| 1. |
- Bohl Kullberg, Erika, et al.
(author)
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Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents
- 2002
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 13:4, s. 737-743
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Journal article (peer-reviewed)abstract
- Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG−DSPE lipid molecules in a micellar solution and the EGF−PEG−DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA. We found that the optimal transfer conditions were a 1-h incubation at 60 °C. The final conjugate, 125I-EGF−liposome−WSA, contained approximately 5 mol % PEG, 10−15 EGF molecules at the liposome surface, and 104 to 105 encapsulated WSA molecules could be loaded. The conjugate was shown to have EGF-receptor-specific cellular binding in cultured human glioma cells.
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| 4. |
- Johnsson, Stefan
(author)
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Development and evaluation of an independent system for absorbed dose calculations in radiotherapy
- 2003
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Doctoral thesis (other academic/artistic)abstract
- The aim of this work was to develop, implement and evaluate an independent system with which to calculate the absorbed dose, delivered by high-energy X-ray beams, to the prescription point and the depth of dose maximum. The introduction of such a system in the clinical routine may help ensure high-quality treatment and avoidance of errors which may jeopardise the clinical outcome of the treatment (i.e. under- or overdose). A set of equations for calculating the absorbed dose to the prescription point was compiled in a software application (“HandCalc”), which is completely independent of the treatment planning system (TPS). For instance, HandCalc includes models to calculate the absorbed dose from photons scattered in the patient, the transmission of the primary kerma in the patient, the variation of the primary kerma in air with collimator setting (i.e. head scatter), and corrections for heterogeneities in the patient. A new expression for the transmission of the primary kerma in the patient was derived in which the coefficients are strictly defined (and given a physical interpretation) by the first two moments of the spectral distribution of the incident beam. Further investigations also revealed that these moments can be used to determine water-to-air stopping power ratios more accurately than other beam quality indices. In practice, the moments are derived from “in-air equivalent”, narrow-beam measurements using a mini-phantom. The degree of in-air equivalence was investigated with Monte Carlo simulations, which showed that the optimum measurement depth in a mini-phantom is somewhat below the depth of dose maximum. Based upon comparisons with measurements and the TPS, a clinical action level of +/- 4% was chosen for HandCalc. Deviations greater than this are, with all probability, due to erroneous handling of the patient dataset during the preparation phase. An “entrance dose factor” was added in order to correct the dose calculations at the depth of dose maximum where electron equilibrium has not been established. The entrance dose factor was found to vary with beam quality and collimator setting, while no variation was detected with the presence of an acrylic tray (for block support) or with the source-surface distance (SSD). HandCalc was implemented in a hand-held PC which makes dose calculations inside the treatment room at the time of administration of the first fraction possible. An important feature of HandCalc is the built-in report function, which logs results from the calculation for later evaluation. In a study including 700 patients, deviations greater than the action level were found to be due either to limitations in HandCalc or to a systematic deviation between the planned and measured SSD. HandCalc has proven to be a fast and accurate tool for independent dose calculations inside the treatment room and it requires only a limited amount of extra time for the user to perform the calculations. Thus, it can easily be incorporated as part of the daily clinical quality control programme in order to prevent errors which may jeopardise the clinical outcome of the treatment.
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| 5. |
- Johnsson, Stefan, et al.
(author)
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On beam quality and stopping power ratios for high-energy x-rays
- 2000
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In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 45:10, s. 2733-2745
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Journal article (peer-reviewed)abstract
- The aim of this work is to quantitatively compare two commonly used beam quality indices, IPR(20/10) and %dd(10)x, with respect to their ability to predict stopping power ratios (water to air), s(w,air), for high-energy x-rays. In particular, effects due to a varied amount of filtration of the photon beam will be studied. A new method for characterizing beam quality is also presented, where the information we strive to obtain is the moments of the spectral distribution. We will show how the moments enter into a general description of the transmission curve and that it is possible to correlate the moments to s(w,air) with a unique and simple relationship. Comparisons with TPR(20/10) and %dd(10), show that the moments are well suited for beam quality specification in terms of choosing the correct s(w,air).
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| 6. |
- Knöös, Tommy, et al.
(author)
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Independent checking of the delivered dose for high-energy X-rays using a hand-held PC
- 2001
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In: Radiotherapy and Oncology. - 1879-0887. ; 58:2, s. 201-208
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Journal article (peer-reviewed)abstract
- Background and purpose: The requirements on the delivered dose in radical radiation therapy are extremely high. The dose should be within a few percent and also delivered with high accuracy in space. Vendors and users have successfully managed to implement radiation therapy systems, which are able to achieve these demands with high accuracy and reproducibility. These systems include computerized tomography scanners, treatment planning systems, simulators, treatment machines, and record and verify systems. More and more common are also computer networks to assure data integrity when transferring information between the systems. Even if these systems are commissioned and kept under quality assurance programs to maintain their accuracy, errors may be introduced. Especially, the human factor is an uncontrolled parameter that may introduce errors. Thus, unintentional changes or incorrect handling of data may occur during clinical use of the equipment. Having an independent dose calculation system implemented in the daily quality assurance process may assure a high quality of treatments and avoidance of severe errors.Materials and methods: To accomplish this, a system of equations for calculating the absorbed dose to the prescription point from the set-up information, has been compiled into a dose-calculation engine. The model is based on data completely independent of the treatment planning system (TPS). The fundamental parameter in the dose engine is the linear attenuation coefficient for the primary photons. This parameter can readily be determined experimentally. The dose calculation engine has been programmed into a hand-held PC allowing direct calculation of the dose to the prescription point when the first treatment is delivered to the patient.Results and conclusion: The model is validated with measurements and is shown to be within +/-1.0% (1 SD). Comparison against a state-of-the-art TPS shows an average difference of 0.3% with a standard deviation of +/-2.1%. An action level covering 95% of the cases has been chosen, i.e. +/-4.0%. Deviations larger than this are with a high probability due to erroneous handling of the patient set-up data. This system has been implemented into the daily clinical quality control program.
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| 8. |
- Wenner, Jörgen, et al.
(author)
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Short-term outcome after laparoscopic and open 360 degrees fundoplication. A prospective randomized trial.
- 2001
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In: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 15:10, s. 1124-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite the lack of randomized trials supporting the laparoscopic approach, laparoscopic antireflux surgery has gained widespread acceptance during the last decade. The aim of this study was to compare the short-term symptomatic and objective outcome after laparoscopic and open 360 degrees fundoplication in a prospective randomized clinical trial. METHODS: Sixty patients with GERD were randomized to undergo either laparoscopic (LF) or open 360 degrees fundoplication (OF). Endoscopy, esophageal manometry, 24-h pH monitoring, clinical symptom evaluation, and symptom scoring according to a validated questionnaire (the Gastrointestinal Symptom Rating Scale [GSRS]) was performed preoperatively and 6 months after surgery. RESULTS: Five patients randomized to the laparoscopic group were converted to open surgery. Esophageal acid exposure was restored to normal in all patients. Lower esophageal sphincter length and resting pressure were significantly increased after both laparoscopic and open fundoplication (p < 0.001); there were no differences between the groups. No significant differences were seen in symptomatic outcome, although there was a trend toward a higher rate of mild dysphagia (p = 0.051) after laparoscopic surgery. GSRS revealed a decrease in reflux score (p < 0.001) and abdominal pain score (p < 0.001) postoperatively. There were no significant differences in GSRS scores between the two groups. CONCLUSION: Laparoscopic 360 degrees fundoplication is as effective in treating reflux disease as open fundoplication. Six months postoperatively, no significant differences were seen in symptomatic or objective outcome. Long-term evaluation is needed.
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| 9. |
- Zilling, T, et al.
(author)
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Anastomotic diameters and strictures following esophagectomy and total gastrectomy in 256 patients
- 2000
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In: World Journal of Surgery. - 0364-2313. ; 24:1, s. 5-84
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Journal article (peer-reviewed)abstract
- The prevalence of anastomotic strictures in esophageal anastomoses provides us with limited information about the anastomotic healing process. This prospective study evaluates the exact esophageal anastomotic diameters in 256 patients who underwent esophagectomy and esophagogastrostomy without pyloroplasty (n = 107) or total gastrectomy and Roux reconstruction (n = 149). No perioperative chemoradiotherapy was given. Anastomotic strictures and diameters were assessed during endoscopy by a separately inserted (inflated to the anastomotic width) balloon catheter. The anastomotic diameters increased significantly during the first postoperative year in the esophagectomy (p = 0.001) and gastrectomy (p < 0.001) groups. The anastomoses in the gastrectomy group were significantly wider than those in the esophagectomy group 3 (25.7 versus 19.9 mm), 6 (28.5 versus 22.0 mm), and 12 (30.5 versus 23.3 mm) months after surgery (p < 0.001). Neither the anastomotic site (neck or chest) in the esophagectomy group (p = 0.176) nor that in the gastrectomy group (abdomen or chest) (p = 0.577) influenced the anastomotic diameter. Benign anastomotic strictures were most frequently found after 3 months and after esophagectomy. Esophagojejunostomies performed with 2 linear stapling devices or cartridge size 28 mm showed the widest anastomoses with only 1 stricture. Esophagogastric anastomoses following esophagectomy are narrower and develop more strictures than esophagojejunal anastomoses after total gastrectomy, but both dilate during the first year.
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| 10. |
- Öberg, Stefan, et al.
(author)
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Endoscopic surveillance of columnar-lined esophagus - Frequency of intestinal metaplasia detection and impact of antireflux surgery
- 2001
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In: Annals of Surgery. - 1528-1140. ; 234:5, s. 619-626
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Journal article (peer-reviewed)abstract
- Objective To quantify the occurrence of intestinal metaplasia in columnar-lined esophagus (CLE) during endoscopic surveillance and to evaluate the impact of antireflux surgery on the development of intestinal metaplasia. Summary Background Data The malignant potential in segments of CLE is mainly restricted to those containing intestinal metaplasia. Patients with segments of CLE in which no intestinal metaplasia can be detected are rarely enrolled in a surveillance program but may still be at increased risk of developing esophageal adenocarcinoma because intestinal metaplasia may be missed or may develop with time. Methods The occurrence of intestinal metaplasia on biopsy samples was determined on repeated endoscopies in 177 patients enrolled in a surveillance program for CLE. The incidence of intestinal metaplasia in patients with no evidence of intestinal metaplasia on the two first endoscopies was evaluated on the subsequent endoscopies and compared in patients with medically and surgically treated gastroesophageal reflux disease. Results Intestinal metaplasia was found in 53% of the patients (94/ 177) on their first surveillance endoscopy and was more prevalent in long segments of CLE. The prevalence of intestinal metaplasia increased markedly with increasing number of surveillance endoscopies. Intestinal metaplasia tended to be detected early in patients with long segments of CLE; in patients with shorter segments, intestinal metaplasia was also detected late in the course of endoscopic surveillance. Patients with surgically treated reflux disease were 10.3 times less likely to develop intestinal metaplasia compared with a group receiving standard medical therapy. Conclusion Biopsy samples from a single endoscopy, despite an adequate biopsy protocol, are insufficient to rule out the presence of intestinal metaplasia. Patients in whom biopsy specimens from a segment of CLE show no intestinal metaplasia have a significant risk of having undetected intestinal metaplasia or of developing intestinal metaplasia with time. Sampling error is probably the reason for the absence of intestinal metaplasia in segments of CLE longer than 4 cm, whereas development of intestinal metaplasia is common in patients with shorter segments of CLE. Antireflux surgery protects against the development of intestinal metaplasia, possibly by better control of reflux of gastric contents.
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