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Results for “Infusions, Intralesional”

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PubMed1998

Intratumoral infusion of fluid: estimation of hydraulic conductivity and implications for the delivery of therapeutic agents.

We have developed a new technique to measure in vivo tumour tissue fluid transport parameters (hydraulic conductivity and compliance) that influence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to produce a radially symmetrical fluid source in the centre of human tumours in immunodeficient mice. At constant flow, the pressure gradient generated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured as a function of the radial position with micropipettes connected to a servo-null system. To evaluate whether the fluid infused was reabsorbed by blood vessels, infusions were also performed after circulatory arrest. In the colon adenocarcinoma LS174T with a spherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 microl min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm2 mmHg(-1) s. Compliance estimates were 35 microl mmHg(-1) in vivo, and 100 microl mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26T, hydraulic conductivity and compliance were not calculated because of the asymmetric distribution of the fluid infused. The technique will be helpful in identifying strategies to improve the intratumoral and systemic delivery of gene targeting vectors and other therapeutic agents.

Absorption↗

PubMed2003

[Autologous tumor specific immunotherapy of refractory cancers with ex vivo-generated T cells stimulated by autologous tumor cell].

OBJECTIVES: Autologous tumor-cell stimulated cytotoxic T lymphocytes (AuTLs) were prepared from peripheral blood T cells and the T cells were activated ex vivo over a 2-week culturing process in the presence of IL-2 and autologous biopsied tumor-cells from advanced cancer patients. These AuTLs may have potential for efficacy as a locoregional therapy in patients with refractory cancer. METHODS: Twenty-nine of 35 cancer patients (13 esophagus, 5 lung, 3 stomach, 4 breast, 1 melanoma) were enrolled in an early Phase II clinical trial. The patients received direct locoregional intratumoral injection of AuTLs biweekly through medical endoscope or intraarterial infusion reservoir system. Mean 0.25 x 10(9) AuTLs were injected 1 x /2 weeks for 6 weeks. RESULTS: Adverse events related to AuTL were minimal. AuTLs specific for autologous tumor cells were observed in 12 of 29 patients. Seven of these 12 patients (58.3%) had partial response (PR) or stable disease (SD). In contrast, 8 of 23 (34.8%) remaining patients treated by non-specific AuTLs had SD. Infiltration of T effector cells was significantly increased on the biopsied tumor specimens in the immunohistological studies. Furthermore, 11 patients receiving systemic infusion of non-specific LAK/NK T cells without autologous tumor-cell stimulation only had 2 SDs (18.2%). CONCLUSIONS: Our results demonstrated the clinical potential of intra-peritumoral administration of AuTLs. Thus, locoregional immunotherapy with autologous tumor specific AuTLs may be more effective than systemic adoptive immunotherapy using intravenous infusion of autologous tumor non-specific LAK/NK T cells for the treatment of solid cancers.

Breast Neoplasms↗

PubMed2002

Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor.

Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. We have carried out an experimental study in order to evaluate the effect of CPT-11 on the growth of a subcutaneously implanted malignant neuroectodermal tumor, after administration by different routes. The results showed that CPT-11 administration by intraperitoneal injections (at dose 10 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period--one course--to a total of two courses) had no significant antitumor effect. Nevertheless, continuous infusion by intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4 microg/h) showed a significant delay in tumor growth in 4 weeks of the implantation. The best antitumor effects were observed after CPT-11 intratumoral administration (at dose of 5 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period, to a total of three courses) reaching tumor regression in the treated animals. These results suggest the utility of CPT-11, by means of intralesional administration, on malignant tumors of the nervous system.

Animals↗

PubMed1995

[Intracystic infusion therapy of minocycline hydrochloride for benign hepatic cysts].

This paper describes ultrasonically-guided infusion of minocycline hydrochloride solution (MINO infusion therapy) in benign nonparasitic cysts of the liver. MINO infusion therapy was performed in 7 large hepatic cysts and successful results were obtained in 6 lesions. The infusion procedure in the initial 4 hepatic cysts a 7 Fr catheter was placed into the cyst and MINO solution was left in the cyst according to the procedure of ethanol infusion therapy. In the most recent 2 cases the cyst was punctured with a 21G needle, washed with physiologic saline and then infused MINO solution without placement of an indwelling drainage tube. This modified procedure is simple and safe and also yields a good therapeutic result. MINO infusion therapy for benign hepatic cyst is very useful and the modified procedure can be performed safely in elderly patients and in patients with several complications.

Adult↗

PubMed1997

A totally implantable drug delivery system for local therapy of the middle and inner ear.

Local therapy of middle and inner ear diseases is being used, but is restricted to cases of ear drum perforation or to repeated invasive intratympanic drug application by the physician. In accordance with the Medical Device Directive (class III), a bone-anchored, totally implantable drug delivery system (TI-DDS) has been developed. It includes a micropump for subcutaneous, patient-controlled activation, a drug reservoir and a septum port. A thin guide-wired catheter leads from the pump outlet to the point of application in the mastoid or middle ear cavities. Local inner ear therapy with suitable drugs is possible by positioning the catheter's end near the round window membrane. The system requires no battery and will offer a wide range of patient-controlled bolus applications (25 microliters per activation). We first analyzed the three-dimensional implantation geometry of the mastoid cavity. Basic micromechanical problems have been solved in order to create several prototypes. The TI-DDS has already undergone extensive in vitro testing. Recent results of pump rate precision and digital pressure force testing are promising. Local drug treatment for conditions such as lidocaine-sensitive tinnitus, secretory otitis media, Meniere's disease, localized pain and intralesional cancer is under discussion. Furthermore, local application of future biotechnological trophic factors for inner ear treatment is anticipated. The basic engineering is completed and initial animal tests are in preparation.

Animals↗

PubMed1997

[Chemotherapy for primary bile duct cancer].

The prognosis for patients with bile duct cancer (BDC) is still dismal, because of the high incidence of postresection recurrence and frequency of unresectable tumors. Chemotherapy has been applied over 20 years with anticipation of enhanced response rate together with minimal adverse effects and prolonged survival. Despite the scarcity of experiences with chemotherapy dedicated to BDC, some efficacy of chemotherapy on BDC has been indicated by this review of the literature. Chiefly, the administered drugs to unresectable BDC were 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin-C (MMC). Systemic chemotherapy, employing those drugs as single agents or as a combination like FAM (5-FU + ADM + MMC), was most commonly administered. The collective response rate was 18.6% (13/70), including a higher response rate of 29% (4/14) by FAM. Regional chemotherapy by hepatic arterial infusion has been expected to be more effective from the view point of blood supply, however, only a few trials have been reported as long as BDC. The series from the literature show a collective response rate of 50% (3/6) for hepatic arterial infusion therapy. The total number of patients (n = 16) treated by intra-ductal chemotherapy is too small to estimate clinical efficacy despite a relatively high collective response rate of 43.8% (7/16). This paper should encourage further investigation of chemotherapy for BDC.

Antineoplastic Agents↗

PubMed2006

Chemical tumor ablation with use of a novel multiple-tine infusion system in a canine sarcoma model.

PURPOSE: To determine whether larger confluent zones of ablation can be achieved in chemical ablation with use of a multiple-tine infusion device compared with standard needle infusion in a solid tumor model. MATERIALS AND METHODS: Multiple canine venereal sarcomas (N=42) were implanted in nine mildly immunosuppressed dogs (treated with 10 mg/kg cyclosporin A twice daily). Tumors incubated for 8-12 weeks grew to a diameter of 5.4 cm+/-1.0. With ultrasound guidance, 8-56 mL of 100% ethanol or 15% acetic acid (diluted in saturated saline solution) were injected in aliquots (2-8 mL) at multiple distances (radius of 0-2 cm) from the needle axis with use of a multiple-tine infusion device. Presence of fluid reflux at the needle puncture site and resultant coagulation diameters were measured within 1 hour and compared with the results of infusion with a standard 18-gauge needle. RESULTS: Multiple-tine infusion enabled greater fluid infusion (15 mL+/-3 to 53 mL+/-3 depending on protocol) than standard needle injection (8 mL+/-1) before reflux was observed at the puncture site (P<.01). Additionally, progressive gains in contiguous tumor coagulation were achieved because acetic acid was infused as far as 2 cm from the needle axis with the multiple-tine device (P<.01; R(2)=0.59; y=0.5x+2.9). Optimal coagulation was achieved with the infusion of 4-mL aliquots at 0.5 cm and 1.0 cm from the needle, followed by three 4-mL or 8-mL aliquots (40 degrees rotation between infusions) at 1.5 cm and 2.0 cm from the needle (32 mL+/-0 and 53 mL+/-3 total, respectively). This yielded confluent short-axis coagulation diameters of 4.9 cm+/-1.0 and 5.4 cm+/-1.0, respectively, which were significantly greater than the measurement of 3.1 cm+/-0.4 achieved with standard needle infusion (P<.01). Smaller and noncontiguous foci of coagulation foci (1.7 cm+- 0.5) were seen with the use of ethanol for standard needle and multiple-tine infusions. CONCLUSIONS: Chemical ablation with 15% acetic acid with use of a multiple-tine infusion device resulted in larger diameters of contiguous tumor coagulation and enabled greater volumes of infusion than standard needle infusion or ethanol ablation. This suggests that chemical ablation with acetic acid infused with use of a multiple-tine device may overcome some of the difficulties seen with the use of conventional needle chemical ablation injection alone, such as irregular ablation and fluid reflux up the needle tract.

Acetic Acid↗

PubMed2005

Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor--a pharmacokinetic study.

Solvent facilitated perfusion (SFP) has been proposed as a technique to increase the delivery of chemotherapeutic agents to tumors. SFP entails direct injection of the agent into the tumor in a water-miscible organic solvent, and because the solvent moves easily through both aqueous solutions and cellular membranes it drives the penetration of the solubilized anticancer agent throughout the tumor. To test this hypothesis, we compared the pharmacokinetics (PK) of 14C-labeled 1,3-bis-chlorethyl-1-nitrosourea (BCNU) in intra-cerebral 9L rat gliomas after intravenous (IV) infusion in 90% saline--10% ethanol or direct intratumoral (IT) injection of 14C-BCNU in 100% ethanol (DTI-015). Treatment with DTI-015 yielded a peak radioactive count (Cmax) for the 14C label that was 100-1000 fold higher in the tumor than in all other tissues in addition to a concentration in the tumor that was 100-fold higher than that achieved following IV infusion of 14C-BCNU. Pathologic and auto-radiographic analysis of tissue sections following IT injection of 14C-BCNU in ethanol into either tumor or normal rat brain revealed both an enhanced local volume of distribution and an increased concentration of BCNU delivered to tumor compared to non-tumor bearing brain. To investigate the mechanism behind the SFP of BCNU to the tumor both dynamic contrast and perfusion MRI were performed on 9L tumors before and after treatment and demonstrated a decrease in tumor perfusion following IT injection of DTI-015. Finally, initial PK of patient blood samples following administration of DTI-015 into relapsed high-grade glioma indicated a 20-fold decrease in systemic exposure to BCNU compared to IV infusion of BCNU providing further evidence for the enhanced therapeutic ratio observed for DTI-015.

Animals↗

PubMed2004

Cidofovir plasma assays after local injection in respiratory papillomatosis.

OBJECTIVE: To assess cidofovir plasma concentration after intralesional airway administration for recurrent respiratory papillomatosis. DESIGN: Prospective study. SETTING: Tertiary care teaching hospital. PATIENTS AND METHOD: The study comprised 21 patients (10 children and 11 adults). Plasma samples were collected at 10 and 45 minutes (T10, T45) or at 10 and 60 minutes (T10, T60) after injection. The measurements of cidofovir were performed using a high-performance liquid chromatographic method. RESULTS: Plasma samples were collected at T10 and T45 on 19 occasions from the children and on 17 from the adults. A linear relationship was found between plasma concentration and dose in children (mean dose 1.2 mg/kg; mean cidofovir plasma levels 0.91 and 0.81 microg/mL) but not in adults (mean dose 0.2 mg/kg; mean plasma levels 0.21 and 0.31 microg/mL). The same relationships were found between dose and area under the concentration/time curve (AUC). Four plasma samples were taken in children at T10 and T60: mean dose 1.2 mg/kg and mean plasma concentrations 1.11 and 1.24 microg/mL. Maximum plasma concentration averaged 34% (SD 11%) in children and 62% (SD 33%) in adults, with equivalent plasma level after intravenous infusion of the same dose. CONCLUSIONS: The cidofovir plasma levels were below those leading to toxicity. The levels and the AUC were dose dependent in children but not in adults. Diffusion from the injected site was greatest in a few adults and unpredictable. Because of the great individual variation in diffusion in adults, cidofovir should be used at less than the recommended intravenous dose to prevent any risk of systemic toxicity.

Adult↗

PubMed2001

Results of surgery and radio-hyperthermo-chemotherapy for patients with soft-tissue sarcoma.

BACKGROUND: Between 1990 and 1999, we performed radio-hyperthermo-chemotherapy (RHC) in 44 patients with high-grade soft-tissue sarcomas of the limbs. METHODS: Radiotherapy involved the delivery of radiation at a dose of 2 Gy once daily on 16 days, to give a total dose of 32 Gy. Hyperthermia was conducted once a week, with a total of five sessions. Chemotherapy was performed by implanting a reservoir and administering cisplatin (3 mg/kg) three times, and pinorubin (an adriamycin derivative; 1 mg/kg) twice by intra-arterial infusion, at weekly intervals. These drugs were administered alternately during hyperthermia sessions. RESULTS: Tumor shrinkage was observed in 98% (43/44) of the patients. Of the 36 patients with M0 tumors, 30 were disease-free at final follow-up, 2 had no evidence of disease, 1 was alive with disease, and 3 had died of the disease. Amputation was required only in the first patient, and the affected limb was preserved in the other 43 patients. The surgical margin was wide in 9 patients and marginal in 29 patients, and intralesional excision was performed in 5 patients. There was recurrence in only 1 of the 44 patients. CONCLUSION: RHC is currently the most potent and relatively safe treatment method for high-grade soft-tissue sarcomas that is available clinically.

Adolescent↗

PubMed1991

Direct intraarterial wall injection of microparticles via a catheter: a potential drug delivery strategy following angioplasty.

Local delivery into the arterial wall of medications at high concentrations may evolve as a method to reduce postangioplasty restenosis. However, since the atherosclerotic artery has increased vasa vasorum, medications injected in a fluid state may diffuse out of the arterial wall too quickly to have a therapeutic effect. Thus we evaluated whether microparticles as a model for a particulate microcarrier drug delivery system, injected via a porous balloon catheter, could be retained within the atherosclerotic rabbit femoral arterial wall. Arteries were injected with a 5 microns microparticle suspension for 45 seconds at either 3 or 5 atm of infusion pressure immediately following balloon angioplasty. Arteries were obtained immediately following the procedure or at 1, 3, 7, or 14 days after infusion to evaluate for the presence of retained microparticles. Of 34 arteries, 30 contained retained microparticles, with 21 exhibiting microparticles in the neointimia, 12 in the media, and 25 in the adventitia. Microparticles were retained for as long as 14 days, and there was no difference between the distribution or quantity of microparticles at 3 or 5 atm of infusion pressure. The mode of microparticle distribution probably involved deposition within dissection planes, although evidence for vasa vasorum transport was observed. We hypothesize that biodegradable microparticles could serve as a vehicle for intramural drug delivery in the treatment of restenosis.

Angioplasty, Balloon↗

PubMed1993

[A case of post-traumatic eosinophilic pleural effusion improved by direct infusion of corticosteroid into the pleural space].

A 49-year-old man was admitted with non-productive cough and left chest discomfort. About one month prior to the admission, he suffered a non-penetrating injury to the left anterior chest. Although rib fracture or pleural effusion was not reported, left chest discomfort and non-productive cough progressed gradually. Chest X-ray film and chest CT scan on admission showed left massive pleural effusion. Close examination revealed a marked increase of eosinophils in the pleural effusion (77% of total cell counts). Because malignancy, parasitic disease, and collagen disease were differentiated, we diagnosed this case as post-traumatic eosinophilic pleural effusion, and decided to administers corticosteroid therapy; hydrocortisone 300 mg was infused into the left pleural space. Seven days after the treatment, the pleural effusion and peripheral eosinophilia had completely disappeared. This case suggests that direct infusion of corticosteroid into the pleural space provides greater drug availability in the treatment of post-traumatic eosinophilic pleural effusion related to immunological reaction of the pleura. The indication and dosage of corticosteroids should be established, however, because there have been some reports of cases of improvement without any special treatment.

Eosinophilia↗

PubMed2000

Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study.

OBJECT: The gene therapy paradigm of intratumoral activation of ganciclovir (GCV) following transduction of tumor cells by retroviral vectors bearing the thymidine kinase (tk) gene has produced dramatic remissions of malignant gliomas in animal models. In human trials, although the technique has been deemed safe, little antitumor effect has been demonstrated. To evaluate the basis of this inefficacy in human gliomas, the authors conducted a gene-marking trial involving neuropathological and biochemical studies of treated tumor specimens. METHODS: Five patients with malignant recurrent gliomas underwent stereotactic biopsy sampling and intratumoral implantation procedures with three aliquots of 10(6) vector-producing cells (VPCs) in columns. After 5 days, the tumor was resected and the tumor bed reimplanted with VPCs, and a course of GCV was given. Patients received clinical and radiological follow up for 6 months. Tumor specimens were analyzed neuropathologically and for tk gene expression by anti-TK immunohistochemistry and TK enzymatic activity. Four patients tolerated the treatment well but experienced tumor progression. The other developed an abscess after the second operation and died. Increased TK enzymatic activity was demonstrated in the one tumor specimen analyzed. Immunohistochemical evidence of tk gene expression was limited to VPCs. Transduction of tumor cells was not seen. Viable tumor cells were seen near VPCs containing TK. The lymphocytic immune response was mild. CONCLUSIONS: Except for the risk of infection inherent in reoperation, this tk-GCV paradigm was both feasible and safe. Pathological studies indicated that limited dissemination of VPCs and vector from the infusion site and failure to transduce tumor cells with the tk gene are major barriers to efficacy.

Adult↗

PubMed1997

Direct endovascular thrombolytic therapy for dural sinus thrombosis: infusion of alteplase.

PURPOSE: To evaluate the efficacy, safety, and results of direct thrombolytic therapy in intracranial dural sinus thrombosis by infusion of alteplase (recombinant tissue plasminogen activator). METHODS: Nine patients were treated during a 2-year period for intracranial dural sinus thrombosis. A microcatheter was placed directly into the thrombus in the dural sinus via the transfemoral route. Thrombolysis was initiated with a rapid injection of 10 mg of alteplase over 10 minutes, followed in 3 hours by a continuous infusion of 50 mg, then a continuous infusion at 5 mg per hour until complete thrombolysis or a total dose of 100 mg per day had been reached. Repeat thrombolysis was tried the following day if complete recanalization did not occur at 100 mg per day. RESULTS: Successful recanalization with improvement of symptoms was achieved in all cases. Time required for complete thrombolysis was between 8 and 43 hours. The total dose of alteplase ranged from 50 to 300 mg. Complications of a small intrapelvic hemorrhage and oozing at a femoral puncture site occurred in separate cases, but were not related to the amount of infused alteplase. MR venograms obtained 1 to 4 weeks after the procedure showed no evidence of reocclusion of the dural sinuses. CONCLUSION: Direct fibrinolytic therapy with alteplase is safe, fast, and effective in treating dural sinus thrombosis. However, to prevent hemorrhagic complications, further studies are required to determine its optimal dose and proper rate of administration.

Adult↗

PubMed1999

CT fluoroscopy-assisted needle puncture and ethanol injection for hepatocellular carcinoma: a preliminary study.

OBJECTIVE: We assessed the usefulness of real-time CT fluoroscopy for needle guidance and evaluated the clinical usefulness of a unified CT fluoroscopy and angiography system in the treatment of hepatocellular carcinoma. SUBJECTS AND METHODS: A single-session percutaneous ethanol injection was performed with CT fluoroscopy guidance and monitoring for 15 hepatocellular carcinomas with an average size of 2.5 cm (range, 0.7-4.7 cm) in 10 consecutive patients. Of these, seven lesions were not seen on sonography. To mark the lesion for puncture, we performed CT arteriography or arterial injection of iodized oil. A puncture guide was applied to 12 lesions. RESULTS: The average depth from the skin's surface to the lesion was 9.3 cm (range, 4.5-11.5 cm), and the puncture route was transthoracic in five lesions and transabdominal in 13. The overall success rate in puncturing the lesions was 94.4% (17/18 sessions). The average number of punctures was 3.3, and it significantly decreased after introduction of a puncture guide compared with freehand puncture (p < .01). The average amount of injected ethanol was 12.7 ml (range, 4-27 ml). The ratio of injected ethanol dose to calculated ethanol dose was 0.6. Local recurrence occurred in four (26.7%) of 15 lesions after an average of 5 months. CONCLUSION: Using CT fluoroscopy for guidance of the needle and for monitoring ethanol infusion in the target lesion, we have found single-session percutaneous ethanol injection to be possible for hepatocellular carcinomas smaller than 5 cm or not revealed by sonography. The puncture guidance equipment was helpful for accurate insertion of the needle into the lesion, allowing a minimum number of punctures and minimal radiation exposure.

Aged↗

PubMed1999

Enzymatic dissolution of post-operative haemothorax by purified streptokinase.

Enzymatic dissolution of haemothorax is highly effective in the evacuation of proteinaceous material from the pleural space. Its use in postcardiotomy haemothorax has not been described. We report the case of a 4-year-old girl with Fallot's Tetralogy diagnosed at birth. She underwent a total correction of Fallot's Tetralogy at 4 years of age. Chest X-ray taken post-operatively showed a large pleural collection in her right haemithorax. Repeated intraplueral infusion of purified streptokinase into the right upper pleural chest tube greatly reduced the extent of the right haemothorax. Enzymatic dissolution of haemothorax by purified streptokinase has proven to be a rapid and successful method of therapy. It has provided an alternative which is less invasive and has a low morbidity.

Cardiac Surgical Procedures↗

PubMed1996

[Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors].

We performed the locoregional injection of OK-432/fibrinogen/thrombin to unresectable hepatic tumors metastasized from colorectal cancers, which were hardly controlled by arterial infusion chemotherapy. CEA was markedly decreased following this treatment, although abdominal CT did not show a significant reduction of tumor mass. This immuno-injection therapy may be a choice of treatment for metastatic liver tumors, refractory to treatment by conventional chemotherapy.

Antineoplastic Agents↗

PubMed2001

Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.

We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.

Adult↗