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Biomedical subjects

B B Kroon

Publications and source records attributed to B B Kroon.

At least 19 recordsLinked to original sources

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

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

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

Elective lymph node dissection in melanoma: still a controversial issue.

Clinically not suspected regional lymph node areas are usually left in situ in patients with a primary melanoma with a Breslow thickness of 1.5 mm or less. In patients with melanomas more than 4 mm thick, elective dissection has also little or no effect on survival, because the frequent haematogenous micrometastases determine the prognosis. There is no agreement on the policy concerning elective lymph node dissection in patients with melanoma thicknesses between 1.5 and 4 mm. Some favour a wait-and-see policy, basing their arguments on the results of a WHO prospective trial. Others recommend elective node dissections in these patients, based on the results from a number of large, well-analysed retrospective studies and because of objections against the WHO trial. More prospective comparative studies and research aiming at direct clinical detection of microscopical (occult) lymph node metastases will have to be carried out before a consensus may be reached on the benefit of intervention in this category of patients.

Humans

[Revised consensus melanoma of the skin].

A second consensus meeting on cutaneous melanoma was held on June 15, 1990. The present report concisely discusses the recommended policy concerning the diagnosis and treatment of melanoma. The changes in melanoma management in comparison with the first consensus meeting in 1984 are emphasized.

Combined Modality Therapy

[Adjuvant regional isolation perfusion of the extremities of patients with stage I melanoma thicker than 1.5 mm].

The use of isolated regional perfusion with melphalan as an adjuvant treatment for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 25 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (West Germany). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which, besides level of infiltration, ulceration, age and sex, tumour thickness was found to be the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (p = 0.61), time to regional lymph node metastasis (p = 0.11), time to distant metastasis (p = 0.73), disease-free interval (p = 0.42), and survival (p = 0.90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.

Adult

Surgery for melanoma metastatic to the gastrointestinal tract.

Melanoma frequently disseminates to the gastrointestinal tract, being found post-mortem in 60 per cent of patients with disseminated disease, while during life it is diagnosed in only 4 per cent. During the period 1981-87, 835 melanoma patients were referred and 30 developed complaints caused by gastrointestinal metastatic melanoma. Twenty-three patients were treated surgically. The interval between treatment of the primary melanoma and detection of intestinal involvement was a median of 34 months (range 2-87 months). In four patients recurrence in the gut was the first evidence of dissemination. Major complaints were nausea and vomiting, abdominal pain, signs of anaemia, and blood in the stools. Complications were bleeding (ten cases), ileus due to intussusception (five cases), bowel perforation (four cases) and cholecystitis (one case). The metastases, mainly localized in the small bowel, were removed by relatively simple procedures. Symptoms were reduced in 19 patients. Two patients died after operation: one from sepsis due to suture leakage, the other from pneumonia and a cerebrovascular accident. Of the remaining patients, 16 survived a median of 7.5 (range 0.7-32.0) months. Five patients are still alive 72, 72, 70, 7 and 2 months after the metastasectomy, three of whom are tumour-free. The actuarial 5-year survival of all patients is 19 per cent. These results support surgical intervention for patients with complaints and/or complications attributable to gastrointestinal metastatic melanoma.

Adolescent

Lymph node metastasis from melanoma with an unknown primary site.

Twenty-six patients, treated surgically between 1961 and 1986 because of lymph node metastasis from melanoma with an unknown primary, were analysed. Six patients had a history of spontaneous regression of a skin lesion. Following node dissection, the overall actuarial disease-free survival rate was 49 per cent, after both 5 and 10 years. When considered as single factors, female (versus male), one lymph node involved (versus more than one node involved) and site of metastasis in the groin or axilla (versus the neck) were found to have significantly favourable effects on prognosis with 5-year survival rates of 82 per cent (25 per cent), 82 per cent (27 per cent) and 80 per cent (11 per cent) respectively. However, at multifactorial analysis only the site of cervical metastases maintained a significant influence on survival (P = 0.005). As survival in this series is comparable with, or even better than, that of adequately treated patients with lymph node metastasis from a known primary melanoma, a radical node dissection is essential also in these patients.

Adult

Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.

From 1975 to 1986, 26 patients with soft tissue tumors of the extremities underwent a total of 29 perfusions. The cytostatics used were doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) (19 perfusions), melphalan (two perfusions), and a combination of these agents (eight perfusions). Before perfusion most patients had been treated by surgical excision(s), radiotherapy, or systemic chemotherapy. Of 17 patients perfused because of local inoperable tumor, four showed prolonged complete remission of the tumor mass, stable disease was seen in three, and ten showed progression. The complete remissions observed in three patients with aggressive fibromatosis and in one with lymphangiosarcoma occurred after perfusion with doxorubicin combined with melphalan. Doxorubicin added to the perfusate as the sole cytostatic was not effective. Local recurrence was observed in five of nine patients treated by adjuvant perfusion, always after dubiously radical tumor excision. Toxicity was high, especially in the first few years. Tissue necrosis necessitated amputation in three cases (in two after perfusion with doxorubicin and melphalan and in one after repeated perfusion with doxorubicin only). This complication was no longer seen after adjustment of the dosage and dose distribution of doxorubicin, but the morbidity after perfusion with doxorubicin remained considerable.

Adolescent

Contralateral inguinal lymph node metastasis in patients with melanoma of the lower extremities.

A retrospective study was carried out on six patients with contralateral inguinal lymph node metastasis from a melanoma of the lower extremity. All six patients were found to have had a previous homolateral groin dissection and in five patients there was intercurrent disease relapse in the leg before or at the same time as the appearance of contralateral node metastasis. Although the prognosis in these patients is unfavourable, two had a survival period of 24 and 32 months and two were still alive 27 months after contralateral groin dissection. In order to determine possible pathways of dissemination, lymphoscintigraphic studies of the leg were performed in another 16 melanoma patients who in the past had undergone a groin dissection. In 13 of them uptake in the contralateral inguinal lymph nodes was detected, indicating that groin dissection can lead to a different lymphatic flow pattern, which is often directed to the contralateral groin. Contralateral lymph node involvement may be an expression of regional disease. In such patients a contralateral groin dissection is advocated.

Adolescent

Temperature distribution and pH changes during hyperthermic regional isolation perfusion.

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.

Aged

Epithelioid sarcoma.

In a 9-year period we treated 11 patients with an epithelioid sarcoma. Most patients were young adults. The tumour affected mainly the distal upper extremity (hand and fingers: four patients; wrist and forearm: three patients); one patient had an epithelioid sarcoma of the knee. Trunk localizations were seen in two patients and one patient presented with a vulva localization. Treatment consisted of surgery, regional isolation perfusion with doxorubicin (Adriamycin) or melphalan, radiation therapy, systemic chemotherapy or a combination of these modalities. Radical surgery in eight patients resulted in only two local recurrences. Locoregional metastases occurred in five patients. In five patients a therapeutic lymph node dissection was performed, in all instances followed by extensive recurrent disease. Distant metastases were seen in seven patients and mainly affected the skeleton (6x) and the lungs (4x); in the majority of cases these metastases occurred within a year after excision of the primary. Remissions following regional or systemic chemotherapy were not observed. At the time of analysis seven patients had died as a result of their epithelioid sarcoma; two patients were still alive with tumour 18 and 27 months after diagnosis. Only two patients remained tumour free for 17 and 65 months respectively following radical surgery, postoperative radiation therapy and (in one case) adjuvant chemotherapy. It is concluded that epithelioid sarcoma is a rare but exceedingly aggressive tumour. Since early diagnosis can only be auspicious, familiarity with the clinical features is of great importance.

Adult

To perfuse or not to perfuse? A retrospective comparative study to evaluate the effect of adjuvant isolated regional perfusion in patients with stage I extremity melanoma with a thickness of 1.5 mm or greater.

The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.

Adult

Results of radical dissection of the groin in patients with stage II melanoma and histologically proved metastases of the iliac or obturator lymph nodes, or both.

In order to determine the value of the pelvic part of the radical dissection of the groin, the histories of 23 patients with Stage II (UICC) melanoma with histologically proved metastases of the iliac or obturator lymph nodes, or both, were studied. Histologically proved primary melanomas were found in 19 patients, 18 were localized on the leg and one on the trunk. In four patients, the primary melanoma was unknown. Seven patients had received adjuvant radiotherapy. The time between node dissection and the moment of analysis was two years for 17 patients, five years for 11 patients and ten years for ten patients. Calculated actuarially, 42 per cent of the patients were still without distant metastasis after two years and 32 per cent after five and ten years. At the time of the analysis, ten patients were alive, nine without evidence of disease and three having survived for more than five years. Remarkably, the primary tumor of all three patients was "unknown" and they had all had adjuvant radiotherapy. In pooling the data of this series with those from the literature, it appears that, of 78 patients with Stage II melanoma and deep node involvement, 12 had a disease-free survival time of more than five years after therapeutic radical groin dissection. Involvement of deep nodes does not always seem to equate with systemic disease. We think that, when there is an indication for a therapeutic groin dissection, an en bloc superficial and deep lymph node dissection is warranted.

Adult

Regional perfusion treatment with melphalan for melanoma in a limb: an evaluation of drug kinetics.

The time course of tissue levels of melphalan during normothermic isolated limb perfusion, and the overall tissue levels per 60 min of perfusion, were estimated from the known pharmacokinetic parameters for a fixed dose of drug per liter of tissue (Benckhuijsen et al., J. Pharmacol Exp Ther 1986; 237: 583-8). The application of differing total doses of drug resulted in varying concentrations in the perfusate plasma. Above a certain plasma level, uptake into the bulk of the tissues did not increase with the area under the plasma concentration vs time curve or its beta-phase. Similar tissue levels were found after perfusion of regions of less than three and a half liter with 13 mg/l as in regions of 5 to 16 liter after perfusion with 10 mg of melphalan per liter. It cannot be predicted from the available data whether the extent of uptake of melphalan into the tumour tissue is equal to or greater than that into the bulk of the tissues. The estimated uptake of drug into the tissues confirms the validity of the dose calculation per liter of tissue. On the basis of the present results, a refined dosimetric formula will be obtainable that includes the desired area under the plasma concentration vs time curve as a determinant for an optimal dose.

Adult