3 research outputs found
Biochemotherapeutic Strategies and Minimally Invasive Balloon Catheter Techniques in Regional Perfusion
This thesis is based on studies investigating the feasibility of balloon catheter mediated hypoxic perfusion of abdomen, pelvis and liver for treatment of locally advanced malignancies. Within this context the studies focussed on the addition of tumour necrosis factor-alpha (TNF) to these minimal invasive perfusion procedures.
Hypoxic abdominal (HAP) and hypoxic pelvic perfusion (HPP) using balloon catheters, are currently applied modalities for treatment of a wide variety of abdominal and pelvic tumours, yet scientific validation of these procedures is poor. Following the results of several phase I-II trials, both treatments are associated with severe systemic toxicity, significant morbidity and even mortality. The degree of systemic leakage associated with these procedures prohibits addition of TNF. For leakage free liver perfusion surgery is still required, as with current balloon catheter techniques it is not possible to perform leakage free isolated hypoxic hepatic perfusion (IHHP), using either orthograde or retrograde hepatic flow. Experimental and clinical observations suggest that within any perfusion setting, the utilization of TNF is only indicated for treatment of highly vascularised tumours and not for treatment of colorectal tumours.
Balloon catheter technology in its present form does not provide adequate leakage control in any of these settings and is therefore associated with considerable toxicity. It is associated with poor response rates and can not be considered in any setting as a standard of care
Isolated hypoxic hepatic perfusion with tumor necrosis factor-alpha, melphalan, and mitomycin C using balloon catheter techniques: a pharmacokinetic study in pigs
OBJECTIVE: To validate the methodology of isolated hypoxic hepatic
perfusion (IHHP) using balloon catheter techniques and to gain insight
into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and
mitomycin C (MMC) through the regional and systemic blood compartments
when applying these techniques. SUMMARY BACKGROUND DATA: There is no
standard treatment for unresectable liver tumors. Clinical results of
isolated limb perfusion with high-dose TNF and melphalan for the treatment
of melanoma and sarcoma have been promising, and attempts have been made
to extrapolate this success to the isolated liver perfusion setting. The
magnitude and toxicity of the surgical procedure, however, have limited
clinical applicability. METHODS: Pigs underwent IHHP with TNF, melphalan,
and MMC using balloon catheters or served as controls, receiving
equivalent dosages of these agents intravenously. After a 20-minute
perfusion, a washout procedure was performed for 10 minutes, after which
isolation was terminated. Throughout the procedure and afterward, blood
samples were obtained from the hepatic and systemic blood compartments and
concentrations of perfused agents were determined. RESULTS: During
perfusion, locoregional plasma drug concentrations were 20- to 40-fold
higher than systemic concentrations. Compared with systemic concentrations
after intravenous administration, regional concentrations during IHHP were
up to 10-fold higher. Regional MMC and melphalan levels steadily declined
during perfusion, indicating rapid uptake by the liver tissue; minimal
systemic concentrations indicated virtually no leakage to the systemic
blood compartment. During isolation, concentrations of TNF in the
perfusate declined only slightly, indicating limited uptake by the liver
tissue; no leakage of TNF to the systemic circulation was observed. After
termination of isolation, systemic TNF levels showed only a minor
transient elevation, indicating that the washout procedure at the end of
the perfusions was fully effective. CONCLUSIONS: Complete isolation of the
hepatic vascular bed can be accomplished when performing IHHP using this
balloon catheter technique. Thus, as in extremities, an ideal leakage-free
perfusion of the liver can now be performed, and repeated, without major
surgery. The effective washout allows the addition of TNF in this setting
Cardiovascular effects of simultaneous occlusion of the inferior vena cava and aorta in patients treated with hypoxic abdominal perfusion for chemotherapy
BACKGROUND: Animal studies suggest less cardiovascular disturbance if the
aorta and vena cava are occluded simultaneously. We set out to establish
the effects of simultaneous clamping in humans, because oncologists
suggested that perfusion for chemotherapy could be done under local
anaesthesia without invasive haemodynamic monitoring. METHODS: We studied
the cardiovascular effects of the onset and removal of simultaneous
occlusion of the thoracic aorta and inferior vena cava, in seven ASA II
patients. Two stop-flow catheters positioned in the aorta and in the
inferior vena cava were inflated to allow hypoxic abdominal perfusion to
treat pancreatic cancer. We measured the arterial pressure, heart rate
(HR), right atrial pressure (RAP), pulmonary artery pressure (PAP),
pulmonary artery wedge pressure (PAWP) and cardiac output (CO), and
calculated systemic vascular resistance index (SVRi), pulmonary vascular
resistance index (PVRi), left ventricular stroke work index (LVSWi) and
right ventricular stroke work index (RVSWi). Three patients were studied
with transoesophageal echocardiography. RESULTS: Six patients needed
intravenous nitroprusside during the occlusion because mean arterial
pressure (MAP) increased to more than 20% of baseline (SVRi increased by
87%). One minute after occlusion release, all patients had a 50% decrease
in MAP, and mPAP increased by 50%. The procedure had severe cardiovascular
effects, shown by a 100% increase in cardiac index at occlusion release
with in