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Spontaneous activity in perfused hypothalamic slices: dependence on calcium content of perfusate.

We have established a totally-immersed, perfused slice preparation of the hypothalamus which is amenable for electrophysiological and pharmacological studies. The amount and pattern of spontaneous activity in the paraventricular nucleus (PVN) is markedly influenced by varying the amount of Ca++ in the oxygenated physiological medium which continuously perfuses the slice over both upper and lower surfaces. Ca++ concentrations greater than 1 mM virtually abolish spontaneous activity, although the neurons discharge in response to advance of the electrode and are activated by addition of glutamate to the perfusate. However, in a perfusing medium containing 0.75 mM Ca++, most cells display 1-7 Hz spontaneous activity for up to 10 h; some cells display phasic activity similar to that attributed to vasopressin neurons in vivo. Electrical stimulation peripheral to the PVN elicits antidromic potentials in some PVN neurons, sometimes followed by a post-activation depression of activity typical of recurrent inhibition. Under appropriate perfusion conditions, therefore, the hypothalamic slice preparation displays characteristics of the in vivo hypothalamus.

Animals↗

Evaluation of laser speckle flowmetry for imaging cortical perfusion in experimental stroke studies: quantitation of perfusion and detection of peri-infarct depolarisations.

Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitatively using umbelliferone clearance (CBF(umb)). Values of ICT and CBF(umb) were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBF(umb)-derived values of perfusion were closely correlated, with a high degree of significance (P<0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.

Animals↗

Real-time perfusion imaging: a new echocardiographic technique for simultaneous evaluation of myocardial perfusion and contraction.

Myocardial contrast echocardiography (MCE) with high acoustic energy and triggered harmonic imaging is the best established ultrasound technique to date for the assessment of myocardial perfusion. With this technique, however, the ultimate goal of MCE (noninvasive real-time simultaneous assessment of myocardial perfusion and function after an intravenous injection of microbubbles) is not met. Recently, technologic advances have enabled myocardial opacification to be visualized during low-energy real-time imaging. During real-time perfusion imaging, wall motion and myocardial perfusion may be assessed simultaneously, obviating the need of the presently time-consuming combination of different imaging modalities. When high-energy ultrasound bursts are periodically transmitted to produce bubble destruction during low-power imaging, the consecutive frames after destruction delineate the restoration of contrast intensity. Microbubble replenishment rate and peak intensity may be determined subsequently, and provide reliable quantitative parameters of regional microcirculatory flow. This review will introduce the modalities used for real-time perfusion imaging with focus on power pulse inversion imaging and quantitative analysis. Furthermore, we will describe the clinical role the technique may have in the identification of coronary artery disease, quantification of coronary stenosis severity, assessment of myocardial viability, determination of infarction size, and evaluation of reflow and no- or low-reflow after acute myocardial infarction.

Contrast Media↗

[CT perfusion imaging in acute ischemic cerebral infarct: comparison of cerebral perfusion maps and conventional CT findings].

PURPOSE: To evaluate the findings of acute brain ischemia on different functional maps of cerebral perfusion CT in stroke patients and to compare the results with early ischemic changes on conventional CT. METHODS: The baseline CT scans of 45 acute stroke patients were retrospectively evaluated with respect to early CT findings. For each patient the extent of cerebral ischemia as shown on the maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and "time to peak" (TP) was compared and the severity of ischemia was assigned to one of three levels based on the findings of the CBF image. RESULTS: In 75% of all patients conventional CT was performed within 2 hours from symptom onset. 29 of 45 patients showed early signs of ischemia on conventional CT, whereas perfusion CT revealed cerebral ischemia in all patients. Severe ischemia was found in approximately the same rate of incidence in patients with early CT changes (55.2%) and in those with normal findings (43.8%). If the perfusion impairment was judged as mild or moderate the extent of the hypoperfused area was significantly larger on the CBF and TP images than on the CBV map. This was significantly different in patients with severe hypoperfusion where a complete correspondence of the affected area between the three functional maps was found. DISCUSSION: The use of conventional CT for the assessment of stroke in the hyperacute phase is limited. Perfusion CT yields excellent information regarding the severity and extent of ischemia. The use of various perfusion maps helps to differentiate the core of infarction from the ischemic penumbra zone.

Acute Disease↗

[Cerebral perfusion sonography in comparison with perfusion MRT: a study with healthy volunteers].

AIM: Perfusion harmonic imaging (PHI) has been used for several years now in neurological as well as other patients. The aim of the study was to compare PHI with perfusion-weighted MR tomography (pMRT) for the evaluation of cerebral parenchymal perfusion. Furthermore, the influence of different trigger intervals on the contrast kinetics in PHI was analysed. METHOD: Fifteen healthy individuals were evaluated with two transtemporal PHI investigations and one pMRT. In PHI, 62 time-triggered images at two different trigger intervals (1 and 0.4 Hz) were recorded after an intravenous bolus of 2 ml of SonoVue(R). pMRT was carried out according to a standard technique using 0.2 mmol/kg Gadolinium-DTPA (Magnevist) and T2*-weighted EPI-sequences. Time-intensity curves of PHI and pMRT-determined data including peak intensity (PI), time-to-peak-intensity (TTP [s]), and area-under-the-curve (AUC) were calculated off-line from 4 regions of interest: ipsi- and contralateral thalamus (i-TH, k-TH), lentiform nucleus (NUC), and white matter (ML). These parameters were compared between the data sets of the two different trigger intervals. Additionally, ratios of the above parameters were calculated to compare the two methods (TH/NUC and TH/ML). RESULTS: Comparison of the two trigger intervals showed significantly lower AUC-values at the higher trigger interval, while the trigger interval had no significant impact on PI- and TTP- values. A good correlation was seen between the trigger intervals for AUC-values and, to a lesser extent, for PI-values. TTP-values did not correlate. TTP was the only depth-independent parameter. There was no significant difference between PHI and pMRT in 10 of 12 parameter ratios analysed. Merely the PI-ratio of i-TH/ML was significantly different at both trigger intervals. CONCLUSION: Regarding the development of adequate set-ups for transcranial PHI, further parameters with impact on contrast agent kinetics (MI, dose of contrast agent) have to be taken into account in addition to the trigger interval. Our findings suggest that, within certain limits, PHI is an imaging technique representing a valuable alternative to MR perfusion imaging, with the TTP representing the most reliable parameter. The AUC is useful for semi-quantitative evaluation of brain perfusion.

Brain↗

Assessment of perfusion, function, and myocardial metabolism after infarction with a combination of low-dose dobutamine tetrofosmin gated SPECT perfusion scintigraphy and BMIPP SPECT imaging.

BACKGROUND: Tetrofosmin gated single photon emission computed tomography (SPECT) allows simultaneous assessment of regional myocardial perfusion, global and regional left ventricular function, and function at rest and during pharmacologic intervention. SPECT with fatty acid analogues, such as beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), can be used to monitor metabolic changes induced by myocardial ischemia. In this work, the results of both studies obtained in patients with recent myocardial infarction are integrated. METHODS: Twenty patients underwent tetrofosmin and BMIPP scintigraphy with a 3-head camera. Two consecutive tetrofosmin gated SPECT acquisitions were performed 60 minutes after administration of technetium-99m tetrofosmin (925 MBq) at rest (3x20 stops of 9 s; matrix 64x64 over 360 degrees . One acquisition was made at rest, and the second was made during dobutamine infusion (10 microg/kg/min). Regional functional abnormalities were quantified and expressed as wall thickening severity (WTsev) in arbitrary units. Left ventricular ejection fraction and volumes were assessed with the Cedars Sinai algorithm. BMIPP imaging started 20 minutes after iodine 123-BMIPP (150 MBq) administration at rest (3x32 stops of 60 s; matrix 64x64 over 360 degrees; medium energy collimators). Tracer uptake was scored according to a 25-segment model. RESULTS: Sixteen of 18 patients had regional functional abnormalities at baseline (average WTsev 13.7 units). The WTsev score at baseline correlated well with the degree of residual perfusion. During dobutamine infusion, WTsev did not change (from 23.4 to 23.6 units) in 5 patients; it decreased (from 16.1 to 5.9 units) in 11 patients; and it increased (from 13.0 to 22.3 units) in 3 patients. An increase or decrease in WTsev during dobutamine infusion was associated with the presence of a considerable amount of BMIPP mismatched myocardium, whereas no change in WTsev was preferentially associated with a BMIPP matched pattern and perfusion defects with a higher severity score. CONCLUSION: Immediately after infarction, the severity of regional dysfunction at rest correlated well with the perfusion defect severity. Improvement in regional function during dobutamine administration is associated with less severe perfusion defects and a considerable amount of BMIPP mismatched myocardium, both suggesting viability.

Adult↗

Hepatic perfusion scintigraphy. Relationship of liver perfusion and ascites in patients with liver cirrhosis.

Radionuclide studies were performed on 38 patients with biopsy proven liver cirrhosis in an attempt to evaluate the interrelationship between liver perfusion and ascites in cirrhotic patients. Quantitative hepatic scintigraphy was used to evaluate the relative contribution of hepatic arterial and portal venous blood flow to the hepatic circulation. Using a gamma camera and on-line computer system, a bolus of 370 MBq Tc-99m pertechnetate was injected intravenously. Time activity curves of the abdominal aorta and right lobe of the liver were obtained using a region of interest analysis where arterial and portal components were calculated. Ascites was determined by clinical examination and by ultrasonography. Of 38 patients, 10 patients (26.3%) showed normal liver perfusion (group A), 22 patients (58%) showed reduced portal venous perfusion (group B), and 6 patients (15.7%) showed pure arterial hepatic perfusion (group C). The incidence, as well as the advancement, of ascites were significant (P < 0.05) and were most frequent in group C, frequent in group B, and less frequent in group A. The results of this study suggest that the development of ascites in patients with liver cirrhosis is closely correlated with the reduction in portal blood perfusion.

Adult↗

BOLD and perfusion response to finger-thumb apposition after acetazolamide administration: differential relationship to global perfusion.

The authors studied the effects of altering global cerebral blood flow on both blood oxygen level-dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved BOLD-weighted and perfusion-weighted images on eight finger-thumb apposition trials. Subjects were studied on a drug-free day and on a day when acetazolamide was administered between the second and third trials. After acetazolamide administration, resting cortical perfusion increased an average of 20% from preadministration levels, whereas the BOLD response to finger-thumb apposition decreased by an average of 35% in the S1M1 hand area. Contrary to predictions from the exhausted cerebrovascular reserve hypothesis and the oxygen limitation model, an effect of acetazolamide on cerebral blood flow response in the S1M1 hand area was not observed. Across the acetazolamide trials, BOLD response was inversely correlated with resting cortical perfusion for individual subject data. These results suggest that resting perfusion affects the magnitude of the BOLD response and is thus an important confounding factor in fMRI studies, and that the physiologic systems that increase cerebral blood flow in response to acetazolamide administration and systems that increase cerebral blood flow in response to altered neural activity appear to have additive effects.

Acetazolamide↗

Diagnostic accuracy of stress first-pass contrast-enhanced myocardial perfusion MRI compared with stress myocardial perfusion scintigraphy.

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery prepared turbo fast low-angle shot (turbo FLASH) compared with stress myocardial perfusion scintigraphy. Recent studies show that first-pass contrast-enhanced myocardial perfusion MRI can provide noninvasive detection of low-limiting stenosis in the coronary artery. MATERIALS AND METHODS: First-pass contrast-enhanced MR images were acquired at rest and during stress in 40 patients with suspected coronary artery disease. All patients underwent thallium-201 SPECT without attenuation correction and coronary angiography. Two reviewers independently assigned one of five confidence grades without knowing the results of coronary angiography for receiver operating characteristic (ROC) analysis. Luminal stenosis >70% on coronary angiography was used as a reference standard. RESULTS: On coronary angiography, 70% or greater diameter stenosis of the coronary artery was observed in 21 (52.5%) of 40 patients. The areas under the ROC curve for detection of significant stenosis in the individual coronary artery were 0.86 (observer 1) and 0.84 (observer 2) for MRI. These values were 0.79 (observer 1, p = not significant) and 0.72 (observer 2, p = not significant) for 201Tl SPECT. CONCLUSION: The diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery-prepared turbo FLASH was comparable with that of stress 201Tl SPECT. Stress first-pass contrast-enhanced MRI is a noninvasive technique that can be used as an alternative to stress myocardial perfusion scintigraphy.

Contrast Media↗

Left ventricular function and perfusion from gated SPECT perfusion images: an integrated method.

UNLABELLED: A new technique for computing left ventricular function, including left ventricular volumes, mass and ejection fraction, has been developed. This method is a logical extension of the results of a standard perfusion quantification technique; thus, it allows integration of perfusion and functional information. METHODS: Anatomically based models of the endocardial and epicardial surfaces are generated using the myocardial samples for which perfusion values are quantified, for all frames in the cardiac cycle. With these surface points, left ventricular chamber volume and myocardial volume can be computed. A computer simulation was used to determine the sensitivity of the approach to the assumptions of the model. Validation of volume, mass and ejection fraction was performed with correlative MR studies, and ejection fraction and left ventricular volumes were further investigated using correlative first-pass studies. RESULTS: Automated processing was successful in 96% of the cases analyzed. End diastolic volume, end systolic volume, left ventricular mass and left ventricular ejection fraction correlated with MRI with r = 0.97, 0.99, 0.87, and 0.85, respectively. Ejection fraction from tomography correlated with first-pass values with r = 0.82, and end diastolic and end systolic volumes from tomography correlated with first-pass values with r = 0.85 and r = 0.91, respectively. CONCLUSION: The new integrated approach is accurate and robust for computing both perfusion and function from perfusion tomograms.

Computer Simulation↗

ROC analysis of three perfusion display options for ECG-gated perfusion SPECT in severe CAD.

AIM: The simultaneous computation and display of wall motion and perfusion patterns in a single 3D ventricular model would considerably ease the assessment of ECG-gated Tc-99m-sestamibi SPECT, yet the effect on the accuracy of allocating regional perfusion has so far not been validated. METHODS: 3D perfusion mapping (3D Perfusion/Motion Map Software) was compared to the visual assessment of ungated tomographic slices and polar perfusion mapping (Cedars-Sinai PTQ) by correlation analysis and receiver operating characteristics (ROC) analysis at different cut-off levels for coronary stenoses in 50 patients (11 single-, 22 two-, 16 three-vessel disease). Ungated SPECT data were obtained by adding the intervals prior to reconstruction and displaying conventional tomographic slices. All display options were visually assessed in 8 ventricular segments according to a 4-point scoring system and compared to the graded results of coronary angiography. RESULTS: All three display options showed a comparable diagnostic performance for the detection of severe stenoses. The diagnostic gain for the detection of stenoses above 59% was highest for ungated tomographic slices, followed by ungated polar mapping and 3D mapping. Regional assessment revealed a limited performance of 3D mapping in the proximal anterior and distal lateral wall. Polar mapping showed a balanced regional performance. CONCLUSION: 3D Perfusion mapping provides comparable information to conventional display options with the highest diagnostic strength in severe stenoses. Further improvement of the algorithm is needed in the definition of the valve plane.

Angina Pectoris↗

Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch.

UNLABELLED: Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium. METHODS: Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. RESULTS: Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM. CONCLUSION: Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.

Adult↗

[Correlation between the perfusion, perfusion pressure and contractile activity in the nonpregnant uterus].

This paper presents the results of investigations on the dependence between the flow and intravascular pressure and uterine contractile activity. The pressure in the vascular bed was monitored with a pressure transducer and the contractile activity by means of an intrauterine ballon was measured. In a part of experiments, the flow was recorded with a flowmeter. The investigations were performed on 27 nonpregnant human uteri in various phases of the menstrual cycle. Uterus was perfused with a perfusion pump, starting from the perfusion pressure of 50 to 60 mm Hg and on up to maximum values of 140 mm Hg. It has been found that with an increase in the uterine flow, intravascular pressure increases too. This pressure-flow relationship is linear. An increase in flow through the nonpregnant uterus leads to an increase in intravascular pressure from 61.5 mm Hg to 142 mm Hg with a simultaneous increase in the human uterine basal tonus from the 6.2 mm Hg initial value to the average value of 25 mm Hg at the perfusion pressure of 140 mm Hg and an decrease in frequency from 6.6 to 5.2 contractions/10 min. With an increase of flow, however, there is a increase in amplitude which reaches highest values at the 100 mm Hg perfusion pressure and than no significant increase in amplitude is observed. An increase in amplitude is accompanied by an increase in contractile activity. It should be concluded that hemodynamic conditions and the state of vessels play a controlling role in the process of the uterine activity.

Blood Pressure↗

[A trial of antegrade perfusion to the lower half of the body with selective cerebral perfusion for repair of aortic arch aneurysm combined with atherosclerosis obliterance].

A 73-year-old man with aortic arch aneurysm combined with atherosclerosis obliterance underwent aortic arch replacement. As he had bilateral femoral artery obstruction, we instituted ECC with arterial perfusion through the ascending aorta. Then, the left ventricle started dilating due to mild degree of aortic regurgitation. So with selective cerebral perfusion, we perfused the lower half of the body through a Foley balloon catheter which was inserted from the aortic arch antegradely. We could perfuse with the catheter for 20 minutes for core cooling and then during repair until the catheter disturbed the operation. The Foley catheter had given us some difficulties for handling during the procedure. Based on this experience, we have made a catheter which had both a balloon for aortic occlusion and a tube for perfusion and which we could keep away from operative fields, similar to the way we used antegradely insertable aortic occlusion balloon catheter.

Aged↗

Increased pulmonary perfusion worsens ventilation-perfusion matching.

BACKGROUND: Severe exercise and administration of vasopressors may adversely affect pulmonary gas exchange in humans. The role of increases in pulmonary perfusion in worsening ventilation-perfusion (VA/Q) relationships is unclear, however, because concomitant changes in ventilation and alveolar gas composition occur. The purpose of this study was to determine whether increasing of lobar blood flow increased VA/Q heterogeneity in the absence of changes in respiratory parameters. METHODS: Six pentobarbital-anesthetized dogs underwent bilateral thoracotomies, left upper lobectomy, and placement of an electromagnetic flow probe on the left lower lobe (LLL) pulmonary artery, and catheters were inserted into the LLL pulmonary artery distal to the flow probe and confluent trunk of the LLL pulmonary vein. A bronchial divider was inserted to allow separate ventilation of the right lung and LLL. Blood flow to the LLL (QLLL) was increased in random order to two and three times baseline blood flow by opening an arteriovenous fistula and partially occluding the right pulmonary artery. Minute ventilation and alveolar PCO2 of the lobe were unchanged due to use of constant tidal volume and respiratory rate and inspiration of variable amounts of carbon dioxide. VA/Q distributions of the LLL were obtained using the multiple inert gas elimination technique. The tracer inert gas arterial-alveolar difference ([a-A]D) area was used to assess VA/Q mismatch. RESULTS: Increasing QLLL increased mean pulmonary artery pressure in the LLL (LLL Ppa). The PO2 of the LLL pulmonary venous blood remained unchanged, as the mixed venous oxygen tension (PvO2) was markedly increased. VA/Q inequality was increased, indicated by a 40% increase in the [a-A]D area when QLLL was increased to two times greater than baseline QLLL and a 58% increase in the [a-A]D area with three times greater than baseline QLLL. The [a-A]D area was highly correlated with the lobar blood flow (r = 0.97) and LLL Ppa (r = 0.97). CONCLUSIONS: Marked increases in lobar blood flow and Ppa worsened pulmonary gas exchange. The degree of impairment was correlated with the degree of increase in lobar perfusion. However, increased lobar perfusion did not affect LLL pulmonary venous blood oxygenation because the decrease in PO2, due to increased VA/Q mismatch, was opposed by an increase in PO2, due to increased PvO2.

Animals↗

Intractible cutaneous non-Hodgkin's lymphoma of the lower limb. Complete remission after sequential regional isolated hyperthermic perfusion and perfusion with 1-phenylalanine-mustard (melphalan, L-Pam).

A 61-year-old man with an intractible and progressively disabling cutaneous non-Hodgkin's lymphoma (NHL) in the lower limb was treated with sequential regional isolated perfusion at 10-day intervals. The first perfusion was hyperthermic (40.2-43.1 degrees C tumor-temperature); the second was at controlled normothermia with high-dose 1-phenylalanine mustard (melphalan, L-Pam; 11 mg/l perfused tissue). This treatment resulted in a complete remission in the perfused area of significant duration and has prevented amputation.

Chemotherapy, Cancer, Regional Perfusion↗

Toxicity of hyperthermic isolated limb perfusion with cisplatin for recurrent melanoma of the lower extremity after previous perfusion treatment.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem. METHODS: HILP with cisplatin, 20-30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in-transit metastases. RESULTS: During a median follow-up of 20 months (range, 10-25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3-11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor-sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients. CONCLUSIONS: The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Aged↗