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Background: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. Methods: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. Results: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17–1.65, P =0.0002) and 1.12 (95% CI: 0.82–1.53, P =0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31–3.33, P =0.002), pancreatic (HR 1.54; 95% CI: 1.21–1.97, P =0.0005) and lung cancer (HR 1.37; 95% CI: 1.08–1.75, P =0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38–0.66, P <0.00001). Conclusions: Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective–retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.

There exists no consensus in the literature regarding the impact of pre-stereotactic radiosurgery (SRS) embolization on obliteration rates and clinical outcome after radiosurgery treatment of intracranial arteriovenous malformations (AVM). We performed a systematic review of four databases and included studies with at least 10 patients evaluating obliteration rates of intracranial AVMs treated with SRS alone (SRS cohort) and combined pre-SRS embolization followed by SRS (E + SRS cohort). Meta-analytic results were pooled together via random-effects models. A total of 43 studies, with 7103 patients, were included in our analysis. Among our included patients, complete obliteration was achieved in 51.5% (964/1871) of patients in the E + SRS cohort as compared to 61.5% (3217/5231) of patients in the SRS cohort. Meta-analysis of the pooled data revealed that obliteration was significantly lower in the E + SRS cohort (pooled OR = 0.64, 95% CI = 0.54–0.75, p  < 0.0001). The use of pre-SRS embolization was significantly associated with lower AVM obliteration rates when compared to treatment with SRS alone. Our analysis seeks to provide a macroscopic insight into the complex interaction between pre-SRS embolization and brain AVM obliteration rates and prognosis. Pre-SRS embolization may still be beneficial in select patients, and further studies are needed to identify patients who benefit from neoadjuvant AVM embolization.

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations.

Background The telemedicine clinic for follow up after minor surgical procedures in general surgery is now ubiquitously considered a standard of care. However, this method of consultation is not the mainstay for preoperative assessment and counselling of patients for common surgical procedures such as laparoscopic cholecystectomy. The aim of this study was to evaluate the safety of assessing and counselling patients in the telemedicine clinic without a physical encounter for laparoscopic cholecystectomy. Methods We conducted a retrospective analysis of patients who were booked for laparoscopic cholecystectomy for benign gallbladder disease via general surgery telemedicine clinics from March 2020 to November 2021. The primary outcome was the cancellation rate on the day of surgery. The secondary outcomes were complication and readmission rates, with Clavein-Dindo grade III or greater deemed clinically significant. We performed a subgroup analysis on the cases cancelled on the day of surgery in an attempt to identify key reasons for cancellation following virtual clinic assessment. Results We identified 206 cases booked for laparoscopic cholecystectomy from telemedicine clinics. 7% of patients had a cancellation on the day of surgery. Only one such cancellation was deemed avoidable as it may have been prevented by a face-to-face assessment. Severe postoperative adverse events (equal to or greater than Clavien-Dindo grade III) were observed in 1% of patients, and required re-intervention. 30-day readmission rate was 11%. Conclusions Our series showed that it is safe and feasible to assess and counsel patients for laparoscopic cholecystectomy remotely with a minimal cancellation rate on the day of operation. Further work is needed to understand the effect of remote consultations on patient satisfaction, its environmental impact, and possible benefits to healthcare economics to support its routine use in general surgery.

Background Iatrogenic bile duct injuries (BDIs) are mostly associated with laparoscopic cholecystectomy but may also occur following gastroduodenal surgery or liver resection. Delayed diagnosis of type of injury with an ongoing biliary leak as well as the management in a non-specialized general surgical units are still the main factors affecting the outcome. Case presentation Herein we present three types of BDIs (Bismuth type I, IV and V) following three different types of upper abdominal surgery, ie. Billroth II gastric resection, laparoscopic cholecystectomy and left hepatectomy. All of them were complex injuries with complete bile duct transections necessitating surgical treatment. All were also very difficult to treat mainly because of a delayed diagnosis of type of injury, associated biliary leak and as a consequence severe inflammatory changes within the liver hilum. The treatment was carried out in our specialist hepatobiliary unit and first focused on infection and inflammation control with adequate biliary drainage. This was followed by a delayed surgical repair with the technique which had to be tailored to the type of injury in each case. Conclusion We emphasize that staged and individualized treatment strategy is often necessary in case of a delayed diagnosis of complex BDIs presenting with a biliary leak, inflammatory intraabdominal changes and infection. Referral of such patients to expert hepatobiliary centres is crucial for the outcome.

Background:Accumulating evidence implicates the tumour stroma as an important determinant of cancer progression but the protein constituents relevant for this effect are unknown. Here we utilised a bioinformatics approach to identify an extracellular matrix (ECM) gene signature overexpressed in multiple cancer types and strongly predictive of adverse outcome.Methods:Gene expression levels in cancers were determined using Oncomine. Geneset enrichment analysis was performed using the Broad Institute desktop application. Survival analysis was performed using KM plotter. Survival data were generated from publically available genesets.Results:We analysed ECM genes significantly upregulated across a large cohort of patients with ovarian, lung, gastric and colon cancers and defined a signature of nine commonly upregulated genes. Each of these nine genes was considerably overexpressed in all the cancers studied, and cumulatively, their expression was associated with poor prognosis across all data sets. Further, the gene signature expression was associated with enrichment of genes governing processes linked to poor prognosis, such as EMT, angiogenesis, hypoxia, and inflammation.Conclusions:Here we identify a nine-gene ECM signature, which strongly predicts outcome across multiple cancer types and can be used for prognostication after validation in prospective cancer cohorts.

A growing proportion of percutaneous procedures are performed in outpatient centers. The shift from hospitals to ambulatory surgery centers and office-based laboratories has been driven by a number of factors, including declining reimbursements, increased patient demand, and competition for hospital resources. This transition has been dominated by the interventional radiology, cardiology, and vascular surgery fields. Cerebral angiography, in contrast, is still performed almost exclusively in a hospital-based setting, despite sharing many features with other endovascular procedures commonly performed in outpatient centers. As interest grows in performing cerebral angiography in outpatient endovascular centers, much can be learned from the decades of experience that our interventional colleagues have in the outpatient setting. In this article we examine the outpatient experience of other interventional fields and apply key principles to evaluate the prospect of outpatient neurointervention. The literature suggests that cerebral angiography can feasibly be performed in an outpatient center in both private and academic settings, as some groups have begun to do. Outpatient endovascular centers have helped to improve the patient experience, liberate inpatient resources, and control costs in other interventional fields, and might offer neurointerventionalists an opportunity to do the same.

Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4+ T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death.

Background Disseminated diffuse midline glioma (DMG) is a devastating diagnosis. Molecular subtyping has increased our understanding of this tumor. Case Here, we report the case of an 8-year-old girl who presented with symptoms of brainstem dysfunction and was found to have disseminated DMG with lesions in the pons, thalamus and bilateral temporal lobes. Molecular subtyping of the temporal lobe tumor tissue was consistent with H3 K27me3 loss and EZHIP overexpression, falling under the newly designated “H3 K27-altered” AQ5WHO subtype of DMG. Pathology from biopsy of the orbital lesion showed poorly differentiated rhabdoid-like disseminated tumor cells. The patient went on to develop lesions in the peritoneum, infratemporal fossa, and along the lumbosacral nerve roots. Conclusion This unique case illustrates the aggressive behavior of H3 K27-altered tumors and their potential to metastasize.

PurposeRefractory abdominal pain is a cardinal symptom of chronic pancreatitis (CP). Management strategies revolve around pain mitigation and resolution. Emerging evidence from observational studies highlights that surgery may result in superior pain relief when compared to endoscopic therapy; however, its impact on long-term quality of life or functional outcome has yet to be determined.MethodsA search through MEDLINE, PubMed and Web of Science was performed for RCTs that compared endoscopic treatment with surgery for the management of CP. The main outcome measure was the impact on pain control. Secondary outcome measures were the effect on quality of life and the incidence rate of new onset exocrine and endocrine failure. Data was pooled for analysis using either an odds ratio (OR) or mean difference (MD) with a random effects model.ResultsThree RCTs were included with a total of 267 patients. Meta-analysis demonstrated that operative treatment was associated with a significantly higher rate of complete pain control (37%) when compared to endoscopic therapy (17%) [OR (95% confidence interval (CI)) 2.79 (1.53–5.08), p = 0.0008]. No difference was noted in the incidence of new onset endocrine or exocrine failure between treatment strategies.ConclusionSurgical management of CP results in a greater extent of complete pain relief during long-term follow-up. Further research is required to evaluate the impact of the time interval between diagnosis and intervention on exocrine function, combined with the effect of early up-front islet auto-transplantation in order to determine whether long-term endocrine function can be achieved.