Biomedical subjects

B B Kroon

Publications and source records attributed to B B Kroon.

At least 91 records · Page 5Linked to original sources

PubMed1994

Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb.

In 14 consecutive patients with recurrent melanoma of the lower limb a total of 35 biopsies were taken at the end of perfusion treatment to assess melphalan tissue concentrations in tumour, skin/subcutis and muscle tissue. In tumour tissue (n = 12) the mean melphalan concentration was 6.8 micrograms g-1, which was significantly higher than that of healthy skin/subcutis (3.2 micrograms g-1; n = 10), but equal to that of muscle tissue (6.5 micrograms g-1; n = 13). The correlation between melphalan concentration in the tissues and the concentration in the perfusate was studied. The latter was assessed in the form of melphalan peak concentration and the area under the curve (AUC0-->60) of the melphalan concentration-time curve. Tumour concentration proved to be correlated linearly with AUC0-->60 (R = 0.6, P = 0.002) and muscle concentration with melphalan peak concentration (R = 0.8, P = 0.04). There was no relation between skin/subcutis concentrations and the perfusate parameters. Further research is warranted to study the relationship between melphalan tissue concentration, tumour response and regional toxicity.

Chemotherapy, Cancer, Regional Perfusion↗

PubMed1994

Results of regional isolated perfusion for locally inoperable melanoma of the limbs.

In the period 1978-1990, 49 patients with locally inoperable melanoma of the limbs were treated with regional isolated perfusion according to four different perfusion schedules. Perfusion resulted in a complete remission in 28 patients (57%), with a median duration of 10 (1-55+) months, and a partial remission in 10 (21%), with a median duration of 3 (1-9) months. In patients treated with a double (normothermic or sequential hyperthermic) perfusion schedule the complete remission rate was higher. Regional lymph node involvement reduced the chance of achieving complete remission. Twelve patients with complete remission (43%) showed a relapse in the perfused area. The corresponding 3-year limb recurrence-free interval was 46%. This interval was mainly influenced by the number of lesions at the moment of perfusion. Three of the patients who failed to respond eventually required amputation of the affected limb. The median follow-up of the surviving patients was 23 (5-142) months. At the time of analysis 23 patients were still alive, 12 of whom had no evidence of disease. Patients with complete remission had a slightly, though statistically not significant better 3-year survival rate than patients without complete remission (49% vs 33%). Regional isolated perfusion halted progression in all of these 49 patients and resulted in a complete remission for 57%. It is, therefore, an important modality in the management of patients with locally inoperable melanoma and provides a valuable alternative to amputation.

Adult↗

PubMed1994

Lymph node metastases in the neck and parotid gland from an unknown primary melanoma.

A lymph node metastasis in the neck or parotid region from an unknown primary melanoma is an uncommon occurrence. Out of a total of 300 patients with head and neck melanoma treated at the Netherlands Cancer Institute between 1976 and 1992, 17 (5.7%) presented in this way. The most common site for metastatic lymph nodes (18 nodes in 17 patients) was level V (n = 7), followed by the parotid region (n = 4), level II (n = 4), level III (n = 2), and level IV (n = 7). Two patients had local excision of the neck node metastasis only, while the remaining 15 patients underwent more extensive surgical treatment. The 5-year disease-specific survival rate in this group was 48%, with a median survival of 36 months, which is more or less similar to the prognosis of stage II melanoma of the head and neck with a known, surgically treated primary tumour. No relation was found between disease-free interval and sex, the number of positive lymph nodes or the duration of symptoms.

Adult↗

PubMed1994

Report of a symposium on: diagnosis and treatment of cutaneous head and neck melanoma.

A series of presentations and discussions was held during a symposium on the diagnosis and treatment of cutaneous head and neck melanoma. The purpose of this meeting was to define certain guidelines on diagnosis and treatment of head and neck melanoma. The results of this symposium are summarized and condensed in this report. Recommendations are made for diagnostic strategies and for treatment. It is indicated that research efforts in immunology need to be expanded to develop rational immunotherapy.

Head and Neck Neoplasms↗

PubMed1994

Long-term neuropathy after regional isolated perfusion with melphalan for melanoma of the limbs.

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.

Adolescent↗

PubMed1994

Is there an indication for a double perfusion schedule with melphalan for patients with recurrent melanoma of the limbs?

It has been reported that a double perfusion schedule shows a better complete remission rate than does the single procedure for recurrent melanoma of the limb. As more perfusion strategies approach the ideal of a 100% complete remission rate, the main issue now is to prolong the period of disease control in the limb, ie to reduce the limb recurrence rate. The follow up of 42 patients treated with a double perfusion schedule and of 45 patients treated with a single perfusion procedure was updated to compare the duration of limb disease control. Both treatment groups were well balanced with respect to patient and tumour characteristics. For patients treated with a double schedule, the dose of melphalan given in the first perfusion was low (6 mg/l limb volume; 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. In the single perfusion group a normothermic perfusion with 10 mg melphalan/l was carried out. The acute tissue reactions and long-term side effects did not differ between the two treatment modalities. The response rate was significantly higher in the double perfusion group owing to a higher complete remission rate (76% vs 48%; P = 0.006). However, no significant difference was seen in limb disease control rates 3 years after perfusion (double schedule, 36%; single schedule, 30%), nor in overall 3-year survival (double schedule, 52%; single schedule, 45%). When evaluating perfusion regimens with equally high complete remission rates, attention should be focused on the duration of limb disease control.

Adult↗

PubMed1994

Isolated perfusion of the limb with high-dose tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and melphalan for melanoma stage III. Results of a multi-centre pilot study.

We report an update of a multi-centre pilot study previously published. Fifty-three patients (42 women, 11 men) were accrued between October 1988 and May 1992: 34 had stage IIIA, 15 had stage IIIAB, and four had stage IV melanoma. Most of them had more than five in-transit metastases; 50% had been previously treated by regional chemotherapy. Protocol included 90-min isolation perfusion at 40 degrees C with 2-4 mg rTNF-alpha, 0.2 mg rIFN-gamma and 10/13 mg/l melphalan. We prevented severe TNF systemic side effects by administration of dopamine and fluid loading. There has been no toxic death and the toxicity remained acceptable, with only one multi-organ failure (MOF) and no prolonged shock. Response rates remained very high, with 90% complete remission, 10% partial response and no failure. With a median follow-up time of 26 months, there were 12 regional recurrences, 15 distant metastases and nine local and distant recurrences. The median overall survival has been 28 months. We conclude that high-dose rTNF-alpha associated with melphalan in isolation perfusion is the therapy of choice for in-transit melanoma metastases.

Adult↗

PubMed1994

Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion.

To date, little is known about prognostic factors for limb recurrence-free interval and survival in patients with recurrent melanoma of the limbs treated with regional isolated perfusion. Therefore, 216 such patients treated with normothermic perfusion using melphalan during the period 1978 to 1990 were analyzed for patient and tumor related variables using a Cox proportional hazard model. The five year limb recurrence-free interval was 52 percent. For stage II (n = 67), IIIA (n = 71) and IIIAB and IIIB (n = 78) disease separately, these percentages were 53, 56 and 47 percent. In stage II disease, patients with a local recurrence adjacent to scar or skin graft had a significantly better five year limb recurrence-free interval than patients with satellites (75 versus 33 percent; p = 0.0009). Prognostic factors for limb recurrence-free interval were--in order of importance--tumor tissue left in situ, number of previous limb recurrences and total tumor surface area. The overall five year survival rate was 42 percent. For stages II, IIIA and IIIAB and IIIB disease, these percentages were 57, 45 and 25 percent, respectively. There was no survival benefit for patients with a local recurrence. Prognostic factors for survival were, in order of importance, stage of disease, gender, age, Breslow thickness, Clark level of infiltration of the primary melanoma and the number of lesions forming the indication for perfusion. The results of this study will eventually further delineate indications for perfusion.

Adult↗

PubMed1994

Prognostic factors for tumor response and limb recurrence-free interval in patients with advanced melanoma of the limbs treated with regional isolated perfusion with melphalan.

BACKGROUND: At this time little is known about prognostic factors for tumor response and subsequent limb recurrence-free interval in patients suffering from advanced melanoma of the limbs who were treated with regional isolated perfusion. METHODS: A retrospective analysis was done, with a logistic regression model and a Cox proportional hazard analysis, looking at possible patient-, tumor-, and treatment-related prognostic factors in all 120 patients with advanced melanoma of the limbs who were treated with regional isolated perfusion with melphalan in the period 1978 to 1990 at our institutions. RESULTS: Complete remission was achieved in 65 patients (54%) with a median duration of 9+ months (range, 1 to 97+ months), and partial remission was seen in 30 patients (25%). Prognostic factors for complete remission were multiple versus single perfusion schedule, the absence of regional node involvement, and leg versus other tumor sites. The 3-year limb recurrence-free interval was 38%. Factors associated with this interval were one as opposed to more than one lesion, complete remission after perfusion, and female sex. Patients exhibiting complete remission after perfusion had a better overall 3-year survival rate than had patients without complete remission (60% vs 35%; p = 0.0012). CONCLUSIONS: In the present study prognostic factors for tumor response and limb recurrence-free interval could be determined. A multiple perfusion schedule may be more effective in providing complete remission in patients undergoing regional isolated perfusion than single perfusions are.

Adult↗

PubMed1993

Malignant cutaneous melanoma associated with neurofibromatosis in two sisters from a family with familial atypical multiple mole melanoma syndrome. Case reports and review of the literature.

Two cases of malignant melanoma associated with neurofibromatosis in two first-degree female relatives from a family with familial atypical multiple mole melanoma (FAMMM) syndrome are presented. The types of neurofibromatosis and the FAMMM syndrome are discussed in relation to these cases and the family genealogic tree. Although the FAMMM syndrome could probably be seen as the underlying disease in the current cases, review of literature has failed to establish a clear relation. Research into pigmentary disturbance in neurofibromatosis is necessary to give a final explanation. To our knowledge, this is the first report in literature describing the familial occurrence of both diseases and it might present an addition to the tumor spectrum in the FAMMM syndrome.

Adult↗

PubMed1993

A retrospective comparative study evaluating the results of a single-perfusion versus double-perfusion schedule with melphalan in patients with recurrent melanoma of the lower limb.

BACKGROUND: Forty-two patients with measurable recurrent melanoma of the lower limb were treated according to a double-perfusion schedule. METHODS: To assess the advantage of this schedule compared with that of a single-perfusion treatment, a retrospective study was done comparing the 42 patients with 45 patients who had undergone a single-perfusion procedure. Both groups were well balanced with respect to patient and tumor characteristics. For patients treated with a double schedule, the dose of melphalan given in the first perfusion was low (6 mg/l; 1 hour; normothermic conditions) to make it possible to perform a second perfusion (9 mg/l; 1 hour; normothermic conditions) with a planned short interval of 3-4 weeks. In the single-perfusion group, a normothermic perfusion with 10 mg melphalan/l was performed. RESULTS: The toxicity did not differ between the two treatment modalities. The response rate was significantly higher in the double-perfusion group (90% versus 68%; P = 0.007) because of a higher complete remission rate (76% versus 48%; P = 0.006). In both groups, approximately half of the patients with complete remission experienced disease recurrence in the perfused area (50% versus 52%). No significant differences were seen in the two groups in the regional node recurrence rate (33% in the double-perfusion group versus 20% in the single-perfusion group), distant recurrence rate (50% in the double-perfusion group versus 58% in the single-perfusion group), and their corresponding recurrence-free intervals. The overall 3-year survival rate was 46% in both groups. CONCLUSION: In the patient groups studied, the double-perfusion schedule shows a better complete remission benefit than does the single-perfusion procedure. No differences are seen in limb, regional node, and distant recurrence rates in the two groups. Thus, additional improvement of the perfusion methodology is warranted.

Adult↗

PubMed1993

Systemic leakage during isolated limb perfusion for melanoma.

A hazard of regional perfusion for melanoma is incomplete isolation, resulting in leakage of the cytostatic drug into the systemic circulation. Data were analysed retrospectively on 438 melphalan perfusions performed for melanoma of the extremities during the period 1978-1990; continuous isotopic measurement of systemic leakage was carried out. The cumulative systemic leakage after 60 min perfusion was 0.9 per cent (95 per cent confidence interval 0.7-1.1 per cent). Systemic leakage of > or = 1 per cent was detected in 12.6 per cent of perfusions, > or = 5 per cent in 6.2 per cent and > or = 10 per cent in 1.4 per cent. In 2.3 per cent of patients, systemic side-effects in the form of mild transient bone marrow depression occurred. Six variables related to the perfusion technique were assessed by multivariate analysis for their influence on systemic leakage. The level of isolation and diameter of the venous cannula emerged as significant factors. In addition, ligation of the internal iliac vein provided optimal isolation during iliac perfusion.

Adolescent↗

PubMed1993

Adjuvant regional isolated perfusion with melphalan for patients with Clark V melanoma of the extremities.

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.

Adult↗

PubMed1993

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

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

Adult↗

PubMed1993

Regional isolated perfusion with melphalan for patients with subungual melanoma.

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.

Aged↗

PubMed1992

Intestinal obstruction due to diffuse peritoneal fibrosis at 2 years after the successful treatment of malignant peritoneal mesothelioma with intraperitoneal mitoxantrone.

A 44-year-old man who had achieved a complete remission of malignant peritoneal mesothelioma after the intraperitoneal administration of 25 mg/m2 mitoxantrone presented with clinical and radiological signs of intestinal obstruction suggestive of recurrent disease at about 2 years following the initial treatment. However, laparotomy revealed extensive adhesive fibrosis but no sign of malignant mesothelioma. The peritoneal complications of intraperitoneal cytostatic treatment are discussed.

Adult↗

PubMed1992

The role of regional isolated perfusion in the eradication of melanoma micrometastases in the inguinal nodes: a comparison between an iliac and femoral perfusion procedure.

Regional perfusion therapy of melanoma is followed by an apparent decrease in lymph node metastases. When regional isolated perfusion is performed by cannulating the blood vessels at the iliac level, at least the middle and distal parts of the inguinal nodal zone are included. This is not the case with femoral perfusion. These two types of perfusion were therefore compared to determine whether iliac perfusion eradicates micrometastases present in the inguinal nodes. The regional node recurrence rate and time to regional node relapse of 97 patients treated with iliac perfusion were compared with those of 20 patients who received femoral perfusion. Prognostic factors such as sex, MD Anderson stage of disease, Breslow thickness and Clark level of the primary melanoma, and number of nodules of those with recurrent melanoma were equivalent in both groups. All patients were perfused with melphalan under normothermic conditions during the period 1978-1990. Five of 20 patients (25%) receiving femoral perfusion and 31 of 97 patients (32%) receiving iliac perfusion (P = 0.7, chi 2 test) developed inguinal node metastases after a median period of 25 (8-40) and 19 (2-71) months, respectively (Mann-Whitney U test, P = 0.9). There was no statistically significant difference in the 5-year survival rate (55% versus 62%, respectively; log rank test P = 0.5). Since no advantage could be seen in terms of reduction of inguinal node relapse for iliac perfusion, it is concluded that perfusion of the distal nodes is not the major cause of reduction of regional node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Dermatofibrosarcoma protuberans: treatment and prognosis.

Dermatofibrosarcoma protuberans (DFSP) is a rare tumor of the skin with a strong tendency to recur locally. Nineteen cases of DFSP are presented. In eight of them a total of 20 local recurrences occurred, in five after irradical and in three after 'narrow' excisions. After wide excision (greater than 2 cm) for primary or wide re-excision for recurrent tumor, all patients remained free of tumor with a mean follow-up of 13.2 years (range 2-28 years). An extensive literature review revealed 913 cases of DFSP. The overall recurrence rate is about 50%; after adequate wide excision, 13%. Recurrent tumor is safely treated by wide re-excision and the recurrence rate is then 12%. Regional and distant recurrences are infrequent. Eleven cases (1%) were reported to have regional lymph node metastases and 37 (4%, 17 of whom were histologically confirmed) distant metastases, principally in the lung. The prognosis after appearance of regional or distant recurrence is bad. The role of radiotherapy in the management of this tumor is unclear. Primary or recurrent DFSP is best treated by surgical excision with a minimal margin of 2- preferably 3-cm of surrounding skin including the underlying fascia. Elective lymph node dissection is not advised.

Adult↗