Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

Laparoscopic ischemic conditioning of the stomach prior to esophagectomy induces gastric neo-angiogenesis.

BACKGROUND: The risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis. METHODS: Twenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size. RESULTS: Between November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention. CONCLUSION: The data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site.

Combined regression score predicts outcome after neoadjuvant treatment of oesophageal cancer.

BACKGROUND: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.

TEsoNet: knowledge transfer in surgical phase recognition from laparoscopic sleeve gastrectomy to the laparoscopic part of Ivor-Lewis esophagectomy.

BACKGROUND: Surgical phase recognition using computer vision presents an essential requirement for artificial intelligence-assisted analysis of surgical workflow. Its performance is heavily dependent on large amounts of annotated video data, which remain a limited resource, especially concerning highly specialized procedures. Knowledge transfer from common to more complex procedures can promote data efficiency. Phase recognition models trained on large, readily available datasets may be extrapolated and transferred to smaller datasets of different procedures to improve generalizability. The conditions under which transfer learning is appropriate and feasible remain to be established. METHODS: We defined ten operative phases for the laparoscopic part of Ivor-Lewis Esophagectomy through expert consensus. A dataset of 40 videos was annotated accordingly. The knowledge transfer capability of an established model architecture for phase recognition (CNN + LSTM) was adapted to generate a "Transferal Esophagectomy Network" (TEsoNet) for co-training and transfer learning from laparoscopic Sleeve Gastrectomy to the laparoscopic part of Ivor-Lewis Esophagectomy, exploring different training set compositions and training weights. RESULTS: The explored model architecture is capable of accurate phase detection in complex procedures, such as Esophagectomy, even with low quantities of training data. Knowledge transfer between two upper gastrointestinal procedures is feasible and achieves reasonable accuracy with respect to operative phases with high procedural overlap. CONCLUSION: Robust phase recognition models can achieve reasonable yet phase-specific accuracy through transfer learning and co-training between two related procedures, even when exposed to small amounts of training data of the target procedure. Further exploration is required to determine appropriate data amounts, key characteristics of the training procedure and temporal annotation methods required for successful transferal phase recognition. Transfer learning across different procedures addressing small datasets may increase data efficiency. Finally, to enable the surgical application of AI for intraoperative risk mitigation, coverage of rare, specialized procedures needs to be explored.

[Reconstruction and functional results after gastric resection]. / Rekonstruktionen und funktionelle Ergebnisse nach Magenresektion.

Depending on the extent of gastric resection, namely total, proximal or distal gastrectomy, different methods of reconstruction are available. These reconstructive procedures have not changed with the implementation of minimally invasive or robotic techniques in general but the spectrum of possible anastomotic techniques has been substantially expanded. Functional, in particular nutritional disorders with subsequent impairment of the health-related quality of life, are often diagnosed after gastric resections. The partial preservation of a gastric reservoir has a positive impact on the extent of these disorders. After total gastrectomy, the placement of a jejunal pouch significantly reduces the incidence of postoperative dumping symptoms. Following proximal gastrectomy, double-tract reconstruction offers certain functional advantages as compared to the simple Roux­Y reconstruction. In Germany, these reconstructive techniques are only used to a low extent and should be include in the repertoire of oncological gastric surgery with appropriate indications.

The ISCON-trial protocol: laparoscopic ischemic conditioning prior to esophagectomy in patients with esophageal cancer and arterial calcifications.

BACKGROUND: Anastomotic leakage is the most important surgical complication following esophagectomy. A major cause of leakage is ischemia of the gastric tube that is used for reconstruction of the gastrointestinal tract. Generalized cardiovascular disease, expressed by calcifications of the aorta and celiac axis stenosis on a pre-operative CT scan, is associated with an increased risk of anastomotic leakage. Laparoscopic ischemic conditioning (ISCON) aims to redistribute blood flow and increase perfusion at the anastomotic site by occluding the left gastric, left gastroepiploic and short gastric arteries prior to esophagectomy. This study aims to assess the safety and feasibility of laparoscopic ISCON in selected patients with esophageal cancer and concomitant arterial calcifications. METHODS: In this prospective single-arm safety and feasibility trial based upon the IDEAL recommendations for surgical innovation, a total of 20 patients will be included recruited in 2 European high-volume centers for esophageal cancer surgery. Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications" of the thoracic aorta accordingly to the Uniform Calcification Score (UCS) or a stenosis of the celiac axis accordingly to the modified North American Symptomatic Carotid Endarterectomy Trial (NASCET) score on preoperative CT scan, who are planned to undergo esophagectomy are eligible for inclusion. The primary outcome variables are complications grade 2 and higher (Clavien-Dindo classification) occurring during or after laparoscopic ISCON and before esophagectomy. Secondary outcomes include intra- and postoperative complications of esophagectomy and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography. DISCUSSION: We hypothesize that in selected patients with impaired vascularization of the gastric tube, laparoscopic ISCON is feasible and can be safely performed 12-18 days prior to esophagectomy. Depending on the results, a randomized controlled trial will be needed to investigate whether ISCON leads to a lower percentage and less severe course of anastomotic leakage in selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896399 . Registered 4 January 2019.

Ubiquitous atmospheric production of organic acids mediated by cloud droplets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.

Theoretical and experimental study of peroxy and alkoxy radicals in the NO3-initiated oxidation of isoprene.

The initial stages of the nitrate radical (NO3) initiated oxidation of isoprene, in particular the fate of the peroxy (RO2) and alkoxy (RO) radicals, are examined by an extensive set of quantum chemical and theoretical kinetic calculations. It is shown that the oxidation mechanism is highly complex, and bears similarities to its OH-initiated oxidation mechanism as studied intensively over the last decade. The nascent nitrated RO2 radicals can interconvert by successive O2 addition/elimination reactions, and potentially have access to a wide range of unimolecular reactions with rate coefficients as high as 35 s-1; the contribution of this chemistry could not be ascertained experimentally. The chemistry of the alkoxy radicals derived from these peroxy radicals is affected by the nitrate moiety, and can lead to the formation of nitrated epoxy peroxy radicals in competition with isomerisation and decomposition channels that terminate the organic radical chain by NO2 elimination. The theoretical predictions are implemented in the FZJ-NO3-isoprene mechanism for NO3-initiated atmospheric oxidation of isoprene. The model predictions are compared against peroxy radical (RO2) and methyl vinyl ketone (MVK) measurements in a set of experiments on the isoprene + NO3 reaction system performed in the SAPHIR environmental chamber (IsopNO3 campaign). It is shown that the formation of NO2 from the peroxy radicals can prevent a large fraction of the peroxy radicals from being measured by the laser-induced fluorescence (ROxLIF) technique that relies on a quantitative conversion of peroxy radicals to hydroxyl radicals. Accounting for the relative conversion efficiency of RO2 species in the experiments, the agreement between observations and the theory-based FZJ-NO3-isoprene model predictions improves significantly. In addition, MVK formation in the NO3-initiated oxidation was found to be suppressed by the epoxidation of the unsaturated RO radical intermediates, allowing the model-predicted MVK concentrations to be in good agreement with the measurements. The FZJ-NO3-isoprene mechanism is compared against the MCM v3.3.1 and Wennberg et al. (2018) mechanisms.

Experimental and theoretical study on the impact of a nitrate group on the chemistry of alkoxy radicals.

The chemistry of nitrated alkoxy radicals, and its impact on RO2 measurements using the laser induced fluorescence (LIF) technique, is examined by a combined theoretical and experimental study. Quantum chemical and theoretical kinetic calculations show that the decomposition of ß-nitrate-alkoxy radicals is much slower than ß-OH-substituted alkoxy radicals, and that the spontaneous fragmentation of the α-nitrate-alkyl radical product to a carbonyl product + NO2 prevents other ß-substituents from efficiently reducing the energy barrier. The systematic series of calculations is summarized as an update to the structure-activity relationship (SAR) by Vereecken and Peeters (2009), and shows increasing decomposition rates with higher degrees of substitution, as in the series ethene to 2,3-dimethyl-butene, and dominant H-migration for sufficiently large alkoxy radicals such as those formed from 1-pentene or longer alkenes. The slow decomposition allows other reactions to become competitive, including epoxidation in unsaturated nitrate-alkoxy radicals; the decomposition SAR is likewise updated for ß-epoxy substituents. A set of experiments investigating the NO3-initiated oxidation of ethene, propene, cis-2-butene, 2,3-dimethyl-butene, 1-pentene, and trans-2-hexene, were performed in the atmospheric simulation chamber SAPHIR with measurements of HO2 and RO2 radicals performed with a LIF instrument. Comparisons between modelled and measured HO2 radicals in all experiments, performed in excess of carbon monoxide to avoid OH radical chemistry, suggest that the reaction of HO2 with ß-nitrate alkylperoxy radicals has a channel forming OH and an alkoxy radical in yields of 15-65%, compatible with earlier literature data on nitrated isoprene and α-pinene radicals. Model concentrations of RO2 radicals when including the results of the theoretical calculations described here, agreed within 10% with the measured RO2 radicals for all species investigated when the alkene oxidation is dominated by NO3 radicals. The formation of NO2 in the decomposition of ß-nitrate alkoxy radicals prevents detection of the parent RO2 radical in a LIF instrument, as it relies on formation of HO2. The implications for measurements of RO2 in ambient and experimental conditions, such as for the NO3-dominated chemistry during nighttime, is discussed. The current results appear in disagreement with an earlier indirect experimental study by Yeh et al. on pentadecene.

[Evidence in minimally invasive oncological surgery of the esophagus]. / Evidenz in der minimal-invasiven onkologischen Chirurgie des Ösophagus.

BACKGROUND: Thoracoabdominal esophagectomy still plays a major role in the oncological treatment for esophageal cancer. Minimally invasive procedures were developed to reduce the high rate of postoperative morbidity and mortality without negatively affecting the oncological outcome. OBJECTIVE: What evidence supports minimally invasive oncological surgery of the esophagus? Do patients benefit from minimally invasive esophagectomy compared to an open approach? Is the reduction of surgical access trauma specifically advantageous? MATERIAL AND METHODS: Review, evaluation and critical analysis of the international literature. RESULTS: A reduction in postoperative morbidity by decreasing surgical trauma was confirmed by three prospective randomized clinical trials, while showing at least similar oncological outcomes. Diverse retrospective analyses and meta-analyses also came to the same result. CONCLUSION: A minimization of surgical access trauma during thoracoabdominal esophagectomy reduces postoperative morbidity compared to conventional open surgery. Recent evidence suggests that oncological outcomes are not altered depending on the surgical approach.

[Perioperative enhanced recovery after surgery program for Ivor Lewis esophagectomy : First experiences of a high-volume center]. / Perioperatives "Enhanced-recovery-after-surgery"-Programm der Ivor-Lewis-Ösophagektomie : Erste Erfahrungen eines High-volume-Zentrums.

BACKGROUND AND OBJECTIVE: Transthoracic esophagectomy is generally accepted as the standard of surgical care for patients with esophageal cancer. Despite improvements in the perioperative management this surgical procedure is associated with a clinically relevant morbidity. Fast-track protocols (synonym: enhanced recovery after surgery, ERAS) are conceived to perioperatively maintain the physiological homoeostasis and thereby to accelerate postoperative rehabilitation and reduce morbidity. In this prospective observational study the initial experiences of a high-volume center with the implementation of an ERAS protocol after transthoracic esophagectomy were analyzed. MATERIAL AND METHODS: A total of 26 patients with esophageal cancer and a low index of comorbidities prior to hybrid Ivor Lewis esophagectomy were included in this study. According to an ERAS protocol all patients underwent a standardized perioperative treatment pathway aiming to discharge the patients from the inpatient treatment on postoperative day 10. The primary outcome parameter was the rate of major complications (Clavien-Dindo IIIb/IV), which was compared to a cohort of 52 non-ERAS patients. RESULTS AND CONCLUSION: The ERAS programs with the various core elements can be implemented in patients scheduled for transthoracic esophagectomy, although the organizational and personnel expenditure of this fast-track protocol is high. The length of hospital stay appears to be reduced without compromising patient safety. The limiting variable of the ERAS protocol remains the early and adequate enteral feeding load of the gastric conduit before discharge on postoperative day 10.

Two-stage hybrid Ivor-Lewis esophagectomy as surgical strategy to reduce postoperative morbidity for high-risk patients.

BACKGROUND: Ivor-Lewis esophagectomy (ILE) is the standard surgical care for esophageal cancer patients but postoperative morbidity impairs quality of life and reduces long-term oncological outcome. Two-stage ILE separating the abdominal and thoracic phase into two distinct surgical procedures has proven to enhance microcirculation of the gastric conduit and therefore most likely reduces complications. However, two-stage ILE has not been evaluated systematically in selected groups of patients scheduled for this procedure. This investigation aims to demonstrate the feasibility of two-stage ILE in high-risk patients. PATIENTS AND METHODS: In this retrospective analysis of data obtained from a prospective database, a consecutive series of 275 hybrid ILE (hILE) were included. Patients were divided into two groups based on one- or two-stage hILE. Postoperative complications were assessed according to ECCG (Esophageal Complication Consensus Group) criteria and compared using the Clavien-Dindo score. Indication for two-stage esophagectomy was classified as pre- or intraoperative decision. RESULTS: 34 out of 275 patients (12.7%) underwent two-stage hILE. Patients of the two-stage group were significantly older. In 21 of 34 patients (61.8%) the decision for a two-stage procedure was made prior to esophagectomy, in 13 (38.2%) patients intraoperatively after completion of the laparoscopic gastric mobilization. The most frequent preoperative reason to select the two-stage procedure was a stenosis of the coeliac trunc and superior mesenteric artery (n = 10). The predominant cause for an intraoperative change of strategy was a laparoscopically diagnosed hepatic fibrosis/cirrhosis (n = 5).Overall morbidity and major' complications (CD > IIIa) were comparable for both groups (11.7% in both groups). The overall anastomotic leak rate was 12.4% and was non-significant lower for the two-stage procedure. CONCLUSION: Two-stage hILE is a feasible concept to individualize the surgical treatment of patients with well-defined clinical risk factors for postoperative morbidity. It can also be applied after completion of the abdominal phase of IL esophagectomy without compromising the patient safety.

Navigated laparoscopic microwave ablation of tumour mimics in pig livers: a randomized ex-vivo experimental trial.

BACKGROUND: In order to efficiently perform laparoscopic microwave ablation of liver tumours precise positioning of the ablation probe is mandatory. This study evaluates the precision and ablation accuracy using the innovative laparoscopic stereotactic navigation system CAS-One-SPOT in comparison to 2d ultrasound guided laparoscopic ablation procedures. METHODS: In a pig liver ablation model four surgeons, experienced (n = 2) and inexperienced (n = 2) in laparoscopic ablation procedures, were randomized for 2d ultrasound guided laparoscopic or stereotactic navigated laparoscopic ablation procedures. Each surgeon performed a total of 20 ablations. Total attempts of needle placements, time from tumor localization till beginning of ablation and ablation accuracy were analyzed. RESULTS: The use of the laparoscopic stereotactic navigation system led to a significant reduction in total attempts of needle placement. The experienced group of surgeons reduced the mean number of attempts from 2.75 ± 2.291 in the 2d ultrasound guided ablation group to 1.45 ± 1.191 (p = 0.0302) attempts in the stereotactic navigation group. Comparable results could be observed in the inexperienced group with a reduction of 2.5 ± 1.50 to 1.15 ± 0.489 (p = 0.0005). This was accompanied by a significant time saving from 101.3 ± 112.1 s to 48.75 ± 27.76 s (p = 0.0491) in the experienced and 165.5 ± 98.9 s to 66.75 ± 21.96 s (p < 0.0001) in the inexperienced surgeon group. The accuracy of the ablation process was hereby not impaired as postinterventional sectioning of the ablation zone revealed. CONCLUSION: The use of a stereotactic navigation system for laparoscopic microwave ablation procedures of liver tumors significantly reduces the attempts and time of predicted correct needle placement for novices and experienced surgeons without impairing the accuracy of the ablation procedure.

Improved Tissue Processing in Esophageal Adenocarcinoma After Ivor Lewis Esophagectomy Allows Histological Analysis of All Surgically Removed Lymph Nodes with Significant Effects on Nodal UICC Stages.

BACKGROUND: In esophageal carcinoma, the numbers of metastatic and total removed lymph nodes (LN) are well-established variables of long-term prognosis. The overall rate of retrieved LN depends on neoadjuvant treatment, the extent of surgical lymphadenectomy, and the modality of the pathological workup. The question in this study is whether technically extended histopathological preparation can increase the number of detected (metastatic) LN with an impact on nodal UICC staging. PATIENTS AND METHODS: A cohort of 77 patients with esophageal adenocarcinoma was treated with Ivor Lewis esophagectomy including standardized two-field lymphadenectomy. The specimens were grossed, and all manually detectable LN were retrieved. The remaining tissue was completely embedded by the advanced "acetone compression" retrieval technique. The primary outcome parameter was the total number of detected lymph nodes before and after acetone workup. RESULTS: A mean number of 23,1 LN was diagnosed after standard manual LN preparation. With complete embedding of the fatty tissue using acetone compression, the number increased to 40.5 lymph nodes (p < 0.0001). The mean number of metastatic LN increased from 3.2 to 4.2 nodal metastases following acetone compression (p < 0.0001). Additional LN metastases which caused a change in the primary (y)pN stage were found in ten patients (13.0%). CONCLUSIONS: Advanced lymph node retrieval by acetone compression allows a reliable statement on the real number of removed LN. Results demonstrate an impact on the nodal UICC stage. A future multicenter study will examine the prognostic impact of improved lymph node retrieval on long-term oncologic outcome.

Citrin deficiency mimicking mitochondrial depletion syndrome.

BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. CASE PRESENTATION: We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70-1)_(212 + 1_231-1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. CONCLUSIONS: As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.

Technical Note: GATE-RTion: a GATE/Geant4 release for clinical applications in scanned ion beam therapy.

PURPOSE: GATE-RTion is a validated version of GATE for clinical use in the field of light ion beam therapy. This paper describes the GATE-RTion project and illustrates its potential through clinical applications developed in three European centers delivering scanned proton and carbon ion treatments. METHODS: GATE-RTion is a collaborative framework provided by the OpenGATE collaboration. It contains a validated GATE release based on a specific Geant4 version, a set of tools to integrate GATE into a clinical environment and a network for clinical users. RESULTS: Three applications are presented: Proton radiography at the Centre Antoine Lacassagne (Nice, France); Independent dose calculation for proton therapy at the Christie NHS Foundation Trust (Manchester, UK); Independent dose calculation for protons and carbon ions at the MedAustron Ion Therapy center (Wiener Neustadt, Austria). CONCLUSIONS: GATE-RTion builds the bridge between researchers and clinical users from the OpenGATE collaboration in the field of Light Ion Beam Therapy. The applications presented in three European facilities using three completely different machines (three different vendors, cyclotron- and synchrotron-based systems, protons, and carbon ions) demonstrate the relevance and versatility of this project.

[Neoadjuvant chemoradiotherapy or chemotherapy for locally advanced esophageal cancer?] / Neoadjuvante Radiochemotherapie oder Chemotherapie beim lokal fortgeschrittenen Ösophaguskarzinom?

BACKGROUND: According to international guidelines neoadjuvant chemoradiotherapy and chemotherapy are recommended for the treatment of locally advanced esophageal cancer. The treatment approach depends on the tumor entity (adenocarcinoma vs. squamous cell carcinoma). OBJECTIVE: What benefits do patients with locally advanced esophageal cancer have from neoadjuvant treatment? Is there information in the international literature on whether a particular neoadjuvant treatment is preferred? Does the type of neoadjuvant treatment depend on factors other than the tumor entity? Is there a standard in the drug composition of chemotherapy or a clearly defined chemoradiotherapy regimen? MATERIAL AND METHODS: A review, evaluation and critical analysis of the international literature were carried out. RESULTS: Patients with locally advanced esophageal cancer benefit from a neoadjuvant treatment. The current data situation for squamous cell carcinoma of the esophagus demonstrates a better response to neoadjuvant chemoradiotherapy compared to chemotherapy alone. Locally advanced adenocarcinoma of the esophagus can be treated with combined neoadjuvant chemoradiotherapy as well as by chemotherapy alone. Both lead to an improvement in the prognosis. There are often differences particularly among radiation treatment regimens in the different centers. Furthermore, the localization of the tumor can also be important for treatment decisions. CONCLUSION: A neoadjuvant treatment is clearly recommended for locally advanced esophageal cancer. Currently, chemoradiotherapy according to the CROSS protocol is preferred for squamous cell carcinoma. For adenocarcinoma both chemotherapy according to the FLOT protocol as well as chemoradiotherapy in a neoadjuvant treatment concept lead to an improvement in the prognosis.

[Personal Factors of the Bio-Psycho-Social Model (WHO): A Revised Classification by the German Society for Social Medicine and Prevention (DGSMP)]. / Personbezogene Faktoren im bio-psycho-sozialen Modell der WHO: Systematik der Deutschen Gesellschaft für Sozialmedizin und Prävention (DGSMP).

BACKGROUND: In 2010, the ICF working group of Faculty II "Applied Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention, DGSMP proposed a classification of personal factors (PF) for the German-speaking area. Meanwhile, the International Classification of Functioning, Disability and Health (ICF) and WHO's bio-psycho-social model were increasingly integrated into the German Social Code (Book IX for Rehabilitation and Participation). It was a legislative decision that the needs assessment for the rehabilitation process must be "comprehensive". AIM: This publication aims to present an updated classification of PF to support the socio-medical assessment. For this purpose other published papers proposing a classification of PF were analyzed, especially the publication of Geyh et al. METHODS: The multiprofessional working group re-examined the basic structure, consistency and selection of factors of the 2010 classification using a qualitative approach and modified them if meaningful and necessary. The principles for the selection of factors were the same as in the 2010 publication (comprehensive, manageable, universal, impartial, relevant, unambiguous, focusing on finality, not regarding causality and non-discriminatory). RESULTS: A fundamental revision was not necessary; the basic structure remained primarily unchanged. Some items were included, excluded, summarized, shifted and editorially or content-related altered. Legal expertise shows that the classification of PF and their individual use for the socio-medical assessment, if necessary for the individual rehabilitation allocation, incur no problems with regard to data-protection regulations. PERSPECTIVES: The revised classification is ready to support users to describe and document relevant influences of the life background of individuals in a structured manner. Thus, influences on functioning and participation can be described comprehensively and transparently based on the bio-psycho-social model. A justiciable allocation of benefits for persons with disabilities is facilitated.