Jw Oosterhuis

Isolated regional perfusion in malignant melanoma of the extremities

AbstractIsolated perfusion for regional chemotherapy is only practical for tumors located on the extremity, because this is the only site where adequate vascular occlusion can be achieved. Indications for perfusion in clinical stage I melanoma patients are determined by microstaging of the tumor. At our institution, patients with Clarks levels III, IV, or V and a Breslow thickness of ≥1.5 mm are eligible. Lower limb perfusions are started through an iliac perfusion. Two perfusions are performed for foot lesions, local recurrences, satellitosis, or intransit metastases.nFlow rates for leg perfusion vary from 600 to 1,000 ml/min. During the past few years, higher flows (up to about 1,200 ml/min) have been utilized. Less toxicity developed with better tissue perfusion, and the dosage of cytostatics could be increased. The dosage of cytostatic drugs is calculated by limb volume, as determined by immersion in water. In our opinion, hyperthermia yields superior results for cases of local recurrence or intransit métastases. It is not known if a combination of cytostatic drugs might improve results compared to a single drug.RésuméLa chimiothérapie régionale par perfusion isolée ne sapplique quaux mélanomes malins situés au niveau des extrêmités car cest le seul siège qui permet de réaliser une occlusion vasculaire satisfaisante. Les indications de la perfusion pour les malades porteurs dune tumeur de stade clinique I sont déterminées par le stade microscopique de la tumeur. Pour les auteurs, les malades avec des lésions de type III, IV, V de Clark et une lésion dune épaisseur de plus de 1.5 mm relèvent de ce traitement. Les perfusions du membre inférieur se font par voie iliaque; 2 sont pratiquées pour les lésions du pied, les récidives locales, les lésions satellites et les métastases.Les taux du flux pour la perfusion de la jambe varient de 600 à 1,000 ml/mm. Au cours des dernières années, des flux plus importants (jusquà 1,200 ml/mm environ) avaient été utilisés. Une diminution de la toxicité grâce à une meilleure perfusion tissulaire et du dosage des cytostatiques pourrait être obtenue. La dose des agents cytostatiques à employer est calculée à partir du volume du membre déterminé par limmersion de celui-ci dans leau. Selon lopinion des auteurs, lhyperthermie donne de meilleurs résultats en présence de récidive locale ou de métastases. Actuellement on ignore si une combinaison de drogues peut avoir une efficacité supérieure à une drogue unique.ResumenLa perfusión aislada para quimioterapia regional sólo es de utilidad práctica para tumores localizados en una extremidad, porque ésta es la única ubicación donde se puede realizar oclusión vascular adecuada. Las indicaciones para perfusión en melanomas en estado clínico I son determinadas por la clasificación microscópica del estado del tumor. En nuestra institución los pacientes con melanomas de niveles III, IV, o V y un espesor de Breslow de ≥1.5 mm son elegibles. Las perfusiones de las extremidades inferiores son iniciadas a través de una perfusión iliaca. Se realizan 2 perfusiones para lesiones del pie, para recurrencias locales, satelosis, o metástasis en tránsito.Los flujos para la perfusión de la pierna varían entre 600 y 1,000 ml/min. En el curso de los últimos años se han utilizado flujos mayores (hasta de 1,200 ml/min). Con la mejor perfusión se desarrolla menos toxicidad y la dosis de los agentes citotóxicos puede ser aumentada. La dosis de las drogas citotóxicas es calculada sobre el volumen de la extremidad determinado por inmersión en agua. En nuestra opinión la hipotermia da mejores resultados en casos de recurrencia local o de metástasis en tránsito. No se sabe si una combinación de drogas citostáticas puede dar mejores resultados que el uso de una droga única.

Cisplatin and platinum pharmacokinetics during hyperthermic isolated limb perfusion for human tumours of the extremities.

Cisplatin and platinum pharmacokinetics during hyperthermic isolated limb perfusion for human tumours of the extremities

SERUM LACTATE-DEHYDROGENASE ISOENZYME-1 ACTIVITY IN PATIENTS WITH TESTICULAR GERM-CELL TUMORS CORRELATES WITH THE TOTAL NUMBER OF COPIES OF THE SHORT ARM OF CHROMOSOME-12 IN THE TUMOR

SummaryThe aim of our study was to assess the relationship between the serum lactate dehydrogenase isoenzyme 1 (S-LDH-1) activity in patients with testicular germ cell tumors and the number of copies of the short arm of chromosome 12 (12p) present in tumor. Twenty-seven adult patients with measurable tumor lesions were studied. Twenty-five had three or more copies of chromosome 12 per cell in the tumors. Nineteen had one or more copies of a specific chromosomal abnormality, an isochromosome of the short arm of chromosome 12, i(12p). Fourteen had increased S-LDH-1 levels. S-LDH-1 activity correlated significantly with the product of total tumor volume and the total number of copies of the short arm of chromosome 12 present per cell (total tumor 12p). We conclude that the total number of copies of the short arm of chromosome 12 in the tumors is most probably a factor contributing to the LDH-1 activity released from the tumors.

Retinoic acid and cisdiaminodichloroplatinum in the treatment of murine teratocarcinomas in vivo in a nullipotent model

Induction of differentiation as a treatment modality for nonseminomatous germ cell tumors (NSGCTs) may promote the development of residual mature teratoma (RMT), which is usually associated with primary tumors that are capable of spontaneous somatic differentiation. Therefore, we studied the combination of a cytotoxic drug and a differentiation-inducing agent in vivo in three murine teratocarcinoma models with different levels of spontaneous somatic differentiation: E86-379 (moderate differentiation); NF-1 (poor differentiation); and MH-15 (no differentiation). We used retinoic acid (RA) as differentiation-inducing agent and cisdiaminodichloroplatinum (CDDP) as cytotoxic drug, plus a combination of both. In four separate experiments, the combination of RA and CDDP gave a significant further reduction of tumor size as compared with treatment with either RA or CDDP alone. Morphologically intact tumor after treatment with combined RA-CDDP contained a smaller proportion of undifferentiated tissue (embryonal carcinoma) than after CDDP alone. However, somatic differentiation was not induced in the tumor model lacking spontaneous somatic differentiation. Toxicity was reflected in loss of body weight and death of some animals and closely paralleled the degree of tumor reduction in all experiments.