[The two-in-one hit model of the short-cut carcinogenesis of colorectal carcinomas in MLH1-associated Lynch syndrome]. / Das Two-in-one-hit-Modell der beschleunigten Genese von kolorektalen Karzinomen beim MLH1-assoziierten Lynch-Syndrom.

In a recently published study a new genetic hypothesis was established that explained the existence of CTNNB1 mutations in Lynch syndrome-associated colorectal carcinomas (MLH1-LS-CRC). This hypothesis states that a mitotic recombination on chromosome 3p simultaneously leads to inactivation of the mismatch repair gene MLH1 and to the activation of CTNNB1. This explains the increased frequency of CTNNB1 mutations in MLH1-LS-CRC compared with other colon carcinomas. To test this hypothesis, various experiments were carried out that show that the first phase of recombination occurs in non-cancerous tissues, which favours the development of CTNNB1 mutations. This mechanism could explain the rapid tumour progression in MLH1-LS-CRC. The results highlight the importance of mitotic recombination in carcinogenesis and provide an insight into the genetic basis of colorectal carcinoma in the context of Lynch syndrome.

Pretibial hematomas - A real-world single-center study.

We analyzed treatment, outcome, and risk factors for skin necrosis of 60 patients aged ≥65 years treated for a pretibial hematoma in the province of Kymenlaakso, Finland, between 2015 and 2019. Reviewing patients' medical records revealed two cohorts with distinct trajectories in outcome. By comparing the cohorts, we were able to discover factors associated with the prognosis for generating skin necrosis and the need for operative treatment. Thirty-five (58.3%) patients healed without any management, and 25 (41.7%) patients were treated with hematoma evacuation, mostly for having generated skin necrosis (72%). Among operatively treated patients' descriptions, such as "parchment skin" and "poor skin quality" were observed frequently (80%) in the medical records. This pathology, dermatoporosis, was statistically significant (p<0.0001) among patients with a complicated outcome of a pretibial hematoma. In addition to dermatoporosis, patients with hematoma evacuation were more fragile having a higher Charlson comorbidity index (p = 0.005), a greater need for a walking aid (p = 0.0002), and overall compromised independency (p = 0.033). Hospitalization and rehabilitation were prolonged in the operatively treated cohort, 6.4 days vs. 2 days, respectively. We recorded a delay in the diagnosis and hematoma evacuation (mean 6, range 0-51 days). In addition, six (10%) patients were misdiagnosed for having erysipelas or deep vein thrombosis indicating that pretibial hematomas are not recognized. Skin quality should be documented, and prompt surgical hematoma evacuation should be executed in fragile patients with dermatoporosis. This could prevent skin necrosis and the further need of wound care or surgical care, long hospitalization, and rehabilitation periods.

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender.

BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.

Pretibial lacerations among elderly patients: A province-wide study from Kymenlaakso, Finland, 2015-2019.

In this retrospective cohort study, we analysed treatment and outcomes among ≥65-year-old patients who experienced a traumatic pretibial laceration in the province of Kymenlaakso, Finland, between 2015 and 2019. We reviewed computerised medical records for 116 patients with a pretibial laceration, 107 of whom we analysed in further detail. Patients were traced from injury to healing, including rehabilitation periods in health care centres. As expected, the majority of patients were elderly women (67%). Most lacerations were superficial and small, explaining why treatment was mostly conservative. Only 11 (9.48%) patients were treated operatively with surgical debridement or a split-thickness skin graft. The number of overall complications in wounds was high, with a complication rate of 30.2%. Most complications were local wound infections. We found that wound healing took more than 3 months in 32% of patients. Thorough patient tracing revealed numerous follow-up visits and long rehabilitative hospitalisation periods, indicating a significant decline in patient independence and the excessive use of resources. Successful wound healing was eventually observed in 89.66% patients. Furthermore, no terminology regarding pretibial lacerations was found in patient records. This study indicates that pretibial lacerations remain poorly recognised and understood in Finland.

Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases: a population-based study.

BACKGROUND: This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. METHODS: A retrospective population-based study was conducted on patients with metastatic colorectal cancer in Central Finland in 2000-2015. Clinical and histopathological data were retrieved and descriptive analysis was conducted to determine the pattern of metastatic disease, defined as synchronous, early metachronous (within 12 months of diagnosis of primary disease) and late metachronous (more than 12 months after diagnosis). Subgroups were compared for resection and overall survival (OS) rates. RESULTS: Of 1671 patients, 296 (17·7 per cent) had synchronous metastases, and 255 (19·6 per cent) of 1302 patients with resected stage I-III tumours developed metachronous metastases (94 early and 161 late metastases). Liver, pulmonary and intraperitoneal metastases were the most common sites. The commonest metastatic patterns were a combination of liver and lung metastases. The overall metastasectomy rate for patients with synchronous metastases was 16·2 per cent; in this subgroup, 3- and 5-year OS rates after any resection were 63 and 44 per cent respectively, compared with 7·1 and 3·3 per cent following no resection (P < 0·001). The resection rate was higher for late than for early metachronous disease (28·0 versus 17 per cent respectively; P = 0·048). Three- and 5-year OS rates after any resection of metachronous metastases were 78 and 62 per cent respectively versus 42·1 and 18·2 per cent with no metastasectomy (P < 0·001). Similarly, 3- and 5-year OS rates after any metastasectomy for early metachronous metastases were 57 and 50 per cent versus 84 and 66 per cent for late metachronous metastases (P = 0·293). CONCLUSION: The proportion of patients with metastatic colorectal cancer was consistent with that in earlier population-based studies, as were resection rates for liver and lung metastases and survival after resection. Differentiation between synchronous, early and late metachronous metastases can improve assessment of resectability and survival.

ANTECEDENTES: El objetivo de este estudio de base poblacional fue analizar la incidencia, la forma de presentación y los resultados del tratamiento multimodal del cáncer colorrectal metastásico (metastatic colorectal cancer, mCRC). MÉTODOS: Se realizó un estudio retrospectivo de base poblacional en pacientes con mCRC en la región central de Finlandia entre 2000 a 2015. Se recuperaron los datos clínicos e histopatológicos y se realizó un análisis descriptivo con el objetivo de analizar la forma de presentación de la enfermedad metastásica. La enfermedad metastásica se definió como sincrónica, metacrónica precoz (< 12 meses) y metacrónica tardía (> 12 meses después del diagnóstico de la enfermedad primaria) y se compararon las tasas de resección y de supervivencia global (overall survival, OS) en estos subgrupos. RESULTADOS: De los 1.671 pacientes revisados, 296 (17,7%) presentaron metástasis sincrónicas, mientras que de los 1.302 pacientes resecados en estadios I-III, 255 (19,6%) tuvieron metástasis metacrónicas: 94 precoces y 161 tardías. La localización metastásica más frecuente fue el hígado, los pulmones y el peritoneo. La combinación más frecuente fue la de metástasis hepáticas y pulmonares. La tasa de resección para pacientes con metástasis sincrónicas fue del 16,2%; en este subgrupo, la OS a 3 y 5 años después de cualquier tipo de resección fue del 62,6% y 44,2% versus 7,1% y 3,3% en los pacientes sin resección, respectivamente (P < 0,001). La tasa de resección fue mayor en la enfermedad metacrónica tardía que en la enfermedad metacrónica precoz (28% versus 17%, P = 0,048). Las tasas de OS a 3 y 5 años después de cualquier resección en los casos de metástasis metacrónicas fueron del 77,8% y 61,9% versus 42,1% y 18,2% en los pacientes sin metastasectomía, P < 0,001. Las tasas de OS a 3 y 5 años después de cualquier metastasectomía en los casos de metástasis metacrónicas precoces fueron del 57,4% y 50,3%, versus 84,3% y 65,6% en las tardías (P = 0,29) CONCLUSIÓN: La proporción de pacientes con mCRC fue similar a la de estudios anteriores de base poblacional, así como las tasas de resección para metástasis hepáticas y pulmonares y la supervivencia después de la resección. Diferenciar entre metástasis sincrónicas, metacrónicas precoces y tardías puede mejorar la posibilidad de resecabilidad y la supervivencia.

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study.

To prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers' attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p < 0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p < 0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery.

Indoor air problems and experiences of injustice in the workplace: A quantitative and a qualitative study.

This study explores subjective injustice experiences of individuals suffering from suspected or observed indoor air problems in their workplaces in two studies. We focus on injustice experiences because they influence how individuals cope with and recover from health problems. The first study reports associations between the perceived harmfulness of the indoor environment (ie, mold/inadequate ventilation) and subjective injustice experiences in workplaces in a representative sample of Finnish working-aged people (N = 4633). Altogether, 37% of the respondents perceived their workplaces' indoor environments to be harmful. Multivariate logistic regression analyses revealed that the risks of reporting subjective injustice experiences (eg, information, attitudes, and remuneration) were significantly higher for those reporting harmful indoor environments compared to those who reported no such problems (OR 1.28-1.95 for different situations). The second study explored injustice experiences more closely by qualitatively analyzing the content of 23 essays. These essays were written by people who suffered from suspected or observed indoor air problems in their workplaces. The respondents reported multidimensional experiences of injustice, which related to conflicts, and moral exclusions. Awareness of these psychosocial effects is important for the prevention of unnecessary escalation of psychosocial problems in workplaces with observed and suspected indoor air problems.

Biokinetic analysis of tissue boron (¹°B) concentrations of glioma patients treated with BNCT in Finland.

A total of 98 patients with glioma were treated with BPA-F-mediated boron neutron capture therapy (BNCT) in Finland from 1999 to 2011. Thirty-nine (40%) had undergone surgery for newly diagnosed glioblastoma and 59 (60%) had malignant glioma recurrence after surgery. In this study we applied a closed 3-compartment model based on dynamic (18)F-BPA-PET studies to estimate the BPA-F concentrations in the tumor and the normal brain with time. Altogether 22 patients with recurrent glioma, treated within the context of a clinical trial, were evaluated using their individual measured whole blood (10)B concentrations as an input to the model. The delivered radiation doses to tumor and the normal brain were recalculated based on the modeled (10)B concentrations in the tissues during neutron irradiation. The model predicts from -7% to +29% (average, +11%) change in the average tumor doses as compared with the previously estimated doses, and from 17% to 61% (average, 36%) higher average normal brain doses than previously estimated due to the non-constant tumor-to-blood concentration ratios and considerably higher estimated (10)B concentrations in the brain at the time of neutron irradiation.

Treatment provided in the Public Dental Service in Finland in 2009.

OBJECTIVES: To analyse treatment measures provided in the Public Dental Service (PDS) and to discuss the therapy given against treatment needs as expressed in the national clinical epidemiological studies. METHODS: In 2009, the Chief Dentists of the PDS units collected data from their local registers on patients and treatment provided. Data were obtained from 166 PDS units (86%). Treatment patterns were compared between age groups, provider groups and geographical areas using chi-square tests. RESULTS: Altogether 8.9 million treatments were provided for 1.7 million patients. Examinations, restorative treatment and anaesthesia accounted for 61.3% of all treatments. Preventive measures (8.4%) and periodontal treatment (6.3%) were small proportions of the total. Prosthetic treatment was uncommon (0.5%). Working age adults received half of all treatments (53.2%), the young a third (36.4%) and the elderly 10.4%. Dental hygienists or dental assistants provided 29.7% of all treatment for children and adolescents, 11.1% for adults and 14.1% for the elderly. CONCLUSION: Relatively healthy children had plenty of examinations and preventive measures, and adults had mostly restorative care when their needs were more periodontal and prosthetic care, indicating that treatment given was not fully in line with needs.

Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer.

BACKGROUND: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics. METHODS: Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.

Comparing ischaemic stroke in six European countries. The EuroHOPE register study.

BACKGROUND AND PURPOSE: The incidence of hospitalizations, treatment and case fatality of ischaemic stroke were assessed utilizing a comprehensive multinational database to attempt to compare the healthcare systems in six European countries, aiming also to identify the limitations and make suggestions for future improvements in the between-country comparisons. METHODS: National registers of hospital discharges for ischaemic stroke identified by International Classification of Diseases codes 433-434 (ICD-9) and code I63 (ICD-10), medication purchases and mortality were linked at the patient level in each of the participating countries and regions: Finland, Hungary, Italy, the Netherlands, Scotland and Sweden. Patients with an index admission in 2007 were followed for 1 year. RESULTS: In all, 64,170 patients with a disease code for ischaemic stroke were identified. The number of patients registered per 100,000 European standard population ranged from 77 in Scotland to 407 in Hungary. Large differences were observed in medication use. The age- and sex-adjusted all-cause case fatality amongst hospitalized patients at 1 year from stroke was highest in Hungary at 31.0% (95% confidence interval 30.5-31.5). Regional differences in age- and sex-adjusted 1-year case fatality within countries were largest in Hungary (range 23.6%-37.6%) and smallest in the Netherlands (20.5%-27.3%). CONCLUSIONS: It is feasible to link population-wide register data amongst European countries to describe incidence of hospitalizations, treatment patterns and case fatality of ischaemic stroke on a national level. However, the coverage and validity of administrative register data for ischaemic stroke should be developed further, and population-based and clinical stroke registers should be created to allow better control of case mix.

Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole, or both?

OBJECTIVE: To evaluate cefuroxime and metronidazole antibiotic prophylaxis. DESIGN: Observational nonrandomised 1-year prospective cohort study. SETTING: Fifty-three hospitals in Finland. POPULATION: A total of 5279 women undergoing hysterectomy for benign indications, with cefuroxime given to 4301 and metronidazole given to 2855. Excluding other antibiotics, cefuroxime alone was given to 2019, metronidazole alone was given to 518, and they were administered in combination to 2252 women. METHODS: Data on 1115 abdominal hysterectomies (AHs), 1541 laparoscopic hysterectomies (LHs), and 2133 vaginal hysterectomies (VHs) were analysed using logistic regression adjusted for confounding factors. MAIN OUTCOME MEASURES: Postoperative infections. RESULTS: Cefuroxime had a risk-reductive effect for total infections (adjusted odds ratio, OR, 0.29; 95% confidence interval, 95% CI, 0.22-0.39), but the independent effect of metronidazole and the interaction effect of cefuroxime and metronidazole were nonsignificant. In subgroup analyses of AHs, LHs, and VHs involving those receiving the two main antibiotics only, the effect of cefuroxime alone nonsignificantly differed from that of cefuroxime and metronidazole in combination for all types of infection. The absence of cefuroxime, assessed by comparing metronidazole alone with cefuroxime and metronidazole in combination, led to an increased risk for total infections in AHs (adjusted OR 3.63; 95% CI 1.99-6.65), in LHs (OR 3.53; 95% CI 1.74-7.18), and in VHs (OR 4.05; 95% CI 2.30-7.13), and also increased risks for febrile events in all categories (AHs, OR 2.86; 95% CI 1.09-7.46; LHs, OR 13.19; 95% CI 3.66-47.49; VHs, OR 12.74; 95% CI 3.01-53.95), wound infections in AHs (OR 6.88; 95% CI 1.09-7.49), and pelvic infections in VHs (OR 4.26; 95% CI 1.76-10.31). CONCLUSIONS: In this study, cefuroxime appeared to be effective in prophylaxis against infections. Metronidazole appeared to be ineffective, with no additional risk-reductive effect when combined with cefuroxime.

CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.

OBJECTIVE: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. METHODS: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aß plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aß42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. RESULTS: The patients with Aß plaques in the cortical biopsy had lower (p = 0.009) CSF Aß42 levels than those with no Aß plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aß42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aß42 and highest tau and p-tau 181 levels in CSF. The Aß42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aß was independently predicted by the APOE ε4 carrier status and age but not by CSF Aß42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aß42 and high CSF tau and p-tau levels, respectively.

Pharmaceutical thrombosis prophylaxis, bleeding complications and thromboembolism in a national cohort of hysterectomy for benign disease.

BACKGROUND: Pharmaceutical thrombosis prophylaxis (PTP) with low-molecular-weight heparin (LMWH) is highly effective in preventing venous thromboembolic events (VTEs) and fatal pulmonary embolism. Important risk factors for VTEs are surgery and immobilization, along with malignancy. Many studies involving gynaecological malignancies show no increased risk for bleeding complications with PTP. Little is known about the PTP-associated risk for bleeding complications with hysterectomy for benign disease, or about current VTE incidence in the less-invasive hysterectomy methods. METHODS: Our observational prospective national 1-year cohort from 1 January to 31 December 2006 in 53 hospitals represented 79.4% (5297 of 6645) of hysterectomies performed for benign cause in Finland in 2006. We evaluated PTP use and VTE incidence. Operative and post-operative bleeding complications were analysed with logistic regression adjusted for confounders: age, BMI, experience of the gynaecological surgeon, hospital type, indication for hysterectomy, uterine weight, operative haemorrhage, concomitant surgery, adhesiolysis and antibiotic prophylaxis. RESULTS: Hysterectomies were performed by three main approaches: 2345 vaginal hysterectomies (VHs, 44%), of which 1433 were for uterine prolapse and 912 for other indications, 1679 laparoscopic hysterectomies (LHs, 32%) and 1255 abdominal hysterectomies (AHs, 24%). PTP was given to 64.8% of patients (3420 of 5279) and was identified as LMWH in 3313 patients (97%); 107 left unidentified. By type of hysterectomy, PTP was given in VH for uterine prolapse to 73.2% of patients, VH for other indication to 51.6%, in LH to 59.4% and in AH to 71.9%. For all hysterectomies analysed together, PTP doubled the odds for post-operative haemorrhage or haematoma. By type of hysterectomy, PTP associated with post-operative haemorrhage or haematoma in VH for prolapse [2.7% of PTP given, versus 0.8% of no PTP; odds ratio (OR): 4.82, 95% confidence interval (CI): 1.38-16.83]; and in AH (3.1% versus 1.4%; OR: 2.87, 95% CI: 1.03-7.98), and in AH also with post-operative transfusion (3.1% versus 1.4%; OR: 3.34, 95% CI: 1.41-7.88). For LH and VH for indications other than prolapse, the effect of PTP on post-operative haemorrhage was non-significant. For VH, the risk for post-operative haemorrhage fell with age. Operative mean haemorrhage with all hysterectomy types, and operative bleeding complications in AH and VH also fell with age. Obesity increased haemorrhage and operative bleeding complications for LH and VH, whereas post-operative bleeding complications were less for the obese in AH. VTEs were 6 of 5279 (0.1%): two PEs each occurred after AH and VH, and two deep venous thromboses after LH. CONCLUSIONS: With a relatively wide PTP coverage (64.8%), VTEs were rare (0.1%). All affected had received PTP. Analysis of efficacy, meaning interpretation of how many VTEs or deaths were prevented, cannot be done from our observational study but related to safety in hysterectomy for benign disease, PTP associated with post-operative bleeding complications with AH and with VH for prolapse. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov protocol (NCT00744172).

SU-E-J-54: Bone Detection in MR Images and Absorbed Dose in a Material Behind Bones in Radiotherapy.

PURPOSE: To determine whether bones could be localized accurately by using MR images only in radiotherapy treatment planning. Furthermore, to measure absorbed dose in a material behind different parts of the bone, and to evaluate dose calculation error in a pseudo-CT image by assuming a single electron density for the bones. METHODS: A dedicated phantom was constructed using fresh deer bones and gelatine. The accuracy of the bone edge location and the bone diameter in MR images were evaluated by comparing those in the images with the actual measures. The absorbed dose behind the bones was measured by a matrix detector at 6 and 15 MV. Thedose calculation error in the bulk density pseudo-CT image was quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00, Elekta CMS Software). RESULTS: The examination of bone position revealed that the bones can be localized within a 1-mm-pixel-size in the MR images. The measured dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15 MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations illustrated that the bulk density pseudo-CT image used causes errors up to nearly 2% to the dose behind the middle part, but also, the edge of the femur. CONCLUSIONS: This research ascertains that the bone localization is not a restrictive issue for radiotherapy treatment planning by using MR imageonly. The work indicates also that the decrease in absorbed dose is not necessarily dependent on the diameter of the bone. Future research shouldinvestigate the generation of more complex pseudo-CT images and the dosecalculations by using these. Supported by Elekta.

Epithermal neutron beam interference with cardiac pacemakers.

In this paper, a phantom study was performed to evaluate the effect of an epithermal neutron beam irradiation on the cardiac pacemaker function. Severe malfunction occurred in the pacemakers after substantially lower dose from epithermal neutron irradiation than reported in the fast neutron or photon beams at the same dose rate level. In addition the pacemakers got activated, resulting in nuclides with half-lives from 25 min to 115 d. We suggest that BNCT should be administrated only after removal of the pacemaker from the vicinity of the tumor.

Effect of the calibration in water and the build-up cap on the Mg(Ar) ionization chamber measurements.

Magnesium-walled argon gas flow ionization chamber (Mg(Ar)) is used for photon dose measurements in the epithermal neutron beam of FiR 1 reactor in Finland. In this study, the photon dose measurements were re-evaluated against calculations applying a new chamber calibration factor defined in water instead of in air. Also, effect of the build-up cap on the measurements was investigated. The new calibration factor provides improved agreement between measured and calculated photon dose. Use of the build-up cap does not affect the measured signal in water in neutron beam.

Plasma Abeta42 and Abeta40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study.

BACKGROUND: Single measurements of plasma Aß are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma Aß levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. OBJECTIVE: To examine the relation of baseline and serial plasma Aß levels to cognitive change in follow-up. METHODS: 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aß levels were measured using ELISA. RESULTS: Subjects who declined cognitively during the follow-up had lower levels of plasma Aß42 at the baseline. Plasma Aß42 and the Aß42/Aß40 ratio decreased (-2.4 pg/ml for Aß42 in 6 years) in those who declined in follow-up, whereas Aß42 and the Aß42/Aß40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aß40. CONCLUSIONS: Low or decreasing plasma Aß42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aß42 may be useful in the detection of the subjects who are at risk for cognitive decline.

Comparative study of dose calculations with SERA and JCDS treatment planning systems.

Three treatment planning systems developed for clinical boron neutron capture therapy (BNCT) use are SERA developed by INL/Montana State University, NCTPlan developed by the Harvard-MIT and the CNEA group and JAEA computational dosimetry system (JCDS) developed by Japan Atomic Energy Agency (JAEA) in Japan. Previously, performance of the SERA and NCTPlan has been compared in various studies. In this preliminary study, the dose calculations performed with SERA and JCDS systems were compared in single brain cancer patient case with the FiR 1 epithermal neutron beam. A two-field brain cancer treatment plan was performed with the both codes. The dose components to normal brain, tumor and planning target volume (PTV) were calculated and compared in case of one radiation field and combined two fields. The depth dose distributions and the maximum doses in regions of interest were compared. Calculations with the treatment planning systems for the thermal neutron induced ((10)B and nitrogen) dose components and photon dose were in good agreement. Higher discrepancy in the fast neutron dose calculations was found. In case of combined two-field treatment plan, overall discrepancy of the maximum weighted dose was approximately 3% for normal brain and PTV and approximately 4% for tumor dose.

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery.

BACKGROUND: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. METHODS: Thirty (>or=75 years, gender M9/F21) and 20 (