Biomedical subjects

K Cleary

Publications and source records attributed to K Cleary.

At least 19 recordsLinked to original sources

PubMed2005

Feasibility of four-dimensional conformal planning for robotic radiosurgery.

Organ motion can have a severe impact on the dose delivered by radiation therapy, and different procedures have been developed to address its effects. Conventional techniques include breath hold methods and gating. A different approach is the compensation for target motion by moving the treatment beams synchronously. Practical results have been reported for robot based radiosurgery, where a linear accelerator mounted on a robotic arm delivers the dose. However, not all organs move in the same way, which results in a relative motion of the beams with respect to the body and the tissues in the proximity of the tumor. This relative motion can severely effect the dose delivered to critical structures. We propose a method to incorporate motion in the treatment planning for robotic radiosurgery to avoid potential overdosing of organs surrounding the target. The method takes into account the motion of all considered volumes, which is discretized for dose calculations. Similarly, the beam motion is taken into account and the aggregated dose coefficient over all discrete steps is used for planning. We simulated the treatment of a moving target with three different planning methods. First, we computed beam weights based on a 3D planning situation and simulated treatment with organ motion and the beams moving synchronously to the target. Second, beam weights were computed by the 4D planning method incorporating the organ and beam motion and treatment was simulated for beams moving synchronously to the target. Third, the beam weights were determined by the 4D planning method with the beams fixed during planning and simulation. For comparison we also give results for the 3D treatment plan if there was no organ motion and when the plan is delivered by fixed beams in the presence of organ motion. The results indicate that the new 4D method is preferable and can further improve the overall conformality of motion compensated robotic radiosurgery.

Biophysical Phenomena↗

PubMed2002

Spine needle biopsy simulator using visual and force feedback.

OBJECTIVE: Biopsy with an inserted needle is an important procedure for lesion detection in the spine, but is difficult to perform due to the presence of many critical organs near the spine. This article presents a spine needle biopsy simulator, based on visual and force feedback, which can be used to plan the optimal path of a needle and to practice the procedure without risk. MATERIALS AND METHODS: The simulator is composed of a 3D human model, a visual-feedback component, a force-feedback component, and an evaluation module. The human model is based on 3D CT data. The visual-feedback component provides an oblique section, multiplanar reformatting images, and a volume-rendered image. Of these, the oblique section display is very useful for planning a 3D path for the needle. During simulation, the force-feedback component generates and provides realistic forces acting on the biopsy needle in real time by synchronizing them to visual feedback. After each simulation, the evaluation module provides a performance analysis for the trainee. RESULTS: For an XCT abdomen volume data set of 256 x 256 x 256, the update rate of image rendering due to needle movement is over 25 Hz, with a force-feedback rate of 1 kHz. This performance proved to be good enough for the trainee to learn the relationship between visual and force feedback. CONCLUSIONS: The simulator is useful for the planning of and training in complicated 3D spine needle biopsy procedures. It may be used as an educational tool for beginners, a practice tool to increase expertise, or a test bed for new procedures.

Algorithms↗

PubMed2001

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal.

PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease. RESULTS: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Adenocarcinoma↗

PubMed2001

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation.

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.

Adolescent↗

PubMed2001

T4 rectal cancer treated with preoperative chemoradiation to the posterior pelvis followed by multivisceral resection: patterns of failure and limitations of treatment.

PURPOSE: To analyze the overall pattern of treatment failure and sites of pelvic disease recurrence relative to the radiation fields used in treating patients with clinically staged T4 rectal cancer with preoperative chemoradiation followed by multivisceral resection. METHODS AND MATERIALS: Between 1990 and 1998, 45 patients with T4 rectal cancer were treated with preoperative chemoradiation. Clinical staging was according to the system of the American Joint Cancer Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and physical examination. A diagnosis of T4 disease required evidence of invasion of a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6), vaginal mucosal involvement on pelvic examination (n = 6), or a combination of these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3-field belly-board technique. The median total dose was 45 Gy in all patients (range 45-63). Nine patients received a boost with external beam radiotherapy (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk). Resection was not performed in 13 (29%) of the 45 patients because of metastases detected before resection or patient refusal. Multivisceral resection and pelvic exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively. We compared the location of pelvic disease recurrence with the RT simulation films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic and distant recurrent rates and the overall survival rate. RESULTS: The median length of follow-up was 31.0 months for all patients and 40.0 months for patients alive at last follow-up. When only the resected cases were considered, the local recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall survival rate was 69%. When all patients were considered, the local recurrence rate was similar (24%), but the rate of distant recurrence (51%) was higher and the overall survival rate lower (50%). Pelvic disease was controlled in all 8 patients whose disease responded well to chemoradiation (either a histologically complete response or microscopic residual disease). Three of 4 patients with close or positive margins had pelvic recurrences despite intraoperative RT and brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field. Elective external iliac nodal irradiation was not used, and nodal metastases were not seen in that region. In 1 case, marginal recurrence occurred in a common iliac node at the superior edge of the treatment field. CONCLUSIONS: Despite aggressive multimodality therapy including multivisceral resection, a high rate of pelvic and distant disease recurrence occurred in patients with clinically staged T4 disease. Regional disease recurred almost exclusively in the radiation field. The intraoperative RT and interstitial brachytherapy doses used did not prevent pelvic disease recurrence in patients with close or positive margins. Novel strategies such as higher preoperative doses of RT with or without altered fractionation or more effective radiosensitizers are needed to improve locoregional control in patients with T4 disease. Future strategies must also include more effective systemic therapy.

Adult↗

PubMed2001

Image-guided robotic delivery system for precise placement of therapeutic agents.

The effectiveness of conventional solid tumor treatment is limited by the systemic toxicity and lack of specificity of chemotherapeutic agents. Present treatment modalities are frequently insufficient to eliminate competent cancer cells without exceeding the limits of toxicity to normal tissue. The coming generation of cancer therapeutics depends on the precise targeting and sustained release of antitumor agents to overcome these limitations. We are developing an image-guided, robotic system for precise intratumoral placement of anticancer drugs and sustained release devices to advance this new treatment paradigm. The robotic system will use intraoperatively obtained computed tomographic (CT) images from a mobile CT scanner for guidance. The concept is to track patient anatomy and localize instruments using currently available optical tracking technology. Tracking will also be used to register patient anatomy with the images. The physician can then use the registered image to select an appropriate tumor target and entry location and to plan the instrument path. This path will then be transmitted to the robot, which orients and drives the instrument to the desired target under physician control. Achievement of the target is confirmed via intraoperative CT. This system will provide instrument guidance that is precise, direct, and controllable. Error due to poor target visualization and hand unsteadiness should be reduced greatly. The basic components of the system (robot, mobile CT, tracking) have been demonstrated in our laboratory, and the integration of the components is in progress. In future work, we plan to fuse preoperative PET imaging with intraoperative CT to allow functional as well as anatomic image guidance.

Antineoplastic Agents↗

PubMed2001

Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer.

PURPOSE: To assess pelvic chemoradiotherapy (CXRT) without colostomy as a component of the multidisciplinary management of patients presenting with metastatic rectal cancer. METHODS AND MATERIALS: Eighty patients with synchronous distant metastases from rectal cancer were treated with initial CXRT. Hypofractionated radiotherapy was administered usually with concurrent 5-FU (92%, 300 mg/m(2)/day, M-F). Three-field belly-board technique was used in 89%. Group 1 had CXRT alone (n = 55). Group 2 (n = 25) patients were selected for primary disease resection, and sometimes HAI chemotherapy (n = 10) or hepatic resection (n = 5). Subsequently, 78% received systemic chemotherapy. RESULTS: Symptoms from primary tumor resolved in 94%. Endoscopic complete clinical response rate was 36%. Two-year survival (11% vs. 46%, p < 0.0001) and symptomatic pelvic control (PC, 81% vs. 91%, p = 0.111) were higher in Group 2, but colostomy-free rate (CFR) was lower (79% vs. 51% p = 0.02). CFR was 87% in Group 1 patients managed initially without fecal diversion (n = 50). Examining all patients using multivariate analysis, pelvic pain at presentation (p < 0.00001), BED (biologic equivalent dose at 2 Gy/fraction) < 35 Gy (p = 0.077), and poor differentiation (0.079) predicted worse PC. Poor differentiation (p = 0.017) and selection for CXRT alone (p < 0.0001) predicted worse survival. There were 4 RTOG of Grade 3 or greater acute complications, 5 severe perioperative complications, and no significant late treatment-related complications. CONCLUSION: Durable PC can be safely achieved without colostomy in most patients presenting with primary rectal cancer and synchronous systemic metastases using hypofractionated pelvic chemoradiation. A BED greater than 35 Gy is recommended. Selected patients appear to benefit from resection of primary disease. Higher doses should be investigated in patients with pelvic pain.

Adult↗

PubMed2001

State of the art in surgical robotics: clinical applications and technology challenges.

Although it has been over 15 years since the first recorded use of a robot for a surgical procedure, the field of medical robotics is still an emerging one that has not yet reached a critical mass. Although robots have the potential to improve the precision and capabilities of physicians, the number of robots in clinical use is still very small. In this review article, we begin with a short historical review of medical robotics, followed by an overview of clinical applications where robots have been applied. The clinical applications are then discussed; they include neurosurgery, orthopedics, urology, maxillofacial surgery, radiosurgery, ophthalmology, and cardiac surgery. We conclude with a listing of technology challenges and research areas, including system architecture, software design, mechanical design, imaging compatible systems, user interface, and safety issues.

Computer Systems↗

PubMed2001

Final report of the meeting "modeling & simulation in medicine: towards an integrated framework". July 20-21, 2000, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

Explore the source record for details and available documents.

Anatomy, Cross-Sectional↗

PubMed2001

A caution regarding lymphatic mapping in patients with colon cancer.

BACKGROUND: The value of lymphatic mapping and sentinel lymph node biopsy in the treatment of colon cancer is controversial. The purpose of this study was to determine the accuracy of lymphatic mapping in patients with colon cancer. METHODS: Forty-eight patients with colon cancer underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye followed by standard surgical resection. The sentinel lymph nodes underwent thin sectioning as will as immunohistochemical staining for cytokeratin, in addition to standard hematoxylin and eosin staining. RESULTS: In 47 (98%) patients, a sentinel lymph node was identified. Sixteen patients had lymph nodes containing metastatic disease, and in 6 patients the sentinel lymph node was positive for disease. In no patient was the sentinel lymph node the only site of metastatic disease. In 10 patients the sentinel lymph node was negative for disease, whereas the nonsentinel lymph nodes contained metastatic disease (false negative rate = 38%). CONCLUSIONS: The role of lymphatic mapping and sentinel lymph node biopsy in colon cancer is not as clear as its role in other tumors. Further large prospective studies are needed to evaluate the accuracy and potential benefit of this procedure in patients with colon cancer.

Aged↗

PubMed2001

Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer.

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.

Adult↗

PubMed2001

The use of a mobile computed tomography scanner in the pediatric intensive care unit to evaluate airway stenting and lung volumes with varying levels of positive end-expiratory pressure.

OBJECTIVE: Presentation of a case report describing the use of a mobile computed tomography (CT) scanner in the pediatric intensive care unit (PICU) to radiographically evaluate tracheobronchial stenting and lung volumes while using different levels of positive end-expiratory pressure (PEEP) and positioning in a critically ill infant. DESIGN: Case report of a single patient. SETTING: Pediatric intensive care unit in a University Hospital. PATIENT: A 6-month-old premature infant with bronchopulmonary dysplasia, tracheobronchomalacia, and progressive respiratory failure. INTERVENTIONS: CT scans of the chest were performed by using a mobile CT scanner in the PICU. Serial CT scans were performed at PEEP levels of 5, 10, 15, and 20 cm H(2)O in both the supine and prone position. Scheduled medical care and standard monitoring were continued during the course of the CT scans. MEASUREMENTS AND MAIN RESULTS: Identical anatomic levels demonstrating the trachea, bronchi, and lung parenchyma were compared while different levels of PEEP and supine or prone positioning were used. From these comparisons, the level of PEEP in which lung volumes were optimized was radiographically determined. No significant changes in large airway caliber were observed. There was no difference noted between prone and supine positioning. CT scans were completed with minimal disruption to the patient's care. CONCLUSIONS: Mobile CT scanners can be used in the PICU for the diagnostic evaluation of critically ill children. This option allows for the continuation of medical therapies and monitoring in the intensive care setting while avoiding the potential complications of transporting a critically ill child to the radiology department. The use of mobile CT scanners may disrupt PICU routine and is more expensive than use of fixed CT scanners. Mobile CT scanners may be useful in radiographically determining the optimal level of PEEP in infants with tracheobronchomalacia and bronchopulmonary dysplasia.

Journal Article↗

PubMed2000

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer.

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.

Adult↗

PubMed2000

Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease.

Daclizumab, a humanized monoclonal IgG1 directed against the alpha chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3( + )25(+) lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)

Adolescent↗

PubMed2000