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Background: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history., Methods: During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed., Results: Most women (70 out of 73) accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother., Conclusion: The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services.

Hypothesis: In patients with truly unresectable melanoma of the extremities, results after isolated limb perfusion (ILP) are absent in the literature. Complete response rates are probably lower than the reported 54% for locoregional recurrent melanoma. In these patients, ILP with melphalan and tumor necrosis factor alpha (TNF-alpha) could be superior to ILP with melphalan alone., Design: Retrospective analysis with a median follow-up period of 21 months (interquartile range, 9-40 months)., Setting: Two tertiary care cancer centers in the Netherlands., Patients: We assessed all 130 consecutive patients who underwent ILP for unresectable melanoma of the extremities, performed between 1978 and 2001. Of these patients, 38% had stage IIIA melanoma and 45% had stage IIIAB melanoma according to criteria of the MD Anderson Cancer Center. Lesions were considered unresectable on the basis of their size, number, or localization., Interventions: Forty ILPs were performed with melphalan, and 90 were done with TNF-alpha and melphalan., Main Outcome Measures: Response rate, disease-free survival, limb salvage rate, and overall survival., Results: In 45% of the patients, a complete response was attained after ILP with melphalan (95% confidence interval, 29%-61%) compared with 59% after ILP with TNF-alpha and melphalan (95% confidence interval, 49%-69%; P = .14). The time to complete response was 3 months (interquartile range, 2-6 months) vs 2 months (interquartile range, 1-3 months; P = .01), respectively. The recurrence rate and median limb recurrence-free survival were not significantly different for both ILP types. The overall limb salvage rate was 96%. Overall 5-year survival was 29% (95% confidence interval, 20%-38%). The ILP type was not an independent prognostic factor for complete response, nor was limb recurrence-free survival, whereas stage IIIA was a favorable prognostic factor (P = .01 and P = .02, respectively). Favorable prognostic factors for improved survival were complete response (P<.001) and a tumor size of 3 cm or less (P = .01)., Conclusions: In more than half of the patients with truly unresectable melanoma of the extremities, a complete response was obtained after ILP with melphalan with or without TNF-alpha. The ILP type was not an independent prognostic factor for complete response, limb recurrence-free survival, or overall survival.

Background: The influence of isolated limb perfusion (ILP) on the limb recurrence-free interval (LRFI) and the number of lesions per recurrence was studied for patients with frequently recurring regional in-transit metastases previously managed by excisional surgery., Methods: All 43 patients who had their first ILP for a third or further limb recurrence were selected from our computer database of 451 patients who underwent therapeutic ILP for recurrent extremity melanoma in our centers. Eighteen patients had resectable and 25 had locally unresectable lesions at the time of ILP. The patients had a total of 269 intervals between treatment of their primary melanoma and last recurrence or last follow-up. Median follow-up was 35 months (interquartile range, 14-64 months)., Results: The median LRFI decreases over time from primary melanoma to the third or further recurrence for which ILP was performed (P < 0.001). The median LRFI is 4.7 times longer (95% confidence interval [CI], 2.8-7.9; P < 0.001) after ILP in comparison with the last interval before ILP. Patients with resectable lesions have a median LRFI that is 5.9 times longer (95% CI, 2.7-13; P < 0.001). In all patients, the number of lesions increases by 22% per recurrence number (95% CI, 10%-35%; P = 0.02). At the same recurrence number, patients before ILP have a 2.6-fold higher (95% CI, 1.6-4.5) mean number of lesions than do patients after ILP (P < 0.001)., Conclusions: ILP lengthens the LRFI and decreases the number of lesions per recurrence significantly in patients with repeatedly recurrent limb melanoma. Therefore, ILP could be a valuable adjunct to excisional surgery for in-transit metastases in these patients whose LRFIs tend to shorten over time.

Background: The present AJCC/TNM staging system is of limited value for prediction of prognosis for patients with retroperitoneal sarcoma. The objective of the present study was to develop a postsurgical classification system that would enable comparison of outcomes for patients with primary retroperitoneal soft-tissue sarcoma., Methods: Four classes were defined: I, low-grade/complete resection/no metastasis; II, high-grade/complete resection/no metastasis; III, any-grade/incomplete resection/no metastasis; and IV, any-grade/any resection/distant metastasis. The prognostic value of this classification system was analyzed in a population-based multicenter group(MCG) of patients with primary retroperitoneal soft-tissue sarcoma (n = 124) and in a cohort of patients treated in a single tertiary referral center (SCG; n = 107)., Results: Overall 5-year survival rates were 55% in the SCG and 43% in the MCG (P = 0.02). Class III (incomplete resection) was more frequent in the MCG than in the SCG (33% vs. 16%; P = 0.02). In the SCG, stage-specific 5-year survival rates were 89%, 40%, 26%, and 17% for classes I, II, III, and IV, respectively (P < 0.001), in comparison with 68%, 46%, 24%, and 0% in the MCG (P < 0.001). In a comparison of class-specific survival between the groups, only class I patients in the SCG had significantly better survival than class I patients in the MCG (P = 0.048)., Conclusions: Classification based on grade, completeness of resection, and distant metastasis offers a reproducible prognostic tool that can be used to evaluate treatment strategies for primary retroperitoneal soft-tissue sarcoma. The probability of complete resection was significantly higher in the SCG than in the MCG. In patients with low-grade, completely resected sarcoma, there is a significant survival benefit with treatment in a high-volume tertiary center of excellence.

Purpose: To explore long-term psychosocial consequences of carrying a BRCA1/2 mutation and to identify possible risk factors for long-term psychological distress., Patients and Methods: Five years after genetic test disclosure, 65 female participants (23 carriers, 42 noncarriers) of our psychological follow-up study completed a questionnaire and 51 participants were interviewed. We assessed general and hereditary cancer-related distress, risk perception, openness to discuss the test result with relatives, body image and sexual functioning., Results: Carriers did not differ from noncarriers on several distress measures and both groups showed a significant increase in anxiety and depression from 1 to 5 years follow-up. Carriers having undergone prophylactic surgery (21 of 23 carriers) had a less favorable body image than noncarriers and 70% reported changes in the sexual relationship. A major psychological benefit of prophylactic surgery was a reduction in the fear of developing cancer. Predictors of long-term distress were hereditary cancer-related distress at blood sampling, having young children, and having lost a relative to breast/ovarian cancer. Long-term distress was also associated with less open communication about the test result within the family, changes in relationships with relatives, doubting about the validity of the test result, and higher risk perception., Conclusion: Our findings support the emerging consensus that genetic predisposition testing for BRCA1/2 does not pose major mental health risks, but our findings also show that the impact of prophylactic surgery on aspects such as body image and sexuality should not be underestimated, and that some women are at risk for high distress, and as a result, need more attentive care.

Purpose: To evaluate the tolerance of a low dose chemotherapy regimen for desmoid tumours., Patients and Methods: Patients with desmoids for whom radical resection was impossible or related to extensive mutilation were treated with chemotherapy. Treatment consisted of intravenous methotrexate at a dose of 50mg and vinblastine at a dose of 10mg weekly, scheduled to be given for a total period of 1 year. Doses were reduced and/or delayed on an individual basis, depending on the observed type of toxicity., Results: Ten patients (six males; four females), median age 43 years (range17-75), median WHO performance score 1 (range 0-1), were treated. None of them was able to complete the treatment as scheduled, due to observed side effects, while in two patients treatment was also discontinued because of progressive disease. In six patients, less than 50% of the projected administrations and dose could be given. Severe organ toxicity was noted in three patients (one interstitial pneumonitis, two toxic hepatitis), which, however, was reversible in all cases., Discussion: Methotrexate and vinblastine given at this dose and schedule lead to an unacceptable level of toxicity for a long-term treatment, and cannot be recommended for standard use.

Purpose. In the clinical work-up of a retroperitoneal mass, the diagnosis of soft tissue sarcoma is often not considered. Incidence rates of various malignant and benign retroperitoneal tumours were studied to determine the incidence of soft tissue sarcoma in comparison with other neoplasms in the retroperitoneal space.Method. Nation-wide data on retroperitoneal tumours, collected prospectively over a 5-year period (1 January 1989- 1 January 1994), were supplied by the Netherlands Cancer Registry and The Dutch Network and National Database for Pathology.Results. Seven hundred and six patients with a primary retroperitoneal neoplasm were identified; 566 patients had a malignant tumour (80%). A soft tissue sarcoma (STS) was the most frequently diagnosed malignant tumour (n = 192), The agestandardised incidence of retroperitoneal STS was 2.5 per million person-years. The male/female ratio for STS was 0.73. In females, STS comprised 41%of all malignant retroperitoneal tumours, carcinoma of unknown primary tumour site (CUP) comprised 31%, and malignant lymphomas (ML) comprised 22%, whereas in males these values were 28% (STS), 30% (CUP), and 32% (ML), respectively.Discussion. Soft tissue sarcomas, albeit rare, are relatively common primary tumours in the retroperitoneum, especially in women.

Background: The optimal toxic reaction of the normal tissues in perfused limbs after isolated limb perfusion (ILP) is unknown. Theoretically, more severe limb toxicity could reflect a concomitant increased toxic effect to the tumor and improved outcomes. We determined whether there is a relation between limb toxicity and treatment outcomes after ILP for recurrent limb melanoma., Study Design: Among 252 patients with recurrent melanoma of the limbs, treatment outcomes in 192 patients (76%) with no or mild acute limb toxicity were compared with those in 60 (24%) with more severe reactions. Multivariate analysis was used to identify prognostic factors for complete response, limb recurrence-free interval, and survival., Results: Among 112 patients with measurable disease, 65 patients (58%) had a complete response and 27 (42%) experienced a relapse in the perfused limb. For complete response, uninvolved regional lymph nodes (p = 0.0025) and ILP using tumor necrosis factor-alpha (p = 0.0076) appeared to be favorable prognostic factors in multivariate analysis. There was no evidence of a relation between limb toxicity and complete response either in univariate (p = 0.16) or multivariate analysis (p = 0.46). For limb recurrent-free interval, only the number of lesions was a significant prognostic factor (p = 0.047); limb toxicity was not (p = 0.095). In 140 patients with recurrent melanoma excised before or at the moment of ILP, independent prognostic factors for survival were gender, the number of positive nodes, and stage of disease. There was no relation between limb toxicity and survival in either univariate (p = 0.53) or multivariate analysis (p = 0.94). Forty-eight (34%) of the 140 patients had a relapse in the perfused limb. No prognostic factors for limb recurrent-free interval could be identified; limb toxicity was not related to relapse time in univariate or multivariate analyses (p = 0.16 and p = 0.14, respectively)., Conclusions: More severe acute limb toxicity is not associated with improved outcomes. One should aim at grade II toxicity (slight erythema or edema, compatible with complete recovery) at the most to increase the therapeutic ratio of ILP.

The impact of a family history of breast cancer on the local recurrence (LR) risk after breast-conserving therapy (BCT) was performed within the framework of a large, multicentre matched case-control study of risk factors for LR after BCT (BORST study). Family history was assessed for 218 breast cancer patients with LR (cases) and 480 patients without LR (controls). Detailed histological tumour features were determined by review of the primary tumour. The risk of LR for patients with a positive family history was similar to or less than that of non-familial patients (unadjusted odds ratio (ORunadj) 0.66 (95% confidence interval (CI) 0.40-1.08)). Familial patients were older than non-familial patients (P = 0.07) and their tumours had a lower histological grade (P = 0.07). A second primary tumour occurred significantly more often in familial patients (P = 0.02). Adjustment for these factors did not essentially alter the results (ORadj 0.71 (0.38-1.32)). Separate analyses according to age at onset (younger and older than 50 years) and time to LR/site of LR produced similar results. The sole presence of a positive family history of breast cancer does not appear to be a risk factor for local recurrence after BCT. Whilst this might be different for genetically predisposed patients, a positive family history does not appear to be a contra-indication for BCT.

Background: Controversy exists concerning the roles of mammography and physical examination in the detection of local recurrence after conservation therapy for breast carcinoma. In addition, the prognostic factors for and optimal treatment of patients with local recurrence are uncertain., Methods: At eight radiotherapy institutes, two cancer institutes, and one surgical clinic in the Netherlands, regular follow-up of patients who underwent breast conservation therapy between 1980 and 1992 identified 266 patients with local recurrence in the breast. These patients exhibited no clinical signs of distant metastases at the time of diagnosis of the local recurrence. Data on the method of detection were available for 189 patients (72%). Local recurrence was diagnosed by mammography alone in 47 cases (25%). Of all patients, 85% underwent salvage mastectomy, 8% underwent local excision, 4% received systemic treatment only, and 3% remained untreated. Specimens of the primary tumor were available for review from 238 of the 266 patients (89%)., Results: Local recurrences detected by mammography alone were smaller than those detected by physical examination (P = 0.04). At 5 years from the date of salvage treatment, the overall survival rate for all 266 patients was 61% (95% confidence interval [CI], 55-67%), and the distant recurrence free survival rate was 47% (95% CI, 40-53%). For the 25 patients with noninvasive recurrence, these figures were 95% and 94%, respectively. Skin involvement, the extent of recurrence (< or = 10 mm vs. >10 mm), and both lymph node status and histologic grade of the primary disease were strong predictors for distant metastases in patients with invasive recurrence., Conclusions: Patients with invasive local recurrence more than 1 cm in size are at a substantial risk for distant disease. The better distant disease free survival for patients with recurrence measuring 1 cm or less may indicate that early detection can improve the treatment outcome. Recurrence with skin involvement should be considered generalized disease.

Systemic exposure to melphalan is minimized during isolated limb perfusion (ILP) by isolating a limb from the rest of the body. Consequently, there should be no toxicity to vital organs. At present systemic toxicity after ILP has not been studied in detail. Therefore, the incidence, nature and risk factors of systemic toxicity was retrospectively studied in 368 patients who underwent a single ILP with melphalan between 1978-1990. Some form of systemic toxicity occurred in 98 patients (27%). Nausea and vomiting after the 1st post-ILP day was seen in 73 patients (20%), and in seven (2%) treatment was required. Bone marrow depression was encountered in seven patients (2%): WHO grade II in five, and grade III in two. Miscellaneous systemic side-effects, including fever and minimal scalp hair loss, occurred in 19 patients (5%). Leakage from the isolated circuit to the systemic circulation was measured with radioactive tracers. Mean cumulative leakage during ILP was 0.9%. Systemic toxicity was not increased in patients with leakage greater than 1% or 5%. Female sex was associated with an increased incidence of systemic toxicity (P<0.05). Age over 60 years (P<0.05) and more severe acute regional toxicity (P<0.05) were correlated with nausea and vomiting. The miscellaneous systemic side-effects were more frequently encountered in women than in men (P<0.05). In conclusion, systemic toxicity was rarely severe, with nausea and vomiting being the most frequently encountered side-effects. Age over 60 years, female sex and more severe acute regional toxic reactions were correlated with an increased incidence of systemic side-effects. Systemic leakage during ILP was not associated with toxicity, probably due to the low incidence of significant leakage.

Background: Melanoma recurring locoregionally after isolated limb perfusion (ILP) constitutes a therapeutic dilemma. Major amputation is a deterrent option for local control and palliation in these patients who have a rather poor prognosis. Little is known about the feasibility and efficacy of repeat ILP in these situations., Study Design: From 1978 to 1993, 28 patients with recurrent melanoma after ILP were retreated with various ILP procedures using melphalan. Eighteen patients underwent reperfusion by a single and four by a multiple normothermic schedule. Hyperthermia was applied in six repeat ILP procedures., Results: A complete remission was achieved in 14 (74 percent) of 19 patients with measurable disease, with a median limb recurrence-free interval of 11 months. A partial remission was obtained in one patient (5 percent). Two patients had no change of disease and two patients had progressive disease. In the remaining nine patients, all macroscopic tumor tissue was excised before or during the repeat ILP procedure. The median limb recurrence-free interval of these nine patients was 15 months. After a median follow-up period of 30 months after repeat ILP, seven (25 percent) of the 28 total patients were alive without disease. Acute regional tissue toxicity was more severe after repeat ILP than after the first procedure (p < 0.05). Long-term regional morbidity occurred in 11 percent of the patients., Conclusions: A high complete remission rate can be obtained with repeat ILP using melphalan. However, the high limb recurrence rate and relatively short limb recurrence-free interval need improvement. Increased acute regional toxicity after repeat ILP can be explained by the use of more intensive schedules.

Objective: To determine the influence of acute regional toxic reactions on the incidence and characteristics of long-term morbidity after regional isolated perfusion with melphalan., Design: Retrospective study., Setting: The Amsterdam and Rotterdam perfusion centers, the Netherlands., Patients: All patients with melanoma who were treated between 1978 and 1990 and had a minimum follow-up of 1 year after perfusion (n = 367)., Intervention: Fifty-four patients (15%) had perfusion of the upper limb, 313 (85%) had perfusion of the lower limb, and 164 patients (45%) underwent regional lymph node dissection at the time of perfusion., Main Outcome Measure: Incidence and characteristics of morbidity 1 year after perfusion and the influence of acute regional toxic reactions on long-term morbidity., Results: One hundred sixty patients (44%) showed some degree of objective or subjective morbidity; most (104 [28%]) had lymphedema. Other long-term morbidity consisted of muscle atrophy or fibrosis (42 [11%]), limb malfunction (55 [15%]), neuropathy (13 [4%]), pain (28 [8%]), and recurrent infection (11 [3%]). Miscellaneous complications were seen in 14 patients (4%). Seventy-one patients (19%) had more than one complication. Acute regional toxic reactions had a statistically significant effect on the incidence of long-term morbidity (P < .01). Moderate to severe acute regional toxic reactions were strongly linked to the occurrence of muscle atrophy or fibrosis (P < .001) and limb malfunction (P < .001). Regional lymph node dissection was statistically significantly related to lymphedema (P = .05)., Conclusion: Improvement of the perfusion technique should be pursued in an effort to reduce acute regional toxic reactions, and thereby long-term morbidity, without compromising the therapeutic effect.

The incidence of long-term (> or = 3 months) neuropathy in 350 melanoma patients treated with single normothermic or 'mild' hyperthermic perfusion with melphalan in the period 1978 to 1990 was studied. Long-term neuropathy was encountered in 14 patients; in 10/51 patients (20%) after perfusion at the axillary level and in 4/247 patients (2%) after perfusion at the iliac level. After brachial and femoro-popliteal perfusions no long-term neuropathy was observed. Neuropathy, mainly consisting of paresis/paralysis of the hand and/or fingers, anaesthesia, and/or paraesthesiae, improved over a mean period of 16 (3-43) months in eight patients, but three patients still had serious neuropathy one year after perfusion. In another six patients little improvement was seen and four died with permanent neuropathy. Acute regional toxicity after perfusion and the application of 'mild' hyperthermia did not seem to influence the incidence of long-term neuropathy. This complication is probably a result of the isolating Esmarch rubber bandage being applied too tightly during perfusion at a proximal level. At the axillary level, where the brachial plexus lacks the protection from enveloping tissues, nerve damage is especially prone to occur. We recommend applying this bandage no tighter than is necessary to maintain the isolation of the circuit. This implies meticulous surgical isolation of the vascular system and accurate monitoring of leakage.

Objective: Analysis of short-term and long-term complications after cemented osteosynthesis for pathological fractures., Design: Retrospective study., Setting: South Municipal Hospital and the Daniël den Hoed Cancer Centre, Rotterdam, The Netherlands., Subjects: 199 patients consecutive surgically treated between 1978 to 1990 for 233 fractures (161 actual and 72 impending) caused by metastatic lesions of the femur, humerus and tibia., Interventions: Local resection of the tumour was followed by endoprostheses (n = 52) and by internal plate osteosynthesis (n = 167); 14 fractures were treated with intramedullary nails. Bone cement was added in 211 cases (91%)., Main Outcome Measures: Pain relief, mobilisation, complications., Results: Pain relief was achieved in about 90%. 145 (76%) who were treated for fractures of the lower extremity were able to walk again. There were 13 local complications: 26 (11%) implanted devices failed (cumulative probability 40%, after 60 months). In 11 cases the fixation failed after 7 weeks. The failure rate was 16% in the subtrochanteric region treated with an angled blade (probability 70% after four years). The patients' survival rate was 55% after six months and 20% at two years., Conclusion: Despite the poor life expectancy, our results indicate that hemiarthroplasty or osteosynthesis with bone cement for treatment of pathological (impending) fractures is a safe way to restore limb function and to improve quality of life.

In order to gain some insight into the cause of acute regional toxicity after isolated perfusion using melphalan, 15 patient-related and perfusion-technique-related factors were tested in a logistic regression model. Acute toxicity was graded according to Wieberdink's grading system. In a group of 425 patients, 362 (85%) encountered no or slight toxicity with a grade I or II reaction, and 63 (15%) patients encountered more severe toxicity with a grade III, IV, or V reaction. Most patients were treated with a standard dose of 10 or 13 mg melphalan per liter of perfused tissue for leg and arm perfusions, respectively. Factors associated with a more severe toxicity reaction proved to be tissue temperatures of 40 degrees C or higher, female gender, a deterioration of the gas values of the venous perfusate during perfusion, and perfusion at a proximal level of isolation. Consideration of these prognostic factors may lead to a further decrease of acute regional toxicity in perfusion.

Introduction: One of the risks of therapeutic irradiation is the development of secondary malignant tumors. In this paper three cases are reported of angiosarcoma of the breast following breast-conserving surgery and irradiation for primary breast cancer, and the literature is reviewed., Methods and Materials: Until now, 13 other cases of postirradiation angiosarcoma of the breast have been reported. The mean interval between treatment of primary breast cancer and the development of angiosarcoma in these 16 patients is 76 months. The clinical aspect is typical with multiple bluish or purple nodules of the skin, purple discolorations, erythematous maculas or areas, sometimes combined with ulceration, edema, or a palpable mass. Mammography does not necessarily raise suspicion and the interpretation of fine-needle aspiration or biopsy may be difficult., Results: In all patients mastectomy was performed, Follow-up data are available for 12 cases. Two patients died of extensive local recurrences and one of distant metastases., Conclusion: Angiosarcoma of the previously irradiated breast is an extremely rare tumor and diagnosis may be difficult. The number of patients with long-term follow-up after breast-conserving therapy is growing fast. Therefore, the authors advise to pay special attention to uncommon skin changes of the treated breast, since clinical suspicion is the main clue to the diagnosis of postirradiation angiosarcoma. The primary therapy is (simple) mastectomy if wide tumor-free margins can be achieved. There is no indication for standard adjuvant chemotherapy or irradiation.

From 1978 to 1990, 32 patients with Clark V melanoma were treated by wide excision of the primary and adjuvant regional isolated perfusion with melphalan. M.D. Anderson stage of disease was stage I in 22 and stage IIIb in 10 patients. Five-year survival rates were 58% and 27%, respectively. Seven patients developed a recurrence in the perfused limb [stage I, 2, stage IIIb, 5 patients (P = 0.03)], and 4 of 17 patients developed regional lymph node metastases. Of the well-known prognostic variables, only ulceration of the primary tumor significantly influenced survival (P = 0.03). We did not see any improvement in survival rates compared with literature data on nonperfused patients. In the absence of data on locoregional recurrence rates in nonperfused Clark V melanoma patients, we cannot say whether adjuvant perfusion diminished this risk. Therefore, the results of the prospective randomized EORTC/WHO trial in primary high-risk extremity melanoma have to be awaited.

From 1978 to 1990, 24 patients with subungual melanoma (MD Anderson Stage I, 17, Stage III, 7 patients) were treated with amputation of a digit and regional isolated perfusion with melphalan. The lesions were located on the big toe in 14 (58%) patients. Median delay in definitive treatment was 21 months, while 14 patients (58%) had been subjected to some form of inadequate treatment before correct diagnosis was made. Median follow-up for the living patients was 48 months. Overall 5-year survival was 54% (Stage I, 68%, Stage III, 19% (log-rank P = 0.003)). Sex and site of the lesion did not influence survival. Compared to literature data of patients treated by amputation alone, no improvement in survival could be demonstrated despite perfusion treatment. Moreover, two limb and 7 regional node recurrences were seen. The benefit of adjuvant perfusion in the treatment of Stage I subungual melanoma has not been demonstrated in this study. The results of prospective randomized trials in primary high-risk extremity melanoma have to be awaited.

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.

One hundred and twenty-three dual lumen silicone rubber central venous catheters were inserted into 101 patients with hematological malignancies undergoing intensive treatment. There was a perioperative complication rate of 13%. Open and closed techniques for inserting the catheter were compared. The operating time needed for introducing the catheter by the closed technique (average, 51 minutes) was significantly shorter (p less than 0.001) than the time needed for the open technique (70 minutes), whereas complication rates were equal in both techniques. On average, the catheters functioned for 149 days. Complications leading to removal were observed in 29.3% of patients, most of which were catheter-related infections (20.4%). Thromboembolic complications leading to removal were less frequent (4.1%) and appeared significantly earlier (p less than 0.001). These data indicate that introduction of the catheter by direct puncture of the subclavian vein is a quick and safe technique, and that this type of catheter is suitable for long-term use, both for infusion and for blood sampling.

A 61-year-old man with an intractible and progressively disabling cutaneous non-Hodgkin's lymphoma (NHL) in the lower limb was treated with sequential regional isolated perfusion at 10-day intervals. The first perfusion was hyperthermic (40.2-43.1 degrees C tumor-temperature); the second was at controlled normothermia with high-dose 1-phenylalanine mustard (melphalan, L-Pam; 11 mg/l perfused tissue). This treatment resulted in a complete remission in the perfused area of significant duration and has prevented amputation.

Hyperthermic perfusion was given as a palliative treatment in three patients with a bulky tumour in the leg. During the treatment, temperature and pH data were collected in both tumour and normal tissues. The hyperthermia dose administered was 2 h at 41.9-42.7 degrees C. It was found that the temperature distribution was far from homogeneous. In one case tumour pH could be monitored throughout the whole treatment procedure. The tumour pH showed a steep decrease during the initial phase of the perfusion, from a mean value of 7.11 to 5.94 at the start of the hyperthermic phase. Subcutis pH decreased only 0.29 units during the whole procedure. In all three patients considerable tumour regression was observed, without severe toxicity. Hyperthermic perfusion appeared to be an effective debulking treatment. The pH decrease in tumour tissue, immediately before hyperthermia, may be responsible for the remarkable effectiveness of the hyperthermic treatment.