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Biomedical subjects

C H Carrasco

Publications and source records attributed to C H Carrasco.

At least 37 records · Page 2Linked to original sources

Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study.

BACKGROUND: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin. METHODS: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m2, three patients were treated at 90 mg/m2, and five patients received 120 mg/m2. A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation. RESULTS: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p < 0.01). Because all catheters were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was 120 mg/m2. CONCLUSIONS: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will allow use of higher doses of chemotherapeutic agents to treat HCC.

Adult↗

Management of tracheal and bronchial stenoses with the Gianturco stent.

Thirty-six cancer patients with symptomatic tracheobronchial stenoses received Gianturco tracheobronchial stents over a 9-year period. Symptoms improved in 28 patients (78%). The overall median survival was 1 month 3 weeks (range, 4 days to 35 months). The median survival for patients who showed improvement after receiving stents was 3 months compared with 1 week for those who did not respond. Complications were minimal. The Gianturco stent may palliate symptoms of tracheobronchial compression in selected cancer patients.

Adult↗

Hepatic arterial infusion of verapamil and doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration: pharmacological evaluation of reduction in systemic drug exposure and assessment of hepatic toxicity.

Tumour resistance to chemotherapeutic drugs through expression of the multidrug resistance phenotype is a major impediment in the treatment of hepatic malignancies. We performed hepatic arterial infusion of verapamil (at a dose known to block P-glycoprotein activity) and doxorubicin combined with complete hepatic venous isolation and extracorporeal chemofiltration in non-tumour-bearing pigs with normal livers to evaluate the pharmacology and toxicology of this drug combination. The complete hepatic venous isolation-chemofiltration system significantly reduced system exposure to both verapamil and doxorubicin (P < 0.01). Hepatic arterial infusion of verapamil (2 mg/kg) alone did not result in hepatocellular toxicity. However, the combination of verapamil and doxorubicin (3 mg/kg or 5 mg/kg) produced significant elevations in liver enzymes (P < 0.01), and gross histological evidence of liver damage in 90% of the treated animals. The results of this study indicate that hepatic arterial infusion of verapamil and doxorubicin, in an attempt to improve treatment response in unresectable liver tumours expressing the multidrug resistance phenotype, may not be tolerated by patients with limited hepatic reserve.

Animals↗

Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial.

A pilot study was conducted in patients who had advanced epithelial ovarian carcinoma, and who were refractory to platinum-based chemotherapy, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IP) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IP. TIL were expanded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) or rIL-2 using a four-step method of expansion that included a hollow fiber bioreactor (artificial capillary culture system). Patients received IP TIL suspended in dextrose 5% in sodium chloride 0.2% containing 0.1% human albumin and 6 x 10(5) IU rIL-2 on day 1, followed by 6 x 10(5) IU rIL-2/m2 body surface area, administered daily by bolus IP injection, on days 2-4, 8-11, and 15-18. In the absence of disease progression, two additional 4-day cycles of IP rIL-2 were administered. Patients (n = 3) whose TIL failed to grow in vitro received IP IL-2 alone. Eight patients received rIL-2 expanded TIL (10(10)-10(11) range) plus rIL-2 followed by several cycles of rIL-2 alone. One of these patients was treated twice with TIL plus rIL-2. Expanded TIL were primarily CD3+CD4+TCR alpha beta+ (eight TIL-derived T-cell lines). One TIL-derived T-cell line was comprised mostly of CD3+CD8+TCR alpha beta+ cells. Eleven patients (eight treated with TIL plus rIL-2 and three patients treated with rIL-2 alone) received a total of 38 cycles of rIL-2 without TIL. Grade 3 clinical toxicity (peritonitis) occurred in 1 of 9 cycles of TIL plus rIL-2 and 1 of 38 cycles of rIL-2 alone. Each cycle was 4 days long. Grade 3 anemia occurred in 1 of 9 TIL plus rIL-2 cycles and 3 of 38 cycles of rIL-2 alone. There were no measurable responses; however, four of eight patients treated with IP TIL plus rIL-2 had some indication of clinical activity: ascites regression (two patients), tumor and CA-125 reduction (one patient), and surgically confirmed stable tumor and CA-125 values (one patient). The schedule of IP TIL plus low-dose rIL-2 shows manageable toxicity and is worthy of further evaluation in patients with epithelial ovarian cancer who have less tumor burden.

Adult↗

A phase I-II trial of mitoxantrone by hepatic arterial infusion in patients with hepatocellular carcinoma or colorectal carcinoma metastatic to the liver.

BACKGROUND: Mitoxantrone is an anthraquinone derivative that has demonstrated encouraging preclinical and clinical activity against a variety of human carcinoma cell lines and malignancies. Three Phase II studies of systemically administered mitoxantrone in patients with colorectal carcinoma failed to demonstrate any therapeutic activity, as did four Phase II studies of intravenous mitoxantrone in hepatocellular carcinoma. Two additional trials demonstrated limited activity when administered intravenously to patients with hepatocellular carcinoma. However, because this drug exhibits a steep dose-response curve, a Phase I-II trial of mitoxantrone by hepatic arterial infusion was initiated. METHODS: Patients with hepatocellular carcinoma and metastatic colorectal carcinoma with liver only or liver-predominant disease were eligible for therapy. All patients underwent the placement of a percutaneous hepatic arterial catheter before each course of therapy, and the first cohort of patients was treated at 10 mg/m2/course on day 1 on a 28-day cycle. Dosages were escalated in increments of 2 mg/m2/course based on side effects and tolerance. RESULTS: Twenty-eight patients with bidimensionally measurable unresectable, liver-predominant disease were entered into this trial. The therapy was well tolerated, with only 5 courses of 55 being complicated by neutropenia and none associated with fever. Only one patient required a dosage reduction on the basis of toxicity (neutropenia). No complete or partial responses were observed. CONCLUSION: These data are consistent with a lack of therapeutic activity of mitoxantrone when administered by hepatic arterial infusion for the treatment of hepatocellular carcinoma or metastatic colorectal cancer.

Adult↗

Diagnosis of eosinophilic granuloma of bone by fine-needle aspiration with concurrent institution of therapy: a cytologic, histologic, clinical, and radiologic study of 27 cases.

Twenty-seven patients with eosinophilic granuloma (EG) of bone seen at our institution between 1979 and 1991 underwent fine-needle aspiration (FNA) with or without concurrent Tru-Cut biopsy. The 16 males and 11 females ranged in age from 2 1/2 to 61 years (median, 10 yr). Twenty-four patients had monostotic lesions. The clinicoradiologic differential diagnosis included osteomyelitis and Ewing's sarcoma (young patients) and primary and metastatic malignancies (older patients). Twenty-four of 28 FNAs (one patient had two FNAs) were diagnostic of EG, and 10 cases were diagnosed by FNA alone. Smears in these cases showed histiocytes, often with grooved or infolded nuclei, and abundant eosinophils. Multinucleated giant cells, foamy histiocytes, neutrophils, lymphocytes, and plasma cells were present in variable numbers. Four FNAs were misdiagnosed: two as osteomyelitis where smears contained abundant neutrophils, sparse eosinophils, and histiocytes misinterpreted as foamy histiocytes, and two as metastatic carcinoma (in adults) where histiocytes in a scant specimen (one case) and skin appendiceal structures without lesional tissue (one case) were misinterpreted. These cases were correctly diagnosed on repeat FNA (one case), Tru-Cut (two cases), or excisional biopsy (one case); however, three cases diagnosed by FNA had nondiagnostic concurrent Tru-Cut biopsies. Treatment consisted of intralesional injection of 125 mg of methylprednisolone (22 cases). Progressive or complete healing of all lesions occurred. FNA is a rapid and useful technique for the immediate diagnosis of EG that allows concurrent institution of therapy.

Adolescent↗

An anatomical study of the tarsal tunnel using low pressure compartmental infusion.

The anatomy of the tarsal tunnel is demonstrated using a low-pressure compartmental infusion technique. This is done by infusing colored radiopaque contrast material into three fresh cadaveric specimens. Thin section photography and computed tomography are then used to identify the boundaries and contents of the tarsal tunnel as it traverses the ankle, hindfoot, and midfoot. The tarsal tunnel is shown to communicate proximally with the deep posterior compartment of the leg and distally with the intermediate compartment of the forefoot. The relationships of the structures contained within the tarsal tunnel are shown in detail.

Ankle↗

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration.

BACKGROUND: Hepatic arterial infusion of doxorubicin has produced tumor response in hepatic malignancies; however, the limited success of these treatments is related in part to dose-limiting systemic toxicities. The purpose of this study was to determine whether a novel venous isolation-chemofiltration system could limit systemic exposure to doxorubicin after hepatic arterial infusion. METHODS: Doxorubicin (1 or 3 mg/kg) was infused in the hepatic arteries of domestic pigs after complete hepatic venous isolation was achieved with a dual-balloon vena cava catheter. The hepatic vein effluent was pumped through an extracorporeal carbon chemofiltration circuit. Doxorubicin levels were measured in prefilter (hepatic vein), postfilter, and systemic serum at intervals up to 1 hour after drug infusion. RESULTS: Complete hepatic venous isolation with extracorporeal chemofiltration significantly reduced (> 90%) the postfilter and systemic levels of doxorubicin compared with prefilter levels (p < 0.01). At the time animals were killed 7 days after infusion of doxorubicin (3 mg/kg), tissue levels of doxorubicin in the liver showed a 16-fold increase compared with levels in the heart (p < 0.01). CONCLUSIONS: For chemotherapeutic drugs like doxorubicin with a low first-pass extraction by the liver, the novel system described herein achieved significant reduction in systemic drug exposure. This system will allow dose intensification of doxorubicin administered by hepatic arterial infusion to treat hepatic malignancies.

Alanine Transaminase↗

Regional biologic therapy. Hepatic arterial infusion of recombinant human tumor necrosis factor in patients with liver metastases.

Twenty-two chemotherapy-resistant patients with liver metastases received 46 courses of recombinant human tumor necrosis factor (rhTNF) administered by 5-day continuous infusion through percutaneously inserted hepatic arterial catheters. The maximum tolerated daily dose of rhTNF was 150 micrograms/m2. This is six times the maximum tolerated daily dose of rhTNF that could be given systemically (intravenous) on the same schedule. The dose-limiting toxicity resulted in severe, although transient, hypophosphatemia (less than 1.0 mg/dl) associated with myocardial dysfunction. Objective tumor response (partial tumor response or greater) was observed in 2 of 14 patients (14%) with colorectal cancer and lasted as long as 3 months. Three additional minor responses occurred among these patients with colorectal cancer. Plasma carcinoembryonic antigen levels also decreased significantly (greater than 25%) in 7 of the 14 (50%) patients with colorectal cancer. Regional biologic therapy with rhTNF as a sole modality has definite antitumor activity in colorectal cancer metastatic to the liver and warrants additional study in previously untreated patients.

Adult↗

Use of the Gianturco self-expanding stent in stenoses of the superior and inferior venae cavae.

Twenty-eight patients with severe superior and inferior vena cava syndromes were treated with self-expandable Gianturco stents. Nineteen patients responded, seven did not respond, and two were unevaluable. Fourteen of the 19 who responded had complete or near complete resolution of their syndrome, and five had a partial remission. Five of the responders did not derive any benefit from stent placement because of additional problems that led to their death within 3 weeks of the stent placement procedure. The main cause for failure was the relatively weak expansile force of the stent. Complications included stent migrations without untoward effects in one patient, stent misplacement in one patient, fracture of the stent wire in two patients, and hemorrhage that could be attributed to the stent in one patient. This uncontrolled study suggests that caval obstruction syndromes in some patients may be effectively palliated with Gianturco stents.

Adult↗

Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum.

Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5-year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data.

Bone Neoplasms↗

Chondrosarcoma: MR imaging with pathologic correlation.

Magnetic resonance (MR) images of 21 surgically confirmed chondrosarcomas were retrospectively reviewed in conjunction with plain radiographs and computed tomographic scans and correlated with pathologic findings. The tumors appeared lobulated, and signal intensity, as analyzed visually (intermediate on T1-weighted, high on T2-weighted images), was similar for all lesions, regardless of pathologic type. Size of lesion was not an indicator of grade. The appearances of mesenchymal and dedifferentiated chondrosarcomas mimicked that of conventional chondrosarcoma. Extraskeletal chondrosarcoma was visualized as a lobulated soft-tissue mass. In all cases, MR imaging accurately depicted intraosseous and soft-tissue extent of tumor noted at surgery and pathologic examination. Histologic type or grade of chondrosarcoma generally cannot be characterized on the basis of visual analysis of signal intensity noted on routine MR images. However, MR imaging is excellent for exact delineation of tumor extent.

Bone Neoplasms↗

MDA-image: an environment of networked desktop computers for teleradiology/pathology.

MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.

Clinical Laboratory Information Systems↗

Case report 680. Intraosseous meningioma of the sphenoid bone.

Two cases of intraosseous meningioma of the calvaria with hyperostosis are presented and compared with the appearance on plain films and CT of en plaque meningioma, metastatic disease from such primary sites as prostatic cancer, and fibrous dysplasia. It is emphasized that intraosseous meningioma in the calvaria is relatively uncommon, occurring most often in the sphenoid bone (probably because of its numerous articulations). The relationship of the development of intraosseous meningioma to the entrapment of dura containing arachnoid cells is discussed in considering the cause of such lesions, and it is stressed that calvarial fractures and cranial sutures may contribute to the entrapment of arachnoidal tissue and later the formation of a meningioma.

Adult↗

Percutaneous urinary diversion in patients with hormone-refractory prostate cancer.

Twenty-two patients with hormone-refractory prostate cancer underwent percutaneous urinary diversion; at the time, all but one had metastatic disease. Eleven patients received postnephrostomy therapy. The median survival time for all the patients was one hundred nineteen days. Overall, 41 percent of the patients' remaining lifetime was spent in the hospital. Six never left the hospital and 10 required rehospitalization; the remaining 6 patients were never rehospitalized. The median survival time for this group of patients was shorter than the expected survival of similar patients without ureteral obstruction. It appears that percutaneous urinary diversion does not improve the quality of life of these patients.

Adenocarcinoma↗

Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.

When chemotherapeutic drugs with low liver extraction are used for hepatic arterial infusion (HAI), dosage limits are usually determined by systemic rather than hepatic toxicity. If such agents could be administered by HAI at dosages limited by hepatic toxicity, regional drug exposure and therapeutic efficacy might be significantly enhanced. We report herein a novel system that achieves complete hepatic venous isolation using a dual-balloon vena cava catheter that can be inserted percutaneously. This catheter is connected to a carbon filter in an extracorporeal venous bypass circuit to recover drug that is not absorbed by the liver after HAI. The hemodynamic response to this system was evaluated in six pigs. When the animals were placed on the extracorporeal circuit, we observed a 22% decrease in cardiac output that was well tolerated without significant change in blood pressure. When the filter was incorporated into the circuit, cardiac output was significantly reduced (50%); however, continuous infusion of phenylephrine rapidly normalized blood pressure, heart rate, cardiac output, and left ventricular filling pressures. Initial testing of chemofiltration efficacy was performed in four of the six animals, the remaining two animals being used only to assess hemodynamic response. One each of the four tested animals received either doxorubicin (3 or 9 mg/kg), mitomycin C (1 mg/kg), or cisplatin (1 mg/kg) by HAI. The filter removed over 90% of hepatic venous doxorubicin and mitomycin C and 65% of hepatic venous cisplatin. This feasibility study confirms that hepatic venous isolation with chemofiltration can significantly reduce systemic exposure to high-dose chemotherapeutic agents given by HAI.

Animals↗

Open-floored concave compensating filter for angiography.

An open-floored concave compensating filter was designed that produced a radiograph of uniform density, caused no artifacts due to its shape or position, and required little or no increase in exposure in most applications. Selective celiac, hepatic, shoulder, and pelvic angiography was performed with use of the filter; image quality was noticeably improved.

Angiography↗