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Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings. [ABSTRACT FROM AUTHOR]

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Objective: To describe the initial experience with irreversible electroporation (IRE) to treat pelvic tumor recurrences.Methods: A retrospective single-center analysis was performed. Adverse events were recorded using Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Clinical outcome was determined using pain- and general- symptom assessment, including Seddon's peripheral nerve injury (PNI) types. Radiological outcome was evaluated by comparing baseline with three-month 18F-FDG PET-CT follow-up.Results: Eight patients (nine tumors [recurrences of primary rectal (n = 4), anal (n = 1), sigmoid (n = 1), cervical (n = 1), and renal cell carcinoma (n = 1)]) underwent percutaneous IRE as salvage therapy. Median longest tumor diameter was 3.7 cm (range 1.2-7.0). One CTCAE grade III adverse event (hemorrhage) and eight CTCAE grade II complications occurred in 6/8 patients: vagino-tumoral fistula (n = 1), lower limb motor loss (n = 3; PNI type II) with partial recovery in one patient, hypotonic bladder (n = 2; PNI types I and II) with complete recovery in one patient, and upper limb motor loss (n = 2; PNI type II) with partial recovery in both patients. No residual tumor tissue was observed at 3-month follow-up. After a median follow-up of 12 months, local progression was observed in 5/9 lesions (4/5 were >3 cm pre-IRE); one lesion was successfully retreated. Debilitating preprocedural pain (n = 3) remained unchanged (n = 1) or improved (n = 2).Conclusion: IRE may represent a suitable technique to treat pelvic tumor recurrences, although permanent neural function loss can occur. Complete ablation seems realistic for smaller lesions; for larger lesions symptom control should be the focus. [ABSTRACT FROM AUTHOR]

Background and Aim. To provide a comprehensive quantitative assessment of nutritional status, digestion and absorption, and quality of life (QoL) in patients with locally advanced pancreatic cancer (LAPC). Methods. Sixteen patients with LAPC were prospectively assessed for weight loss (WL), body mass index (BMI), fat-free mass index (FFMI), handgrip strength (HGS), dietary macronutrient intake, serum vitamin levels, resting and total energy expenditure (REE and TEE, indirect calorimetry), intestinal absorption capacity and fecal losses (bomb calorimetry), exocrine pancreatic function (fecal elastase-1 (FE1)), and gastrointestinal quality of life (GIQLI). Results. Two patients had a low BMI, 10 patients had WL > 10%/6 months, 8 patients had a FFMI < P10, and 8 patients had a HGS < P10. Measured REE was 33% higher (P=0.002) than predicted REE. TEE was significantly higher than daily energy intake (P=0.047). Malabsorption (<85%) of energy, fat, protein, and carbohydrates was observed in, respectively, 9, 8, 12, and 10 patients. FE1 levels were low (<200 μg/g) in 13 patients. Total QoL scored 71% (ample satisfactory). Conclusion. Patients with LAPC have a severely impaired nutritional status, most likely as a result of an increased REE and malabsorption due to exocrine pancreatic insufficiency. The trial is registered with PANFIRE clinicaltrials.gov NCT01939665. [ABSTRACT FROM AUTHOR]

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1–2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1–2 hours, this took 24 hours in blood vessels and 7 days in nerves. [ABSTRACT FROM AUTHOR]

Background: Because sunitinib can induce extensive necrosis in metastatic renal cell cancer (mRCC), we examined whether criteria defined by Choi might be valuable to predict early sunitinib efficacy.Methods: Computed tomography was used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield units (HUs). According to Choi criteria partial response (PR) was defined as > or =10% decrease in size or > or =15% decrease in attenuation.Results: A total of 55 mRCC patients treated with sunitinib were included. At first evaluation, according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7 patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour attenuation decreased from 66 to 47 HUs (P< or =0.001). In patients with PR, Choi criteria had a significantly better predictive value for progression-free survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191 respectively). The predictive value for RECIST increased (P=0.001 and <0.001 respectively), when best response during treatment was taken into account.Conclusion: Choi criteria could be helpful to define early mRCC patients who benefit from sunitinib, but the use of these criteria will not change the management of these patients. [ABSTRACT FROM AUTHOR]

This article reports on the design of a capacitive pressure sensor fabricated in non-silicon materials. The sensor consists of a thin membrane placed parallel to a rigid reference plane. The membrane and the reference plane act as two electrodes of a capacitor. Deflection of the membrane due to pressure differences results in changes in capacity. These capacity changes are processed to calculate the pressure on the membrane.Several thermo-mechanical performance aspects of the sensor were addressed during the design stage. Promising variants of the sensor were built and subjected to mechanical tests. In addition, numerical techniques were utilized to assess the performance of certain variants before building and testing physical prototypes.The application of this combination of physical experiments and numerical simulations is demonstrated for the selection of a suitable membrane material and membrane dimensions (diameter and thickness), the specification of the substrate thickness in case the sensor is mounted on the backside of an electronics housing, and the selection of a suitable solder interconnect material and interconnect dimensions. A critical aspect in the latter case was the creep behaviour of the solder material, which had to be minimized in order to obtain an acceptable long-term accuracy of the sensor.A sensor membrane and an interconnect design were finally specified on the basis of the outcome of the design studies. It proved to meet the functional demands imposed by the targeted application on a laboratory scale. It will be subjected to reliability and lifetime assessment tests in a next phase. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. [ABSTRACT FROM AUTHOR]

The thermoregulatory effects of dopamine (DA, 400 μg), injected intracerebroventricularly (i.c.v.) in rabbits, were investigated at different ambient temperatures ( T). The effects at 20° C T were compared with those of 5-hydroxytryptamine (5-HT, 200 μg) and noradrenaline (NA, 200 μg). At 20° C T DA induced a dilatation of the ear vessels but did not change rectal temperature ( T). I.c.v. injection of 5-HT induced panting and fall in T while after NA a rise in T and constriction of the ear vessels were observed. At 32° C T no change in T was observed after DA. At 5° C T DA caused a short-lasting decrease in T. After treatment with the DA antagonist haloperidol (400 μg, i.c.v.) a hypothermia was observed after DA at 20° C T. Haloperidol did not influence the response after 5-HT or NA. The 5-HT antagonist methysergide (500 μg, i.c.v.) blocked panting and the hypothermia normally caused by i.c.v. 5-HT at 20° C T; instead of decreasing, T tended to increase after 5-HT. After pretreatment with methysergide T rose immediately after i.c.v. injection of DA. These results suggest that the hypothermia after i.c.v. DA in the rabbit is secondarily mediated by serotonergic structures in the pathway between heat sensors and heat loss effectors. The hyperthermic effect of i.c.v. DA, which showed after pretreatment with methysergide and was apparently blocked by haloperidol, is probably the result of an activation of DA receptors in the pathway from cold sensors to heat production effectors. The hyperthermia after i.c.v. NA could be due to an inhibition of the heat loss pathway. [ABSTRACT FROM AUTHOR]

Analysis of two historical cohorts In percutaneous computed tomography (CT)-guided liver ablation, decent visualization of the lesion and ablation zone is indispensable to achieve an efficacious treatment and impair oncological outcomes. At the cost of adding procedure-time and marginal patient-burden, transcatheter CTHA-guided ablation was associated with a superior LTPFS compared to conventional CT fluoroscopy. [Extracted from the article]