GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Effect of home-based online training and activity feedback on oxygen uptake in patients after surgical cancer therapy: a randomized controlled trial.

BACKGROUND: Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity. METHODS: Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior. RESULTS: One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: - 1079; 95% CI - 2157 to - 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life. CONCLUSIONS: Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed. TRIAL REGISTRATION: DRKS-ID: DRKS00020499 ; Registered 17 March 2020.

In vivo evaluation of a hyperspectral imaging system for minimally invasive surgery (HSI-MIS).

BACKGROUND: Hyperspectral Imaging (HSI) is a reliable and safe imaging method for taking intraoperative perfusion measurements. This is the first study translating intraoperative HSI to an in vivo laparoscopic setting using a CE-certified HSI-system for minimally invasive surgery (HSI-MIS). We aim to compare it to an established HSI-system for open surgery (HSI-Open). METHODS: Intraoperative HSI was done using the HSI-MIS and HSI-Open at the Region of Interest (ROI). 19 patients undergoing gastrointestinal resections were analyzed in this study. The HSI-MIS-acquired images were aligned with those from the HSI-Open, and spectra and parameter images were compared pixel-wise. We calculated the Mean Absolute Error (MAE) for Tissue Oxygen Saturation (StO2), Near-Infrared Perfusion Index (NIR-PI), Tissue Water Index (TWI), and Organ Hemoglobin Index (OHI), as well as the Root Mean Squared Error (RMSE) over the whole spectrum. Our analysis of parameters was optimized using partial least squares (PLS) regression. Two experienced surgeons carried out an additional color-change analysis, comparing the ROI images and deciding whether they provided the same (acceptable) or different visual information (rejected). RESULTS: HSI and subsequent image registration was possible in 19 patients. MAE results for the original calculation were StO2 orig. 17.2% (± 7.7%), NIR-PIorig. 16.0 (± 9.5), TWIorig. 18.1 (± 7.9), OHIorig. 14.4 (± 4.5). For the PLS calculation, they were StO2 PLS 12.6% (± 5.2%), NIR-PIPLS 10.3 (± 6.0), TWIPLS 10.6 (± 5.1), and OHIPLS 11.6 (± 3.0). The RMSE between both systems was 0.14 (± 0.06). In the color-change analysis; both surgeons accepted more images generated using the PLS method. CONCLUSION: Intraoperative HSI-MIS is a new technology and holds great potential for future applications in surgery. Parameter deviations are attributable to technical differences and can be reduced by applying improved calculation methods. This study is an important step toward the clinical implementation of HSI for minimally invasive surgery.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

The role of intraoperative hyperspectral imaging (HSI) in colon interposition after esophagectomy.

BACKGROUND: Colon conduit is an alternative approach to reconstructing the alimentary tract after esophagectomy. Hyperspectral imaging (HSI) has been demonstrated to be effective for evaluating the perfusion of gastric conduits, but not colon conduits. This is the first study to describe this new tool addressing image-guided surgery and supporting esophageal surgeons to select the optimal colon segment for the conduit and anastomotic site intraoperatively. PATIENTS AND METHODS: Of 10 patients, eight who underwent reconstruction with a long-segment colon conduit after esophagectomy between 01/05/2018 and 01/04/2022 were included in this study. HSI was recorded at the root and tip of the colon conduit after clamping the middle colic vessels, allowing us to evaluate the perfusion and appropriate part of the colon segment. RESULTS: Anastomotic leak (AL) was detected in only one (12.5%) of all the enrolled patients (n = 8). None of the patients developed conduit necrosis. Only one patient required re-anastomosis on postoperative day 4. No patient needed conduit removal, esophageal diversion, or stent placement. There was a change in the anastomosis site to proximal in two patients intraoperatively. There was no need to change the side of colon conduit intraoperatively in any patient. CONCLUSION: HSI is a promising and novel intraoperative imaging tool to objectively assess the perfusion of the colon conduit. It helps the surgeon to define the best perfused anastomosis site and the side of colon conduit in this type of operation.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Alternative intraoperative optical imaging modalities for fluorescence angiography in gastrointestinal surgery: spectral imaging and imaging photoplethysmography.

INTRODUCTION: Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. MATERIAL AND METHODS: The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. RESULTS: The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. CONCLUSIONS: Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine.

Tyrosine-modified linear PEIs for highly efficacious and biocompatible siRNA delivery in vitro and in vivo.

Therapeutic gene silencing by RNA interference relies on the safe and efficient in vivo delivery of small interfering RNAs (siRNAs). Polyethylenimines are among the most studied cationic polymers for gene delivery. For several reasons including superior tolerability, small linear PEIs would be preferable over branched PEIs, but they show poor siRNA complexation. Their chemical modification for siRNA formulation has not been extensively explored so far. We generated a set of small linear PEIs bearing tyrosine modifications (LPxY), leading to substantially enhanced siRNA delivery and knockdown efficacy in vitro in various cell lines, including hard-to-transfect cells. The tyrosine-modified linear 10 kDa PEI (LP10Y) is particularly powerful, associated with favorable physicochemical properties and very high biocompatibility. Systemically administered LP10Y/siRNA complexes reveal antitumor effects in mouse xenograft and patient-derived xenograft (PDX) models, and their direct application into the brain achieves therapeutic inhibition of orthotopic glioma xenografts. LP10Y is particularly interesting for therapeutic siRNA delivery.

[New intraoperative fluorescence-based and spectroscopic imaging techniques in visceral medicine - precision surgery in the "high tech"-operating room]. / Neue intraoperative fluoreszenzbasierte und spektroskopische Bildgebungsverfahren in der Viszeralmedizin ­ Präzisionschirurgie im "Hightech"-OP.

INTRODUCTION: Fluorescence angiography (FA) with indocyanine green (ICG) and hyperspectral imaging (HSI) are novel intraoperative visualization techniques in abdominal, vascular and transplant surgery. With the purpose of precision surgery, and in order to increase patient's safety, these new tools aim at reducing postoperative morbidity and mortality. This review discusses and highlights recent developments and the future potential of real-time imaging modalities. METHODS: The underlying mechanisms of the novel imaging methods and their clinical impact are displayed in the context of avoiding anastomotic leaks, the most momentous complications in gastrointestinal surgery after oncologic resections. RESULTS: While FA is associated with the admission of a fluorescence agent, HSI is contact-free and non-invasive. Both methods are able to record physiological tissue properties in real-time. Additionally, FA also measures dynamic phenomena. The techniques take a few seconds only and do not hamper the operative workflow considerably. With regard to a potential change of the surgical strategy, FA and HSI have an equal significance. Our own advancements reflect, in particular, the topics of data visualization and automated data analyses together with the implementation of artificial intelligence (AI) and minimalization of the current devices to install them into endoscopes, minimal-invasive and robot-guided surgery. CONCLUSION: There are a limited number of studies in the field of intraoperative imaging techniques. Whether precision surgery in the "high-tech" OR together with FA, HSI and robotics will result in more secure operative procedures to minimize the postoperative morbidity and mortality will have to be evaluated in future multicenter trials.

[Prevention of gastrointestinal cancer]. / Prävention gastrointestinaler Tumore.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.

[Barrett-Screening: Rational, current concepts and perspectives]. / Barrett-Screening: rationale, aktuelle Konzepte und Perspektiven.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness - 8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials.

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

In-depth characterization of the Wnt-signaling/ß-catenin pathway in an in vitro model of Barrett's sequence.

BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett's esophagus progression, but with rarely detected mutations in APC and ß-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3ß was performed in an in vitro cell culture model of Barrett's esophagus. Representing the Barrett's sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. RESULTS: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett's metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1-10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. CONCLUSION: Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett's esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett's progression and the underlying pathological mechanisms.

Fluorescent analogs of peptoid-based HDAC inhibitors: Synthesis, biological activity and cellular uptake kinetics.

Fluorescent tagging of bioactive molecules is a powerful tool to study cellular uptake kinetics and is considered as an attractive alternative to radioligands. In this study, we developed fluorescent histone deacetylase (HDAC) inhibitors and investigated their biological activity and cellular uptake kinetics. Our approach was to introduce a dansyl group as a fluorophore in the solvent-exposed cap region of the HDAC inhibitor pharmacophore model. Three novel fluorescent HDAC inhibitors were synthesized utilizing efficient submonomer protocols followed by the introduction of a hydroxamic acid or 2-aminoanilide moiety as zinc-binding group. All compounds were tested for their inhibition of selected HDAC isoforms, and docking studies were subsequently performed to rationalize the observed selectivity profiles. All HDAC inhibitors were further screened in proliferation assays in the esophageal adenocarcinoma cell lines OE33 and OE19. Compound 2, 6-((N-(2-(benzylamino)-2-oxoethyl)-5-(dimethylamino)naphthalene)-1-sulfonamido)-N-hydroxyhexanamide, displayed the highest HDAC inhibitory capacity as well as the strongest anti-proliferative activity. Fluorescence microscopy studies revealed that compound 2 showed the fastest uptake kinetic and reached the highest absolute fluorescence intensity of all compounds. Hence, the rapid and increased cellular uptake of 2 might contribute to its potent anti-proliferative properties.

Comparative analysis of high field MRI and histology for ex vivo whole organ imaging: assessment of placental functional morphology in a murine model.

OBJECTIVES: The purpose of our study was to evaluate MRI as a tool to examine placental morphology in a murine model in comparison to classical histology techniques. METHODS: Assessment of placental samples (n = 24) from C57Bl/6 J mice was performed using MR imaging and histomorphological analyses. To optimize image contrast for MRI, a protocol for gadolinium-mediated enhancement of placental tissue was established. To test method sensitivity, placental zone assessment with MRI and histology was applied to a model of prenatal stress exposure known to affect placental morphology (n = 10). Mean data acquisition time for both methods was estimated. Difference between groups was calculated using the Mann-Whitney U test. RESULTS: Tissue fixation with formaldehyde and staining with gadolinium resulted in the best image quality. Placental functional zones were identified and measured with both MRI and histology. MRI and histology were able to detect changes in the L/Jz ratio upon a prenatal stress challenge (p = 0.001; p = 0.003). Data acquisition time was shorter using MRI assessment. CONCLUSIONS: Ex vivo MRI analyses of murine placental functional morphology with MRI are feasible and results are comparable to time-consuming histology. Both MRI and histology allow the detection of experimentally induced morphological tissue alterations.

[Barrett-Screening: Rational, current concepts and perspectives]. / Barrett-Screening: Rationale, aktuelle Konzepte und Perspektiven.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness-8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials.

Stress biomarkers in minimally invasive and conventional colorectal resections.

INTRODUCTION: Any surgical procedure develops a stress situation for the patient, which can modulate the individual outcome. At present, there is only limited information about stress response in colorectal resections by laparoscopic compared to conventional surgery. Therefore, our objectives were the feasibility and the investigation of stress biomarkers including copeptin and steroid hormones before, during and after colorectal surgery. METHODS: Eleven patients underwent minimally invasive and ten patients conventionally open colorectal surgery. Blood samples were collected before, during and 24 h after surgery and copeptin, NT-proBNP, cortisol, cortisone, interleukin-6 and glucose were analyzed. RESULTS: Both, minimally invasive and conventional-open colorectal surgery caused a fast but heterogeneous response of stress biomarkers. However, the postoperative decrease of cortisol, cortisone and glucose differed between both groups. The stress biomarkers decreased faster down to baseline after minimally invasive surgery, while in open surgery cortisol, cortisone and glucose did not return to baseline within 24 h after operation. CONCLUSIONS: We show in this feasibility study for the first time an increase of copeptin in combination with glucocorticoids as stress biomarkers by open surgery compared to minimally invasive procedures in patients undergoing colorectal surgery. Exceeding an individual threshold of 'stress burden' may have unfavorable effects on the long-time clinical outcome.

Upregulation of VEGFR1 in a rat model of esophagogastric anastomotic healing.

INTRODUCTION: Anastomotic leakage after gastrointestinal surgery is a significant cause of morbidity and mortality. Esophagogastric and colorectal anastomoses are vulnerable to leakage. Extended knowledge of growth factors and their receptors is needed to understand anatomic healing. METHODS: The expression pattern of vascular growth factor receptor (VEGFR1-3), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFRα/ß) and keratinocyte growth factor receptor (KGFR) were analyzed by semiquantitative-PCR in the rat intestinal tract and in esophagogastric anastomosis 5d after surgery. RESULTS: VEGFR1, VEGFR2, EGFR, KGFR and PDGFRα expression was observed throughout the intestinal tract including esophagus, stomach, small bowl and colon. VEGFR3 was not found in gastric samples and PDGFRß expression was not detected in the small bowl. Semiquantitative analyses of the VEGFR1, PDGFRα and EGFR expression in esophagogastric anastomotic tissues revealed a 2-fold upregulation of the VEGFR1 in gastric samples, while no change was observed in the esophageal anastomotic side. CONCLUSION: Our results revealed a distinct expression pattern of the investigated growth factor receptors in rat intestinal tract. Showing higher expression levels of growth factor receptors at the gastric anastomotic tissue at the fifth postoperative day suggests a different contribution of the gastric and the esophageal side to the anastomotic healing.