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Background: Arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis patients. A correct microsurgical vascular anastomoses is essential to the optimal care of patients. Loupes can help surgeons perform such procedures, but often cause neck or back pain and fatigue. Aim: This study aimed to evaluate whether a video telescopic operating microscope (VITOM®; Karl Storz Endoscopy GmbH, Tuttlingen, Germany) could be used as a substitute for loupes to create microsurgical vascular anastomoses. Methods: We evaluated microsurgical anastomoses with VITOM® in 10 patients (6 male, 4 female) from January 2019 to December 2019. The created anastomoses were 7 side-to-side, 2 side-to-end and 1 end-to-end. Results: A valid thrill was always present on palpation. Surgical procedures had an average time of 87.6 min, ranging from 49 to 110 min. Eight patients had AVF maturation; in the remaining 2, one had a thrombosis after 25 days and one couldn’t be dialyzed due to low flow in AVF. Conclusions: The VITOM® system makes it possible to carry out anastomosis in difficult cases. It is both safe and useful for the training of young surgeons.

Cancer is a disease resulting from aberrant communication between cells of a multicellular organism. The glycan coat that surrounds the cells is an important player in cellular communication. While altered cell surface glycans are known biomarkers for cancer, glycan biosynthesis itself has not been considered a potential oncogenic pathway. So, to understand the oncogenic potential of the glycan biosynthetic pathways we have analyzed the copy number alterations (CNA) of genes encoding for glycosylation regulators (glycogenes) in cancer genome datasets and identify novel glyco-oncogenes and glyco-tumor suppressor genes (TSGs). CNA of oncogenes and TSGs is an important cancer-associated genetic alteration that associates with worst prognosis. Nevertheless, identity of the driver genes in the copy number altered segments of the genome remains obscure in most cases. We developed a prioritization pipeline based on bioinformatic and experimental criteria to identify putative driver genes. In addition to correctly identifying several well-established oncogenes/TSGs, this pipeline discerns several novel oncogenes and TSGs, some of which are glycogenes. Further, among glyco-oncogenes there is an enrichment for glycosphingolipid biosynthetic pathway and trans-Golgi associated lysosomal sorting machinery and among glyco-TSGs there is an enrichment for early N-glycan biosynthetic enzymes. As a proof-of-principle we show that one of the identified glycooncogene B4GALT5, encoding a key enzyme in the glycosphingolipid pathway exhibits oncogenic property of promoting increased growth of hepatocellular carcinoma cells. Thus, this study identifies glycosylation pathways with oncoregulatory properties and opens up a new group of enzymes as potential therapeutic targets for cancer.

Bleedings occurring during a surgical intervention can be caused by haemostatic defects, but they are generally due to ineffective local haemostasis. Current coagulation systems may not be sufficient to achieve a good haemostasis, causing, at the same time, tissue dama-ge. Furthermore, the availability of such devices does not eliminate difficulties linked to the isolation of vessels, a crucial step of surgical procedures that require the removal of an organ or part of it, in case of inflammation or neoplasm. This difficulty is even more evident, and weighs more on operative times, when the surgeon engages with video-assisted surgery, where anatomical structures are difficult to detect and the manoeuvres of dissection and separation become more complex. The use of pre-operative radio-guided embolization of organ main arterial vessels with different embolic agents, could represent a great advantage, especially for mini-invasive procedures, such as laparoscopy in patients with high bleeding risk.

Introduction. Haemorrhoids are a very common disease, with a great economic burden. Many treatments have been developed for trying to solve the problem, being the standard not yet found. In 1995, Doppler-guided haemorrhoidal artery ligation was introduced, aiming to reduce postoperative pain and complications. In this work, an evolution of the aforementioned surgical technique was described. Materials and Methods.183 patients treated with standard Doppler-Guided Haemorrhoidal Artery Ligation were statistically compared with 225 patients dealt with Colour Doppler-Guided Haemorrhoidal Artery Ligation. The procedures were performed under local anaesthesia with patients in lithotomy position. A special proctoscope and a dedicated Colourdoppler US probe were employed in the second group. Superior haemorrhoidal artery terminal branches were consecutively ligated according to provided technique in the first group and under vision in the second. In all cases, each ligation was followed by mucopexy. Results. No significant differences between the two groups, in terms of post-operative pain, early complications (bleeding, urinary retention, incontinence) or patient satisfaction, were demonstrated. Recurrence rate was significantly higher in patients treated with standard DG-HAL. No late complications (after one-year follow-up) were registered in both groups. Conclusions. Colour Doppler-Guided Haemorrhoidal Artery Ligation represents an ideal management for 1-day surgery, and fulfils the requirements of minimally invasive surgery in patients with III-IV grade haemorrhoids. The absence of complications and the evidence of significant wellness of patients are the best advantages. Colour Doppler-Guided Haemorrhoidal Artery Ligation is a safe and easy procedure with good results and a very short-time training. It could be considered an easy and reliable method to treat symptomatic haemorrhoids.

Background: Shp1, a tyrosine-phosphatase-1 containing the Src-homology 2 (SH2) domain, is involved in inflammatory and immune reactions, where it regulates diverse signalling pathways, usually by limiting cell responses through dephosphorylation of target molecules. Moreover, Shp1 regulates actin dynamics. One Shp1 target is Src, which controls many cellular functions including actin dynamics. Src has been previously shown to be activated by a signalling cascade initiated by the cytosolic-phospholipase A2 (cPLA2) metabolite glycerophosphoinositol 4-phosphate (GroPIns4P), which enhances actin polymerisation and motility. While the signalling cascade downstream Src has been fully defined, the mechanism by which GroPIns4P activates Src remains unknown. Methods: Affinity chromatography, mass spectrometry and co-immunoprecipitation studies were employed to identify the GroPIns4P-interactors; among these Shp1 was selected for further analysis. The specific Shp1 residues interacting with GroPIns4P were revealed by NMR and validated by site-directed mutagenesis and biophysical methods such as circular dichroism, isothermal calorimetry, fluorescence spectroscopy, surface plasmon resonance and computational modelling. Morphological and motility assays were performed in NIH3T3 fibroblasts. Results: We find that Shp1 is the direct cellular target of GroPIns4P. GroPIns4P directly binds to the Shp1-SH2 domain region (with the crucial residues being Ser 118, Arg 138 and Ser 140) and thereby promotes the association between Shp1 and Src, and the dephosphorylation of the Src-inhibitory phosphotyrosine in position 530, resulting in Src activation. As a consequence, fibroblast cells exposed to GroPIns4P show significantly enhanced wound healing capability, indicating that GroPIns4P has a stimulatory role to activate fibroblast migration. GroPIns4P is produced by cPLA2 upon stimulation by diverse receptors, including the EGF receptor. Indeed, endogenously-produced GroPIns4P was shown to mediate the EGF-induced cell motility. Conclusions: This study identifies a so-far undescribed mechanism of Shp1/Src modulation that promotes cell motility and that is dependent on the cPLA2 metabolite GroPIns4P. We show that GroPIns4P is required for EGF-induced fibroblast migration and that it is part of a cPLA2/GroPIns4P/Shp1/Src cascade that might have broad implications for studies of immune-inflammatory response and cancer. [Figure not available: see fulltext.]

Magnetron-based marine radar technology is mature, affordable, reliable, and very effective for maritime safety applications. Commercial systems may be procured at a modest cost as compared to fully coherent solid-state systems. Magnetron oscillators inherently generate random phase signals. Phase instability on a pulse-to-pulse basis impedes this class of marine radars from success in applications requiring coherency such as moving target indication (MTI) or in generating target imagery. This limitation may be overcome by incorporating radio frequency sampling and cross-correlation of the transmit and receive signal technology to augment the current capability of available systems. In this research, the pulse train on transmit and receive is correlated in order to reject interference and detect image targets. Sampling the transmit signal and target echo on receive permits fully coherent processing. Marine radars traditionally operate non-coherently, and as such, offer limited surveillance in clutter rich environments. In this study, the authors report on a non-coherent marine radar that has been modified to produce a pseudo-coherent or coherent-on-receive sensor system. This is crucial to MTI and target image formation. In laboratory experiments, they employed a magnetron oscillator-based system to generate an inverse synthetic aperture radar image. The image was formed using four different algorithms: filtered back-projection (FBP), time domain back-projection (TDBP), an algebraic reconstruction technique, and frequency domain back-projection. In their research, TDBP produces exquisite imagery of steel rods, and it is the standard developed in this study. FBP performed poorly as compared to all other algorithms.

To date, the exact pathophysiology of haemorrhoids is poorly understood. The different philosophies on haemorrhoids aetiology may lead to different approaches of treatment. A pathogenic theory involving a correlation between altered anal canal microflora, local inflammation, and muscular dyssynergia is proposed through an extensive review of the literature. Since the middle of the twentieth century, three main theories exist: (1) the varicose vein theory, (2) the vascular hyperplasia theory, and (3) the concept of a sliding anal lining. These phenomena determine changes in the connective tissue (linked to inflammation), including loss of organization, muscular hypertrophy, fragmentation of the anal subepithelial muscle and the elastin component, and vascular changes, including abnormal venous dilatation and vascular thrombosis. Recent studies have reported a possible involvement of gut microbiota in gut motility alteration. Furthermore, dysbiosis seems to represent the leading cause of bowel mucosa inflammation in any intestinal district. The alteration of the gut microbioma in the anorectal district could be responsible for haemorrhoids and other anorectal disorders. A deeper knowledge of the gut microbiota in anorectal disorders lays the basis for unveiling the roles of these various gut microbiota components in anorectal disorder pathogenesis and being conductive to instructing future therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in anorectal disorders.

Background: Nowadays, the “gold standard” treatment for gallbladder stones is laparoscopic cholecystectomy but the risk of iatrogenic biliary duct injuries is increased compared to “open” surgery. Intraoperative cholangiography (IOC) can be useful to avoid biliary injuries but it can also be a no-safe procedure in center in which it is not routinely performed. Aim and objective: The aim of our study is to trust the efficacy of IOC in a patient with common bile duct (CBD) and gallbladder stones using a biliary-nose tube. Materials and methods: 135 patients with gallbladder and CBD stones were treated with sequential therapy and randomly divided into two groups. Laparoscopic cholecystectomy was performed within 24/48 h. During endoscopic retrograde cholangiopancreatography, a biliary-nose catheter was left to perform cholangiography during the following surgical procedure. Group A had also a cholangiography at the beginning of the surgical procedure in order to evidence biliary duct structure. Results: Cholangiography avoided a lesion of the biliary ducts in nine patients. Only a patient had a residual stone in the CBD. The dissection at Calot’s triangle was faster in group A patients without differences between the surgeons involved. Conclusion: The biliary-nose tube can be useful in patients with gallbladder and CBD who underwent cholecystectomy for different reasons: it lets the surgeon performing IOC faster and without risk linked to the technique used; it reduces the risk of biliary injuries; and surgeons feel more safe and calm during the surgical procedure.

Introduction. Endometriosis has been described as the presence of endometrial tissue outside uterine cavity. Scar endometriosis (SE) is a rare disease reported in 0.03-1.08% of women following gynaecologic surgery. In our retrospective observational cohort study we studied anamnesis, symptoms, surgical procedures and outcomes linked to scar endometriosis in our medical experience from 2004 to 2018. Methods. We reviewed the medical records of 46 patients with a histopathological diagnosis of SE. All patients had a history of at least one previous caesarean section (n=46, 100%). Forty-two patients (91,3%) complained gradually growing nodular abdominal mass near or adjacent to caesarean incision scar, while only 4 patients (8,6%) complained aspecific abdominal pain. Ultrasound scan was performed in all patients (n=46, 100%) and mean size of the nodules at US was 26,8 ± 13,8 mm. Results. All patients underwent surgery. Seven patients (15,2%) needed mesh implantation, while 39 patients (84,8%) underwent local resection with reconstruction of muscle fascia. Mean follow-up was 31,6 ± 14 months and no patients reported local recurrence of disease. Conclusion. high suspicion of scar endometriosis are painful no- dule in the abdominal scar. Wide surgical excision is the treatment of choice.

Significance Proteins are modified by many posttranslational modifications (PTMs) with crucial regulatory functions. A PTM attracting increasing interest is ADP-ribosylation, capable of altering crucial cellular targets. We show that mono-ADP-ribosylation by PARP12 of the protein Golgin-97 regulates transport to the plasma membrane of a specific group of functionally crucial cargo proteins. PARP12 is shown to be part of a regulatory cascade initiated by PKD and involving the direct phosphorylation and activation of PARP12. These events define, through Golgin-97 mono-ADP-ribosylation, a Golgi sorting mechanism for specific basolateral cargoes, including E-cadherin. Defects in this cascade impair E-cadherin transport and formation of cell–cell contacts, with potential consequences for the formation of adherens junctions, polarization of epithelial cells, and development of epithelial–mesenchymal transformation., Adenosine diphosphate (ADP)-ribosylation is a posttranslational modification involved in key regulatory events catalyzed by ADP-ribosyltransferases (ARTs). Substrate identification and localization of the mono-ADP-ribosyltransferase PARP12 at the trans-Golgi network (TGN) hinted at the involvement of ARTs in intracellular traffic. We find that Golgin-97, a TGN protein required for the formation and transport of a specific class of basolateral cargoes (e.g., E-cadherin and vesicular stomatitis virus G protein [VSVG]), is a PARP12 substrate. PARP12 targets an acidic cluster in the Golgin-97 coiled-coil domain essential for function. Its mutation or PARP12 depletion, delays E-cadherin and VSVG export and leads to a defect in carrier fission, hence in transport, with consequent accumulation of cargoes in a trans-Golgi/Rab11–positive intermediate compartment. In contrast, PARP12 does not control the Golgin-245–dependent traffic of cargoes such as tumor necrosis factor alpha (TNFα). Thus, the transport of different basolateral proteins to the plasma membrane is differentially regulated by Golgin-97 mono-ADP-ribosylation by PARP12. This identifies a selective regulatory mechanism acting on the transport of Golgin-97– vs. Golgin-245–dependent cargoes. Of note, PARP12 enzymatic activity, and consequently Golgin-97 mono-ADP-ribosylation, depends on the activation of protein kinase D (PKD) at the TGN during traffic. PARP12 is directly phosphorylated by PKD, and this is essential to stimulate PARP12 catalytic activity. PARP12 is therefore a component of the PKD-driven regulatory cascade that selectively controls a major branch of the basolateral transport pathway. We propose that through this mechanism, PARP12 contributes to the maintenance of E-cadherin–mediated cell polarity and cell–cell junctions.