Quality of life in restorative versus non-restorative resections for rectal cancer:systematic review

BACKGROUND: Low rectal cancers could be treated using restorative (anterior resection, AR) or non-restorative procedures with an end/permanent stoma (Hartmann’s, HE; or abdominoperineal excision, APE). Although the surgical choice is determined by tumour and patient factors, quality of life (QoL) will also influence the patient's future beyond cancer. This systematic review of the literature compared postoperative QoL between the restorative and non-restorative techniques using validated measurement tools. METHODS: The review was registered on PROSPERO (CRD42020131492). Embase and MEDLINE, along with grey literature and trials websites, were searched comprehensively for papers published since 2012. Inclusion criteria were original research in an adult population with rectal cancer that reported QoL using a validated tool, including the European Organization for Research and Treatment of Cancer QLQ-CR30, QLQ-CR29, and QLQ-CR38. Studies were included if they compared AR with APE (or HE), independent of study design. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Outcomes of interest were: QoL, pain, gastrointestinal (GI) symptoms (stool frequency, flatulence, diarrhoea and constipation), and body image. RESULTS: Nineteen studies met the inclusion criteria with a total of 6453 patients; all papers were observational and just four included preoperative evaluations. There was no identifiable difference in global QoL and pain between the two surgical techniques. Reported results regarding GI symptoms and body image documented similar findings. The ROBINS-I tool highlighted a significant risk of bias across the studies. CONCLUSION: Currently, it is not possible to draw a firm conclusion on postoperative QoL, pain, GI symptoms, and body image following restorative or non-restorative surgery. The included studies were generally of poor quality, lacked preoperative evaluations, and showed considerable bias in the data

Dividend Stickiness in Japan

markdownabstract__Abstract__ The paper describes the introduction of an emphasis on ‘personal security’ in human security thinking and practice, as part of the ultimately unsuccessful attempt to compartmentalize the pursuit of security. It reviews the past twenty years of attention to ‘personal security’: both in compartments that consider organized physical violence or threats to personal safety and property (‘citizen security’), and as parts of more wide-ranging examination of threats to fulfilment of basic needs and rights, for example in comprehensive mapping exercises undertaken in various UNDP Regional and National Human Development Reports or in studies of women’s security. The paper reflects on the complex process of opening-up conventional security thinking and practice, seeking value-added and depth without shrinking into preconceived compartments

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Keratinocyte Skin Cancers in General Surgery: The Impact of Anaesthesia, Trainee Supervision, and Choice of Reconstruction

Background. Keratinocyte skin cancers are common in Australia, incurring disproportionately high health expenditure in comparison with mortality. General surgeons often excise these lesions as day-surgery. Balancing individual complexities of these cancers with trainee supervision and health expenditure is key to deliver efficacious care and maintain day-surgery volume for patients during a pandemic. Methods. A retrospective, cross-sectional study was performed, examining 414 procedures from January 2019 to December 2020. Pathology was reviewed, and benign lesions excluded. Complete excision was based on 5 mm margins for squamous cell carcinoma (SCC), 0.5 mm microscopic margins for low-risk basal cell carcinoma (BCC) subtypes, and 3 mm for high-risk. Results of trainee-performed local anesthetic (LA) excision and general anesthetic (GA) excision (consultant scrubbed) were compared. Results. 288 excisions were reviewed for completeness, location, and reconstruction modality. 69% were BCC (199), and 31% were SCC (89). These were excised under GA (72.5%) and LA (27.5%). 25.6% of BCC excisions were “close,” and 22.6% were “positive” under GA, whilst 31% were “close” and 15.5% were “positive” under LA. 52.8% of SCC excisions were “close,” and 7.8% were “positive” under GA, compared with 42.8% “close” and 9.5% “positive” under LA. Complex reconstruction (skin graft, flap) was more common under GA (38% SCC and 36.1% BCC), but occurred at a modest rate under LA (22% BCC and 28.5% SCC). Conclusions. The results confirm that comparable margins and reconstruction options are achievable when excising keratinocyte cancers under LA by surgical trainees. This is fundamental in cost and timesaving, as well as reducing risk of aerosolisation of virus during GA, in a pandemic

Bedeutung und Anwendung

Title Page, Table of Contents, Motivation iv Concepts v Introduction vii 1 Fundamentals 1 1.1 Meaning of isostasy and rigidity 1 1.1.1 Isostasy according to Pratt 1 1.1.2 Isostasy according to Airy 2 1.1.3 Isostasy according to Vening-Meinesz 2 1.1.4 Elastic thickness and flexural rigidity 4 1.2 Methods for estimation of flexural parameters 5 1.2.1 Spectral methods 5 1.2.2 Advantage and disadvantage of spectral methods 10 1.2.3 Convolution method 11 1.2.4 Advantage and disadvantage of the convolution method 12 1.2.5 Conclusion 12 1.3 Gravity inversion according to Parker algorithm 13 1.3.1 Introduction 13 1.3.2 Method 13 1.3.3 Synthetic example 14 1.4 Internal loads 16 1.4.1 Calculation of gravity effect of sediments with slice program 16 1.4.2 Pseudo topography 17 2 Theoretical basics and development of the analytical solution 19 2.1 Differential equation 19 2.1.1 Plate theory according to Kirchhoff 19 2.1.2 Beam on elastic foundation 20 2.1.3 Application in geological sciences 23 2.2 Formula according to Hertz 25 2.2.1 Investigation of the Logarithm function 27 2.2.2 Investigation of the Sine function 29 2.2.3 Summary of the behavior of the functions 30 2.3 New analytical solution 31 2.3.1 Introduction 31 2.3.2 Modification and substitution 31 2.3.3 Investigation of the graph 33 2.3.4 Unification of the analytical solution 35 2.4 Transfer function 38 2.4.1 Introduction 38 2.4.2 Transfer function 39 2.4.3 Verification of the analytical solution 41 2.4.4 Conclusion. 42 2.5 Comparison with FFT solution 43 2.5.1 Comparison with flexure curves 43 2.5.2 Investigation of dependence from grid parameters 44 2.5.3 Boundary cases for elastic thickness 47 2.5.4 Comparison with Vening-Meinesz solution 49 2.5.5 Conclusion 50 2.6 Software concept 51 2.6.1 Introduction 51 2.6.2 Flexure curves and CMI 52 2.6.3 Radius of convolution 52 2.6.4 Iterative estimation of elastic thickness 54 2.6.5 Elastic thickness distribution 56 2.6.6 Reference depth 57 2.7 Comparison with Finite Element modeling 59 2.7.1 Influence of input parameters 61 2.7.2 Conclusion 69 3\. Application of the analytical solution 70 3.1 Pacific Ocean 71 3.1.1 Input data 71 3.1.2 Preliminary investigations 72 3.1.3 Estimation of gravity CMI 73 3.1.4 Estimation of rigidity And elastic thickness 76 3.1.5 Discussion and conclusion. 77 3.2 Central Andes 80 3.2.1 Input data 80 3.2.2 Preliminary investigation 82 3.2.3 Estimation of rigidity and elastic thickness 83 3.2.4 Discussion and conclusion. 86 3.3 Southern Andes 91 3.3.1 Input data 91 3.3.2 Estimation of rigidity and elastic thickness 92 3.3.3 Discussion and conclusion. 93 4 Discussion of results 98 4.1 Thick plate theory 98 4.2 Influence of temperature 99 4.2.1 Introduction 99 4.2.2 Synthetic example 99 4.2.3 Application in geological sciences 101 4.3 Significance of input parameters 105 4.3.1 Deviation of height 106 4.3.2 Deviation of gravity 107 4.3.3 Deviation of Young's modulus 107 4.3.4 Deviation of Poisson ratio 108 4.3.5 Deviation of density of crust 109 4.3.6 Deviation of density of mantle 109 4.3.7 Deviation of elastic thickness 110 4.3.8 Conclusion 111 4.4 Variation of Young's modulus 112 4.5 Visco-elastic behavior 116 4.6 Final comments and future directions 122 5 Appendix I 5.1 Density-porosity formula I 5.2 Comparison of flexure curves III 5.2.1. FFT solution compared with Logarithm and Sine function III 5.2.2. Comparison of output from computer program with FFT IV 5.3 FE models V 5.3.1. Calculation input parameters and results VI 5.3.2. Settings of the FE models IX Acknowledgement, References X Notation XI Abbreviations XIV Index of Tables XV Index of Figures XVI ReferencesIn 1939 a new concept was introduced by Vening-Meinesz proposing that the flexural strength of the lithosphere must be considered for isostatic models. A 4th order differential equation describing the flexure of a thin plate was developed. In the past the equation has been solved in frequency space using spectral methods (coherence and admittance). However, the admittance and coherence techniques have been questioned when applied to continental lithosphere. Both methods require an averaging process; therefore the variation in rigidity may be retrieved only to a limited extent. A large spatial window with a side length of at least 375 km is required over the study area. And, in where the input topography is characterized by low topographic variation, the method becomes unstable. These problems can be overcome by calculating the flexural rigidity with the convolution approach and furthermore with the use of a newly derived analytical solution of the differential equation mentioned above. This solution was developed out of three solutions from Hertz and has been made applicable to geological science. The analytical solution has been applied to both oceanic lithosphere (Nazca plate) and continental lithosphere (Central and Patagonian Andes). The resulting flexural rigidity values and their variations have been compared with the ideas and concepts developed by the members of the SFB267 community, and correlate well with tectonic units and fault systems. In the past the elastic thickness has been used synonymously for the flexural rigidity. However, the analytical solution leads to a new interpretation and meaning of the elastic thickness. It is shown that it is sufficient to operate with a constant value for both gravity and Poisson's ratio, as the variation of either parameter does not lead to a significant change in the distribution of flexural rigidity. Young's modulus is shown to be the driving factor for the flexural deformation. A temperature moment must also be taken into account in flexural investigations. Thus, the variation of the elastic thickness can be explained by temperature distribution and a change of the Young's modulus. A new definition of elastic thickness can be obtained: the value of the calculated elastic thickness is equivalent to the value of thickness of a corresponding plate described by a constant Young's modulus. Computations using the differential equation are valid for the crust/mantle interface (Moho) as well as the lithosphere/ asthenosphere boundary. The calculated boundary surface can be shifted at the position of the boundary at which a significant change of Young's modulus takes place.Im Jahre 1939 wurde von Vening-Meinesz eine Theorie entwickelt, welche die Rigidität der Lithosphärenplatte innerhalb isostatischer Betrachtungen berücksichtigte. Dazu wurde eine Differentialgleichung 4. Ordnung verwendet, welche die Deformation einer dünnen Platte beschreibt. In der Vergangenheit wurde die Gleichung mittels der Spektralmethoden im Frequenz-Bereich gelöst. Aber bezüglich der Anwendung der Kohärenz- und Admittanzmethode auf die Kontinente wurde ihre Nützlichkeit aufgrund der Nachteile, welche durch den Spektralansatz entstehen, in Frage gestellt. Dieser Ansatz bedingt eine Durchschnittsbildung, welche im Falle einer sich räumlich stark variierenden Rigidität dazu führen kann, dass jene Variation nur bis zu einem begrenzten Mabe aufgelöst wird. Für das Untersuchungsgebiet ist eine Seitenlänge von mindestens erforderlich. Ein weiteres Problem tritt im Falle niedriger Topographie auf, da kleinere Spektralwerte zu Instabilitaeten innerhalb der Anwendung führen können. Durch die Verwendung der Konvolutionsmethode und der neu entwickelten analytischen Lösung der obig eingeführten Differentialgleichung werden diese Nachteile überwunden. Diese analytische Lösung wurde aus drei verschiedenen Lösungen nach Hertz entwickelt und für die geologischen Wissenschaften anwendbar gemacht. Die analytische Lösung wurde auf die ozeanische Lithosphäre im Bereich des Pazifik (Nazca-Platte) und auf die kontinentale Lithosphäre im Bereich der Zentral - und der Patagonischen Anden angewendet. Die resultierende Rigiditätsverteilung wird mit den von den Mitgliedern der SFB267 Gemeinschaft entwickelten Ideen und Konzepten verglichen, und ist durch eine gute Korrelation mit den tektonischen Einheiten und Störungssystemen charakterisiert. Bisher wurde die elastische Dicke und die flexurelle Rigidität synonym verwendet. Aber die analytische Lösung führte zu einem neuen Verständnis und Interpretation der elastischen Dicke. In Anbetracht der Untersuchungen zur Signifikanz der Inputparameter ist es zulässig mit einem konstanten Wert für die Schwere und dem Poisson-Verhältnis zu arbeiten, denn dies wird nicht zu signifikanten Unterschieden im Ergebnis führen. Dies gilt nicht für das Elastizitätsmodul, denn dieser Parameter ist ein entscheidender Faktor für das Deformationsverhalten. Daher kann die elastische Dicke auch als äquivalente Plattendicke für eine Platte konstanten Elastizitätsmoduls definiert werden. Zudem wurde herausgefunden, daß das Temperaturmoment in den weiteren Untersuchungen mit berücksichtigt werden muss. Damit kann die beobachtete Variation der elastischen Dicke durch die Temperaturverteilung und die Veränderung des Elastizitätsmoduls erklärt werden. Zusätzlich wurde gezeigt, daß die Berechnungen mittels der Differentialgleichung und der analytischen Lösung sowohl für die Krusten/Mantel Grenze als auch die Lithosphären/Asthenosphären Grenze gültig sind. Dabei ist entscheidend, an welcher Grenzfläche sich das Elastizitätsmodul ändert