| 1. |
- Lindnér, Per, 1956, et al.
(författare)
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Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon (133Xe) clearance.
- 2004
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Ingår i: Hepato-gastroenterology. - 0172-6390. ; 51:57, s. 781-6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to identify in a standardized experimental rat liver tumor system the drugs which are most appropriate in influencing the relationship between liver tumor and normal liver parenchyma blood flow as estimated with 133Xe washout clearance method, and thereby positively influencing the kinetics of chemotherapeutic drugs. A battery of vasoactive drugs, which according to a literature review were considered to be active, were tested.
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| 2. |
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| 3. |
- Öman, Mikael, et al.
(författare)
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133Xe clearance estimates the effect of vasopressin on peritoneal blood flow in rats.
- 2004
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Ingår i: Hepato-gastroenterology. - 0172-6390. ; 51:58, s. 1037-41
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Tidskriftsartikel (refereegranskat)abstract
- When assessing the peritoneal microcirculation with invasive methods, interference with the mechanisms of vaso-regulation may occur. The 133Xe clearance technique renders the possibility, by minimal invasiveness, to estimate the influence of a vasoactive agent on the peritoneal microcirculation.
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| 4. |
- Öman, Mikael, et al.
(författare)
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Effect of carcinomatosis and intraperitoneal 5-fluorouracil on peritoneal blood flow modulated by vasopressin in the rat as measured with the 133Xe-clearance technique.
- 2004
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Ingår i: Cancer chemotherapy and pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 54:3, s. 213-8
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Tidskriftsartikel (refereegranskat)abstract
- Intraperitoneal administration of 5-fluorouracil for the treatment of gastrointestinal malignancies results in a greater total drug exposure in the peritoneal fluid than in plasma. Drugs are eliminated from the peritoneal cavity mainly by capillaries leading to the portal venous system and to a lesser extent by lymphatics. The drug itself and the presence of peritoneal carcinomatosis may affect elimination of the drug. The 133Xe-clearance technique allows the influence of a vasoactive agent on the peritoneal blood flow to be estimated with minimal invasiveness. The aim of the present study was to explore whether intraperitoneal 5-FU or peritoneal carcinomatosis affects the peritoneal blood flow and its reactivity to intravenous vasopressin, as measured indirectly with the 133Xe-clearance technique.
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| 5. |
- Öman, Mikael, 1956-
(författare)
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Intraperitoneal 5-Fluorouracil treatment of cancer - clinical and experimental studies
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Pancreas cancer is a most aggressive malignancy. More than 80% of patients diagnosed with pancreas cancer, exhibit such advanced disease, that curative surgery is impossible. Systemic chemotherapy prolongs survival to 5-9 months. High concentrations of chemotherapeutic agents in the abdominal cavity and in the lymphatics draining the area is achieved by intraperitoneal administration. Vasopressin decreases splanchnic blood flow, reducing the intraperitoneal uptake of drugs, thus raising the local and lymphatic dose intensity.Aim: The aim of the study was to investigate the feasibility and tumour response of intraperitoneal 5-Fluorouracil (5-FU) treatment in non-resectable pancreas cancer, using vasopressin to improve the pharmacokinetic profile. Further, to study the effect of vasopressin on peritoneal blood flow, altered by intraperitoneal 5-FU or the presence of peritoneal carcinomatosis.Methods: In the animal experiments, the 133Xe-clearance technique and as a comparison Laser doppler flow, were used to identify changes of peritoneal blood flow caused by vasopressin in unmanipulated animals and in animals with peritoneal carcinomatosis or animals given intraperitoneal 5-FU. In the clinical studies, 68 (39 women/29 men) patients, with a non-resectable ductal pancreas cancer and a Karnovsky Index ≥70 were included. Patients were treated with 750-1500 mg/m2 5-FU intraperitoneally through a Port-a-cath and Leucovorin 100 mg/m2 intravenously on two consecutive days every 21 days until progression. Seventeen patients, receiving 750 mg/m2 5-FU, were given concomitant vasopressin 0.1 IU/min during 180 minutes, alternatively day 1 or 2.Results: In the animal experiments, vasopressin 0.07 IU/kg/min significantly reduced the 133Xe-clearance. Intraperitoneal 5-FU decreased the basal peritoneal blood flow and abrogated the vasopressin effect for 1-2 days. The presence of peritoneal carcinomatosis did not influence the basal peritoneal blood flow, nor the reduction of peritoneal blood flow caused by vasopressin. In the clinical studies, the treatment with intraperitoneal 5-FU was well tolerated, with no WHO Grade 3 or 4 toxicity with doses up to 1250 mg/m2. Thirty patients achieved at least stable disease at three months. The median survival time was 8.0 (range 0.8-54.1) months. There was a significant reduction of 5-FU Cmax on day 2, but no significant reduction of AUC, when vasopressin was given.Conclusion: Peritoneal blood flow changes caused by vasopressin can be estimated with the 133Xe-clearance technique. Intraperitoneal 5-FU but not peritoneal carcinomatosis decreases the vasopressin induced 133Xe-clearance reduction, 1-2 days after administration. In patients with non-resectable pancreas cancer, intraperitoneal 5-FU up to 1250 mg/m2 for two days every third week can be given without WHO grade 3 and 4 toxicity. The treatment is well tolerated with few and minor side effects. Tumour responses were observed. Addition of vasopressin does not significantly enhance the pharmacokinetics of intraperitoneal 5-Flurorouracil, but adds toxicity.
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