Engaging carers in neuropsychological rehabilitation for brain cancer survivors: The "I'm aware: Patients And Carers Together" (ImPACT) program.

BACKGROUND: Cognitive impairment is a common late effect in child and adult brain cancer survivors (BCS). Still, there is a dearth of research aimed at therapeutic interventions and no standard treatment options for most BCS. OBJECTIVE: To describe 1) a novel neuropsychological rehabilitation program for BCS - the "I'm aware: Patients And Carers Together" (ImPACT) program, and 2) two studies that aim to assess the feasibility of the ImPACT program in child and adult BCS, respectively. The program adapts the holistic neuropsychological approach pioneered by Leonard Diller and Yehuda Ben-Yishay to an outpatient setting. METHODS: Two feasibility studies are described: 1) A single-armed study with 15 child BCS (10-17 years) (ImPACT Child); and 2) a randomized waitlist-controlled trial with 26 adult BCS (>17 years) (ImPACT Adult). In both studies, patients will undergo an 8-week program together with a cohabiting carer. Primary outcomes (i.e., cognitive and neurobehavioral symptoms), and secondary outcomes (i.e., behavioral and psychological symptoms, e.g., quality of life, fatigue) will be assessed at four time points: pre-, mid-, and post intervention, and 8 weeks follow-up. Adult waitlist controls will be assessed at equivalent time points and will be included in the intervention group after all study assessments. Semi-structured interviews will be conducted at follow-up. EXPECTED OUTCOMES: Results will provide feasibility data in support of future larger scale trials. DISCUSSION: The findings could potentially improve the management of cognitive impairment in BCS and transform available services. The program can be delivered in-person or remotely and harnesses existing resources in patients' lives.

Patients' needs in proton therapy: A survey among ten European facilities.

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Associations between patient-reported outcomes and radiation dose in patients treated with radiation therapy for primary brain tumours.

AIM: This study aimed to explore associations between radiation dose and patient-reported outcomes in patients with a primary non-glioblastoma brain tumour treated with radiation therapy (RT), with a focus on health-related quality-of-life (HRQoL) and self-reported cognitive function. METHODS: In this cross-sectional study, 78 patients who had received RT for a non-glioblastoma primary brain tumour, underwent neuropsychological testing and completed questionnaires on HRQoL, cognitive function, fatigue, depression, anxiety and perceived stress. The study explores the association between HRQoL scores, self-reported cognitive function and radiation doses to total brain, brainstem, hippocampus, thalamus, temporal lobes and frontal lobes. In addition, we examined correlations between neuropsychological test scores and self-reported cognitive function. RESULTS: The median time between RT and testing was 4.6 years (range 1-9 years). Patients who had received high mean radiation doses to the total brain had low HRQoL scores (Cohen's d = 0.50, p = 0.04), brainstem (d = 0.65, p = 0.01) and hippocampus (d = 0.66, p = 0.01). High mean doses to the total brain were also associated with low scores on self-reported cognitive functioning (Cohen's d = 0.64, p = 0.02), brainstem (d = 0.55, p = 0.03), hippocampus (d = 0.76, p < 0.01), temporal lobes (d = 0.70, p < 0.01) and thalamus (d = 0.64, p = 0.01). Self-reported cognitive function correlated well with neuropsychological test scores (correlation range 0.27-0.54.). CONCLUSIONS: High radiation doses to specific brain structures may be associated with impaired HRQoL and self-reported cognitive function with potentially negative implications to patients' daily lives. Patient-reported outcomes of treatment-related side-effects and their associations with radiation doses to the brain and its sub-structures may provide important information on radiation tolerance to the brain and sub-structures.

Delineation atlas of the Circle of Willis and the large intracranial arteries for evaluation of doses to neurovascular structures in pediatric brain tumor patients treated with radiation therapy.

BACKGROUND: Survivors of pediatric brain tumors are susceptible to neurovascular disease after radiotherapy, with dose to the chiasm or Circle of Willis (CW) as risk factors. The aims of this study were to develop a delineation atlas of neurovascular structures, to investigate the doses to these structures in relation to tumor location and to investigate potential dose surrogates for the CW dose. MATERIAL AND METHODS: An atlas of the CW, the large intracranial arteries and the suprasellar cistern (SC) was developed and validated. Thirty proton plans from previously treated pediatric brain tumor patients were retrieved and grouped according to tumor site: 10 central, 10 lateralized, and 10 posterior fossa tumors. Based on the atlas, neurovascular structures were delineated and dose metrics (mean dose (Dmean) and maximal dose (Dmax)) to these structures and the already delineated chiasm were evaluated. The agreement between dose metrics to the CW vs. chiasm/SC was investigated. The minimal Hausdorff distance (HDmin) between the target and SC was correlated with the SC Dmean. RESULTS: The median Dmean/Dmax to the CW were 53 Gy(RBE)/55 Gy(RBE) in the central tumors, 18 Gy(RBE)/25 Gy(RBE) in the lateralized tumors and 30 Gy(RBE)/49 Gy(RBE) in the posterior fossa tumors. There was a good agreement between the Dmax/Dmean to the CW and the SC for all cases (R2=0.99), while in the posterior fossa group, the CW Dmax was underestimated when using the chiasm as surrogate (R2=0.76). Across all patients, cases with HDmin < 10 mm between the target and the SC received the highest SC Dmean. CONCLUSION: The pattern of dose to neurovascular structures varied with the tumor location. For all locations, SC doses could be used as a surrogate for CW doses. A minimal distance larger than 10 mm between the target and the SC indicated a potential for neurovascular dose sparing.

Metastasis directed treatment of brain metastases from colorectal cancer - a Danish population-based cohort study.

Background: Brain metastases (BMs) are an uncommon presentation of metastatic colorectal cancer (mCRC) with reported incidence of about 2-4%. Today, there is an increased awareness towards a metastasis directed treatment approach with either surgical resection, stereotactic radiotherapy (SRT) or both. We examined patient characteristics and survival for patients treated with a localized modality for BM from CRC in a nationwide population-based study.Methods: A registry-based cohort study of all patients with a resected primary colorectal cancer and localized treatment of BM during 2000-2013. We computed descriptive statistics and analysed overall survival by the Kaplan-Meier method and Cox regression.Results: A total of 38131 patients had surgery for a primary CRC and 235 patients were recorded with a metastasis directed treatment for BM, comprising resection alone (n = 158), SRT alone (n = 51) and combined resection and SRT (n = 26). Rectal primary tumor (48.9% vs. 36.2%, p < .001) and lung metastasectomy (11.9 vs 2.8%, p < .001) were more frequent in the BM group. The median survival of patients receiving localized treatment for BM was 9.6 months (95% confidence interval (CI) 7.2-10.8). The 1- and 5-year overall survival were 41.7% (95% CI 35-48%) and 11.2% (95% CI 6.9-16.3%). In multivariate analysis, nodal stage was associated with increased mortality with a hazard ratio of 1.63 (95% CI 1.07-2.60, p = .03) for N2 stage with reference to N0.Conclusion: We report a median overall survival of 9.6 months for patients receiving localized treatment for BM from CRC. Lung metastases and rectal primary tumor are more common in the population treated for BM.

Stereotactic body radiation therapy for early-stage hepatocellular carcinoma - a systematic review on outcome.

Background: Hepatocellular carcinoma (HCC) incidence is rising worldwide, especially due to increased detection of early-stage or small-sized tumors. Nevertheless, most of the patients are still not qualified for surgical resection at diagnosis due to the localization of the tumor, underlying liver disease or comorbidities. Stereotactic body radiation therapy (SBRT) is a radiotherapy modality which can deliver a high dose of radiation to the target tissue with a high degree of precision. It shows promise in terms of efficacy and morbidity.Material and methods: The aim of this systematic review is to summarize current knowledge on patient-specific outcomes of SBRT for small HCC including overall survival, local control, the effect of dose escalation and the toxicity of the treatment. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After a comprehensive database search, 16 studies (973 patients with 1034 lesions) were included in qualitative and quantitative analyses; 14 of them were retrospective.Results: Average tumor diameter was 23 mm and 95% of patients were in good general condition. Median BED10 (biologically equivalent dose calculated for α/ß ratio of 10 Gy) was 100 Gy (range 59.5-180 Gy). Mean weighted local control across studies was 94%, 92% and 93% at 1, 2, and 3 years, respectively. Mean weighted overall survival across studies was 90.9%, 67.5% and 73.4% at 1, 2, and 3 years, respectively. There were 171 grade 1-2 toxicities (17.5%) and 53 ≥ grade 3 toxicities (5.3%). There was no treatment-associated mortality.Conclusion: SBRT offers high local control with overall survival that is comparable with radiofrequency ablation and surgery. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of published studies. Therefore, there is a need for better reporting and prospective studies to univocally recommend SBRT as a definitive treatment option in the guidelines for small HCCs.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

A biological modeling based comparison of two strategies for adaptive radiotherapy of urinary bladder cancer.

Background Adaptive radiotherapy is introduced in the management of urinary bladder cancer to account for day-to-day anatomical changes. The purpose of this study was to determine whether an adaptive plan selection strategy using either the first four cone beam computed tomography scans (CBCT-based strategy) for plan creation, or the interpolation of bladder volumes on pretreatment CT scans (CT-based strategy), is better in terms of tumor control probability (TCP) and normal tissue sparing while taking the clinically applied fractionation schedules also into account. Material and methods With the CT-based strategy, a library of five plans was created. Patients received 55 Gy to the bladder tumor and 40 Gy to the non-involved bladder and lymph nodes, in 20 fractions. With the CBCT-based strategy, a library of three plans was created, and patients received 70 Gy to the tumor, 60 Gy to the bladder and 48 Gy to the lymph nodes, in 30-35 fractions. Ten patients were analyzed for each adaptive plan selection strategy. TCP was calculated applying the clinically used fractionation schedules, as well as a rescaling of the dose from 55 to 70 Gy for the CT-based strategy. For rectum and bowel, equivalent doses in 2 Gy fractions (EQD2) were calculated. Results The CBCT-based strategy resulted in a median TCP of 75%, compared to 49% for the CT-based strategy, the latter improving to 72% upon rescaling the dose to 70 Gy. A median rectum V30Gy (EQD2) of 26% [interquartile range (IQR): 8-52%] was found for the CT-based strategy, compared to 58% (IQR: 55-73%) for the CBCT-based strategy. Also the bowel doses were lower with the CT-based strategy. Conclusions Whereas the higher total bladder TCP for the CBCT-based strategy is due to prescription differences, the adaptive strategy based on CT scans results in the lowest rectum and bowel cavity doses.

Diffusion chamber system for testing of collagen-based cell migration barriers for separation of ligament enthesis zones in tissue-engineered ACL constructs.

A temporary barrier separating scaffold zones seeded with different cell types prevents faster growing cells from overgrowing co-cultured cells within the same construct. This barrier should allow sufficient nutrient diffusion through the scaffold. The aim of this study was to test the effect of two variants of collagen-based barriers on macromolecule diffusion, viability, and the spreading efficiency of primary ligament cells on embroidered scaffolds. Two collagen barriers, a thread consisting of a twisted film tape and a sponge, were integrated into embroidered poly(lactic-co-caprolactone) and polypropylene scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A diffusion chamber system was designed and established to monitor nutrient diffusion using fluorescein isothiocyanate-labeled dextran of different molecular weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide staining. Cell spreading on the scaffold surface was measured using histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the penetration of ligament cells through both barrier types. The diffusion chamber was suitable to characterize the diffusivity of dextran molecules through embroidered scaffolds with or without integrated collagen barriers. The diffusion coefficients were generally significantly lower in scaffolds with barriers compared to those without barriers. No significant differences between diffusion coefficients of both barrier types were detected. Both barriers were cyto-compatible and prevented most of the ACL cells from crossing the barrier, whereby the collagen thread was easier to handle and allowed a higher rate of cell spreading.

In vitro characterization of self-assembled anterior cruciate ligament cell spheroids for ligament tissue engineering.

Tissue engineering of an anterior cruciate ligament (ACL) implant with functional enthesis requires site-directed seeding of different cell types on the same scaffold. Therefore, we studied the suitability of self-assembled three-dimensional spheroids generated by lapine ACL ligament fibroblasts for directed scaffold colonization. The spheroids were characterized in vitro during 14 days in static and 7 days in dynamic culture. Size maintenance of self-assembled spheroids, the vitality, the morphology and the expression pattern of the cells were monitored. Additionally, we analyzed the total sulfated glycosaminoglycan, collagen contents and the expression of the ligament components type I collagen, decorin and tenascin C on protein and for COL1A1, DCN and TNMD on gene level in the spheroids. Subsequently, the cell colonization of polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) polymer scaffolds was assessed in response to a directed, spheroid-based seeding technique. ACL cells were able to self-assemble spheroids and survive over 14 days. The spheroids decreased in size but not in cellularity depending on the culture time and maintained or even increased their differentiation state. The area of P[LA-CL] scaffolds, colonized after 14 days by the cells of one spheroid, was in average 4.57 ± 2.3 mm(2). Scaffolds consisting of the polymer P[LA-CL] were more suitable for colonization by spheroids than PDS embroideries. We conclude that ACL cell spheroids are suitable as site-directed seeding strategy for scaffolds in ACL tissue engineering approaches and recommend the use of freshly assembled spheroids for scaffold colonization, due to their balanced proliferation and differentiation.

Embroidered polymer-collagen hybrid scaffold variants for ligament tissue engineering.

Embroidery techniques and patterns used for scaffold production allow the adaption of biomechanical scaffold properties. The integration of collagen into embroidered polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) scaffolds could stimulate neo-tissue formation by anterior cruciate ligament (ACL) cells. Therefore, the aim of this study was to test embroidered P(LA-CL) and PDS scaffolds as hybrid scaffolds in combination with collagen hydrogel, sponge or foam for ligament tissue engineering. ACL cells were cultured on embroidered P(LA-CL) and PDS scaffolds without or with collagen supplementation. Cell adherence, vitality, morphology and ECM synthesis were analyzed. Irrespective of thread size, ACL cells seeded on P(LA-CL) scaffolds without collagen adhered and spread over the threads, whereas the cells formed clusters on PDS and larger areas remained cell-free. Using the collagen hydrogel, the scaffold colonization was limited by the gel instability. The collagen sponge layers integrated into the scaffolds were hardly penetrated by the cells. Collagen foams increased scaffold colonization in P(LA-CL) but did not facilitate direct cell-thread contacts in the PDS scaffolds. The results suggest embroidered P(LA-CL) scaffolds as a more promising basis for tissue engineering an ACL substitute than PDS due to superior cell attachment. Supplementation with a collagen foam presents a promising functionalization strategy.

Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir.

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer.

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.

Real-time segmentation of multiple implanted cylindrical liver markers in kilovoltage and megavoltage x-ray images.

Gold markers implanted in or near a tumor can be used as x-ray visible landmarks for image based tumor localization. The aim of this study was to develop and demonstrate fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in cone-beam CT (CBCT) projections, for real-time motion management. Thirteen patients treated with conformal stereotactic body radiation therapy in three fractions had 2-3 cylindrical gold markers implanted in the liver prior to treatment. At each fraction, the projection images of a pre-treatment CBCT scan were used for automatic generation of a 3D marker model that consisted of the size, orientation, and estimated 3D trajectory of each marker during the CBCT scan. The 3D marker model was used for real-time template based segmentation in subsequent x-ray images by projecting each marker's 3D shape and likely 3D motion range onto the imager plane. The segmentation was performed in intra-treatment kV images (526 marker traces, 92,097 marker projections) and MV images (88 marker traces, 22,382 marker projections), and in post-treatment CBCT projections (42 CBCT scans, 71,381 marker projections). 227 kV marker traces with low mean contrast-to-noise ratio were excluded as markers were not visible due to MV scatter. Online segmentation times measured for a limited dataset were used for estimating real-time segmentation times for all images. The percentage of detected markers was 94.8% (kV), 96.1% (MV), and 98.6% (CBCT). For the detected markers, the real-time segmentation was erroneous in 0.2-0.31% of the cases. The mean segmentation time per marker was 5.6 ms [2.1-12 ms] (kV), 5.5 ms [1.6-13 ms] (MV), and 6.5 ms [1.8-15 ms] (CBCT). Fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in CBCT projections was demonstrated for a large dataset.

PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair.

The availability of autologous articular chondrocytes remains a limiting issue in matrix assisted autologous chondrocyte transplantation. Non-articular heterotopic chondrocytes could be an alternative autologous cell source. The aims of this study were to establish heterotopic chondrocyte cocultures to analyze cell-cell compatibilities and to characterize the chondrogenic potential of nasoseptal chondrocytes compared to articular chondrocytes. Primary porcine and human nasoseptal and articular chondrocytes were investigated for extracellular cartilage matrix (ECM) expression in a monolayer culture. 3D polyglycolic acid- (PGA) associated porcine heterotopic mono- and cocultures were assessed for cell vitality, types II, I, and total collagen-, and proteoglycan content. The type II collagen, lubricin, and Sox9 gene expressions were significantly higher in articular compared with nasoseptal monolayer chondrocytes, while type IX collagen expression was lower in articular chondrocytes. Only ß1-integrin gene expression was significantly inferior in humans but not in porcine nasoseptal compared with articular chondrocytes, indicating species-dependent differences. Heterotopic chondrocytes in PGA cultures revealed high vitality with proteoglycan-rich hyaline-like ECM production. Similar amounts of type II collagen deposition and type II/I collagen ratios were found in heterotopic chondrocytes cultured on PGA compared to articular chondrocytes. Quantitative analyses revealed a time-dependent increase in total collagen and proteoglycan content, whereby the differences between heterotopic and articular chondrocyte cultures were not significant. Nasoseptal and auricular chondrocytes monocultured in PGA or cocultured with articular chondrocytes revealed a comparable high chondrogenic potential in a tissue engineering setting, which created the opportunity to test them in vivo for articular cartilage repair.

Bladder dose accumulation based on a biomechanical deformable image registration algorithm in volumetric modulated arc therapy for prostate cancer.

Variations in bladder position, shape and volume cause uncertainties in the doses delivered to this organ during a course of radiotherapy for pelvic tumors. The purpose of this study was to evaluate the potential of dose accumulation based on repeat imaging and deformable image registration (DIR) to improve the accuracy of bladder dose assessment. For each of nine prostate cancer patients, the initial treatment plan was re-calculated on eight to nine repeat computed tomography (CT) scans. The planned bladder dose-volume histogram (DVH) parameters were compared to corresponding parameters derived from DIR-based accumulations as well as DVH summation based on dose re-calculations. It was found that the deviations between the DIR-based accumulations and the planned treatment were substantial and ranged (-0.5-2.3) Gy and (-9.4-13.5) Gy for D(2%) and D(mean), respectively, whereas the deviations between DIR-based accumulations and DVH summation were small and well within 1 Gy. For the investigated treatment scenario, DIR-based bladder dose accumulation did not result in substantial improvement of dose estimation as compared to the straightforward DVH summation. Large variations were found in individual patients between the doses from the initial treatment plan and the accumulated bladder doses. Hence, the use of repeat imaging has a potential for improved accuracy in treatment dose reporting.

[Osteochondrosis dissecans and osteochondral lesions of the talus: clinical and biochemical aspects]. / Die Osteochondrosis dissecans und osteochondrale Läsionen des Talus: klinische und biomechanische Aspekte.

BACKGROUND: The natural course of osteochondral lesions of the talus are varied and the disease pattern is not clearly defined. There is an ongoing discussion among clinicians concerning the aethiopathology and the correct treatment. METHODS: In this article all relevant studies are analysed with regard to aetiology, long-term outcome and the different established treatment options. Against the background of the current biomechanical understanding, an approach is made to this controversially discussed disease pattern utilising our own biomechanical laboratory results. RESULTS: The available literature deals with longitudinal analyses regarding the natural history of the disease, conservative treatment, surgical options like debridement and anterograde drilling, retrograde drilling, osteochondral transplantation and autologous chondrocyte transplantation (ACT). Biomechanical trials describe high loads in the anterolateral parts of the joint. In most of the published studies the average age of the patients is around 28 years, younger patients have more favourable outcomes compared to older ones. In children the highest rate of spontaneous and advantageous course of the disease can be expected. Around 75% of the published outcomes relating to surgical therapy are satisfactory while 10% of the patients will suffer from osteoarthritis in the long term. CONCLUSION: While the aetiopathology of the disease remains unclear, histopathological studies reveal subcortical bone necrosis. In 90% of the cases there is an ankle sprain in the past medical history although a direct correlation with trauma as exclusive trigger is not obvious. A possible approach is an osteochondral fracture in combination with an already existing osteonecrosis. A staged treatment regime is advised. In asymptomatic cases conservative treatment is advocated independent of the stage. Symptomatic patients with Hepple stages I, II and V and intact cartilage surface should undergo retrograde drilling in combination with a subchondral filling with cancelleous bone. If a cartilage defect is present (Hepple stages III, IV, V), an osteochondral transplantation is reasonable. Only if the defect zone is >2.5 cm2 should a debridement combined with a transplantation of cancellous bone and an ACT be considered. The sole anterograde drilling in our opinion should only be performed as an exception.

Emotional difficulties in seventh grade children in Denmark.

The present study investigates the prevalence of emotional difficulties and quality of life in a sample of 834 children from 56 seventh grade (aged 12-14 years) classes. Data was derived from a study of mental well-being developed by the National Council for Children, Denmark. The sample selection ensured that the children were nationally representative. Data was collected using the Strength and Difficulties Questionnaire (SDQ) and the Health Behaviour in School-aged Children (HBSC). Results indicated that 10.8% of children had concerns regarding emotional difficulties (6.6% definite concern; 4.2% some concern), and that significantly more girls than boys (44 girls and 10 boys) reported this concern. A novel finding was that emotional difficulties were related to children's perception of having low quality of life. Findings furthermore suggested that children's perception of a low home economy, less time spent on leisure activities, and female gender were all associated with emotional difficulties.

The desmopressin stimulation test in dogs with Cushing's syndrome.

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.

FDG-PET improves management of patients with colorectal liver metastases allocated for local treatment: a consecutive prospective study.

BACKGROUND AND AIM: Colorectal cancer is a common cancer in the Nordic countries and 50% of the patients develop liver metastases. Liver resection may result in long term survival. Proper staging is therefore essential and CT is the standard imaging modality. We examined whether additional FDG-PET improves therapeutic management of patients with colorectal liver metastases. PATIENTS AND METHODS: Fifty-four consecutive patients were enrolled. Each patient had a treatment plan made based on our standard evaluation. The patients then had a PET scan and the treatment plan was re-evaluated, taking these results into account. RESULTS: In 76% of the cases, PET did not change the treatment plan due to complete concordance with CT. In another 19% of the cases, the plan was altered due to finding of more liver lesions by PET than by CT (four patients), fewer or no liver lesions (three patients), and extrahepatic lesions not visible on CT (three patients). In 5% of the cases, non-concordance between PET and CT did not change the therapeutic plan. CONCLUSION: Pre-treatment FDG-PET, used supplementary to CT, improved the treatment plan in one fifth of the patients with colorectal liver metastases.