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Biomedical subjects

J M Klaase

Publications and source records attributed to J M Klaase.

At least 37 records · Page 2Linked to original sources

Monitoring of impending myocardial damage after pleuropneumonectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma using biochemical markers.

In five patients who were treated for malignant pleural mesothelioma (MPM) with pleuropneumonectomy and intraoperative photodynamic therapy (IPDT), impending myocardial damage was monitored using ECG, the classical biochemical markers (creatine kinase [CK], total activity; CKMB, mass; and myoglobin), and the new cardiac markers troponin I (cTnI) and troponin T (cTnT). In the peroperative and postoperative period all classical markers were elevated, in contrast to cTnI and cTnT, because of the concomitant skeletal muscle damage. Sequential electrocardiogram monitoring showed no signs of myocardial damage. From this study in patients with MPM treated with pleuropneumonectomy and IPDT it can be concluded that measurement of cTnI and cTnT for the detection of myocardial damage is more suitable than measurement of the classical markers.

Biomarkers↗

Relation between limb toxicity and treatment outcomes after isolated limb perfusion for recurrent melanoma.

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.

Adolescent↗

Troponin I, troponin T, CKMB-activity and CKMB-mass as markers for the detection of myocardial contusion in patients who experienced blunt trauma.

Myocardial contusion is an infrequent, but sometimes serious complication in patients who experienced deceleration (blunt) trauma. We investigated the assessment of the new cardiac markers troponin I (cTnI) and troponin T (cTnT) in relation to the conventional CKMB-activity, the CKMB-activity/CK-total ratio, CKMB-mass and the CKMB-mass/CK-total ratio for the detection of myocardial contusion in 89 patients with blunt trauma (38 patients with thoracic injuries and 51 patients without thoracic injuries). All parameters were analysed at admission (t1) and 24 h after admission (t2). For the patients with thoracic injuries, at t1 cTnI was elevated in three, and cTnT in four patients; at t2 both cTnI and cTnT were elevated in nine patients. At t1, eighteen to thirty patients had increased levels of the conventional parameters; at t2 this was true for six to thirty-five patients. For the patients without thoracic injuries all cTnI and cTnT levels were within the reference ranges at t1. At t2 one patient, who experienced an acute myocardial infarction, had elevated cTnI and cTnT levels. At t1, five to thirty-five patients had increased levels of the conventional parameters; at t2 this was true for four to forty-two patients. From this study we conclude that the conventional parameters are not useful for the detection of myocardial contusion in patients experiencing blunt trauma. The parameters cTnI and cTnT are equally accurate and more reliable for the selection of patients who require intensive cardiac monitoring. If at admission the cTnI or the cTnT levels are within the reference ranges, a second analysis after admission is necessary to reach a reliable conclusion concerning myocardial contusion as a result of trauma on basis of the troponin levels.

Adolescent↗

[The elevation of serum creatine kinase-MB level in trauma patients: misleading impression of myocardial damage].

OBJECTIVE: To determine the frequency of increase of serum values, not of cardiac origin, of creatine kinase-MB (CK-MB) in trauma patients. DESIGN: Prospective. SETTING: University Hospital, Groningen, the Netherlands. METHODS: 51 trauma patients without chest injury (without myocardial contusion) but with (among others) soft tissue injuries, were included. At admission (time point t1) an ECG and chest X-ray were made and blood was collected for measurement of CK total, CK-MB activity and CK-MB mass. If the CK-MB activity/CK total fraction exceeded 3%, CK electrophoresis was performed. Blood analysis was repeated after 24 hours (t2). RESULTS: CK-MB activity was elevated in 27 patients (53%) at t1 and in 3 (6%) at t2. The fraction CK-MB activity/CK total exceeded 3% in 96% and 33% of these patients at t1 and t2, respectively. In all these cases a CK-BB band was detected by electrophoresis (CK-BB interferes with the CK-MB activity measurement). CK-MB mass was elevated in 11 patients (22%) at t1 and in 19 (37%) at t2. CONCLUSION: CK-MB was frequently elevated in trauma patients owing to skeletal muscle damage and to interference with CK-MB activity measurements. For the detection of myocardial damage in trauma patients, CK-MB measurements are of little use.

Adolescent↗

[Thyroglossal cyst].

The thyroglossal cyst is a wellknown cause of a swelling in the neck. The generally accepted technique of treatment was described in 1928, but many recurrences are still seen in daily clinical practice. The radical technique of removal of cysts and sinuses of the thyroglossal duct according to Sistrunk is the method of choice. Over an 8-year period 40 cases were treated in this fashion in the University Hospital Groningen, the Netherlands, with an average follow-up of 5 years and 3 months; in 29 it was the first operation. Only 1 patient of the 23 treated according to Sistrunk had a recurrence for which he had to be treated again. Six patients were treated otherwise; 3 of them had a recurrence. It is concluded that the first surgery (according to Sistrunk), if correctly performed, offers the best chance for cure.

Adolescent↗

Increased kyphosis by a combination of fractures of the sternum and thoracic spine.

A 67-year-old patient suffered a fall and sustained injuries to the thorax, combined with fractures of the ribs, sternum and thoracic spine. Her pre-existing kyphosis (caused by osteoporotic vertebral collapse) increased in severity. There was a clear relationship between a sternal fracture, deterioration of thoracic kyphosis and a fracture of the thoracic spine.

Accidental Falls↗

[Toe tourniquet syndrome].

In two boys aged 4 months and one girl aged 2 months one or two toes were red and oedematous, while in one boy aged 3 weeks one toe had become necrotic. In the first-mentioned three children the affected toes were encircled by a hair, the hair was removed under anaesthesia, after which the children recovered. In the last-mentioned child, amputation through the proximal phalanx was necessary. The toe tourniquet syndrome occurs mainly in infants. Strangulation of the toes by circular foreign material. such as hair or fibre, causes oedema and increasing constriction. Timely treatment is followed by good recovery. Delayed or incomplete treatment can lead to necrosis which may necessitate amputation.

Constriction, Pathologic↗

Value of laboratory tests in monitoring acute regional toxicity after isolated limb perfusion.

BACKGROUND: Severe limb toxicity following isolated limb perfusion (ILP) can lead to compartmental compression syndrome and severe rhabdomyolysis, occasionally necessitating amputation of the affected limb. We determined whether laboratory tests for muscle damage and inflammation could predict impending limb toxicity. METHODS: All 184 consecutive ILPs performed in our institute from 1988 to 1994 were included in this study. Creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and white blood cell (WBC) counts were determined on post-ILP days 1-4, 6, 8, and 15. RESULTS: "Late peak" CK patterns, characterised by a peak on or after the 5th post-perfusion day, were strongly associated with severe limb toxicity (p < 0.001). Severe toxicity did develop in 40% of the limbs when CK values exceeded 1000 IU/L on the 2nd to 5th post-ILP day (p < 0.001). There was a correlation between the peak CK and the individual grades of toxicity (r = 0.6, p < 0.001). Serum LDH and ASAT values peaked 2.9 and 3.4 days after the CK peak respectively. Severe limb toxicity was statistically significantly associated with higher WBC counts from the 2nd post-ILP day onwards. CONCLUSIONS: CK values exceeding 1000 IU/L after the 1st and WBC counts increasing after the 2nd post-ILP day could be predictors of impending limb toxicity. These patients should be observed closely for signs of compartmental compression syndrome and severe rhabdomyolysis.

Adult↗

Systemic toxicity after isolated limb perfusion with melphalan for melanoma.

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.

Adolescent↗

Physiological implications of hyperbaric oxygen tensions in isolated limb perfusion using melphalan: a pilot study.

Controversy exists concerning the optimal pO2 of the perfusate during isolated limb perfusion (ILP) with melphalan. Therefore we studied the implications of hyperbaric oxygen tensions in the perfusate. In 12 consecutive patients, subcutaneous pO2 (Continucath 1000), tissue and tumor pH, and blood gas values were monitored throughout the ILP procedure. ILP started with an oxygen flow through the bubble oxygenator which was set routinely at one half of the flow of the perfusate; 30 min before the end of ILP, the oxygen flow was tripled. Mean arterial pO2 before and during ILP (before and after increasing the oxygen supply) was 19.4, 25.5 and 49.4 kPa, respectively. Mean subcutaneous pO2 values before, during (before and after increasing the oxygen supply), and post-ILP, were 7.4, 10.1, 16.3, and 9.1 kPa, respectively. Tissue pH values in the subcutis and muscle decreased during routine oxygen supply (p = 0.001); muscle pH moved towards starting values after increase of the oxygen supply (p = 0.011). In 4 patients, tumor pH was recorded showing a rise after increasing the oxygen supply (from 7.10 to 7.22; p = 0.11). In conclusion, high pO2 in the perfusate improves muscle pH during ILP. However, a concomitant rise in tumor pH may unfavorably influence the therapeutic effect of ILP, as it has been shown that low pH increases the cytotoxicity of melphalan.

Adult↗

Repeat isolated limb perfusion with melphalan for recurrent melanoma of the limbs.

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.

Adult↗

Long-term morbidity after regional isolated perfusion with melphalan for melanoma of the limbs. The influence of acute regional toxic reactions.

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.

Adult↗

A retrospective comparative study evaluating the results of mild hyperthermic versus controlled normothermic perfusion for recurrent melanoma of the extremities.

The aim of this study was to investigate the role of mild hyperthermia (39-40 degrees C) in isolated cytostatic perfusion for patients with recurrent melanoma of the extremities. A total of 218 patients treated with mild hyperthermic perfusion was compared to 166 patients perfused under controlled normothermic conditions (37-38 degrees C). Only patients whose lesions had been excised before or at the moment of perfusion were eligible for this study. A variety of prognostic factors was controlled for in a Cox proportional hazards analysis. The application of mild hyperthermia did not influence limb recurrence-free interval nor survival (corrected P values 0.46 and 0.18, respectively). In this retrospective comparative study, no benefit for mild hyperthermia in regional isolated perfusion could be identified.

Adolescent↗

Severe acute regional toxicity after normothermic or 'mild' hyperthermic isolated limb perfusion with melphalan for melanoma.

Incidence, nature and cause of severe acute regional toxicity were studied in 181 patients who underwent normothermic (37-38 degrees C) or 'mild' hyperthermic (38-40 degrees C) isolated limb perfusion (ILP) with melphalan. The known risk factors for toxicity (sex, tissue temperature, blood gas values, isolation level and melphalan peak concentration) were analysed. Severe acute regional toxicity occurred in 30 patients (16%). The limb was painful, swollen, red and warm in 19, often with a smooth and glistening aspect. Blistering scattered over the extremity was seen in 11 cases. In another 11 patients, late blistering limited to the footsole or handpalm developed. Twenty-six patients with severe toxicity had undergone ILP at the iliac isolation level (p < 0.05). Sex and tissue temperature did not predict toxicity. Venous perfusate blood gas values were severely deteriorated in four patients; high calculated melphalan peak concentrations occurred in nine patients. Irreversible long-term morbidity as a sequence of severe toxicity occurred in 10 of the 30 patients. Only one of the 11 patients with late blisters limited to sole or palm developed long-term morbidity (p < 0.05). Thus, the only risk factor for severe acute regional toxicity that could be identified was iliac isolation level. However, in 27 of the 30 patients two or more risk factors were found.

Adult↗

[Characteristics of patients with recurrence of primary melanoma at least 10 years following surgical treatment].

OBJECTIVE: Assessment of incidence and risk factors of late recurrence (after a disease-free interval of at least 10 years) following treatment for primary melanoma. METHODS: Retrospective study taking into account a total of 2579 melanoma patients admitted to the Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis in the period 1956 to 1991; patients with ocular melanoma were excluded. RESULTS: Twenty-three patients had a disease-free interval of at least 10 years (median 11 years; range: 10-21) after treatment for primary melanoma: 17 women and 6 men, with a median age of 43 years (20-62). This group predominantly consisted of women with a primary melanoma localised on the extremities. Most of them had melanomas of intermediate thickness (Breslow thickness: 1-2 mm). Patients with a first recurrence locoregionally (16) had a 5-year survival rate of over 50%; 6 of the 7 patients with a first relapse at distant sites died within a few months. CONCLUSION: Melanoma patients who are discharged from follow-up after a disease-free interval of 10 years are advised to continue loco-regional self-examination.

Adult↗

Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities.

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.

Adult↗

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↗