High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy.

Colonoscopy and endoscopic ultrasound play pivotal roles in the assessment of rectal diseases, especially rectal cancer and inflammatory bowel diseases. Optical coherence tomography (OCT) offers a superior depth resolution, which is a critical factor for individualizing the therapeutic concept and evaluating the therapy response. We developed two distinct rectoscope prototypes, which were integrated into a 1300 nm MHz-OCT system constructed at our facility. The rapid rotation of the distal scanning probe at 40,000 revolutions per minute facilitates a 667 Hz OCT frame rate, enabling real-time endoscopic imaging of large areas. The performance of these OCT-rectoscopes was assessed in an ex vivo porcine colon and a post mortem human in-situ colon. The OCT-rectoscope consistently distinguished various layers of the intestinal wall, identified gut-associated lymphatic tissue, and visualized a rectal polyp during the imaging procedure with 3D-reconstruction in real time. Subsequent histological examination confirmed these findings. The body donor was preserved using an ethanol-glycerol-lysoformin-based technique for true-to-life tissue consistency. We could demonstrate that the novel MHZ-OCT-rectoscope effectively discriminates rectal wall layers and crucial tissue characteristics in a post mortem human colon in-situ. This real-time-3D-OCT holds promise as a valuable future diagnostic tool for assessing disease state and therapy response on-site in rectal diseases.

Localization Pattern of Dispatched Homolog 2 (DISP2) in the Central and Enteric Nervous System.

Dispatched homolog (DISP) proteins have been implicated in the regulation of hedgehog signaling during embryologic development. Although DISP2 has recently been associated with neuronal development and control of cognitive functions, its localization pattern in the mammalian central and peripheral nervous system has not yet been investigated. In this study, the Disp2 expression profile was assessed in human tissues from publicly available transcriptomic datasets. The DISP2 localization pattern was further characterized in the human and rat central nervous system (CNS), as well as within the colonic enteric nervous system (ENS) using dual-label immunohistochemistry. Colocalization of DISP2 with neuronal and glial markers was additionally analyzed in murine primary ENS culture. At transcriptomic level, DISP2 expression was predominant in neuronal cell types of the CNS and ENS. DISP2 immunoreactivity was mainly located within PGP9.5-positive neurons rather than in S100-positive glial cells throughout the nervous system. Investigation of human and rat brain tissues, colonic specimens, and murine ENS primary cultures revealed that DISP2 was located in neuronal cell somata, as well as along neuronal processes both in the human and murine CNS and ENS. Our results indicate that DISP2 is prominently localized within neuronal cells of the CNS and ENS and support putative functions of DISP2 in these tissues.

Beyond Total Mesorectal Excision: Compartment-based Anatomy of the Pelvis Revisited for Exenterative Pelvic Surgery.

OBJECTIVE: Magnetic resonance imaging-based subdivision of the pelvis into 7 compartments has been proposed for pelvic exenteration. The aim of the present anatomical study was to describe the topographic anatomy of these compartments and define relevant landmarks and surgical dissection planes. BACKGROUND: Pelvic anatomy as it relates to exenterative surgery is complex. Demonstration of the topographic peculiarities of the pelvis based on the operative situs is hindered by the inaccessibility of the small pelvis and the tumor bulk itself. MATERIALS AND METHODS: Thirteen formalin-fixed pelvic specimens were meticulously dissected according to predefined pelvic compartments. Pelvic exenteration was simulated and illustrated in a stepwise manner. Different access routes were used for optimal demonstration of the regions of interest. RESULTS: All the 7 compartments (peritoneal reflection, anterior above peritoneal reflection, anterior below peritoneal reflection, central, posterior, lateral, inferior) were investigated systematically. The topography of the pelvic fasciae and ligaments; vessels and nerves of the bladder, prostate, uterus, and vagina; the internal iliac artery and vein; the course of the ureter, somatic (obturator nerve, sacral plexus), and autonomic pelvic nerves (inferior hypogastric plexus); pelvic sidewall and floor, ischioanal fossa; and relevant structures for sacrectomy were demonstrated. CONCLUSIONS: A systematic approach to pelvic anatomy according to the 7 magnetic resonance imaging-defined compartments clearly revealed crucial anatomical landmarks and key structures facilitating pelvic exenterative surgery. Compartment-based pelvic anatomy proved to be a sound concept for beyond TME surgery and provides a basis for tailored resection procedures.

The retrocolic fascial system revisited for right hemicolectomy with complete mesocolic excision based on anatomical terminology: do we need the eponyms Toldt, Gerota, Fredet and Treitz?

AIM: Right hemicolectomy with complete mesocolic excision (CME) requires the removal of an intact mesocolic envelope. The study aimed to determine, on the basis of macroscopic and microscopic anatomical studies, the optimal surgical dissection planes for CME to preserve fascial integrity. Unequivocal anatomical nomenclature was applied to describe the retrocolic fascial system and compared to frequently used eponyms (Toldt, Gerota, Fredet, Treitz). METHOD: Stepwise macroscopic dissections, cross-section studies and histological analysis were performed on body donors to identify the components of the retrocolic fascial system. Based on these anatomical findings, the optimal surgical dissection planes for CME were validated in laparoscopic training courses on body donors and in robot-assisted surgical procedures in patients. RESULTS: The mesocolic tissue and lymphovascular pedicles were enveloped by the ventral and dorsal mesocolic leaf (mesocolic fascia). The mesocolic fascia was attached to the parietal peritoneal fascia ('fascia of Toldt') along the parieto-mesocolic interface, and further cranially to the pre-duodenopancreatic fascia along the mesocolic-duodenopancreatic interface ('space of Fredet'). Dorsally, the parietal peritoneal fascia was separated from the anterior renal fascia ('fascia of Gerota') by the parieto-renal interface. Dissection along this interface in front of the anterior renal fascia followed by incision of the parietal peritoneal fascia at the duodenal border and opening the mesocolic-duodenopancreatic interface yielded the best macroscopic appearance of specimens and was considered optimal for CME. CONCLUSION: The retrocolic fascial system as well as the surgical dissection planes for CME can be described by clearly defined anatomical terms rather than potentially confusing eponyms.

Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, are routinely used as antidiabetic drugs. Recent studies indicate that beside its beneficial effects on blood glucose level, empagliflozin may also exert vascular anti-inflammatory and neuroprotective properties. In the brain, microglia are crucial mediators of inflammation, and neuroinflammation plays a key role in neurodegenerative disorders. Dampening microglia-mediated inflammation may slow down disease progression. In this context, we investigated the immunomodulatory effect of empagliflozin on activated primary microglia. As a validated experimental model, rat primary microglial cells were activated into a pro-inflammatory state by stimulation with LPS. The influence of empagliflozin on the expression of pro-inflammatory mediators (NO, Nos2, IL6, TNF, IL1B) and on the anti-inflammatory mediator IL10 was assessed using quantitative PCR and ELISA. Further, we investigated changes in the activation of the ERK1/2 cascade by Western blot and NFkB translocation by immunostaining. We observed that empagliflozin reduces the expression of pro- and anti-inflammatory mediators in LPS-activated primary microglia. These effects might be mediated by NHE-1, rather than by SGLT2, and by the further inhibition of the ERK1/2 and NFkB pathways. Our results support putative anti-inflammatory effects of empagliflozin on microglia and suggest that SGLT2 inhibitors may exert beneficial effects in neurodegenerative disorders.

Anti-inflammatory properties of Honokiol in activated primary microglia and astrocytes.

Honokiol has been used in traditional medicine for the treatment of inflammatory diseases. Activation of glial cells plays an essential role in neurodegenerative disorders. In this study, we show that Honokiol reduces the inflammatory response to LPS of primary cultures of microglia and astrocytes through the inhibition of pro-inflammatory mediators (iNOS, IL-6, IL-1ß and TNF-α) and the simultaneous stimulation of anti-inflammatory cytokines (IL-10). Expression of KLF4 was induced in microglia and astrocytes after treatment with LPS and this response was mitigated by Honokiol. These findings extend our understanding of the anti-inflammatory properties of Honokiol on central glial cells and support its use as a therapeutic compound in neuroinflammatory disorders.