A Narrative Review of the Applications of Ex-vivo Human Liver Perfusion

Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words “ex-vivo liver or hepatic perfusion”. All relevant studies in English describing experiments using ex-vivo perfusion of human livers between 2016 and 2021, inclusive, were included. Of 21 reviewed studies, 19 used ex-vivo human liver perfusion in the context of allogeneic liver transplantation. The quality and size of the studies varied considerably. Human liver perfusion was almost exclusively limited to whole organs and “split” livers, although one study did describe the successful perfusion of tissue sections following a partial hepatectomy. This review of recent literature involving ex vivo human liver perfusion demonstrates that the technique is not limited to whole liver perfusion. Split liver perfusion is extremely valuable allowing one lobe to act as a control and increasing the number available for research. This review also highlights the present lack of any reports of segmental liver perfusion. The discarded donor liver is a scarce resource, and the successful use of segmental perfusion has the potential to expand the available experimental models to facilitate pre-clinical experimentation

Oesophageal Metastasis from Colorectal Cancer

Metastasis to the oesophagus is most frequently described in association with lung or breast cancer. Diagnosis is frequently complicated as often only normal tissue is present in endoscopic biopsy specimens. Although oesophagectomy for metastasis has been described, few patients are suitable for curative resection. We report the case of a 62-year-old man who developed an oesophageal metastasis from colorectal cancer and review the available literature

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography:an international expert consensus

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.]

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Bioavailability and pharmacodynamics of curcumin in humans with resectable colorectal primaries and secondary hepatic metastases

Curcumin, a constituent of the spice turmeric, is a potent antioxidant with chemopreventive properties in several rodent models of carcinogenesis. In animal models of inherited colorectal cancer dietary curcumin reduced the levels of malondialdehyde-DNA (MiG) adduct, which reflects oxidative DNA changes, and reduced adenoma burden. We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in humans by oral dosing, as measured by the biomarkers MiG (immunoslotblot assay), COX-2 (Western blotting) and P-catenin (immunohistochemistry). Furthermore, we attempted to determine the metabolism and distribution of curcumin in humans in vivo following oral administration. The concentrations of curcumin in normal and malignant colorectal tissue were 12.7 5.7 and 7.7 1.8 nmol/g, respectively, after the 3.6 g dose, 19.6 14.8 and 6.7 1.8 nmol/g, respectively, after 1.8 g and 0.9 0.4 nmol/g and zero respectively following 0.45g (mean SD). Trace levels of curcumin glucuronide and sulphate were detected in the colorectal mucosa and portal blood. All results were validated by co-elution chromatography with authentic reference compounds and by mass spectrometry. In line with most translational research, the study suffered from inherent errors due to difficulties in standardising warm ishcaemic time and in standardising sampling techniques in the recruited patients. In spite of these caveats, administration of curcumin (3,600 mg) appeared to decrease MjG levels in malignant colorectal tissue significantly to 2.0 1.8 adducts per 107 nucleotides (p<0.05), but did not affect MjG levels in normal mucosa. MiG levels in normal and malignant liver tissue were not affected by curcumin treatment. COX-2 expression in primary colorectal tumours was not inhibited by curcumin treatment. Curcumin administration had no effect of expression of p-catenin in either colorectal or hepatic malignant tissue. Concentrations of curcumin achieved in human colorectal mucosa were equivalent to those shown to elicit biochemical changes in vitro consistent with chemopreventive activity. In addition, short-term administration of 3.6g oral curcumin inhibited oxidative DNA damage in human primary colorectal tumours. These results suggest that Phase II clinical trials of curcumin should use at least 3.6g as a dosing regimen

Koiter's asymptotic numerical methods for shell structures using a corotational formulation

Università degli Studi della Calabria, Dottorato di Ricerca in Meccanica Computazionale, Ciclo XXII,a.a. 2009Università degli Studi della Calabri

Haemorrhage from Pancreatic Pseudocysts Presenting as Upper Gastrointestinal Haemorrhage

Haemorrhage is a rare but frequently fatal complication of pancreatic pseudocysts. The high mortality associated with pancreatic haemorrhage makes prompt and aggressive management essential. Occasionally, haemorrhage may present atypically, leading to delay in its diagnosis and management. This report details a case of pancreatic haemorrhage presenting as an upper gastrointestinal bleed and discusses the subsequent management. When managing patients with pancreatic pseudocysts who present with the stigmata of upper gastrointestinal bleeding, the possibility that the bleeding originates from the pancreas must always be borne in mind