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Tahar Benhidjeb,1,2,&ast; Isabel Benhidjeb,3,&ast; Michael Stark,2 Stefan Kreisel,4 Martin Krüger,5 Jesco Pfitzenmaier,3,&ast; Jan Schulte am Esch1,&ast; 1Department of General and Visceral Surgery, Center for General, Vascular, Thoracic and Visceral Surgery, Protestant Hospital of Bethel Foundation, University Hospital OWL, Campus Bielefeld Bethel, University of Bielefeld, Bielefeld, Germany; 2The New European Surgical Academy (NESA), Berlin, Germany; 3Department of Urology, Center for Computer-Assisted and Robotic Urology, Protestant Hospital of Bethel Foundation, University Hospital OWL, Campus Bielefeld Bethel, University of Bielefeld, Bielefeld, Germany; 4Department of Psychiatry and Psychotherapy, Section Gerontopsychiatry, Protestant Hospital of Bethel Foundation, University Hospital OWL, Campus Bielefeld Bethel, University of Bielefeld, Bielefeld, Germany; 5Department of Internal Medicine and Gastroenterology, Protestant Hospital of Bethel Foundation, University Hospital OWL, Campus Bielefeld Bethel, University of Bielefeld, Bielefeld, Germany&ast;These authors contributed equally to this workCorrespondence: Tahar Benhidjeb, Department of General and Visceral Surgery, Center for General, Vascular, Thoracic and Visceral Surgery, Protestant Hospital of Bethel Foundation, University Hospital OWL, Campus Bielefeld Bethel, University of Bielefeld, Schildescher Str. 99, Bielefeld, 33611, Germany, Email tahar.benhidjeb@yahoo.de; tahar.benhidjeb@evkb.deIntroduction: Despite that NOTES produces at least matchable clinical long-term results when compared to laparoscopy, still a restraint within the medical community and among patients is evident. Consequently, it might be meaningful to evaluate factors of patient’s NOTES perception to promote its acceptance. NOTES is still quite novel and questionnaires regarding its perception by the public is still lacking even so in the Middle East. Aim of our survey is to investigate the viewpoint of female healthcare staff on NOTES.Materials and Methods: A total of 350 questionnaires along with written information about Minimally Invasive Surgery and NOTES were distributed among the female staff in a Tertiary-care Hospital in Abu Dhabi, 257 were returned completely anonymously and voluntarily and entered into a database with a response rate of 73%. We surveyed factors like religion, medical background, age as well as history of previous laparoscopy, endoscopy, birth and other aspects that may impact a woman’s perception of both transgastric and transvaginal NOTES for cholecystectomy and ovariectomy, respectively.Results: Univariate analyses revealed the majority of Muslim women to be more receptive to NOTES as a choice of surgical technique for cholecystectomy and for ovariectomy, respectively, when compared to Christians and Hindus. However, when compared to Muslims, Christian and Hindu groups had a larger share of medical professions. Women with a medical background would opt significantly less for NOTES. Among younger women, NOTES cholecystectomy was refused due to anxiety concerning future pregnancies and sexual dysfunction. Multinomial logistic regression analysis determined medical background and with independent predictive value for the overall choice of interventional technique (p< 0.001). Marital status played a significant role only in the comparison of laparoscopy vs transgastric NOTES when performing cholecystectomy and ovariectomy (p< 0.01).Conclusion: In this first study emanating from the Middle East, medical education and partly life stage rather than cross-cultural differences seem to influence NOTES perception in women.Keywords: natural orifice translumenal endoscopic surgery, perception, Arab female

The liver as the largest organ in the human body is composed of a complex macroscopic and microscopic architecture that supports its indispensable function to maintain physiological homeostasis. Optical imaging of the human liver is particularly challenging because of the need to cover length scales across 7 orders of magnitude (from the centimeter scale to the nanometer scale) in order to fully assess the ultrastructure of the entire organ down to the subcellular scale and probe its physiological function. This task becomes even more challenging the deeper within the organ one hopes to image, because of the strong absorption and scattering of visible light by the liver. Here, we demonstrate how optical imaging methods utilizing highly specific fluorescent labels, as well as label-free optical methods can seamlessly cover this entire size range in excised, fixed human liver tissue and we exemplify this by reconstructing the biliary tree in three-dimensional space. Imaging of tissue beyond approximately 0.5 mm length requires optical clearing of the human liver. We present the successful use of optical projection tomography and light-sheet fluorescence microscopy to derive information about the liver architecture on the millimeter scale. The intermediate size range is covered using label-free structural and chemically sensitive methods, such as second harmonic generation and coherent anti-Stokes Raman scattering microscopy. Laser-scanning confocal microscopy extends the resolution to the nanoscale, allowing us to ultimately image individual liver sinusoidal endothelial cells and their fenestrations by super-resolution structured illumination microscopy. This allowed us to visualize the human hepatobiliary system in 3D down to the cellular level, which indicates that reticular biliary networks communicate with portal bile ducts via single or a few ductuli. Non-linear optical microscopy enabled us to identify fibrotic regions extending from the portal field to the parenchyma, along with microvesicular steatosis in liver biopsies from an older patient. Lastly, super-resolution microscopy allowed us to visualize and determine the size distribution of fenestrations in human liver sinusoidal endothelial cells for the first time under aqueous conditions. Thus, this proof-of-concept study allows us to demonstrate, how, in combination, these techniques open up a new chapter in liver biopsy analysis.

Structured illumination microscopy (SIM) is a fast and gentle super-resolution fluorescence imaging technique, featuring live-cell compatible excitation light levels and high imaging speeds. To achieve SIM, spatial modulation of the fluorescence excitation light is employed. This is typically achieved by interfering coherent laser beams in the sample plane, which are often created by spatial light modulators (SLMs). Digital micromirror devices (DMDs) are a form of SLMs with certain advantages, such as high speed, low cost and wide availability, which present certain hurdles in their implementation, mainly the blazed grating effect caused by the jagged surface structure of the tilted mirrors. Recent works have studied this effect through modelling, simulations and experiments, and laid out possible implementations of multi-color SIM imaging based on DMDs. Here, we present an implementation of a dual-color DMD based SIM microscope using temperature-controlled wavelength matching. By carefully controlling the output wavelength of a diode laser by temperature, we can tune two laser wavelengths in such a way that no opto-mechanical realignment of the SIM setup is necessary when switching between both wavelengths. This reduces system complexity and increases imaging speed. With measurements on nano-bead reference samples, as well as the actin skeleton and membrane of fixed U2OS cells, we demonstrate the capabilities of the setup. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

BackgroundDiaphragmatic lesions as a result from blunt or penetrating trauma are challenging to detect in the initial trauma setting. This is especially true when diaphragmatic trauma is part of a polytrauma. Complications of undetected diaphragmatic defects with incarcerating bowel are rare but as in our patient can be serious. Case presentationA 57-year-old female presented to the Emergency Room of our Hospital in a critical condition with 3 days of increasing abdominal pain. The initial clinical examination showed peritonism with tinkling peristaltic bowel sounds of mechanical obstruction. A thoraco-abdominal CT-scan demonstrated colon prolapsed through the left diaphragmatic center with a large sero-pneumothorax under tension. As the patient was hemodynamically increasingly unstable with developing septic shock an emergency laparotomy was performed. After retraction of the left colon, which had herniated through a defect of the tendinous center of the left diaphragm and was perforated due to transmural ischemia, large amounts of feces and gas discharged from the left thorax. A left hemicolectomy resulting in a Hartmann type procedure was performed. A fully established pleural empyema required meticulous debridement and lavage conducted via the 7-10cm in diameter phrenic opening followed by a diaphragmatic defect reconstruction. Due to pneumonia and recurring pleural empyema redo-debridement of the left pleural space via thoracotomy were required. The patient was discharged on day 56. A thorough history of possible trauma revealed a bicycle-fall-trauma 7 months prior to this hospitalization with a surgically stabilized fracture of the left femur and conservatively treated fractures of ribs 3-9 on the left side. ConclusionThis is the first report on a primarily established empyema at the time of first surgical intervention for faeco-pneumothorax secondary to delayed diagnosed diaphragmatic rupture following abdomino-thoracic blunt trauma with colic perforation into the pleural space, requiring repetitive surgical debridement in order to control local and systemic sepsis. Thorough investigation should always be undertaken in cases of blunt abdominal and thoracic trauma to exclude diaphragmatic injury in order to avoid post traumatic complications.

Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial&ndash, mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (NMYC) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.

We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

Einleitung: Bei Nachweis kolorektaler Lebermetastasen besteht die einzige potentiell kurative Therapieoptionen unverändert in der operativen Therapie. Aufgrund des häufig sehr unterschiedlichen Metastasierungsausmaßes, stellen diese Patienten jedoch eine ausgesprochen heterogene Subgruppe[for full text, please go to the a.m. URL], 131. Kongress der Deutschen Gesellschaft für Chirurgie