Transarterial chemoperfusion : a loco-regional treatment option for malignoma of the pelvis, pancreas, and liver

Zielsetzung: Evaluation der lokoregionären transarteriellen Chemoperfusion (TACP) bei nicht kurativ therapierbaren und unter systemischer Chemotherapie progredienten fortgeschrittenen Stadien, Rezidivtumoren oder Metastasen maligner Tumoren des Beckens, des Pankreas und der Leber anhand des lokalen Tumoransprechens, des Überlebens und des Ansprechens tumorassoziierter Symptome (Becken und Pankreas). Material und Methodik: Bei 24 Patienten wurden TACP des Beckens durchgeführt. Die behandelten Tumorentitäten waren kolorektales Karzinom (KRK) (n = 11), Ovarial- (n = 3), Cervix-, Mamma- (BC) (je n = 2), Magen-, Nebennieren-, Anal-, Prostata-, Nierenzell- und Gartner-Gang-Karzinom (je n = 1). Bei 40 Patienten wurden TACP des Pankreas bei Pankreaskarzinom durchgeführt (n = 28 fortgeschrittene Tumorstadien, n = 12 Lokalrezidive). Bei 55 Patienten wurden TACP der Leber durchgeführt. Die behandelten Tumorentitäten waren KRK, BC (je n = 12), cholangiozelluläres Karzinom (CCC) (n = 10), Pankreas- (n = 4), Ovarial- (n = 3), Magen-, Cervix-, Papillen- (je n = 2), Prostata-, Ösophaguskarzinom, Leiomyosarkom (je n = 1) und cancer of unknown primacy (CUP) (n = 5). Mitomycin C (6-8,5 mg/m²) wurde in Kombination mit Gemcitabine (1000-1500 mg/m²) über 1 h durch einen je nach Tumorlokalisation und -gefäßversorgung in der A. iliaca interna (Becken), dem Truncus coeliacus (Pankreas) oder der A. hepatica (Leber) platzierten Angiographiekatheter verabreicht. Mindestens 3 TACP wurden pro Patient in vierwöchigen Abständen ambulant durchgeführt. Danach wurde das Therapieansprechen evaluiert und über eine Weiterführung entschieden. Das radiologische Tumoransprechen wurde mittels MRT oder CT bestimmt und nach der RECIST-Klassifikation (Response Evaluation Criteria In Solid Tumors) in complete response (CR), partial response (PR), stable disease (SD) und progressive disease (PD) eingeteilt. Eine deutliche Verbesserung klinischer Symptome wurde als clinical response (Rc), eine Stabilisierung als clinical stable disease (SDc) und eine Verschlechterung bestehender oder ein Auftreten neuer Symptome als clinical progression (PDc) bewertet. Die Überlebenszeiten wurden nach der Kaplan-Meier-Methode berechnet. Ergebnisse: Bei allen Patienten konnten mindestens 3 TACP durchgeführt werden. Ein vorzeitiger Therapieabbruch oder eine Verlängerung der Therapieintervalle war bei keinem Patienten notwendig. Es kam zu keinen relevanten Komplikationen. Bei Patienten, bei denen eine TACP des Beckens durchgeführt wurde, konnten tumorassoziierte Beschwerden (Schmerzen, Blutungen etc.) in 54% (21/39 Einzelsymptome) gebessert werden. Radiologisch zeigten sich insg. 4 (17%) PR, 12 (50%) SD und 8 (33%) PD. Für Patienten mit KRK als größte Einzelgruppe betrug das radiologische Ansprechen 2 PR, 7 SD und 2 PD bei einem medianen Überleben von 11,5 Monaten. Tumorinduzierte Schmerzen konnten bei 20/32 (62,5%) der Patienten verringert werden, bei denen eine TACP des Pankreas durchgeführt wurde. Radiologisch fanden sich 3 (7,5%) CR, 9 (22,5%) PR, 16 (40%) SD und 12 (30%) PD. Das mediane Überleben lag bei 8,1 Monaten. Patienten mit Therapieansprechen (CR + PR) lebten signifikant länger als solche mit Tumorprogress (13,0 vs. 6,0 Monate; p = 0,013). Bei Patienten, bei denen eine TACP der Leber durchgeführt wurde, fanden sich insg. 1 CR, 19 PR, 19 SD und 16 PD. Davon entfielen 5 PR, 3 SD und 4 PD auf KRK, 1 CR, 4 PR und 6 SD auf BC und 2 PR, 2 SD und 6 PD auf CCC. Das mediane Überleben betrug 9,7 Monate bei KRK, 11,4 Monate bei BC und 6,0 Monate bei CCC. Schlussfolgerung: Die TACP mit Mitomycin/Gemcitabine stellt ein gut verträgliches, minimalinvasives, komplikationsarmes, ambulant einsetzbares Verfahren zur palliativen Therapie von fortgeschrittenen Stadien, Rezidivtumoren und Metastasen maligner Tumoren des Beckens, des Pankreas und der Leber dar. Es konnte sogar in multipel vorbehandelten, therapieresistenten Tumoren ein Ansprechen/eine Wachstumskontrolle (= CR+PR+SD) in 17%/67% (Becken), 30%/70% (Pankreas) bzw. 36%/71% (Leber) erzielt werden. Patienten mit Pankreaskarzinom, die auf die Therapie mit der TACP ansprachen, hatten einen signifikanten Überlebensvorteil gegenüber Patienten mit Tumorprogress. In 54% (Becken) bzw. 62,5% (Pankreas) konnten lokale tumorassoziierte Beschwerden gebessert werden. Aus diesen Gründen sollte die intraarterielle Chemotherapie als Option in der palliativen onkologischen Betreuung des Patienten in Erwägung gezogen werden.Purpose: The purpose of this study was to evaluate local transarterial chemoperfusion (TACP) as a palliative treatment option for incurable advanced tumor stages, locally recurrent tumors, and metastases of various malign neoplasia in the pelvis, pancreas, and liver, which did not respond to prior systemic chemotherapy and/or radiotherapy. Radiological tumor response, survival, and clinical response (in pelvis and pancreas only) were retrospectively analyzed. Materials and methods: TACP of the pelvis was performed in 24 patients. Treated tumor entities were colorectal (CRC) (n = 11), ovarian (n = 3), cervical (n = 2), breast (BC) (n = 2), gastric, adrenal, anal, prostate, Gartner´s duct, and renal cell carcinoma (each n = 1). TACP of the pancreas was performed in 40 patients with pancreatic carcinoma (28 with advanced tumor stages, 12 with locally recurrent tumors). TACP of the liver was performed in 55 patients. Treated tumor entities were CRC, BC (each n = 12), cholangiocarcinoma (CCC) (n = 10), pancreatic (n = 4), ovarian (n = 3), gastric, cervical, papillary (each n = 2), prostate, esophageal carcinoma, leiomyosarcoma (each n = 1), and cancer of unknown primacy (CUP) (n = 5). Combined gemcitabine (1000-1500 mg/m²) and mitomycin C (6-8,5 mg/m²) was administered intra-arterially within one hour through a fluoroscopy catheter placed in the internal iliac artery (pelvis), the celiac trunc (pancreas), or the hepatic artery (liver), depending on tumor localization and vascularization. At least 3 TACPs were performed on an outpatient basis in four-week-intervals. Tumor size was measured by CT or MRI scans. Radiological response was classified according to RECIST (Response Evaluation Criteria In Solid Tumors) in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Clinical response to treatment was classified as clinical response (Rc), if symptoms improved explicitly, as clinical stable disease (SDc), if there was a stabilization of complaints, and clinical progression (PDc), in case of worsening of existing symptoms, or appearance of new symptoms. Survival times were calculated according to the Kaplan-Meier method. After the third session therapy response was evaluated. In case of clinical and radiological progression, therapy was stopped and the case was discussed for further treatment options. If radiological response and clinical progression was found, therapy was continued. If clinical response with radiological progression was found, therapy was continued. Therapy could be aborted by the patient at any time. Results: A minimum of 3 TACPs could be conducted in all patients. No prolongation of the therapy intervals and no early discontinuation of the therapy were required. No major side effects or complications occurred. For TACP of the pelvis, an improvement of tumor-induced symptoms (e.g. pain, bleeding, etc.) was found in 54% (21/39 single symptoms). Radiologically, in total 4 (17%) patients showed PR, 12 (50%) SD, and 8 (34%) PD. For CRC patients – the biggest subgroup – radiological response was 2 PR, 7 SD, and 2 PD, with a median survival of 11.5 months. For TACP of the pancreas, tumor-induced pain could be relieved in 62.5% (20/32) of the patients. The radiological results were 3 (7.5%) CR, 9 (22.5%) PR, 16 (40%) SD, and 12 (30%) PD. Median survival since first TACP was 8.1 months. Responders (CR+PR) showed a significant survival advantage over patients with tumor progression (13.0 vs. 6.0 months; p = 0.013). For TACP of the liver, the radiological results were 1 CR, 19 PR, 19 SD, and 16 PD, in total. Of that, 5 PR, 3 SD, and 4 PD accounted for CRC, 1 CR, 4 PR, and 6 SD for BC, and 2 PR, 2 SD, and 6 PD for CCC patients. Median survival since first TACP was 9.7 months for CRC, 11.4 months for BC, and 6.0 months for CCC patients. Conclusion: TACP with the novel combination of mitomycin/gemcitabine represents a well tolerable, minimally invasive, and safe technique for the palliative treatment of advanced tumor stages, locally recurrent tumors, and metastases of the pelvis, the pancreas, and the liver. Even in multiple pretreated, therapy-resistant tumors a tumor response/growth control (= CR+PR+SD) could be achieved in 17%/67% (pelvis), 30%/70% (pancreas), and 36%/71% (liver). Patients with pancreatic carcinoma who responded to TACP had a significantly survival benefit compared to patients with tumor progression. Tumor-related complaints could be relieved in 54% (pelvis) and 62.5% (pancreas). For all these reasons, intraarterial chemotherapy should be considered as a treatment option in palliative, oncological patient care

Influence of microphone housing on the directional response of piezoelectric mems microphones inspired by Ormia ochracea

The influence of custom microphone housings on the acoustic directionality and frequency response of a multiband bio-inspired MEMS microphone is presented. The 3.2 mm by 1.7 mm piezoelectric MEMS microphone, fabricated by a cost-effective multi-user process, has four frequency bands of operation below 10 kHz, with a desired first-order directionality for all four bands. 7×7×2.5 mm3 3-D-printed bespoke housings with varying acoustic access to the backside of the microphone membrane are investigated through simulation and experiment with respect to their influence on the directionality and frequency response to sound stimulus. Results show a clear link between directionality and acoustic access to the back cavity of the microphone. Furthermore, there was a change in direction of the first-order directionality with reduced height in this back cavity acoustic access. The required configuration for creating an identical directionality for all four frequency bands is investigated along with the influence of reducing the symmetry of the acoustic back cavity access. This paper highlights the overall requirement of considering housing geometries and their influence on acoustic behavior for bio-inspired directional microphones

A multi-colour 2D and 3D structured illumination microscope using MEMS scanning mirrors

We present our latest results on a structured illumination microscope (SIM) implementation using individual microelectromechanical systems (MEMS) micromirrors with three-axis full angular, radial and phase control of the illumination pattern in the sample. Results of a simultaneous multi-color 2D SIM and 3D SIM implementation are shown with digital system adjustment to select the optimal imaging conditions and adapt to variable microscope objectives used in the system. Calibration and cell images of 2D and 3D samples will be shown to verify the resolution enhancement and axial sectioning potential

Lung Cancer Screening with Submillisievert Chest CT: Potential Pitfalls of Pulmonary Findings in Different Readers with Various Experience Levels

Purpose To assess the interreader variability of submillisievert CT for lung cancer screening in radiologists with various experience levels. Method Six radiologists with different degrees of clinical experience in radiology (range, 1-15 years), rated 100 submillisievert CT chest studies as either negative screening finding (no nodules, benign nodules, nodules 10 mm). Each radiologist interpreted scans randomly ordered and reading time was recorded. Interobserver agreement was assessed with ak statistic. Reasons for differences in nodule classification were analysed on a case-by-case basis. Reading time was correlated with reader experience using Pearson correlation (r). Results The overall interobserver agreement between all readers was moderate (k = 0.454; p < 0.001). In 57 patients, all radiologists agreed on the differentiation of negative and indeterminate/positive finding. In 64 cases disagreement between readers led to different nodule classification. In 8 cases some readers rated the nodule as benign, whereas others scored the case as positive. Overall, disagreement in nodule classification was mostly due to failure in identification of target lesion (n = 40), different lesion measurement (n = 44) or different classification (n = 26). Mean overall reading time per scan was of 2 min 2 s (range: 7s-7 min 45 s) and correlated with reader-experience (r =-0.824). Conclusions Our study showed substantial interobserver variability for the detection and classification of pulmonary nodules in submillisievert CT. This highlights the importance for careful standardisation of screening programs with the objective of harmonizing efforts of involved radiologists across different institutions by defining and assuring quality standards

Influence of microphone housing on the directional response of piezoelectric MEMS microphones inspired by Ormia ochracea

The influence of custom microphone housings on the acoustic directionality and frequency response of a multi-band bio-inspired MEMS microphone is presented. The 3.2mm by 1.7mm piezoelectric MEMS microphone, fabricated by a cost-effective multi-user process, has four frequency bands of operation below 10 kHz, with a desired first order directionality for all four bands. 7x7x2.5 mm3 3D-printed bespoke housings with varying acoustic access to the backside of the microphone membrane are investigated through simulation and experiment with respect to their influence on the directionality and frequency response to sound stimulus. Results show a clear link between directionality and acoustic access to the back cavity of the microphone. Further, there was a change in direction of the first order directionality with reduced height in this back cavity acoustic access. The required configuration for creating an identical directionality for all four frequency bands is investigated along with the influence of reducing the symmetry of the acoustic back cavity access. This work highlights the overall requirement of considering housing geometries and their influence on acoustic behavior for bio-inspired directional microphones

Optimizing photoswitching performance of organic dyes for SMLM through a single MEMS mirror

Whilst SMLM is able to localize molecules with nanometre precision it is only able to achieve this if the imaging parameters have been properly optimised. Key parameters we have investigated for optimisation are homogeneous excitation illumination and the optimal pH and thiol concentrations for photoswitching buffers. Typical SMLM experiments make use of conventional gaussian illumination modes meaning either a compromise in the excitation intensity is made due to overfilling of the objective lens, or an uneven illumination field of view (FOV) is observed which can cause intensity driven photoswitching differences in dye molecules located at different points in the FOV. We demonstrate the use of a single microelectromechanical system (MEMS) mirror as a cost-effective method to generate a flat-field of illumination across the FOV resulting in consistent SMLM metrics. We also show a workflow employing an intensity gradient through the MEMS in which we screen for optimal pH and thiol concentrations to obtain the best results for brightness and photoswitching performances of the carbocyanine dye Alexa Fluor 647. Finally, we have monitored the performance of the oxygen scavenger system based on glucose and glucose oxidase in open or closed environments, determining the amount of acidification present in prolonged imaging experiments

Semi-automated volumetry of pulmonary nodules: Intra-individual comparison of standard dose and chest X-ray equivalent ultralow dose chest CT scans

PURPOSE To assess the performance of semi-automated volumetry of solid pulmonary nodules on single-energy tin-filtered ultralow dose (ULD) chest CT scans at a radiation dose equivalent to chest X-ray relative to standard dose (SD) chest CT scans and assess the impact of kernel and iterative reconstruction selection. METHODS Ninety-four consecutive patients from a prospective single-center study were included and underwent clinically indicated SD chest CT (1.9 ± 0.8 mSv) and additional ULD chest CT (0.13 ± 0.01 mSv) in the same session. All scans were reconstructed with a soft tissue (Br40) and lung (Bl64) kernel as well as with Filtered Back Projection (FBP) and Iterative Reconstruction (ADMIRE-3 and ADMIRE-5). One hundred and forty-eight solid pulmonary nodules were identified and analysed by semi-automated volumetry on all reconstructions. Nodule volumes were compared amongst all reconstructions thereby focusing on the agreement between SD and ULD scans. RESULTS Nodule volumes ranged from 58.5 (28.8-126) mm$^{3}$ for ADMIRE-5 Br40 ULD reconstructions to 72.5 (39-134) mm$^{3}$ for FBP Bl64 SD reconstructions with significant differences between reconstructions (p < 0.001). Interscan agreement of volumes between two given reconstructions ranged from ICC = 0.605 to ICC = 0.999. Between SD and ULD scans, agreement of nodule volumes was highest for FBP Br40 (ICC = 0.995), FBP Bl64 (ICC = 0.939) and ADMIRE-5 Bl64 (ICC = 0.994) reconstructions. ADMIRE-3 reconstructions exhibited reduced interscan agreement of nodule volumes (ICCs from 0.788 - 0.882). CONCLUSIONS The interscan agreement of node volumes between SD and ULD is high depending on the choice of kernel and reconstruction algorithm. However, caution should be exercised when comparing two image series that were not identically reconstructed

Influence of microphone housing on the directional response of piezoelectric MEMS microphones inspired by Ormia ochracea

The influence of custom microphone housings on the acoustic directionality and frequency response of a multi-band bio-inspired MEMS microphone is presented. The 3.2mm by 1.7mm piezoelectric MEMS microphone, fabricated by a cost-effective multi-user process, has four frequency bands of operation below 10 kHz, with a desired first order directionality for all four bands. 7x7x2.5 mm3 3D-printed bespoke housings with varying acoustic access to the backside of the microphone membrane are investigated through simulation and experiment with respect to their influence on the directionality and frequency response to sound stimulus. Results show a clear link between directionality and acoustic access to the back cavity of the microphone. Further, there was a change in direction of the first order directionality with reduced height in this back cavity acoustic access. The required configuration for creating an identical directionality for all four frequency bands is investigated along with the influence of reducing the symmetry of the acoustic back cavity access. This work highlights the overall requirement of considering housing geometries and their influence on acoustic behavior for bio-inspired directional microphones

Falsification Of The Atmospheric CO2 Greenhouse Effects Within The Frame Of Physics

The atmospheric greenhouse effect, an idea that many authors trace back to the traditional works of Fourier (1824), Tyndall (1861), and Arrhenius (1896), and which is still supported in global climatology, essentially describes a fictitious mechanism, in which a planetary atmosphere acts as a heat pump driven by an environment that is radiatively interacting with but radiatively equilibrated to the atmospheric system. According to the second law of thermodynamics such a planetary machine can never exist. Nevertheless, in almost all texts of global climatology and in a widespread secondary literature it is taken for granted that such mechanism is real and stands on a firm scientific foundation. In this paper the popular conjecture is analyzed and the underlying physical principles are clarified. By showing that (a) there are no common physical laws between the warming phenomenon in glass houses and the fictitious atmospheric greenhouse effects, (b) there are no calculations to determine an average surface temperature of a planet, (c) the frequently mentioned difference of 33 degrees Celsius is a meaningless number calculated wrongly, (d) the formulas of cavity radiation are used inappropriately, (e) the assumption of a radiative balance is unphysical, (f) thermal conductivity and friction must not be set to zero, the atmospheric greenhouse conjecture is falsified.Comment: 115 pages, 32 figures, 13 tables (some typos corrected

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/P-SPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/P-SPECT an essential method for the diagnosis of PE. When V/P-SPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/P-SPECT interpretation are discussed. In conclusion, V/P-SPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.Peer reviewe