Hepatic adrenal rest tumor in a patient with multifactorial liver cirrhosis: a case report with CT and MRI findings and pathologic correlation

AbstractBackgroundAdrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver.Case presentationAn 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient's postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver.ConclusionsHepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery

Significance of Serum Oxidative and Antioxidative Status in Congenital Central Hypoventilation Syndrome (CCHS) Patients

Congenital central hypoventilation syndrome (CCHS) is a rare neurological genetic disorder that affects sleep-related respiratory control. Currently, no drug therapy is available. In light of this, there is a need for lifelong ventilation support, at least during sleep, for these patients. The pathogenesis of several chronic diseases is influenced by oxidative stress. Thus, determining oxidative stress in CCHS may indicate further disorders in the course of this rare genetic disease. Liquid biopsies are widely used to assess circulating biomarkers of oxidative stress. In this study, ferric reducing ability of plasma, thiobarbituric acid-reactive substances, advanced oxidation protein products (AOPPs), and advanced glycation end-products were measured in the serum of CCHS patients to investigate the relationship between oxidative stress and CCHS and the significance of this balance in CCHS. Here, AOPPs were found to be the most relevant serum biomarker to monitor oxidative stress in CCHS patients. According to this communication, CCHS patients may suffer from other chronic pathophysiological processes because of the persistent levels of AOPPs

Structure of the myenteric plexus in normal and diseased human ileum analyzed by X-ray virtual histology slices

BACKGROUND The enteric nervous system (ENS) is situated along the entire gastrointestinal tract and is divided into myenteric and submucosal plexuses in the small and large intestines. The ENS consists of neurons, glial cells, and nerves assembled into ganglia, surrounded by telocytes, interstitial cells of Cajal, and connective tissue. Owing to the complex spatial organization of several interconnections with nerve fascicles, the ENS is difficult to examine in conventional histological sections of 3-5 μm. AIM To examine human ileum full-thickness biopsies using X-ray phase-contrast nanotomography without prior staining to visualize the ENS. METHODS Six patients were diagnosed with gastrointestinal dysmotility and neuropathy based on routine clinical and histopathological examinations. As controls, full-thickness biopsies were collected from healthy resection ileal regions after hemicolectomy for right colon malignancy. From the paraffin blocks, 4-µm thick sections were prepared and stained with hematoxylin and eosin for localization of the myenteric ganglia under a light microscope. A 1-mm punch biopsy (up to 1 cm in length) centered on the myenteric plexus was taken and placed into a Kapton® tube for mounting in the subsequent investigation. X-ray phase-contrast tomography was performed using two custom-designed laboratory setups with micrometer resolution for overview scanning. Subsequently, selected regions of interest were scanned at a synchrotron-based end-station, and high-resolution slices were reported. In total, more than 6000 virtual slices were analyzed from nine samples. RESULTS In the overview scans, the general architecture and quality of the samples were studied, and the myenteric plexus was localized. High-resolution scans revealed details, including the ganglia, interganglional nerve fascicles, and surrounding tissue. The ganglia were irregular in shape and contained neurons and glial cells. Spindle-shaped cells with very thin cellular projections could be observed on the surface of the ganglia, which appeared to build a network. In the patients, there were no alterations in the general architecture of the myenteric ganglia. Nevertheless, several pathological changes were observed, including vacuolar degeneration, autophagic activity, the appearance of sequestosomes, chromatolysis, and apoptosis. Furthermore, possible expulsion of pyknotic neurons and defects in the covering cellular network could be observed in serial slices. These changes partly corresponded to previous light microscopy findings. CONCLUSION The analysis of serial virtual slices could provide new information that cannot be obtained by classical light microscopy. The advantages, disadvantages, and future possibilities of this method are also discussed

Structure of the myenteric plexus in normal and diseased human ileum analyzed by X-ray virtual histology slices

BACKGROUNDThe enteric nervous system (ENS) is situated along the entire gastrointestinal tract and is divided into myenteric and submucosal plexuses in the small and large intestines. The ENS consists of neurons, glial cells, and nerves assembled into ganglia, surrounded by telocytes, interstitial cells of Cajal, and connective tissue. Owing to the complex spatial organization of several interconnections with nerve fascicles, the ENS is difficult to examine in conventional histological sections of 3-5 μm.AIMTo examine human ileum full-thickness biopsies using X-ray phase-contrast nanotomography without prior staining to visualize the ENS.METHODSSix patients were diagnosed with gastrointestinal dysmotility and neuropathy based on routine clinical and histopathological examinations. As controls, full-thickness biopsies were collected from healthy resection ileal regions after hemicolectomy for right colon malignancy. From the paraffin blocks, 4-µm thick sections were prepared and stained with hematoxylin and eosin for localization of the myenteric ganglia under a light microscope. A 1-mm punch biopsy (up to 1 cm in length) centered on the myenteric plexus was taken and placed into a Kapton® tube for mounting in the subsequent investigation. X-ray phase-contrast tomography was performed using two custom-designed laboratory setups with micrometer resolution for overview scanning. Subsequently, selected regions of interest were scanned at a synchrotron-based end-station, and high-resolution slices were reported. In total, more than 6000 virtual slices were analyzed from nine samples.RESULTSIn the overview scans, the general architecture and quality of the samples were studied, and the myenteric plexus was localized. High-resolution scans revealed details, including the ganglia, interganglional nerve fascicles, and surrounding tissue. The ganglia were irregular in shape and contained neurons and glial cells. Spindle-shaped cells with very thin cellular projections could be observed on the surface of the ganglia, which appeared to build a network. In the patients, there were no alterations in the general architecture of the myenteric ganglia. Nevertheless, several pathological changes were observed, including vacuolar degeneration, autophagic activity, the appearance of sequestosomes, chromatolysis, and apoptosis. Furthermore, possible expulsion of pyknotic neurons and defects in the covering cellular network could be observed in serial slices. These changes partly corresponded to previous light microscopy findings.CONCLUSIONThe analysis of serial virtual slices could provide new information that cannot be obtained by classical light microscopy. The advantages, disadvantages, and future possibilities of this method are also discussed

Inter-hospital cardiorespiratory telemonitoring of newborns and infants: a wellworking example of a hub and spoke network

Abstract Background Patients who experience cardiorespiratory events usually have to be moved to specialized centers to perform cardiorespiratory studies. To avoid the transfer of these patients to specialized centers, a network has been created based on an interchange system, where the recordings were uploaded in unspecialized centers (spokes) and downloaded by the Sleep Disorders Breathing (SDB) Center (hub) to be analyzed. Methods The inter-hospital network was established in November 2008. Initially only 3 non-tertiary hospitals in the Tuscany Region joined the network. Currently, 12 Tuscany hospitals are included. Results From November 2008 to December 2020, 625 recordings were collected belonging to 422 infants. No recurrent life-threatening episode or infant death occurred in the study population and none of the infants needed to be readmitted or be moved to a tertiary center, except infants who underwent home monitoring. The discharge diagnoses belong to the following categories: apnoea, respiratory problem of the newborn, syncope, gastroesophageal reflux, altered consciousness, transient loss of consciousness and cyanosis. Conclusions This study shows that the inter-hospital network is an efficient system that allows accurate and safe management of infants at risk for apnoea, bradycardia, and hypoxemia to remain in unspecialized centers, avoiding unnecessary transfers of patients and over – hospitalizations

3d phase‐contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects

Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. Results: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. Conclusions: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction

3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects

Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. Results: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. Conclusions: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction

Urinary Biomarkers as a Proxy for Congenital Central Hypoventilation Syndrome Patient Follow-Up

Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system and in particular of the respiratory control during sleep. No drug therapy is, to date, available; therefore, the survival of these patients depends on lifelong ventilatory support during sleep. Reactive oxygen species (ROS)-induced oxidative stress is a recognized risk factor involved in the pathogenesis of several chronic diseases. Therefore, monitoring systemic oxidative stress could provide important insights into CCHS outcomes. Because ROS-induced oxidative products are excreted as stable metabolites in urine, we performed an HPLC-MS/MS analysis for the quantitative determination of the three main representative oxidative biomarkers (i.e., diY, MDA, and 8-OHdG) in the urine of CCHS patients. Higher levels of urinary MDA were found in CCHS patients compared with age-matched control subjects. The noteworthy finding is the identification of urinary MDA as relevant biomarker of systemic oxidative status in CCHS patients. This study is a concise and smart communication about the impact that oxidative stress has in CCHS, and suggests the monitoring of urinary MDA levels as a useful tool for the management of these patients

Evaluation of the enteric nervous system by three-dimensional holographic imaging in x-ray phase contrast nanotomography

IntroductionThe enteric nervous system (ENS) in dysmotility has been studied by classical light microscopy including immunohistochemistry. However, the procedure is rather time-consuming and only small components of the ENS in two dimensions can be analyzed. Novel x-ray imaging techniques, employed in this study, allow to obtain high-resolution three-dimensional scans of soft biological tissue over a longer segment with an overview of interganglionar neural connections, and different intraganglionar cell types, which would normally show no contrast with standard x-ray absorption microtomography.Aims & Methods. The aim of the present study was to evaluate the ENS in a three-dimensional manner, to get a more complete architecture of the neural tissue in sickness and health. Full-thickness biopsies of ileum from a patient with Ehler-Danlos syndrome and secondary severe gastrointestinal dysmotility and from a healthy resection border of proximal colon due to resection of the colonic carcinoma were embedded in paraffin and sectioned. Representative areas of the ENS with presence of myenteric ganglia were identified in H&E stained microscopic sections. By a 1-mm punch, a biopsy was extracted from the paraffin block and put into a plastic tube. The samples were scanned, without any further preparation, in two different tomography instruments developed at the Institute for X-ray Physics of Georg-August-Universität, Göttingen [1]. The first instrument, a laboratory setup, allowed to image the whole 1-mm sample with a ~1mm effective voxel size, enabling an identification of the neural tissue structure. Selected regions of interest were then scanned in the second instrument, synchrotron based (GINI-X, P10, DESY, Hamburg), which allows to image regions of 320x320x320 mm3 with an effective voxel size of 176 nm. At this resolution, individual cells inside the ganglia can be distinguished.From the coarser-resolution tomographic scans, the neural tissue structure has been extracted with semi-automatic segmentation methods. Preliminary digital quantification of the volume of the neural tissue over total biopsy volume was performed from the segmented volumes. A more-in-depth digital analysis, currently in progress, will allow to measure parameters such as the length and average diameter of the ganglia.ResultsThe myenteric ganglia from the control were normal regarding both size and cellularity. Neurons and glia cells could be recognized. Between the ganglia, the nerve-bundles were thick and sharply demarcated. In contrast, the ganglia from the patient were smaller and the interganglional nerves were uneven/irregular with alternating thin and “small nodular” regions. Preliminary digital quantification showed that the ratio of neural tissue volume over total biopsy volume in the patient (0.9%) was significantly diminished compared to the control (7.3%). ConclusionThree-dimensional nanotomography may be a useful tool and can give valuable information on the changes of the size and interganglionar neural connections of the ENS in dysmotility diseases which cannot be obtained/received by classical methods.References[1] Töpperwien, M., van der Meer, F., Stadelmann, C. and Salditt, T., 2018. Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography. Proceedings of the National Academy of Sciences, 115(27), pp.6940-6945