hypotriploid range. In the malignant component of the retroperitoneal metastasis, a hypertriploid peak was observed. These findings suggest further clonal evolution in a phenotypically mature, genotypically abnormal residual metastatic tumor after chemotherapy. It is stressed that the mature appearance of the residual lesions may be deceiving and that these lesions are highly susceptible to resume malignant behavior. Cancer 58:264–268, 1986.

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?

Abstract 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)-α 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-α 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-α 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.

Pigmented villonodular synovitis

SummaryPigmented villonodular synovitis is a benign disease of the synovial membrane of joints, tendon sheaths, or bursae, which nevertheless can cause marked local destruction. Its diagnosis is often delayed because complaints and symptoms are nonspecific. Familiarity with the disease may ensure an earlier diagnosis and consequently early onset of therapy, which may prevent serious damage. This paper describes 18 patients suffering from localized or diffuse pigmented villonodular synovitis. Findings possibly suggestive of pigmented villonodular synovitis include hemarthrosis, soft tissue swelling, radiological evidence of cyst formation at a distance from the weight-bearing area of a joint, an increased triglyceride concentration, and a positive bone scan. A normal appearance on arthroscopy does not rule out the disease. Therapeutic results are better in the localized than in the diffuse form of the disease.