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At least 307 records · Page 17Linked to original sources

Laser-induced thermotherapy (LITT) of liver metastases: MR-guided percutaneous insertion of an MRI-compatible irrigated microcatheter system using a closed high-field unit.

PURPOSE: To evaluate the efficacy and safety of a new MRI-compatible irrigated laser microcatheter system for thermal ablation of liver metastases. MATERIAL AND METHODS: The new microcatheter system consists of a titanium needle with a diameter of 1.5 mm and a surrounding Teflon catheter with an outer diameter of 1.8 mm (5.5 F). In vitro laser-induced coagulation of bovine liver tissue was performed to determine the optimal perfusion rate of cooling saline flow, maximum laser energy, and ablation time. Laser-induced thermotherapy using the new microcatheter system, an Nd:YAG laser (Dornier), and a flexible laser light guide (Somatex GmbH, Berlin, Germany) was performed in 28 patients with liver metastases. Percutaneous insertion and positioning of multiple microcatheters in the lesion and monitoring of therapy was performed with a closed high-field MRI scanner using T1-weighted gradient-echo sequences during breath-hold. RESULTS: A perfusion rate of 0.75 mL/minute, a laser energy of 15 W, and an ablation time of 20 minutes were found suitable to achieve safe and sufficient ablation of metastatic tissue. The mean volume of induced coagulation in vitro was 23.9 mL. Ablation of liver metastases in patients was technically and clinically successful. CONCLUSION: The new microcatheter system allows for both catheter placement and monitoring of therapy using a single imaging modality. This shortens the procedure and enables more precise puncture and therapy of liver metastases. Due to the miniaturized design of the catheter and the real-time monitoring, the procedure is minimally invasive and very well tolerated by patients. This new technique seems to be a safe and feasible alternative in treating liver metastases.

Aged↗

A phase II study to evaluate the efficacy of commercially available molecularly matched targeted therapies in the second-line setting.

BACKGROUND: Initial studies have shown improved outcomes in patients receiving cancer therapies matched to their molecular alterations. To improve the chances of finding a therapeutic match for patients, this study evaluated the preliminary antitumor activity of 3 commercially available multitargeted agents in the United States, regorafenib, afatinib, and cabozantinib. METHODS: In this phase II trial, patients who did not benefit from first-line treatment for non-small cell lung cancer (NSCLC), upper aerodigestive tract cancers, non-colon gastrointestinal cancers, and urothelial carcinoma underwent next-generation sequencing to identify actionable genomic alterations. Eligible patients, based on identified mutations deemed treatable by regorafenib, cabozantinib, or afatinib, were enrolled to receive matched targeted therapies. Outcomes were monitored via Response Evaluation Criteria in Solid Tumors criteria, with dose modifications per National Cancer Institute Common Terminology Criteria for Adverse Events, v4.03 guidelines for adverse events (AEs). RESULTS: One hundred patients with metastatic cancers were enrolled across tumor types. Median treatment durations were 12 weeks (regorafenib), 10.7 weeks (afatinib), and 24.1 weeks (cabozantinib). The overall objective response rate was 7.0%, with 1 complete response and 8 partial responses. The clinical benefit rate, including responses and stable disease >6 months, was 16.0%. Median progression-free survival ranged from 1.9 months for urothelial carcinoma to 3.2 months for NSCLC. Toxicities were common for all medications; for regorafenib, 90.7% of patients had AEs (50% Grade 3/4); for afatinib, 86% of patients had AEs (54% Grade 3/4); for cabozantinib, 100% of patients had AEs (36% Grade 3/4). The most common AEs were diarrhea, fatigue, nausea, decreased appetite, and stomatitis. CONCLUSIONS: Regorafenib, afatinib, and cabozantinib had modest effects when used as molecularly matched targeted therapies in patients with NSCLC, upper aerodigestive tract cancers, non-colon gastrointestinal cancers, and urothelial carcinoma in the second-line setting. Future research could examine more precise matching of therapies to genomic alterations and evaluate combination therapies.

Humans↗

Impact of filtering upon ventricular tachycardia identification by correlation waveform analysis.

Signal analysis of digitized waveforms has been postulated as a method for improving sensitivity and specificity of ventricular tachycardia (VT) detection in implantable antitachycardia devices. Such improvement may alleviate the problem of unwarranted delivery of therapy by adding precision to the identification of the pathological VT. Morphological analysis could also allow distinct therapies to be initialized for multiple VTs in the same patient. Correlation waveform analysis (CWA) has been demonstrated to be effective in separating benign rhythms from VT in wideband recordings (1-500 Hz) but the effect of filtering has not been previously examined. Bipolar (1 cm) intraventricular recordings (1-500 Hz) of sinus rhythm (SR) and 25 distinct VTs in 18 patients were analyzed by CWA using a signal-averaged SR template. Passages contained 65.9 +/- 19.8 VT depolarizations (range 45-108). Digital filtering was performed on all data passages with varying passbands. Results for passages with a bandwidth of 1-250 Hz were equivalent to wideband results, i.e., greater than or equal to 92% paired sets of SR and VT were separable at a 95% confidence level. A bandwidth of 1-100 Hz decreased discrimination to 84%. At a bandwidth of 1-80 Hz, 80% of cases were successfully separated, but at 10-80 Hz these results improved to 88%. Bandwidths of 20-80 and 30-80 Hz reduced reliability of CWA performance to 72% and 60%, respectively. Filtering at typical pacemaker/defibrillator passbands produced morphological analysis results equivalent to those yielded at wideband settings. Differences in the range between SR versus VT decreased in filtered recordings but overall detection of VT was not degraded.

Algorithms↗

Radioimmunoguided-intraoperative radiation therapy in colorectal carcinoma: a new technique to precisely define the clinical target volume.

PURPOSE: The clinical target volume (CTV) to be irradiated by intraoperative radiation therapy (IORT) after resection is generally based on the surgeon's estimation of close margins. We have developed a new technique, radioimmunoguided-intraoperative radiation therapy (RIG-IORT), that uses an intraoperative hand-held gamma-detecting probe to define areas of residual microscopic disease containing radiolabeled monoclonal antibodies to tumor associated antigen, to more precisely delineate the CTV for IORT. METHODS AND MATERIALS: Patients were injected i.v. with 2 mCi 125I- radiolabeled CC49 antibody approximately 3 weeks before surgery. They then underwent radioimmunoguided surgery (RIGS) with maximal resection of tumor. A hand-held gamma-detecting probe (Neoprobe 1000) was used intraoperatively to detect and resect areas of high radioactivity, representing tumor. Areas with persistently high probe counts after resection were the areas of occult residual disease, and represented the CTV to be irradiated. The IORT was given with either 6-9 MeV electron beam from a dedicated linear accelerator, or with high-dose-rate brachytherapy from a remote afterloader. If all RIGS-positive tissue had been resected, or if widely disseminated disease remained, the patient was not considered for IORT. RESULT: This technique was used in 31 patients with colorectal adenocarcinoma recurrent into the pelvis (n = 23) or paraortic nodes (n = 8). The CTV for IORT was delineated by increased RIGS count in 13 of 19 patients (68%) with microscopic residual, and in 11 of 12 patients (92%) with gross residual. In the other 7 patients, the tumor area did not accumulate the radiolabeled antibody; therefore, these tumor beds were irradiated based on the surgeon's estimation of close margins. Hence, overall, the RIG-IORT technique was used to define the tumor bed for IORT in 24 of 31 patients (77%). This technical report focuses on the development of the RIG-IORT technique and does not address the outcome results of the treated patients. CONCLUSION: A new technique, RIG-IORT, which uses radiolabeled monoclonal antibodies to precisely determine the CTV for IORT, is described. Whether the use of this technique will lead to improved tumor control will only be known upon the outcome analysis of RIG-IORT-treated patients compared with those obtained using traditional IORT techniques.

Adult↗

Accuracy and precision of absorbed dose measurements for neutron therapy.

The occurrence of normal tissue complications and probability of tumor control are steep functions of absorbed dose. Consequently the delivery of the dose to the patient should be performed with a precision better than +/- 2% and an overall uncertainty less than +/- 5%. The sequence of dosimetry procedures to deliver the absorbed dose to the patient is analyzed with emphasis on the physical parameters involved in neutron dosimetry; the results of neutron dosimetry intercomparisons are summarized. The protocols for neutron dosimetry formulated by European and American physicists differ in a number of aspects, including the choice of the phantom material. For the treatment of a specific lesion, e.g., a tumor of the floor of the mouth, different treatment plannings have been suggested. Regarding the determination of total absorbed dose at a reference point in a phantom, the required overall uncertainty can be achieved for neutron energies up to 20 MeV. Because of differences in size, shape and composition between the phantom and the patient, somewhat larger uncertainties are to be anticipated for the actual treatment. Further experimental and theoretical studies are needed to obtain more reliable values for kerma in different elements and neutron sensitivity of the photon dosimeters for neutron energies in excess of 20 MeV.

Europe↗

Optimal antibiotic therapy in bronchopulmonary infections.

Therapy of bronchopulmonary infections has evolved in the past 30 years. Only in the therapy of pneumococcal infections have, precise dosage programs been developed. Therapy of pneumococcal infection is optimal with penicillin G in low dosage. None of the newer agents has altered morbidity or mortality. The best agent for the treatment of pneumonia due to Staphylococcus aureus or members of the Enterobacteriaceae has not been established. Use of combination therapy consisting of an anti-Pseudomonas penicillin and an aminoglycoside has been shown to offer the greatest success in the treatment of Pseudomonas pulmonary infections. The optimal antibiotic and dosage program for the treatment of acute bacterial exacerbations of chronic bronchitis has yet to be defined. Further comparative studies of the chemotherapy of pulmonary infections are necessary.

Aminoglycosides↗

Treatment of community-acquired pneumonias.

Community-acquired pneumonia resulting in hospitalization may have a mortality rate of 10 to 25 percent. The exact incidence of community-acquired pneumonia is unknown because it is not a reportable disease. The etiologic spectrum appears to be changing. Streptococcus pneumoniae causes most of the cases; the rank ordering of other pathogens is uncertain. With the exception of Legionella, colonization of the upper respiratory tract usually precedes clinical pneumonia. Subtle aspiration of the posterior pharyngeal flora accounts for the majority of pneumonias. The need for prompt antibiotic therapy mandates an efficient approach to diagnosis, although it is often difficult to establish a precise etiology. Empiric therapy is often initiated prior to an etiologic diagnosis, and should be as specific as possible. Initial choice of therapy is dictated by the clinical presentation (e.g., "bacterial-like" or "viral-like"), inquiries into the possibility of aspiration or gram-negative pneumonia, and the results of gram-stain examination. When the clinical presentation and Gram-stain results are consistent with pneumococcal pneumonia, penicillin is the drug of choice. A more obtuse presentation in an otherwise healthy patient may call for erythromycin to cover Legionella and Mycoplasma. "Marginally compromised" hosts, such as alcoholics, patients with chronic obstructive pulmonary disease, and elderly nursing home patients, may require empiric broad-spectrum cephalosporin therapy for the first few days. Prevention of pneumonia using available vaccines must be emphasized.

Anti-Bacterial Agents↗

[Radiotherapy and Ewing tumor in children].

Despite high local control rate in Ewing's sarcoma the exact indication of radiation therapy is still controversial as well as the choice of the target volume and the optimal dose of radiation. The importance of the quality of radiotherapy has been stressed in recently published data and has shown a significant impact on long term local control with adequate radiation therapy. The dramatic improvement of precision allowed by the conformal therapy and three dimensional dosimetry allow to expect a decrease of late effects expected for second malignancies. However, late sequellae and radio-induced osteosarcoma still remain the major side effects after radiotherapy. The authors discuss the results of the main trials on Ewing's sarcoma on the choice of dose and target volume. Surgery is still the preferred choice for small tumors if the foreseen outcome is identical.

Bone Neoplasms↗

[Endoscopic pretherapeutic clipping for gastrointestinal tumors. A method for exact definition of the target volume].

BACKGROUND: In many cases it is not possible to exactly define the extension of carcinoma of the gastrointestinal tract with the help of computertomography scans made for 3-D-radiation treatment planning. Consequently, the planning of external beam radiotherapy is made more difficult for the gross tumor volume as well as, in some cases, also for the clinical target volume. PATIENTS AND METHODS: Eleven patients with macroscopic tumors (rectal cancer n = 5, cardiac cancer n = 6) were included. Just before 3-D planning, the oral and aboral border of the tumor was marked endoscopically with hemoclips. Subsequently, CT scans for radiotherapy planning were made and the clinical target volume was defined. Five to 6 weeks thereafter, new CT scans were done to define the gross tumor volume for boost planning. Two investigators independently assessed the influence of the hemoclips on the different planning volumes, and whether the number of clips was sufficient to define the gross tumor volume. RESULTS: In all patients, the implantation of the clips was done without complications. Start of radiotherapy was not delayed. With the help of the clips it was possible to exactly define the position and the extension of the primary tumor. The clinical target volume was modified according to the position of the clips in 5/11 patients; the gross tumor volume was modified in 7/11 patients. The use of the clips made the documentation and verification of the treatment portals by the simulator easier. Moreover, the clips helped the surgeon to define the primary tumor region following marked regression after neoadjuvant therapy in 3 patients. CONCLUSIONS: Endoscopic clipping of gastrointestinal tumors helps to define the tumor volumes more precisely in radiation therapy. The clips are easily recognized on the portal films and, thus, contribute to quality control.

Endoscopy, Gastrointestinal↗

"Triple-H" therapy for cerebral vasospasm following subarachnoid hemorrhage.

The combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy) is often utilized to prevent and treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Although this paradigm has gained widespread acceptance over the past 20 years, the efficacy of triple-H therapy and its precise role in the management of the acute phase of SAH remains uncertain. In addition, triple-H therapy may carry significant medical morbidity, including pulmonary edema, myocardial ischemia, hyponatremia, renal medullary washout, indwelling catheter-related complications, cerebral hemorrhage, and cerebral edema. This review examines the evidence underlying the implementation of triple-H therapy, and makes practical recommendations for the use of this therapy in patients with aneurysmal SAH.

Blood Volume↗

[Nebuliser therapy].

We use the nebuliser therapy to achieve rapid improvement in patients with acute airway limitation. Besides, this drug is effective in asthmatic children, in elderly patients and in patients with end-stage disease who need palliative care. Nowadays nebuliser therapy is used not only for bronchodilatation but also for antibiotic and expectoration treatment. Although nebuliser therapy provides a rapid and effective treatment in airway limitation, the patients who receive home nebuliser therapy may suffer from severe and incurable infections if the hygienic conditions are not achieved. Therefore, the indications of nebuliser therapy should be precisely determined and special care should be given in the choice of the patients who will receive nebuliser therapy.

Administration, Inhalation↗

Efficient and precise programmable DNA knock-in without double-strand breaks.

Programmable gene knock-in holds substantial promise for treating genetic diseases and advancing cell therapies. However, achieving precise and efficient kilobase-scale DNA fragment integration remains challenging1,2. Here we report CRISPR kilobase-scale nickase-targeting (KNIT) editing for efficient, precise and programmable kilobase-scale DNA insertion without double-strand DNA cleavage, which is enabled through the coupling of a Cas9 nickase with a DNA donor recruiting system. KNIT editing facilitates programmable integration of DNA fragments from 0.7 kb to more than 10 kb and is effective across genomic loci and cell types. It achieves up to 89% efficiency and markedly reduces unintended insertion-deletion mutation (indels) rates, translocations and off-target editing. The system supports repeated insertion editing and multiloci gene knock-in with minimal translocations. Its enhanced version, KNIT editor 2, further improves efficiency via a single transfection. Moreover, in mutant cells with a pathological mutation, KNIT editing restores normal gene expression by inserting a therapeutic gene into a safe harbour locus or its native locus. Notably, KNIT editing enables non-viral and programmable chimeric antigen receptor T cell (CAR-T cell) engineering without double-strand breaks and with clinically relevant efficiencies. Moreover, the engineered CAR-T cells exhibit effective antitumour activity in vitro and in mouse models. Therefore, by achieving programmable and site-specific kilobase-scale DNA insertions without double-strand breaks while reducing unintended outcomes, KNIT editing provides a versatile platform for advancing personalized medicine.

Animals↗

Immediate active short arc motion following extensor tendon repair.

Postoperative management of the extensor tendon injury has been altered over the past 15 years from treatment with 4 to 6 weeks of immobilization to controlled passive motion and, now, to active SAM with minimal tension and wrist tenodesis programs. The concepts of immediate motion are supported biochemically in experimental studies, and biomechanically through excursion studies, mathematical analysis of tendon excursion and force application, and study of repair tensile strengths. The results cited in this article and those reported by others demonstrate that early motion for extensor tendons in zones III, IV, V, VI, VII, T IV, and T V is safe and effective if force application is precise. Early referral to therapy, meticulous care in the control of edema, precise positions of postoperative splinting, and controlled motion programs will greatly improve the results of both simple and complex extensor tendon injuries, both in terms of function achieved and in terms of time and expense.

Adolescent↗

Phage therapy in oncology: opportunities for cancer prevention and treatment.

Bacteriophages (phages) are emerging as programmable biological therapeutics in oncology, extending beyond their traditional antimicrobial applications. This review proposes a phage-microbiome-immune-oncology axis that links microbial dynamics, immune modulation, and engineered phages to guide precision cancer prevention and therapy. Phages can eliminate cancer-associated bacteria, remodel the tumor microenvironment, enhance antitumor immunity, and deliver targeted therapeutic payloads. However, several critical challenges must be addressed to realize this therapeutic potential, particularly host immune responses that limit repeat dosing, inefficient tumor penetration, and the need for rigorous clinical validation. By examining phage-host-tumor interactions through robust model systems and highlighting translational opportunities, this review establishes phage therapy as a promising frontier in precision oncology that warrants accelerated clinical development.

Humans↗

Uncertainties in radiation therapy: target definition in carcinoma of the uterine cervix.

In treatment of patients with carcinoma of the cervix, as in any other malignant tumor, accurate identification of target volumes is critical to enhance precision of radiation therapy planning and delivery. These results in improved locoregional tumor control lead to lower incidence of distant metastases and improved survival. Also, radiation therapy morbidity is decreased, enhancing quality of life. Various imaging techniques are available to achieve better target delineation and this can be enhanced with image fusion. Available innovative treatment techniques to optimize the use of radiation therapy for these patients are illustrated.

Female↗

Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus.

BACKGROUND: Endoscopic mucosal resection (EMR) and photodynamic therapy have been proposed as treatments for early stage cancers. EMR is limited by its focal nature whereas photodynamic therapy is dependent on precise staging. The combination of EMR and photodynamic therapy were studied in the treatment of superficial cancer in patients with Barrett's esophagus. METHODS: Seventeen consecutive nonsurgical patients with superficial cancers underwent EMR followed by photodynamic therapy with a porphyrin photosensitizer. Photoradiation was performed at 630 nm for a total dose of 200 J/cm of diffuser. RESULTS: Seventeen patients (15 men; mean age 69 +/- 13 years) underwent EMR. The mean diameter of mucosal resection was 1 cm. The margins were involved by cancer in 3 cases. EMR improved staging in 8 patients (47%). Sixteen (94%) patients remained in remission (median follow-up 13 months). Complications included minor bleeding after EMR in 1 patient (6%), stricture in 5 (30%), cutaneous phototoxicity in 2 (12%), and supraventricular tachycardia in 1 patient (6%). CONCLUSIONS: Combined EMR and photodynamic therapy appears to be an effective and safe therapy for superficial esophageal cancer within Barrett's esophagus. This combination improves cancer staging, removes the superficial cancer, and eliminates remaining mucosa at risk for cancer development.

Adenocarcinoma↗

Image-guided acoustic therapy.

The potential role of therapeutic ultrasound in medicine is promising. Currently, medical devices are being developed that utilize high-intensity focused ultrasound as a noninvasive method to treat tumors and to stop bleeding (hemostasis). The primary advantage of ultrasound that lends the technique so readily to use in noninvasive therapy is its ability to penetrate deep into the body and deliver to a specific site thermal or mechanical energy with submillimeter accuracy. Realizing the full potential of acoustic therapy, however, requires precise targeting and monitoring. Fortunately, several imaging modalities can be utilized for this purpose, thus leading to the concept of image-guided acoustic therapy. This article presents a review of high-intensity focused ultrasound therapy, including its mechanisms of action, the imaging modalities used for guidance and monitoring, some current applications, and the requirements and technology associated with this exciting and promising field.

Humans↗

[Prostate carcinoma associated spontaneous factor VIII:C inhibitor hemophilia. Successful therapy of severe hemorrhagic complication with porcine factor VIII in a 75-year-old patient].

Inhibitors of factor VIII are a rare condition in non-hemophiliacs, but they are frequently responsible for life threatening hemorrhage. Acquired factor VIII:C inhibitors represent the spontaneous development of autoantibodies that partially or completely neutralize the plasma coagulant activity of the clotting factor. The autoantibodies can arise in diverse clinical settings, in older adults they are frequently associated with immunologic disorders or malignancies. We report of a 75-year-old man with acquired factor VIII:C inhibitor associated with adenocarcinoma of the prostate and a successful treatment of a severe bleeding complication with porcine factor VIII. A 75-year-old man was admitted because of a hematoma of his right cheek and an isolated prolonged aPTT. Acquired factor VIII:C inhibitor was identified as the cause and immuno-suppressive therapy was begun. In the clinical course severe hemorrhaging occurred and was successfully treated with porcine factor VIII (Hyate:C). The initially high inhibitor titer of 32 Bethesda Units (BU) disappeared. As the cause of acquired factor VIII:C inhibitor a newly diagnosed adenocarcinoma of the prostate is likely. After complete remission of acquired factor VIII:C inhibitor radiation therapy was begun. Six months after severe hemorrhaging the patient was clinically stable and PSA levels were normal. This case demonstrates the necessity of a precise diagnosis and therapy regimen of this coagulopathy based on clinical and laboratory data. In the absence of hemorrhage immuno-suppressive therapy with corticosteroids is indicated, in a patient with severe bleeding and high inhibitor titer (> or = 5 BU) porcine factor VIII should be administered.

Adenocarcinoma↗