Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience.

BACKGROUND: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. AIMS: To investigate the epidemiology, clinical presentation and survival in patients with BCS. METHODS: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. RESULTS: Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. CONCLUSIONS: Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.

The EQUAL-ESTRO audit on geometric reconstruction techniques in brachytherapy.

BACKGROUND AND PURPOSE: A geometric check procedure of the reconstruction techniques used in brachytherapy treatment planning systems was developed by the EQUAL (European Quality Laboratory) Laboratory in the framework of the ESTRO's (European Society for Therapeutic Radiology and Oncology) project 'ESQUIRE' (Education Science and QUality assurance In Radiotherapy in Europe [Baumann M, Brada M. Towards equity in turbulent Europe ESTRO, European cooperation and the European Commission. Radiother Oncol 2005;75:251-2. Heeren G. The bright but ephemeral life of a rainbow. A chronical of seventeen years of intensive ESTRO-EU cooperation. Radiother Oncol 2005;75:253-7]) by the task group Braphyqs (Brachytherapy physics quality system). PATIENTS AND METHODS: The check is performed by using the so-called 'Baltas' phantom, mailed to the participating centres in order to check the local technique of geometric reconstruction used in dose calculation. RESULTS: To validate the procedures, the check was first tested among the members of the Braphyqs Network. Since November 2002, the system is open to other centres. Until now 152 reconstructions have been checked. Eighty-six percent of the results were within an acceptance level after the first check. For the remaining 14%, a second check has been proposed. The results of the re-checks are in most cases within an acceptance level, except for 2% of the reconstructions. CONCLUSIONS: The geometric check is available from the EQUAL Laboratory for all the brachytherapy centres. The decrease of the deviations observed between the two checks demonstrates the importance of this kind of external audit as some errors were revealed, which were not discovered before with techniques used in clinical quality control routines.

Development of light ion therapy at the Karolinska Hospital and Institute.

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001--summary and conclusions.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) and published in 1996. The assessment reviewed the scientific literature up to 1993 on the use of radiotherapy in the treatment of solid tumours, and estimated the costs associated with radiotherapy. It also described the current practise of radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The SBU has now conducted a follow-up study on radiotherapy for cancer, including a review of the scientific literature from 1994 and a prospective survey of radiotherapy practise in Sweden 2001. The following conclusions were drawn: The role of radiotherapy as an important form of treatment for cancer with both curative and palliative intent has been further confirmed. The use of radiotherapy in Sweden has increased and is now at the internationally recommended level. Radiotherapy in Sweden is mostly given in accordance with the scientific evidence but may still be underutilized in certain situations. The resources for radiotherapy are being utilized more efficiently. The costs of radiotherapy are still 5% of the total cost of cancer care, while the cost of an individual treatment (fraction) has decreased. The need for radiotherapy capacity will increase. In addition, half of the treatment equipment will have to be replaced in the next few years.

Radiotherapy techniques in current use in Sweden.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of radiotherapy techniques in current use in Sweden. The following conclusions were drawn: Radiotherapy demands adequate knowledge of diagnostic methods, anatomy, cancer biology and of the physical and biological properties of ionizing radiation. Well-functioning teamwork on the part of the oncologist, medical physicist and oncology nurse is important. Radiotherapy has a high degree of technical sophistication, including the use of computers, which necessitates expert technical support. Technical development is rapid, and since the previous report, multileaf collimators and electronic portal imaging have been introduced in the clinical routine. The use of brachytherapy for treatment of non-gynaecological malignancies is rapidly increasing. The need for quality assurance in all steps of the radiotherapy procedure is stressed. A critical review of the literature on intraoperative radiotherapy is also included as an Appendix.

Radiotherapy and cancer care in Sweden.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. It included an overview of the organisation of radiotherapy and cancer care in Sweden and education of staff. It further included an update of cancer statistics for Sweden and an estimate of the need for radiotherapy resources by the year 2010. The following conclusions were drawn: Compared with a similar assessment in 1992, the number of departments of oncology at the county hospital level has increased by one, and one more department was scheduled to start radiotherapy during 2002. The speciality of oncology in Sweden includes all types of non-surgical cancer treatment, in contrast to the situation in most countries, where radiation oncology and medical oncology are independent specialities. Gynaecologic oncology is a unique speciality for Sweden. The number of new cancer cases increased by 13% between 1990 and 2000, and continues to increase by more than 1.0% per year. The projections of cancer incidence stated in the previous report were checked against observed data for the year 2000 and found to be an underestimation. To maintain the current capacity for radiotherapy in relation to number of new cancer cases by the year 2010, a total of 65 accelerators would be needed.

Developments in radiotherapy.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome. Improved treatment results may be expected with even more optimized fractionation schedules. The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours. Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning. More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning. New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments. New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients. Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden.

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study.

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.

Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients.

PURPOSE: To study the incidence of various forms of late normal tissue injuries to determine the latency and dose-response relationships. METHODS: We retrospectively analyzed the clinical records of 150 breast cancer patients treated with radiotherapy after mastectomy in the mid to late 1960s. None of the patients had received chemotherapy as a part of their primary treatment. Radiotherapy was delivered to the parasternal, axillary, and supraclavicular lymph node regions. Almost all the patients continued to be checked at regular 3-month to 1-year intervals at our Oncology Department. Detailed records were available for the entire 34 years of the follow-up period. The patients were divided into 3 groups. The prescribed dose was either 11 x 4 Gy (treated with 60Co photons) or 11 x 4 Gy or 14-15 x 3 Gy (treated with both 60Co photons and electrons). The dose recalculation at the brachial plexus where the axillary and supraclavicular beams overlapped was performed in the early 1970s and expressed in cumulative radiation effect (CRE) units. It varied widely among the individual patients. The received dose has now been converted to biologic effective dose(3) units, and from that into the equivalent dose in 2-Gy fractions to plot the dose-response relationships. RESULTS: We present a comparison of the latency and frequency of fibrosis, edema, brachial plexus neuropathy, and paralysis in the three different subgroups and the total group. Dose-response relationships are shown at 5, 10, and 30 years after irradiation. CONCLUSION: The use of large daily fractions, combined with hotspots from overlapping fields, was the cause of the complications. Clear dose-response curves were seen for late radiation injuries. The incidence seen at 5 years did not represent the full spectrum of injuries. Doses that seem safe at 5 years can lead to serious complications later.