Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis.

BACKGROUND: The social impact of degenerative diseases is steadily increasing, because of the continued rise in the mean age of the active population. Articular cartilage lesions are generally associated with disability and symptoms such as joint pain and reduced function, and remain a challenge for the orthopaedic surgeon. Several non-invasive solution have been proposed, but the results achieved to date are far from being completely satisfactory. Recently, new therapeutic approaches, such as the use of mesenchymal stem cells, have been developed. Among the many sources, the adipose tissue is nowadays considered one of the smartest, due to its abundance and easy access. The aim of this retrospective study is to explore whether patients affected by symptomatic knee osteoarthritis treated with micro-fragmented adipose tissue associated with a chondral shaving procedure experience an improvement in symptoms and function. METHODS: Thirty-eight patients affected by symptomatic knee osteoarthritis were treated in 2015 with an arthroscopic procedure associated with an injection of autologous and micro-fragmented adipose tissue. Micro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. Clinical outcomes were determined at 1, 3, 6, and 12 months follow-up using Knee Injury and Osteoarthritis Outcome Score questionnaire and direct physical examination. Safety of the procedure, recording type and incidence of any adverse event, was also assessed. RESULTS: A steady and statistically significant improvement of all the clinical scores from pre-operative evaluation to 1, 3, 6, and 12 months follow-up was observed, with KOOS sport and quality of life being the most improved scores. On average, 92% of the patients clinically improved and 100% of them were satisfied with the treatment. No adverse events nor relevant complications were recorded. CONCLUSION: The result of the study pointed to micro-fragmented adipose tissue as a safe and beneficial adjuvant in the surgical treatment of degenerative knee chondropathy. The procedure is simple, sustainable, quick, minimally invasive, one-step, and safe. After one year, the results are very satisfactory and promising. A longer follow-up is needed to draw definitive conclusions and enlarge the indications. TRIAL REGISTRATION: Registered at clinicaltrials.gov as NCT03527693 on 27 April 2018 (retrospectively registered).

COVID-19 after two years: trajectories of different components of mental health in the Spanish population.

AIMS: Our study aimed to (1) identify trajectories on different mental health components during a two-year follow-up of the COVID-19 pandemic and contextualise them according to pandemic periods; (2) investigate the associations between mental health trajectories and several exposures, and determine whether there were differences among the different mental health outcomes regarding these associations. METHODS: We included 5535 healthy individuals, aged 40-65 years old, from the Barcelona Brain Health Initiative (BBHI). Growth mixture models (GMM) were fitted to classify individuals into different trajectories for three mental health-related outcomes (psychological distress, personal growth and loneliness). Moreover, we fitted a multinomial regression model for each outcome considering class membership as the independent variable to assess the association with the predictors. RESULTS: For the outcomes studied we identified three latent trajectories, differentiating two major trends, a large proportion of participants was classified into 'resilient' trajectories, and a smaller proportion into 'chronic-worsening' trajectories. For the former, we observed a lower susceptibility to the changes, whereas, for the latter, we noticed greater heterogeneity and susceptibility to different periods of the pandemic. From the multinomial regression models, we found global and cognitive health, and coping strategies as common protective factors among the studied mental health components. Nevertheless, some differences were found regarding the risk factors. Living alone was only significant for those classified into 'chronic' trajectories of loneliness, but not for the other outcomes. Similarly, secondary or higher education was only a risk factor for the 'worsening' trajectory of personal growth. Finally, smoking and sleeping problems were risk factors which were associated with the 'chronic' trajectory of psychological distress. CONCLUSIONS: Our results support heterogeneity in reactions to the pandemic and the need to study different mental health-related components over a longer follow-up period, as each one evolves differently depending on the pandemic period. In addition, the understanding of modifiable protective and risk factors associated with these trajectories would allow the characterisation of these segments of the population to create targeted interventions.

Comprehensive Intra-Institution stepping validation of knowledge-based models for automatic plan optimization.

PURPOSE: To develop and apply a stepping approach for the validation of Knowledge-based (KB) models for planning optimization: the method was applied to the case of concomitant irradiation of pelvic nodes and prostate + seminal-vesicles bed irradiation in post-prostatectomy patients. METHODS: The clinical VMAT plans of 52 patients optimized by two reference planners were selected to generate a KB-model (RapidPlan, v.13.5 Varian). A stepping-validation approach was followed by comparing KB-generated plans (with and without planner-interaction, RP and only-RP respectively) against delivered clinical plans (RA). The validation followed three steps, gradually extending its generalization: 20 patients used to develop the model (closed-loop); 20 new patients, same planners (open-loop); 20 new patients, different planners (wide-loop). All plans were compared, in terms of relevant dose-volume parameters and generalized equivalent uniform dose (gEUD). RESULTS: KB-plans were generally better than or equivalent to clinical plans. For RPvsRA, PTVs coverage was comparable, for OARs RP was always better. Comparing only-RPvsRA, PTVs coverage was always better; bowel\bladder V50Gy and D1%, bowel\bladder\rectum Dmean, femoral heads V40Gy and penile bulb V50Gy were significantly improved. For RPvsRA gEUD reduction >1 Gy was seen in 80% of plans for rectum, bladder and bowel; for only-RPvsRA, this was found in 50% for rectum/bladder and in 70% for bowel. CONCLUSION: An extensive stepping validation approach of KB-model for planning optimization showed better or equal performances of automatically generated KB-plan compared to clinical plans. The interaction of a planner further improved planning performances.

Skin DVHs predict cutaneous toxicity in Head and Neck Cancer patients treated with Tomotherapy.

PURPOSE: To explore the association between planning skin dose-volume data and acute cutaneous toxicity after Radio-chemotherapy for Head and Neck (HN) cancer patients. METHODS: Seventy HN patients were treated with Helical Tomotherapy (HT) with radical intent (SIB technique: 54/66 Gy to PTV1/PTV2 in 30fr) ±â€¯chemotherapy superficial body layer 2 mm thick (SL2) was delineated on planning CT. CTCAE v4.0 acute skin toxicity data were available. Absolute average Dose-Volume Histograms (DVH) of SL2 were calculated for patients with severe (G3) and severe/moderate (G3/G2) skin acute toxicities. Differences against patients with none/mild toxicity (G0/G1) were analyzed to define the most discriminative regions of SL2 DVH; univariable and multivariable logistic analyses were performed on DVH values, CTV volume, age, sex, chemotherapy. RESULTS: Sixty-one % of patients experienced G2/G3 toxicity (rate of G3 = 19%). Differences in skin DVHs were significant in the range 53-68Gy (p-values: 0.005-0.01). V56/V64 were the most predictive parameters for G2/G3 (OR = 1.12, 95%CI = 1.03-1.21, p = 0.001) and G3 (OR = 1.13, 95%CI = 1.01-1.26, p = 0.027) with best cut-off of 7.7cc and 2.7cc respectively. The logistic model for V56 was well calibrated being both, slope and R2, close to 1. Average V64 were 2.2cc and 6cc for the two groups (G3 vs G0-G2 toxicity); the logistic model for V64 was quite well calibrated, with a slope close to 1 and R2 equal to 0.60. CONCLUSION: SL2 DVH is associated with the risk of acute skin toxicity. Constraining V64 < 3cc (equivalent to a 4x4cm2 skin surface) should keep the risk of G3 toxicity below or around 10%.

PET textural features stability and pattern discrimination power for radiomics analysis: An "ad-hoc" phantoms study.

PURPOSE: The analysis of PET images by textural features, also known as radiomics, shows promising results in tumor characterization. However, radiomic metrics (RMs) analysis is currently not standardized and the impact of the whole processing chain still needs deep investigation. We characterized the impact on RM values of: i) two discretization methods, ii) acquisition statistics, and iii) reconstruction algorithm. The influence of tumor volume and standardized-uptake-value (SUV) on RM was also investigated. METHODS: The Chang-Gung-Image-Texture-Analysis (CGITA) software was used to calculate 39 RMs using phantom data. Thirty noise realizations were acquired to measure statistical effect size indicators for each RM. The parameter η2 (fraction of variance explained by the nuisance factor) was used to assess the effect of categorical variables, considering η2 < 20% and 20% < η2 < 40% as representative of a "negligible" and a "small" dependence respectively. The Cohen's d was used as discriminatory power to quantify the separation of two distributions. RESULTS: We found the discretization method based on fixed-bin-number (FBN) to outperform the one based on fixed-bin-size in units of SUV (FBS), as the latter shows a higher SUV dependence, with 30 RMs showing η2 > 20%. FBN was also less influenced by the acquisition and reconstruction setup:with FBN 37 RMs had η2 < 40%, only 20 with FBS. Most RMs showed a good discriminatory power among heterogeneous PET signals (for FBN: 29 out of 39 RMs with d > 3). CONCLUSIONS: For RMs analysis, FBN should be preferred. A group of 21 RMs was suggested for PET radiomics analysis.

Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis.

Altered glomerular metabolism of arachidonic acid (AA) has already been demonstrated in experimental nephrotoxic nephritis. The enhanced synthesis of thromboxane A2 (TxA2) in isolated glomeruli that has been found may mediate changes in renal hemodynamics. The objectives of this investigation were: to check whether glomerular AA metabolism is also altered in a model of glomerulopathy in which no leukocyte infiltration or platelet deposition could be demonstrated; to establish a correlation between the altered AA metabolism and proteinuria; and to explore whether the alteration of the prostaglandin (PG) pathway found in isolated glomeruli is an in vitro artifact or reflects a modification in vivo. We used a model of glomerular damage characterized by heavy and persistent proteinuria, which was induced in the rat by a single intravenous injection of adriamycin. At light microscopy, minimal glomerular abnormalities were found in this model. Electron microscopy showed profound alterations of glomerular epithelial cells with extensive fusion of foot processes and signs of epithelial cell activation. Electron microscopy of numerous glomeruli showed no platelet deposition or macrophage and leukocyte infiltration in this model. Isolated glomeruli from nephrotic rats studied 14 or 30 d after a single intravenous injection of adriamycin (7.5 mg/kg) when animals were heavily proteinuric generated significantly more TxB2, the stable breakdown product of TxA2, than normal glomeruli. No significant changes were found in the other major AA metabolites formed through cyclooxygenase. Urinary excretion of immunoreactive TxB2 was also significantly higher in nephrotic than in normal animals. Administration of a selective Tx synthetase inhibitor, UK-38,485, from day 14 to day 18 after adriamycin resulted in a significant reduction of proteinuria compared with pretreatment values. Glomerular synthesis and urinary excretion of TxB2 were normal during the UK-38,485 treatment. Additional experiments showed that elevated glomerular synthesis and urinary excretion of TxB2 were not a consequence of increased substrate availability. Maximal stimulation of the renin-angiotensin axis with furosemide increased glomerular TxB2 synthesis in normal rats, which was significantly lower than in nephrotic animals. Finally, experiments using a unilateral model of adriamycin nephrosis indicated that the enhancement of glomerular TxB2 synthesis is not simply a consequence of the nephrotic syndrome. We conclude that: there is an abnormality of glomerular AA metabolism in nephritic syndrome, which leads to increased TxA2 production; the increased Tx generation correlates with protein excretion and might be responsible for altering the glomerular basement membrane permeability to protein; and the alteration found in isolated glomeruli probably reflects a modification in vivo, in that urinary excretion of immunoreactive TxB2 is also consistently increased in adriamycin nephrosis.

The Derivo Embolization Device, a Second-Generation Flow Diverter for the Treatment of Intracranial Aneurysms, Evaluated in an Elastase-Induced Aneurysm Model.

PURPOSE: In recent years, flow diverters have provided a promising alternative to treat complex intracranial aneurysms. In this study, we compare a second-generation flow-diverting device (Derivo Embolization Device) with its prototype flow diverter, in the treatment of elastase-induced aneurysms in New Zealand white rabbits. METHODS: The Derivo Embolization Device is a self-expanding stent consisting of 48 nitinol wires. The device was implanted across the necks of 17 elastase-induced aneurysms in New Zealand white rabbits. One additional device was implanted in the abdominal aorta of each animal covering the origin of lumbar arteries. Follow-up was performed after 3 months (n = 8) and 6 months (n = 9) under continuous double antiplatelet therapy. Statuses of angiographic and histological aneurysm occlusion as well as patency of branch arteries and neointimal growth were evaluated and compared with its prototype flow diverter. RESULTS: The Derivo Embolization Device provided advanced visibility and flexibility, which led to more accurate navigation and placement. Complete aneurysm occlusion rates were noted in 15 cases (88 %), respectively, compared with 5 cases (28 %) with the first-generation device (p = 0.001). Neointimal growth and diameter stenosis were significantly less with the Derivo Embolization Device and declining after 6 months follow-up in the abdominal aorta. Extreme device oversizing led to distal occlusion of the parent vessel in three cases. Covered branch arteries remained patent throughout the entire period of observation. CONCLUSIONS: The Derivo Embolization Device provides excellent occlusion of elastase-induced aneurysms while preserving branch arteries.

PET guidance in prostate cancer radiotherapy: Quantitative imaging to predict response and guide treatment.

Positron emission tomography (PET) allows a monitoring and recording of the spatial and temporal distribution of molecular/cellular processes for diagnostic and therapeutic applications. The aim of this review is to describe the current applications and to explore the role of PET in prostate cancer management, mainly in the radiation therapy (RT) scenario. The state-of-the art of PET for prostate cancer will be presented together with the impact of new specific PET tracers and technological developments aiming at obtaining better imaging quality, increased tumor detectability and more accurate volume delineation. An increased number of studies have been focusing on PET quantification methods as predictive biomarkers capable of guiding individualized treatment and improving patient outcome; the sophisticated advanced intensity modulated and imaged guided radiation therapy techniques (IMRT/IGRT) are capable of boosting more radioresistant tumor (sub)volumes. The use of advanced feature analyses of PET images is an approach that holds great promise with regard to several oncological diseases, but needs further validation in managing prostate diseases.

In Vitro Evaluation of Intra-Aneurysmal, Flow-Diverter-Induced Thrombus Formation: A Feasibility Study.

BACKGROUND AND PURPOSE: Intracranial aneurysm treatment by flow diverters aims at triggering intra-aneurysmal thrombosis. By combining in vitro blood experiments with particle imaging velocimetry measurements, we investigated the time-resolved thrombus formation triggered by flow diverters. MATERIALS AND METHODS: Two test setups were built, 1 for particle imaging velocimetry and 1 for blood experiments, both generating the same pulsatile flow and including a silicone aneurysm model. Tests without flow diverters and with 2 different flow-diverter sizes (diameter: 4.5 and 4.0 mm) were performed. In the blood experiments, the intra-aneurysmal flow was monitored by using Doppler sonography. The experiments were stopped at 3 different changes of the spatial extent of the signal. RESULTS: No thrombus was detected in the aneurysm model without the flow diverter. Otherwise, thrombi were observed in all aneurysm models with flow diverters. The thrombi grew from the proximal side of the aneurysm neck with fibrin threads connected to the flow diverter and extending across the aneurysm. The thrombus resulting from the 4.0-mm flow diverter grew along the aneurysm wall as a solid and organized thrombus, which correlates with the slower velocities near the wall detected by particle imaging velocimetry. The thrombus that evolved by using the 4.5-mm flow diverter showed no identifiable growing direction. The entire thrombus presumably resulted from stagnation of blood and correlates with the central vortex detected by particle imaging velocimetry. CONCLUSIONS: We showed the feasibility of in vitro investigation of time-resolved thrombus formation in the presence of flow diverters.

Deformable registration-based segmentation of the bowel on Megavoltage CT during pelvic radiotherapy.

During pelvic radiotherapy bowel loops (BL) are subject to inter-fraction changes. MVCT images have the potential to provide daily bowel segmentation. We assess the feasibility of deformable registration and contour propagation in replacing manual BL segmentation on MVCT. Four observers delineated BL on the planning kVCT and on one therapy MVCT in eight patients. Inter-observer variations in BLs contouring were quantified using DICE index. BLs were then automatically propagated onto MVCT by a commercial software for image deformation and subsequently manually corrected. The agreement between propagated BL/propagated+manually corrected BL vs manual were quantified using the DICE. Contouring times were also compared. The impact on DVH of using the deformable-registration method was assessed. The same procedures were repeated on high-resolution planning-kVCT and therapy-kVCT. MVCTs are adequate to visualize BL (average DICE: 0.815), although worse than kVCT (average DICE:0.889). When comparing propagated vs manual BL, a poor agreement was found (average DICE: 0.564/0.646 for MVCT/KVCT). After manual correction, average DICE indexes increased to 0.810/0.897. The contouring time was reduced to 15min with the semi-automatic approach from 30min with manual contouring. DVH parameters of propagated BL were significantly different from manual BL (p<0.0001); after manual correction, no significant differences were seen. MVCT are suitable for BL visualization. The use of a software to segment BL on MVCT starting from BL-kVCT contours was feasible if followed by manual correction. The method resulted in a substantial reduction of contouring time without detrimental effect on the quality of bowel segmentation and DVH estimates.

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model. MATERIALS AND METHODS: Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography. RESULTS: The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was -4.7°C (95% CI, -5.1 to -4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of -1.3°C (95% CI, -1.5 to -1.0°C; P < .0001) and compared with systemic temperature (-1.4°C; 95% CI, -1.7 to -1.0°C; P < .0001). CONCLUSIONS: Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

New fiber configuration for intravenous gas exchange.

Implantation of a membrane oxygenator (IO) into the vena cava for blood oxygenation in patients with acute lung failure has been researched for the last 25 years. Compared to the extra corporeal blood oxygenation, where blood is handled outside the body, IO doesn't present tubes, housings or heat exchangers, thus reducing considerably blood contact surface and setting priming volume to zero. Otherwise, restricted space in the vena cava and unadvantageous blood flow conditions represent so far a limitation for sufficient gas exchange. A new fiber configuration for intravenous use is being developed, which increases the implantable fiber surface and enhances gas exchange due to the increased blood convection. This is made possible by new fiber bundles, which are free to slide on a catheter and after implantation assume a twisted shape characterized by high homogeneity and fiber density.

Combined Selective Cerebral Hypothermia and Mechanical Artery Recanalization in Acute Ischemic Stroke: In Vitro Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment for patients with ischemic stroke. Selective, intracarotid blood cooling may initiate rapid and early brain hypothermia, reduce systemic effects, and allow combined endovascular mechanical thrombectomy. For this approach, a balloon cooling catheter system was designed and studied in vitro to optimize its cooling performance. MATERIALS AND METHODS: Computational fluid dynamics of blood cooling was performed within the common carotid artery lumen by using 3 different catheter designs (1-, 2-, and 4-balloon array). On the basis of these results, a first catheter prototype was manufactured, and its heat-exchange performance was tested in an artificial in vitro circulation simulating the common carotid artery lumen at different flow rates (inflow temperature of 37°C). RESULTS: In the computational fluid dynamics model, the catheter with the 4-balloon array achieved the highest cooling rate of -1.6°C, which may be attributed to disruption of the thermal boundary layers. In the in vitro study, cooling of the blood substitute at flow rates of 400 mL/min (normal common carotid artery flow) and 250 mL/min (reduced common carotid artery flow due to distal MCA occlusion) achieved a temperature drop inside the blood substitute along the cooling balloons of -1.6°C and -2.2°C, respectively. CONCLUSIONS: The feasibility of intracarotid blood cooling using a new catheter system was demonstrated in vitro. A serial 4-balloon array led to an optimized cooling capacity approaching optimum target temperatures of mild therapeutic hypothermia. To determine the therapeutic efficacy of combined selective therapeutic hypothermia and mechanical thrombectomy, further in vivo studies by using a model of temporary ischemia with large-vessel occlusion and recanalization are required.

Preclinical evaluation of the thrombogenicity and endothelialization of bare metal and surface-coated neurovascular stents.

BACKGROUND AND PURPOSE: Stent-assisted coiling is routinely used for the endovascular treatment of complex or wide-neck intracranial aneurysms. However, in-stent thrombosis, thromboembolic events, and ischemic complications remain a major concern associated with stent implants. Therefore, a novel low-profile neurovascular stent with a bare metal surface was investigated with regard to thrombogenicity and endothelialization and compared with the same stent coated with albumin or heparin. MATERIALS AND METHODS: The bare metal and heparin- or albumin-coated stents were loaded in heparin-coated tubing, which was then filled with heparinized human blood (n = 5) and circulated at 150 mL/min and 37°C for 60 minutes. Before and after circulation, measurement of various inflammation and coagulation markers and scanning electron microscopy were performed. Endothelialization of the stents was investigated in an in vitro model including human umbilical vascular endothelial cells. RESULTS: Our results showed that platelet loss and platelet activation and activation of the coagulation cascade, which are induced by the bare metal stents, were significantly reduced by heparin or albumin coating. Adverse effects on erythrocytes, leukocytes, and the complement cascade were not induced by the bare metal or coated stents. Moreover, the bare metal and albumin-coated stents showed good endothelialization properties. CONCLUSIONS: Albumin and heparin coatings clearly improve the thrombogenicity of the stents and thus may represent fundamental progress in the treatment of intracranial aneurysms. Moreover, preclinical evaluation of neurovascular stents under physiologic conditions supports and accelerates the development of more biocompatible neurovascular stents.

The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers.

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.

Postoperative hyperprolactinaemia and early recurrence rate in breast cancer.

Serum levels of prolactin before and after surgery were measured in 90 women with breast cancer until the 5th postoperative month. Surgery-induced hyperprolactinaemia occurred in 51 patients, without significant correlation to any other clinical variable. After a median follow-up of 39 months, irrespective of each other variable (i.e. nodal involvement, oestrogen receptor status, adjuvant therapies), patients with postoperative hyperprolactinaemia had a significantly lower recurrence rate than those in whom surgery was not followed by an abnormal increase in prolactin secretion (3/51 vs. 13/39, P less than 0.001). These results suggest that, despite the stimulatory role of prolactin on mammary tumours, the lack of postoperative hyperprolactinaemia is an unfavourable prognostic factor because of its association with a higher relapse rate.

Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma.

PURPOSE: To assess the impact on local control and survival of intraoperative radiotherapy (IORT) in resectable pancreatic adenocarcinoma. METHODS AND MATERIALS: The outcome of 127 patients surgically treated with curative intent combined with IORT was compared with the therapeutic results of 76 patients treated with surgery as exclusive treatment. RESULTS: Operative mortality and morbidity were similar in IORT and no-IORT patients. In 49 patients with locally limited disease (Stage I-II; LLD), IORT (n = 30) reduced the local failure rate and significantly prolonged time to local failure (TTLF), time to failure (TTF), and overall survival (OS) with respect to surgery alone (n = 19). The multivariate analyses, stratifying patients by age, tumor grade, resection margins, chemotherapy, and external-beam radiotherapy use, confirmed the independent impact of IORT on outcome. In patients with locally advanced disease (Stage III-IVA; LAD), IORT had an impact on local failure rate and on TTLF when combined with beam energies of greater than 6 MeV, whereas no effect on TTF and OS was observed. CONCLUSION: IORT did not increase operative mortality and morbidity and achieved a significant improvement in local control and outcome in patients with LLD. In patients with LAD, beam energies greater than 6 MeV prolonged TTLF.

Dosimetric evaluation of a commercial 3-D treatment planning system using Report 55 by AAPM Task Group 23.

BACKGROUND AND PURPOSE: A relevant part of radiotherapy treatment planning system QA concerns dose calculation verification. Report 55 by AAPM TG-23 is an instrument for performing dosimetric evaluation of treatment planning systems in case of external photon beams. It was employed by different groups in three radiotherapy departments for controlling performances of RTPS CadPlan Varian-Dosetek, versions 2.7.9, 3.0.6 and 3.1.1. MATERIALS AND METHODS: Once the basic data of the AAPM 4 MV and 18 MV X-ray units had been converted into the CadPlan format and the AAPM units configured, the whole set of TG23 tests were carried out on three different systems. According to Report 55, comparisons between values measured by TG-23 and calculated by RTPS were made in terms of dose at selected points and radiological field width at different depths. RESULTS: As far as dose is concerned, 266 data were compared for 4 MV and 297 for 18 MV. Ninety-five-point-nine percent of dose deviations for 4 MV and 92.6% for 18 MV are less than 2%. Most of the relevant discrepancies for both energies occur in a test case where dose has to be calculated under a long narrow block centred on the beam axis. Deviations as much as 6.1% for 4 MV and -7.5% for 18 MV were observed in points at 1 cm depth under the block. Poor results were also observed in the rectangular field 25 x 5, in points outside the field edges under collimators. As regards radiological field width, 58 out of 64 comparisons for 4 MV occurred in the range +/- 2 mm. For 18 MV the biggest deviation was -2.2 mm. CONCLUSIONS: The TG-23 tests demonstrated that the accuracy of the RTPS in dose calculation is good in most of the typical radiotherapy applications. Our results are better than those recently published for other RTPS. The TG-23 package turned out to be an effective instrument for QA and calculation verification, as well as being a powerful method for training purpose in configuring and using a RTPS.

Dose calculation and dosimetry tests for clinical implementation of 1D tissue-deficit compensation by a single dynamic absorber.

BACKGROUND AND PURPOSE: In this study the possibilities for implementing 1D tissue-deficit compensation techniques by a dynamic single absorber were investigated. This research firstly involved a preliminary examination on the accuracy of a pencil beam-based algorithm, implemented for irregularly shaped photon beams in our 3D treatment planning system (TPS) (Cadplan 2.7, Varian-Dosetek Oy), in calculating dose distributions delivered in ID non-uniform fields. Once the reliability of the pencil beam (PB) algorithm for dose calculations in non-uniform beams was verified, we proceeded to test the feasibility of tissue-deficit compensation using our single absorber modulator. As an example, we considered a mantle field technique. MATERIALS AND METHODS: To evaluate the accuracy of the method employed in calculating dose distributions delivered in 1D non-uniform fields, three different fluence profiles, which could be considered as a small sample representative of clinically relevant applications, were selected. The incident non-uniform fluences were simulated by the sum of simple blocked fields (i.e. with rectangular 'strip' blocks, one per beam) properly weighed by the 'modulation factors' Fi, defined in each interval of the subdivided profile as the ratio between the desired fluence and the open field fluence. Depth dose distributions in a cubic phantom were then calculated by the TPS and compared with the corresponding doses (at 5 and 10 cm acrylic depths) delivered by the single absorber modulation system. In the present application, the absorber speed profile able to compensate for the tissue deficit along the cranio-caudal direction and then homogenizing the dose distribution on a 'midline' isocentric plane with sufficient accuracy can be directly derived from anatomic data, such as the SSDs (source-skin distances) along the patient contour. The compensation can be verified through portal dosimetry techniques (using a traditional port film system). RESULTS: The technique was tested in isocentric conditions on the humanoid RANDO phantom in a clinically suitable situation. The agreement between expected/calculated and measured incident/exit dose profiles was found to be within 4%, with deviations generally around 1-2%. As for the PB accuracy investigation for dose calculations in non-uniform fields, calculated versus measured dose profiles were found to be in good agreement, indicating a satisfactory accuracy of the method employed for dose calculation in 1D non-uniform photon beams. A better performance should be expected if the incident fluences could be directly inserted in the TPS. CONCLUSIONS: The results show that the proposed technique should be sufficiently reliable for clinical application. The main advantages are its simplicity and the possibility of application on Linacs which have no complex options for dynamic control of collimators.

Intra- and inter-observer variability in contouring prostate and seminal vesicles: implications for conformal treatment planning.

BACKGROUND AND PURPOSE: Accurate contouring of the clinical target volume (CTV) is a fundamental prerequisite for successful conformal radiotherapy of prostate cancer. The purpose of this study was to investigate intra- and inter-observer variability in contouring prostate (P) and seminal vesicles (SV) and its impact on conformal treatment planning in our working conditions. MATERIALS AND METHODS: Inter-observer variability was investigated by asking five well-trained radiotherapists of contouring on CT images the P and the SV of six supine-positioned patients previously treated with conformal techniques. Short-term intra-observer variability was assessed by asking the radiotherapists to contour the P and SV of one patient for a second time, just after the first contouring. The differences among the inserted volumes were considered for both intra- and inter-observer variability. Regarding intra-observer variability, the differences between the two inserted contours were estimated by taking the relative differences in correspondence to the CT slices on BEV plots (antero-posterior and left-right beams). Concerning inter-observer variability, the distances between the internal and external envelopes of the inserted contours (named projected diagnostic uncertainties or PDUs) and the distances from the mean inserted contours (named mean contour distances or MCDs) were measured from BEV plots (i.e. parallel to the CT slices). RESULTS: Intra-observer variability was relatively small (the average percentage variation of the volume was approximately 5%; SD of the differences measured on BEV plots within 1.8 mm). Concerning inter-observer variability, the percentage SD of the inserted volumes ranged from 10 to 18%. Differences equal to 1 cm in the cranio-caudal extension of P + SV were found in four out of six patients. The largest inter-observer variability was found when considering the anterior margin in the left-right beam of P top (MCD = 7.1 mm, 1 SD). Relatively high values for MCDs were also found for P bottom, for the posterior and lateral margins of P top (2.6 and 3.1 mm, respectively, I SD) and for the anterior margin of SV (2.8 mm, 1 SD). Relatively small values were found for P central (from 1.4 to 2.0 mm, 1 SD) and the posterior margin of SV (1.5 mm, 1 SD). CONCLUSIONS: The application of larger margins taking inter-observer variability into account should be taken into consideration for the anterior and the lateral margins of SV and P top and for the lateral margin of P. The impact of short-term intra-observer variability does not seem to be relevant.