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Biomedical subjects

H Schraffordt Koops

Publications and source records attributed to H Schraffordt Koops.

227 records · Page 13Linked to original sources
PubMedDate not supplied

Isolated limb perfusion in primary and recurrent melanoma: indications and results.

In advanced melanoma of the limbs with in-transit metastasis, melphalan with isolated limb perfusion (M-ILP) produces around 50% complete remissions (CR). The combination of melphalan with tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in isolated limb perfusion (TIM-ILP) gives around 80% CR. A prospective randomised phase II study compared 32 patients who received TIM-ILP with 32 patients who received TM-ILP (without IFNgamma). The overall remission rate (ORR) and the CR rate were superior with TIM-ILP as compared to TM-ILP, 100% vs. 91% and 78% vs. 69% respectively, but the differences are not significant. Given the efficacy of M-ILP on in-transit metastasis, the procedure was tested as an adjunct to surgery in high-risk (Breslow > or = 1.5 mm) primary melanoma of the limbs. Through the combined effort of the melanoma groups of the European Organization for Research and Treatment of Cancer (EORTC), the World Health Organization (WHO), and the North American Perfusion Group, 832 evaluable patients from 16 centres were entered in a phase III study. Median followup is 6.4 years. There was a trend for a longer disease-free interval after M-ILP. The difference is significant if the patients without elective lymph node dissection (ELND) are separately analysed, with a high significance in the 1.5 to 3 mm thickness subgroup. The occurrence of in-transit metastases was reduced from 6.6% to 3.3% by M-ILP. There was, however, no benefit of M-ILP in terms of survival. Prophylactic M-ILP cannot be recommended as a standard adjunct to surgery in high-risk primary limb melanoma. TIM-ILP or TM-ILP is a regional therapy with a very high regional response rate on melanoma in-transit metastasis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Hyperthermic isolated limb perfusion for the treatment of soft tissue sarcomas.

Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents has been used for the local treatment of high-grade soft tissue sarcomas (STS) of the extremities, but in most cases, with a disappointing result. Most such regimens certainly should not be considered superior to surgery plus radiotherapy. Although the majority of extremity STS can be resected locally, some are very large and are in close proximity to bone, nerve or blood vessels. In these cases, amputation is the only means of resecting the tumour. A new combination of drugs used in the set-up of HILP with tumour necrosis factor-alpha and melphalan has emerged as a very promising option for the limb-saving management of locally advanced STS. In recent studies, complete response rates of approximately 30% and partial remission rates of 50% have been achieved, while the overall limb-salvage rate is more than 80%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Controversies concerning adjuvant regional isolated perfusion for stage I melanoma of the extremities.

The use of isolated perfusion with melphalan in an adjuvant setting for stage I extremity melanoma continues to be controversial. In this article, 2 retrospective studies compare patients undergoing perfusion from Groningen, the Netherlands, with matched controls from the Sydney Melanoma Unit in Australia and from 5 hospitals in the Netherlands and Westphalia (a region of Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or more in thickness. In the first study, women with a melanoma of the leg (excluding the foot) and treated with perfusion had a significantly higher survival than women treated with local excision alone. In the second study, a proportional hazards regression analysis for recurrent disease and survival identified no statistically significant difference in favor of adjuvant perfusion. Two other studies from the literature evaluating the efficacy of perfusion are examined. Patients treated at the M.D. Anderson Cancer Center, Houston, with wide local excision and perfusion are compared retrospectively with a group of patients individually matched for prognostic factors from the University of Alabama in Birmingham, U.S.A. and the Sydney Melanoma Unit. A small subset of patients with tumors greater than 2 mm thick benefited from perfusion. A prospective randomized study from the University Hospital, Cologne, West Germany found benefits for all perfused patients with tumors greater than 1.5 mm but their patients did not appear to be individually matched for tumor thickness. It is concluded after critical appraisal of all these studies that there is insufficient convincing evidence to date of an advantage of perfusion over wide local excision alone.

Chemotherapy, Adjuvant↗
PubMedDate not supplied

Limb salvage surgery for primary bone sarcoma of the lower extremities: long-term consequences of endoprosthetic reconstructions.

BACKGROUND: Adjuvant chemotherapy and endoprosthetic replacement for bone sarcomas of the lower extremity is well established. The specific long-term consequences of these endoprosthetic reconstructions for the patient's affected limb are unknown. METHOD: The oncologic results and the survival of the endoprostheses were reviewed in 32 patients with primary bone sarcoma of the femur or proximal tibia. There were 26 high-grade sarcomas, and 6 low-grade sarcomas. A proximal femoral endoprosthesis was used for reconstruction in 4 patients, a total or push-through femoral endoprosthesis in 11 patients, a distal femoral endoprosthesis in 15 patients, and a proximal tibial endoprosthesis in two patients. RESULTS: Median survival was 10 years (range, 1.1 to 18.9 years) for patients with high-grade sarcoma, and 8.1 years (range, 7.1 to 10 years) for patients with low-grade sarcomas. Distant metastases developed in seven patients (22%), all with stage IIB sarcoma, with concomitant local recurrence in 3 patients (9%). Five-year overall and disease-free survival rates for high-grade sarcomas were 81% and 73%, respectively. The overall endoprosthetic survival rate was 87% at 5 years, 80% at 10 years, and 56% at 15 years. Median follow-up of the original endoprostheses was 8.3 years (range, 0.6 to 18.7 years). Endoprosthesis-related complications occurred in 13 patients (41%); most complications were mechanical failures. The highest complication rate was found in distal femoral replacements (60%); amputation was necessary in both patients treated with a proximal tibial endoprosthesis. Five endoprostheses (16%) were revised. An amputation of the involved limb was performed in four patients (13%): in two patients because of local recurrence and in the other two patients because of infection. For patients alive at follow-up, the median functional Enneking evaluation score was 22 points (range, 12 to 28 points), with the highest functional scores in patients with a distal femoral endoprosthesis, and the lowest functional scores in patients with total or push-through femoral replacements. CONCLUSION: Endoprosthetic reconstructions gave satisfying functional results in most patients after long-term survival. However, the proximal tibial and distal femoral endoprosthesis are particularly at risk for long-term endoprosthetic complications requiring additional surgical procedures.

Adolescent↗
PubMedDate not supplied

The role of magnetic resonance imaging and computed tomography in the treatment evaluation of retroperitoneal lymph-node metastases of non-seminomatous testicular tumors.

The role of Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) in the treatment evaluation of retroperitoneal lymph-node metastases of non-seminomatous testicular tumors (NSTT) was prospectively studied in 10 consecutive patients before, during and after chemotherapy. The results thus obtained were compared with laparotomy findings before and after chemotherapy, the histology of the primary testicular tumor, and that of retroperitoneal residual lesions after chemotherapy. MRI and CT proved to be equivalent in detection and in determining the anatomical localization and size of the retroperitoneal lymph node metastases. Unlike CT, MRI revealed unmistakable changes in the structure of the retroperitoneal lymph-node metastases during chemotherapy, for which no histological cause was found except in mature teratoma. In mature teratoma a high T2 signal was found within the metastases, corresponding with a high water content. On the basis of tumor consistency and signal intensity in the T1- and T2-weighted images, MRI cannot yet warrant any conclusion about the ultimate effect of chemotherapy.

Adolescent↗
PubMedDate not supplied

Hyperthermic regional perfusion using membrane- instead of bubble-oxygenators. An experimental and clinical study.

To achieve adequate tissue perfusion during hyperthermic regional perfusion, perfusion pressures should be maintained at near normal mean systemic arterial pressures. During experimental as well as during clinical perfusions however, unphysiologically high perfusion flows were needed to keep the perfusion pressure at the desired level. Since both high perfusion flows and high perfusion pressures have been associated with the post-operative complications such as severe edema and tissue damage, as well as with an increased leakage of perfusate to the systemic circulation, low perfusion flows have been used in regional perfusion. High perfusion flows in our previous experimental studies were attributable to a marked reduction in vascular resistance. This decrease is believed to be caused by the release of vasodilatory constituents of damaged blood cells, and it is the extra-corporeal circuit, and in particular the bubble-oxygenator that is thought to be responsible. The superior haemocompatibility of membrane-oxygenators over bubble-oxygenators has been established in cardio-pulmonary bypass. We compared the use of a membrane-oxygenator with that of a bubble-oxygenator in regional perfusion to see if more normal haemodynamics could be maintained and vasodilatation prevented. In the experimental as well as in the clinical perfusions the use of a bubble-oxygenator required unphysiologically high perfusion flows to maintain the perfusion pressure at the level required to obtain an adequate microcirculation. In contrast the use of a membrane-oxygenator permitted a nearly physiological perfusion flow to maintain an adequate perfusion pressure as well as an adequate micro-circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Dose escalation of dacarbazine combined with interferon alpha-2a, G-CSF and ondansetron in patients with metastatic melanoma.

To define the activity of an individually escalated dacarbazine (DTIC) dose combined with interferon-alpha-2a (IFN), granulocyte-colony stimulating-factor (G-CSF) and ondansetron, 20 patients (pts) with metastatic melanoma were treated with DTIC, ondansetron 8 mg iv, G-CSF 300 micrograms sc and IFN 9 MU sc. Treatment was performed every 21 days to a maximum of 6 courses. DTIC dose was escalated with 250 mg/m2 in case of acceptable toxicity to 1250, 1500 and 1750 mg/m2 in (projected/realized), 14/19, 8/11 and 0/5 pts, respectively. Dose escalation prohibiting toxicities were thrombocytopenia (10 pts), leukopenia (9 pts), and nausea/vomiting (2 pts). Four partial remissions were observed, for a response rate of 20% (95% confidence interval, 6 to 44%). Duration of responses was 1, 2, 3 and 3 months. Median overall survival was 8 months.

Adult↗
PubMedDate not supplied

High-dose methotrexate, vincristine and cisplatin as salvage treatment for relapsed non-seminomatous germ-cell cancer.

Eight patients with non-seminomatous testicular cancer relapsing after primary chemotherapy were treated with salvage chemotherapy consisting of high-dose methotrexate (12 g/m2), vincristine (1.2 mg/m2) weekly for four weeks, followed after an interval of four weeks by 3 times 100 mg/m2 cisplatin (50 mg/m2 on day 1 and 2) every 10 days. This regimen resulted in 2 partial (PR) and 2 complete responses (CR). The two patients achieving CR remain disease-free for 43+ and 53+ months. Toxicity was mainly methotrexate-related and could be ameliorated to a large extent by leucovorin rescue. This small study shows that methotrexate, vincristine, followed by cisplatin is effective in the treatment of relapsed non-seminomatous testicular cancer at the cost of manageable toxicity.

Adult↗