Application of CT in the investigation of angiogenesis in oncology.
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Contrast Media↗
Biomedical subjects
C Charnsangavej
Publications and source records attributed to C Charnsangavej.
9:00-9:15. Antiangiogenic Treatment with Endostatin Results in Uncoupling of Blood Flow and Glucose Metabolism in Human Tumors.
Endostatin is a novel antiangiogenic agent currently in phase I trials. In the context of this trial, we are evaluating the use of non-invasive imaging with PET to determine the relationship between tumor blood flow and glucose metabolism in imaged tumors from treated patients.Ten patients have been treated with escalating daily iv Endostatin doses of 30 to 180 mg/m(2). PET images were obtained before the start of therapy and again after 28 days of treatment. Each patient was scanned with Oxygen-15 labeled water for estimation of tumor blood flow and Flourine-18 labeled FDG to estimate tumor metabolic activity. In most cases, two distinct tumor-bearing sites were analyzed in each patient. Thus, a total of 19 tumors were imaged. Regional blood flow and standard uptake values (SUV) were computed at baseline and 28 days post treatment and the percentage change in blood flow and SUV plotted as a function of Endostatin dose.Both blood flow and glucose metabolism in the imaged tumors were observed to increase in patients treated with </=60 mg/m(2)/d, but became uncoupled in the tumors imaged from patients treated at the 180 mg/m(2)/d dose level. Thus, in patients receiving Endostatin at a dose of 180 mg/m(2)/d, blood flow decreased but glucose metabolism increased. This relationship is displayed in Figure 1 below.
Journal Article↗
9:30-9:45. First Pass FDG Measured Blood Flow in Tumors: A Comparison with O-15 Labeled Water Measured Blood Flow.
The purpose of this study was to determine if the first-pass of FDG can be used to measure regional blood flow in tumors in the absence of perfusion imaging with a known blood flow tracer.PET scans were obtained in patients being evaluated for tumor perfusion and metabolism in a Phase I dose escalating protocol for Endostatin, a novel antiangiogenic agent. A two minutes perfusion scan was done with a bolus injection of 60 mCi of O-15 labeled water followed by a 10 mCi dose of FDG and four sequential scans consisting of a first pass two minutes scan and three 15 minutes scans. Regions of interest were drawn on two tumor sites for each scan. Blood flow was computed using a one-compartment model previously published by the authors. Linear regression analysis was carried out between the first pass FDG measured blood flow and O-15 measured blood flow (Figure 1).Blood flow estimated from the first pass of FDG was linearly correlated with O-15 measured blood flow with an intercept of 0.01, slope of 0.86, and r squared regression coefficient of 0.74 (R = 0.86) for blood flow values of up to 0.6 ml/min/gm of tissue. These results suggests that in the absence of a perfusion tracer, the first pass of FDG provides an estimate of perfusion in a tumor within the limitations of incomplete extraction of FDG compared to O-15 water.
Journal Article↗
Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.
BACKGROUND: There is no agreement regarding the preoperative measurement of liver volumes and the minimal safe size of the liver remnant after extended hepatectomy. METHODS: In 20 patients with hepatobiliary malignancy and no underlying chronic liver disease, volumetric measurements of the liver remnant (segments 2 and 3 +/- 1) were obtained before extended right lobectomy (right trisegmentectomy). The ratios of future liver remnant to total liver volume were calculated by using a formula based on body surface area. In 12 patients, response to preoperative right trisectoral portal vein embolization was evaluated. In 15 patients who underwent the planned resection, preoperative volumes were correlated with biochemical and clinical outcome parameters. RESULTS: The future liver remnants increased after portal vein embolization (26% versus 36%, P < .01). Smaller size liver remnants were associated with an increase in postoperative liver function tests (P < .05) and longer lengths of hospital stay (P < .02). Preliminary data indicates an increase in major complications for liver volumes < or = 25% (P = .02). CONCLUSIONS: A simple method of measurement provides an assessment of the liver remnant before resection. It is useful in evaluating response to portal vein embolization and in predicating the outcome before extended liver resections.
Adult↗
Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy.
The poly(L-glutamic acid)-paclitaxel (PG-TXL) conjugate has been shown to exhibit significantly greater antitumor activity than conventionally formulated paclitaxel (TXL) against solid tumors (Li et al., Cancer Res., 58: 2404-2409, 1998). Here we report that local tumor irradiation enhanced the distribution of PG-TXL given 24 h later to ovarian OCa-1 carcinoma implanted i.m. in C3Hf/Kam mice. Radiation significantly increased tumor uptake of PG-TXL and tumor vascular permeability, caused elevation of the serum concentration of vascular endothelial growth factor, and arrested OCa-1 cells in the G1 phase of cell cycle. The enhancement factors, as measured by incremental tumor growth delay compared with PG-TXL alone, ranged from 1.36-4.44. Complete tumor regression was also observed at a higher radiation dose (>10 Gy) and a higher PG-TXL dose (>80 mg equivalentTXL/kg). Furthermore, combined radiation and PG-TXL produced a significantly greater tumor growth delay than treatment with radiation and TXL when both drugs were given at the same equivalent TXL dose of 60 mg/kg 24 h after tumor irradiation (enhancement factors, 4.44 versus 1.50). These data suggest that conjugation of TXL to poly(L-glutamic acid) is necessary for improved response and that the supra-additive effect of combined radiation and PG-TXL therapy is due in part to modulation of the enhanced permeability and retention effect of macromolecules by radiation. We propose a treatment strategy combining radiation and macromolecular chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.
Animals↗
Irinotecan and cisplatin in advanced gastric or gastroesophageal junction carcinoma.
Chemotherapy for advanced gastric and gastroesophageal junction carcinomas remains suboptimal. Both irinotecan (Camptosar) and cisplatin (Platinol) are active against this group of malignancies. This article focuses on the results of an ongoing phase II trial with this combination in patients with advanced gastric or gastroesophageal junction carcinoma. Data from this trial suggest that the combination of irinotecan and cisplatin is active in untreated as well as previously treated patients with gastric or gastroesophageal junction carcinoma.
Antineoplastic Combined Chemotherapy Protocols↗
Subtraction CT colonography: feasibility in an animal model.
AIM: To determine, in an in vitro animal model, the feasibility of subtracting residual faecal material, during virtual colonoscopy, by uniform mixing of the colonic contents with barium. MATERIALS AND METHODS: Segments of animal colon containing simulated soft-tissue polyps, measuring 3-10 mm, were filled with a faecal substitute consisting of a barium and peanut butter mix that had an attenuation value greater than 200 Hounsfield units. The colonic segments were then examined by CT using 3-10 mm beam collimations, and at pitch factors of 1 and 2. Using subtraction cut-off levels varying from 100-250 Hounsfield units, the barium and peanut butter mix was then subtracted to reveal the underlying polyps. RESULTS: Our optimal technical parameters required 3-mm beam collimation, a helical pitch factor of 2, reconstruction intervals of 3 mm, and a subtraction cut-off level of 150 Hounsfield units. The subtraction technique, in this animal model, had a sensitivity of 94% and a specificity of 80% for polyps measuring greater than 3 mm. CONCLUSION: In this limited animal model, the subtraction technique utilized was technically feasible and had an acceptable sensitivity.
Animals↗
Durable clinical and pathologic response of hepatocellular carcinoma to systemic and hepatic arterial administration of platinol, recombinant interferon alpha 2B, doxorubicin, and 5-fluorouracil: a communication.
The case described here illustrates the antitumor activity of a four-drug systemic combination chemobiotherapy with platinol, recombinant interferon alpha 2b, doxorubicin (Adriamycin), and 5-fluorouracil (5-FU) (PIAF) in a patient with diffuse hepatocellular carcinoma involving the liver and lungs.
Aged↗
Hepatocellular carcinoma and intrahepatic peripheral cholangiocarcinoma: enhancement patterns with quadruple phase helical CT--a comparative study.
PURPOSE: To define the hemodynamic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma by using quadruple phase helical computed tomography (CT) and determine the value of this information in characterizing tumors. MATERIALS AND METHODS: Helical CT of the liver was performed in 45 patients with newly diagnosed HCC or peripheral cholangiocarcinoma. Scans were obtained before and 25 seconds, 70 seconds, and 2-6 minutes after the start of the contrast material injection. The intensity and spatial distribution of contrast material uptake were evaluated during all phases. Time-attenuation curves were established for each lesion. Relative attenuation and lesion conspicuity were assessed. A diagnostic confidence level was assigned to each lesion. RESULTS: In the majority of HCC lesions, a single, early peak of enhancement followed by a continuous decrease in tumor attenuation over time was seen. The greatest tumor conspicuity occurred during the delayed phase. In cholangiocarcinoma, tumor attenuation increased during the delayed phase. In the majority of lesions, the greatest tumor conspicuity was seen during the portal venous phase. In both tumor types, the diagnostic confidence level improved when the delayed phase was used. CONCLUSION: The variation over time in the intensity of contrast enhancement in HCC and cholangiocarcinoma differs sufficiently to make this a useful diagnostic criterion. The delayed phase is particularly important because it amplifies this difference.
Adult↗
Metastases to the pancreas from renal cell carcinoma: findings on three-phase contrast-enhanced helical CT.
OBJECTIVE: Our goal was to define the lesion enhancement characteristics of renal cell carcinoma metastases to the pancreas using three-phase helical CT. MATERIALS AND METHODS: Thin-section three-phase contrast-enhanced CT scans of nine patients with renal cell carcinoma metastases to the pancreas were evaluated. The helical CT protocol included 3-mm collimation and a 2:1 pitch. Scans through the pancreas were obtained in three series beginning 25, 60, and 120 sec after the start of administration of i.v. contrast material delivered at 3 ml/sec. The Hounsfield densities of the pancreatic lesions and normal pancreatic parenchyma during each of the enhancement phases were recorded and compared. RESULTS: The enhancement patterns of the metastatic deposits and the normal pancreas differed. Thirty-four lesions ranging in size from 6 to 110 mm were identified. All metastases showed rapid enhancement during the early (arterial and portal) phases, resulting in differential attenuations (compared with normal pancreatic parenchyma) of approximately 50-100 H. The differential attenuations were approximately 5-45 H on delayed-phase scans, resulting in poorer conspicuity of the lesions. Multifocal metastases were clearly identified on the early-phase scans in seven patients. CONCLUSION: Renal cell carcinoma metastases to the pancreas enhance most conspicuously during the early phases of helical CT. Such metastases may fail to be appreciated in the delayed phase. In patients with suspected renal cell carcinoma metastases to the pancreas, early-phase scanning after i.v. contrast administration should be performed.
Aged↗
Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumors.
Poly(L-glutamic acid)-paclitaxel (PG-TXL) is a new water-soluble paclitaxel derivative that has shown remarkable antitumor activity against both ovarian and breast tumors. The purpose of this study was to test whether the antitumor efficacy of PG-TXL depends on tumor type, as is the case for paclitaxel, and to test whether paclitaxel-resistant tumors could be responsive to PG-TXL. We evaluated the therapeutic activity of PG-TXL against four syngeneic murine tumors (MCa-4, MCa-35, HCa-1, and FSa-II) inoculated i.m. into C3Hf/Kam mice, a human SKOV3ip1 ovarian tumor injected i.p. into nude mice, and a human MDA-MB-435Lung2 breast tumor grown in the mammary fat pad of nude mice. Two paclitaxel-responsive murine tumors, MCa-4 and MCa-35, showed significant growth delay with PG-TXL given as a single i.v. injection at its maximum tolerated dose of 160 mg of equivalent paclitaxel/kg or even at a lower dose of 120 mg of equivalent paclitaxel/kg. The other two murine tumors, HCa-1 and FSa-II, did not respond particularly well to either of the two agents, although significant growth delay was observed for both tumors with PG-TXL. In mice with SKOV3ip1 tumors, the median survival times for mice treated with PG alone and PG-TXL at doses of 60 or 120 mg of equivalent paclitaxel/kg were 43, 61, and 75 days, respectively; no survival difference was found between paclitaxel-treated and Cremophor vehicle-treated mice. In mice with MDA-MB-435Lung2 tumor, PG-TXL at a dose of 120 mg of equivalent paclitaxel/kg produced regression of the tumor in 50% of the animals, and in the remaining mice, micrometastases in the lung were found only in 25% of the animals. In comparison, treatment with paclitaxel at 60 mg/kg did not result in tumor regression, and the rate of lung metastases was 42%. These results clearly demonstrate that PG-TXL has significant therapeutic activity against breast and ovarian tumors tested in this study. Future studies to elucidate the mechanism of action of PG-TXL and to assess its clinical applications are warranted.
Animals↗
Preoperative chemoradiation strategies for localized adenocarcinoma of the pancreas.
Patients who undergo pancreaticoduodenectomy alone for adenocarcinoma of the pancreatic head or uncinate process have a median survival of 12 months, and a high incidence of local tumor recurrence (50%-80%) due to the common finding of positive margins following pathologic evaluation of pancreaticoduodenectomy specimens. The available prospective and retrospective data suggest improved survival duration and local-regional tumor control when pancreaticoduodenectomy is combined with 5-FU-based chemoradiation. However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevent the timely delivery of postoperative chemoradiation. In contrast, chemoradiation delivered prior to pancreaticoduodenectomy is not associated with toxic effects which delay surgery and has not been shown to increase surgical morbidity or mortality. In fact, recent data suggest that pancreaticojejunal anastomotic leaks, the most common major complication following pancreaticoduodenectomy, are decreased in patients who receive preoperative radiation therapy. Current and future multimodality treatment strategies will capitalize on our expanding understanding of tumor growth and metastasis, allowing more effective radiation sensitizing agents to be combined with external-beam irradiation and surgery, followed by the systemic or regional delivery of novel agents that inhibit essential steps in tumor cell growth.
Adenocarcinoma↗
Venous chest anatomy: clinical implications.
This article provides a practical approach to the clinical implications and importance of understanding the collateral venous anatomy of the thorax. Routine radiography, conventional venography, computed tomography (CT), and magnetic resonance (MR) imaging studies provide correlative anatomic models for the demonstration of how interconnecting collateral vascular networks within the thorax maintain venous stability at all times. Five major systems comprise the collateral venous network of the thorax (Fig. 1). These include the paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and anterior jugular venous systems (AJVS). The five systems are presented in the following sequence: (a) a brief introduction to the importance of catheter position and malposition in understanding access to the thoracic venous system, (b) the anatomy of the azygos-hemiazygos systems and their relationship with the paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts interconnecting the internal mammary and azygos-hemiazygos systems by means of the lateral thoracic and intercostal veins, and (e) the interconnecting venous networks on the thoracic side of the thoracoabdominal junction. Certain aspects of the venous anatomy of the thorax will not be discussed in this chapter and include (a) the intra-abdominal anastomoses between the superior and inferior vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos-hemiazygos systems (beyond the scope of this article), (b) potential collateral vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller veins that might anastomose with the major systems, and (c) anatomic variants and pitfalls that may mimic pathologic conditions (space limitations).
Abdomen↗
Patterns of uterine enhancement with helical CT.
OBJECTIVE: The purpose of this study was to evaluate the enhancement characteristics of the normal uterine body and cervix using dynamic contrast-enhanced helical CT. METHODS: Thirty-eight women scheduled for pelvic CT for non-gynecologic malignancies underwent dynamic contrast-enhanced helical CT of the pelvis. Data acquisition was during the arterial phase (30-45 s after the start of injection), the parenchymal phase (90-120 s after the start of injection), and delayed phase (3-9 min after the start of injection). The images were evaluated by four radiologists for the pattern of myometrial and cervical enhancement. Correlation was made with the age and menstrual status of the patients. RESULTS: In the uterine body, three types of enhancement were observed. Type 1 enhancement, seen in 16 patients (42%), was characterized by the visualization of a subendometrial zone of enhancement, 30-120 s after the start of injection. Eight of these patients also showed an enhancing zone in the outer myometrium. Both zones were transitory, and in all cases, the uterus became homogeneous in the delayed phase. This pattern was seen predominantly in premenopausal women with a mean age of 34 years. Type 2 enhancement, seen in 17 cases (45%), was defined by the absence of subendometrial enhancement in the early phase. Enhancement was either diffuse from the outset or originated in the outer myometrium. This pattern was seen nearly equally in premenopausal and postmenopausal women with a mean age of 40 years. Type 3 enhancement was seen in five postmenopausal patients (13%) with a mean age of 53 years and was characterized by faint diffuse enhancement. In the cervix, a zonal pattern of enhancement defining inner and outer stroma was seen in 23 patients (61%). Fifteen patients were premenopausal and eight were postmenopausal. CONCLUSION: In this study, we have shown a transitory zonal distribution of the contrast in the myometrium and cervix using dynamic contrast-enhanced helical CT. The demonstration of these patterns is not constant and depends on individual variables. Of these, the menopausal status and/or age of the patient appear to be most important. While CT is not the primary imaging modality to evaluate the uterus, knowledge of these normal findings might help when confronted with unusual uterine enhancement during routine studies obtained with spiral CT.
Adult↗
Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head.
BACKGROUND: The survival of patients who underwent pancreaticoduodenectomy with or without en bloc resection of the superior mesenteric-portal vein (SMPV) confluence for adenocarcinoma of the pancreatic head was compared. METHODS: To be considered for surgery, patients were required to fulfil the following computed tomography criteria for resectability: (1) absence of extrapancreatic disease, (2) no evidence of tumour extension to the superior mesenteric artery (SMA) or coeliac axis, and (3) a patent SMPV confluence. Tumour adherence to the superior mesenteric vein (SMV) or SMPV confluence was assessed at operation and en bloc venous resection was performed when necessary to achieve complete tumour extirpation. RESULTS: Seventy-five consecutive patients underwent pancreaticoduodenectomy, 44 without venous resection and 31 with en bloc resection of the SMPV confluence. There were no perioperative deaths in either group; late (more than 6 months) occlusion of the reconstructed SMPV confluence contributed to the death of two patients. Median survival in the 31 patients who required venous resection at the time of pancreaticoduodenectomy was 22 months, and that for the 44 control patients was 20 months (P = 0.25). CONCLUSION: Patients with adenocarcinoma of the pancreatic head who require venous resection during pancreaticoduodenectomy for isolated tumour extension to the SMV or SMPV confluence (in the absence of tumour extension to the SMA or coeliac axis) have a duration of survival no different from that of patients who undergo standard pancreaticoduodenectomy. These data suggest that venous involvement is a function of tumour location rather than an indicator of aggressive tumour biology.
Adult↗
Prolonged remission of endometrial cancer with paclitaxel and carboplatin.
Recurrent endometrial cancer has grave prognosis. Chemotherapy and hormonal therapy are mainstays of palliative treatment. Unfortunately the frequency of complete response and duration of progression-free interval are limited. This case report describes a patient with recurrent metastatic endometrial cancer who was initially treated with radiotherapy followed by surgery. Her recurrent tumor progressed during treatment with external radiation and a progestogen. She received paclitaxel (135 mg/m2 i.v. infusion over 24 h) and carboplatin (AUC 7.5 microg x h/ml) every 4 weeks with complete remission after 8 months which has persisted for 22 months. Paclitaxel and carboplatin combination should be considered for the treatment of endometrial cancer.
Adenocarcinoma↗
Evaluation of helical computed tomography scan parameters for vascular imaging.
Helical x-ray computed tomography (hCT) is the volume acquisition of image data in which the data set represents a series of projections obtained in a helical spatial distribution. Data acquisition times and spatial resolution are determined largely by two user defined parameters--collimation and pitch. Each combination of pitch and collimation results in a slice profile which can be considered as the apparent slice thickness. Careful selection of pitch and collimation allows the acquisition of up to 20 cm of axial data in a breathold or first pass of bolus contrast material. This makes helical CT an excellent technique for angiographic (CTA) studies. Additionally, slices can be reconstructed at any interval to reduce partial volume averaging, minimizing the beading artifacts seen in maximum intensity projections (MIP) when interslice resolution is poor. We have evaluated a range of collimation and pitches for clinical CTA. Additionally, three reconstruction filters were included to determine the optimal frequency (spatial) properties for these techniques. Objective and subjective analyses were performed. We found pitches of up to 1.5:1 to be acceptable for all collimations. For a given scan length (z direction), selection of thinner collimation and higher pitch resulted in better SNR and observer scoring for angiographic presentations.
Angiography↗
Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma.
PURPOSE: To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with radiographically resectable localized adenocarcinoma of the pancreatic head were entered onto a preoperative protocol that consisted of a 2-week course of fluorouracil (5-FU) 300 mg/m2 daily 5 days per week and concomitant rapid-fractionation radiation 30 Gy, 3 Gy daily 5 days per week. Radiographic restaging was performed 4 weeks after chemoradiation, and patients with localized disease underwent pancreaticoduodenectomy with EB-IORT 10 to 15 Gy. RESULTS: Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. CONCLUSION: Combined modality treatment with preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and EB-IORT is associated with minimal toxicity and excellent locoregional control. This represents one approach to maximize the proportion of patients who receive all components of combined modality therapy and avoids the toxicity of pancreaticoduodenectomy in patients found to have metastatic disease at the time of restaging.
Adenocarcinoma↗