Design and analysis of coupling methods for modular endoprosthetic systems as an alternative to the conical coupling.

Modular endoprostheses are often used in bone tumor management. However, the conical coupling that connects the various modules has several shortcomings. As an alternative, four new couplings have been developed. To find out if they have sufficient strength and show no movement during loading, each coupling was analysed using the finite element method. Bolt force and friction coefficient was varied to examine their influence. From the analysis it was concluded that coupling B, a dovetail coupling, meets all requirements and is the best alternative to the conical coupling. Sensitivity to bolt force and friction coefficient is very limited.

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.

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era.

BACKGROUND: The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. METHODS: Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. RESULTS: The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. CONCLUSIONS: The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

Frozen section investigation of the sentinel node in malignant melanoma and breast cancer.

BACKGROUND: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients. METHODS: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis. RESULTS: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively. CONCLUSION: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.

Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR: potential clinical relevance.

The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to compare and quantify the difference in sensitivity of the nested RT-PCR for tyrosinase, with respect to the method utilized to produce the template c-DNA. We found a difference of a factor 10 in favor of a specific priming versus a random one. We concluded that this difference can be exploited in the analysis of blood samples. However, in the analysis of lymph node specimens, where the chance of positivity due to tyrosinase positive non-melanoma cells is much higher, the choice of a highly sensitive assay should be made with caution.

High tPA-expression in primary melanoma of the limb correlates with good prognosis.

To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation (PA) system, immunohistochemical stainings for activators of plasminogen (tissue type (tPA) and urokinase type (uPA)), inhibitors of plasminogen activation (type 1 (PAI-1) and type 2 (PAI-2)) and the receptor for uPA (uPAR) were performed on 214 routinely processed melanoma lesions. All lesions were primary cutaneous melanomas, minimally 1.5 mm thick, and derived from patients with only local disease at the moment of diagnosis (clinically stage II (T(3-4)N(0)M(0)), American Joint Committee on Cancer). Median patient follow-up was 6.1 years. Single variables as immunohistochemical staining results (extent of tumour cell staining, pattern of tumour cell staining and for some components also staining of stromal cells), histopathological and clinical parameters as well as treatment variables were analysed in order to assess their prognostic importance, in terms of time to recurrence, time to distant metastasis and duration of survival. The extent of tPA tumour cell positivity, categorized as 0-5%, 6-50% and 51-100%, appeared to be of importance for these end-points. Lesions with 51-100% tPA-positive tumour cells were found to have the best prognosis, whereas lesions with 6-50% tPA-positive tumour cells had the worst. Moreover, the prognostic significance of Breslow thickness, microscopic ulceration and sex was confirmed in this study. Multivariate analyses, incorporating these relevant factors, showed that the extent of tPA tumour cell positivity was an independent prognostic factor for distant metastasis-free interval (P = 0.012) and for the duration of survival (P = 0.043).

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients.

BACKGROUND: The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS: A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS: A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS: Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

Retroperitoneal metastases in testicular cancer: role of CT measurements of residual masses in decision making for resection after chemotherapy.

PURPOSE: To determine the relative importance of computed tomographic (CT) measurements for the prediction of histologic findings in residual masses in patients with nonseminomatous testicular cancer. MATERIALS AND METHODS: Measurements of the maximum transverse size of retroperitoneal metastases before and after chemotherapy were available in 641 patients who underwent resection after chemotherapy while their levels of tumor markers were normal. Radiologic measurements of mass size and clinical characteristics (histologic findings in primary tumor and levels of alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase before chemotherapy) were related to histologic findings in the residual mass with logistic regression analysis. RESULTS: At resection, 302 patients had benign tissue, and 339 had residual tumor (mature teratomas or cancer). Tumor was more frequent in larger masses after chemotherapy but was unrelated to mass size before chemotherapy. Inclusion of the reduction in size significantly improved the logistic regression model, which included mass size after chemotherapy. This model was further improved with the addition of clinical characteristics. Areas under the receiver operating characteristic curves increased from 0.74 to 0.77 and 0.83 with these models. CONCLUSION: A small retroperitoneal mass after chemotherapy is an important predictor of benign histologic findings in residual masses in patients with nonseminomatous testicular cancer. However, better predictions can be made when the reduction in size and clinical characteristics are considered as well. Decisions regarding resection should be based on the combination of these characteristics rather than on only mass size after chemotherapy.

Function and complications after ablative and limb-salvage therapy in lower extremity sarcoma of bone.

BACKGROUND AND OBJECTIVES: The functional results and the complications after several limb-saving and ablative treatments because of lower extremity bone sarcoma were evaluated. METHODS: Seventy-seven surviving patients were evaluated according to the MSTS (American Musculoskeletal Tumor Society) functional rating system. Fifty-two patients had limb-saving and 25 had ablative therapy. Median follow-up was 97 months in the limb-saving group and 112 months in the ablative group. RESULTS: Functional results in the limb-saving group were significantly better than in the ablative group (P = 0.0001). Functional results in patients with tumors about the knee joint were significantly better (P = 0.0064) after limb-saving surgery (i.e., endoprosthesis, knee arthrodesis, or rotationplasty) compared to functional results after ablative surgery (i.e., hip or knee disarticulation or above-the-knee amputation). Complications were 3 times more common after limb-salvage procedures and 4 times more common after endoprosthetic reconstructions compared to after ablative procedures. Complications after limb-saving therapy were fewest in tumors about the knee joint. In 3/28 patients, the endoprosthetic reconstruction had to be converted to an amputation. CONCLUSIONS: Functional results were significantly better after limb-saving compared to after ablative therapy. Complications, however, were more common after limb-saving therapy.

Cardiovascular morbidity in long-term survivors of metastatic testicular cancer.

PURPOSE: To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy. PATIENTS AND METHODS: Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for at least 10 years and whose ages were

Osteosarcoma of the pelvis--oncological results of 40 patients registered by The Netherlands Committee on Bone Tumours.

AIM AND METHODS: We reviewed the oncological outcome in 40 consecutive patients with an osteosarcoma of the pelvic region, registered in the files of the Netherlands Committee on Bone Tumours (NCBT) between 1978 and 1995. RESULTS: Six patients had distant metastases at initial presentation (Enneking stage IIIB), 33 patients had stage IIB osteosarcoma and one patient stage IB osteosarcoma. Patients with metastases were treated with chemotherapy (four) or palliative procedures (two). Patients with non-metastatic osteosarcoma were treated with surgical procedures with (14) or without (four) neoadjuvant chemotherapy, chemotherapy without surgical resection (nine), or palliative procedures (seven). The median survival of stage IIB and IIIB osteosarcoma was 14 months (2-175) and 7.5 months (2-16), respectively. Survival in patients with stage IIB osteosarcoma treated with curative procedures was significantly better (P<0.0006) compared with stage IIB patients treated with palliative intent. Two and 5-year survival for patients with curatively treated stage IIB osteosarcoma was 35% and 26%, respectively; distant metastases had developed in 65% of these patients. On univariate analysis, positive prognostic factors for patients with stage IIB osteosarcoma were complaints of 3 months or less before initial presentation, tumour size of 8 cm or less, osteoblastic subtype, surgical resection of the primary tumour and limb salvage procedures. CONCLUSION: In conclusion, the prognosis of pelvic osteosarcoma remained poor despite modern multimodality treatment regimens, including neoadjuvant chemotherapy.

Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro.

OBJECTIVES: Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states. PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP). The source of production and its mechanism of induction are unknown. We investigated the inducibility of PCT both in vivo and in vitro and compared the behavior of PCT with those of SAA and CRP. DESIGN: A prospective descriptive patient sample study and a controlled liver tissue culture study. SETTING: A university hospital. PATIENTS: Cancer patients who were treated with human tumor necrosis factor-alpha (rhTNF-alpha; 5 patients) or interleukin-6 (rhIL-6; 7 patients). MEASUREMENTS AND MAIN RESULTS: Serial serum samples were collected for analysis of concentrations of PCT, SAA, and CRP. In the TNF-alpha group, frequent sampling was performed on the first day to allow analysis of initial responses. In a human liver slice model, the release of PCT, SAA, and CRP was measured on induction with rhTNF-alpha and rhIL-6 for 24 hrs. We found that PCT displayed acute phase reactant behavior in vivo after administration of both rhTNF-alpha and rhIL-6. After rhTNF-alpha-administration, PCT reached half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA or CRP did. PCT, SAA, and CRP were produced in detectable quantities by liver tissue in vitro. PCT production by liver slices was enhanced after stimulation with rhTNF-alpha or rhIL-6; SAA and CRP concentrations were elevated after stimulation with rhTNF-alpha. CONCLUSIONS: We found that PCT and acute phase proteins such as CRP are induced by similar pathways. The liver appears to be a major source of PCT production. Thus, PCT may be considered an acute phase protein. The different kinetics of PCT, rather than a fundamentally different afferent pathway, may explain its putative diagnostic potential to discriminate bacterial infection from other causes of inflammation.

Sentinel node biopsy for melanoma in the head and neck region.

BACKGROUND: Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region. METHODS: Thirty consecutive patients with clinically localized cutaneous melanoma in the head and neck region were included. Sentinel node biopsy was performed with blue dye and a gamma probe after preoperative lymphoscintigraphy. Average follow-up was 23 months (range, 1-48). RESULTS: In 27 of 30 patients, a sentinel node was identified (90%). Only 53% of sentinel nodes were both blue and radioactive. A sentinel node was tumor-positive in 8 patients. The sentinel node was false-negative in two cases. Sensitivity of the procedure was 80% (8 of 10). CONCLUSIONS: Sentinel node biopsy in the head and neck region is a technically demanding procedure. Although it may help determine whether a neck dissection is necessary in certain patients, further investigation is required before this technique can be recommended for the standard management of cutaneous head and neck melanoma.

Geographic clustering of testicular cancer incidence in the northern part of The Netherlands.

Geographic variations in testicular cancer incidence may be caused by differences in environmental factors, genetic factors, or both. In the present study, geographic patterns of age-adjusted testicular cancer incidence rates (IRs) in 12 provinces in The Netherlands in the period 1989-1995 were analysed. In addition, the age-adjusted IR of testicular cancer by degree of urbanization was evaluated. Cancer incidence data were obtained from the Netherlands Cancer Registry. The overall annual age-adjusted IR of testicular cancer in The Netherlands in the period 1989-1995 was 4.4 per 100000 men. The province Groningen in the north of the country showed the highest annual IR with 5.8 per 100000 men, which was higher (P < 0.05) than the overall IR in The Netherlands (incidence rate ratio (IRR) 1.3, 95% confidence interval (CI) 1.1-1.6). The highest IR in Groningen was seen for both seminomas and non-seminomas. In addition, Groningen showed the highest age-specific IRs in all relevant younger age groups (15-29, 30-44 and 45-59 years), illustrating the consistency of data. The province Friesland, also situated in the northern part of the country, showed the second highest IR of testicular cancer with 5.3 cases per 100000 men per year (IRR 1.2, 95% CI 1.0-1.5, not significant). This mainly resulted from the high IR of seminoma in Friesland. Analysis of age-adjusted IRs of testicular cancer by degree of urbanization in The Netherlands showed no urban-rural differences at analysis of all histological types combined, or at separate analyses of seminomas and non-seminomas. Geographic clustering of testicular cancer seems to be present in the rural north of The Netherlands with some stable founder populations, which are likely to share a relatively high frequency of genes from common ancestors including genes possibly related to testicular cancer. Although this finding does not exclude the involvement of shared environmental factors in the aetiology of testicular cancer, it may also lend support to a genetic susceptibility to testicular cancer development. Testicular cancer cases in stable founder populations seem particularly suitable for searching for testicular cancer susceptibility genes because such genes are likely to be more frequent among affected men in such populations.

Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.

This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) in combination with melphalan with or without interferon-gamma (IFNgamma) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIA or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFalpha and melphalan (TM-ILP) or a three-drug regimen consisting of TNFalpha, melphalan and INFgamma (TIM-ILP). Patients randomized to receive IFNgamma were pretreated for 2 days before the ILP with once daily 0.2 mg IFNgamma subcutaneously and also received the same amount of IFNgamma during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFalpha associated with melphalan may be superior to melphalan alone for ILP.

Surgery versus surveillance in stage I non-seminoma testicular cancer.

Today, the standard treatment for patients with clinical Stage I non-seminomatous testicular germ cell tumors (NSTGCT) following orchidectomy is either primary retroperitoneal lymph node dissection (RPLND) or close surveillance with cisplatin-based polychemotherapy in case of a relapse. Both treatment modalities provide excellent overall survival rates up to 100%. Consequently, selection of the most appropriate management option is not primarily guided by survival considerations. The choice between the available options, each having its merits and its drawbacks, should be made based on a number of factors including treatment-related morbidity, views and expertise of the physician, patient preferences, the expected degree of patient compliance, and prognostic factor analysis. To date, the role of adjuvant chemotherapy as an alternative management option for patients with clinical Stage I NSTGCT at high risk of occult metastases is limited. This systemic treatment modality would be a realistic alternative if the reliability of prognostic factors to identify high-risk Stage I patients could be improved. This review addresses relevant issues in the management of patients with clinical Stage I NSTGCT to provide information that will allow a rational selection of the most appropriate management option.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan in patients with locally advanced soft tissue sarcomas: treatment response and clinical outcome related to changes in proliferation and apoptosis.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan (HILP-TM) with or without IFN-gamma is a promising local treatment in patients with locally advanced extremity soft tissue sarcomas (STSs), with response rates of up to 84%. The mechanisms of the treatment response are poorly understood. Here, we determined the HILP-TM-induced changes in mitotic activity, proliferation, and apoptosis in 37 STSs; the additional effect of IFN-gamma; and the association of HILP-TM with treatment response and clinical outcome. On archival material, obtained before and 6-8 weeks after HILP-TM with (n = 15) or without (n = 22) IFN-gamma, the number of mitoses was counted, and the proliferation fraction was determined by immunohistological staining for the proliferation associated Ki-67 antigen (MIB1). Apoptosis was visualized by enzymatic detection of DNA fragmentation (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Clinical and histological response, follow-up status, and survival were recorded. The number of mitoses dropped 57% and proliferation rate decreased with 40% after HILP-TM, whereas the amount of apoptosis after HILP-TM more than doubled as before HILP-TM. The addition of IFN-gamma to HILP-TM did not influence the changes in tumor parameters and did not affect treatment response. A better clinical response to HILP-TM was correlated with high mitotic activity and low amount of apoptosis in tumor samples before HILP-TM. Patients with highly proliferative STS before and after HILP-TM had a relatively poor prognosis. Furthermore, patients who developed distant metastases after HILP-TM had a relatively high number of dividing cells in the tumor remnants after treatment.

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.

Long-term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy, followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities.

BACKGROUND AND PURPOSE: In the 1980s a combined modality therapy of intraarterial doxorubicin, neoadjuvant radiotherapy and surgery was initiated at the Groningen University Hospital as a limb-saving treatment for locally advanced, primarily irresectable high-grade soft tissue sarcomas (STS) of the extremities. This study presents the short- and long-term results. PATIENTS AND METHODS: Between 1983 and 1987, 11 patients were treated with intraarterial doxorubicin, preoperative radiotherapy (10 x 3.5 Gy) and surgical resection. Non-radical resections received additional postoperative radiotherapy of 20-30 Gy. RESULTS: The limb-salvage rate was 91%, without local recurrences during a median follow-up of 84 months. Six patients died (55%); five from metastatic disease (45%). There were five long-term survivors with a median follow-up of 10 years. Three patients (60%) suffered serious late complications, resulting in disabilitating limb function. CONCLUSION: Although this approach is feasible as a limb-saving treatment for these unfavorable STS, long-term morbidity is high.

Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNF-alpha), interferon gamma, and melphalan has proved to be useful in the treatment of recurrent malignant melanoma and of locally advanced soft tissue sarcomas of the extremities. OBJECTIVE: To determine whether this modality is also effective in the treatment of locally advanced nonmelanoma skin tumors of the extremities. PATIENTS AND METHODS: Fifteen patients with locally advanced primary, recurrent, or metastatic skin tumors of the extremities (12 with squamous cell carcinoma and 3 with Merkel cell carcinoma) underwent HILP with TNF-alpha, interferon gamma, and melphalan. Six tumors were localized in the upper extremity (40%), and 9 in the lower extremity (60%). Treatment-related complications, limb salvage rate, local recurrence, and regional and distant metastases were scored during a median follow-up of 20 months. RESULTS: After HILP, 9 patients (60%) showed a complete response (with histopathological confirmation). Four patients (27%) showed a partial response (with histopathological confirmation in 1 patient), and 2 patients (13%) showed no change (with histopathological confirmation in 1 patient and with clinical evidence in 1 patient). Two patients (13%) showed treatment-related complications. The limb salvage was achieved in 12 patients (80%), and the local recurrences developed in 4 patients (27%). During follow-up, regional lymph node metastases were observed in 2 patients (13%) and distant metastases in 2 patients (13%). CONCLUSION: Based on our results, HILP with TNF-alpha, interferon gamma, and melphalan should be considered as a limb-saving treatment modality in patients with locally advanced nonmelanoma skin tumors of the extremities who would otherwise be candidates for ablative surgery.