Yield of routine staging laparoscopy in patients with gastric cancer in Alberta, Canada.

BACKGROUND: Despite guidelines recommending diagnostic laparoscopy in patients with gastric cancer, implementation is low. We aimed to explore trends in the use of laparoscopy for staging of gastric cancer in Alberta, Canada, determine the rate of positive findings and identify factors predictive of positive staging laparoscopy (SL) findings in this patient population. METHODS: In August 2018, we sent a survey to all general surgeons in Alberta who were members of the Alberta Association of General Surgeons to identify those treating gastric cancer. The survey inquired about type of practice (academic or community), gastric cancer case volume, routine versus selective use of SL and, if selective use of SL, criteria used to select cases. Participants were also asked to provide data from their SL cases from July 2007 to February 2019. We double-checked surgeon records with chart review. The primary outcome was evidence of metastatic disease on SL or cytologic examination or both. We performed logistic regression analysis to identify factors predictive of positive laparoscopy findings. RESULTS: The survey was completed by 41 of 127 surgeons (response rate 32.3%). We reviewed 116 cases from 5 surgeons at 4 centres. Gross metastatic disease or positive findings on cytologic examination or both were identified in 37 patients (31.9%). On univariate analysis, the following were associated with an increased risk of identification of metastatic disease at laparoscopy: visualization of the primary tumour on computed tomography (CT) (odds ratio [OR] 9.8, 95% confidence interval [CI] 1.2-76.5), presence of abdominal lymphadenopathy greater than 1 cm (OR 2.4, 95% CI 1.1-5.4) and presence of ascites (OR 19.1, 95% CI 2.2-161.8). Visualization of the primary tumour on CT (OR 8.4, 95% CI 1.0-68.3) and the presence of ascites (OR 15.9, 95% CI 1.8-137.0) remained statistically significant predictors on multivariate analysis. CONCLUSION: Metastatic disease was identified at SL in almost one-third of cases, which suggests that SL should still be used routinely in gastric cancer staging in Canadian centres. Our study identified several preoperative imaging findings associated with evidence of metastatic disease on laparoscopy; however, further studies are needed to establish robust predictors of positive findings before advocating for a selective SL approach.

Addressing organ shortages: progress in donation after circulatory death for liver transplantation

Reducing wait list mortality among patients awaiting liver transplantation remains a substantial challenge because of organ shortage. In efforts to expand the donor pool there has been a trend toward increased use of donation after circulatory death (DCD) liver grafts. However, these marginal grafts are prone to higher complication rates, particularly biliary complications. In addition, many procured DCD livers are then deemed unsuitable for transplant. Despite these limitations, DCD grafts represent an important resource to address the current organ shortage, and as such there are research efforts directed toward improving the use of and outcomes for transplantation of these grafts. We review the current progress in DCD liver transplantation.

La réduction du nombre de personnes en attente d'une greffe de foie qui décèdent avant la transplantation demeure un défi important en raison de la pénurie d'organes. On remarque actuellement une tendance à la hausse dans l'utilisation de greffons de foie provenant de don après décès circulatoire (DDC) dans le but d'élargir le bassin de donneurs. Ces greffons marginaux sont toutefois associés à des taux de complications plus élevés, particulièrement pour ce qui est des complications biliaires. De plus, de nombreux foies obtenus à la suite d'un DDC sont jugés inadmissibles à la greffe. Malgré ces restrictions, les greffons provenant de DDC représentent une importante ressource pour atténuer la pénurie d'organes. Des initiatives de recherche sont donc actuellement en cours dans le but d'améliorer leur taux d'utilisation et les issues des transplantations. Nous analysons ici l'état actuel des progrès pour les transplantations de foie provenant de DDC.

Avoiding initial hypothermia does not improve liver graft quality in a porcine donation after circulatory death (DCD) model of normothermic perfusion.

BACKGROUND: Normothermic machine perfusion (NMP) of liver grafts donated after circulatory death (DCD) has shown promise in large animal and clinical trials. Following procurement, initial flush with a cold preservation solution is the standard of care. There is concern that initial cooling followed by warming may exacerbate liver injury, and the optimal initial flush temperature has yet to be identified. We hypothesize that avoidance of the initial cold flush will yield better quality liver grafts. METHODS: Twenty-four anaesthetized pigs were withdrawn from mechanical ventilation and allowed to arrest. After 60-minutes of warm ischemia to simulate a DCD procurement, livers were flushed with histidine-tryptophan-ketoglutarate (HTK) at 4°C, 25°C or 35°C (n = 4 per group). For comparison, an adenosine-lidocaine crystalloid solution (AD), shown to have benefit at warm temperatures in heart perfusions, was also used (n = 4 per group). During 12-hours of NMP, adenosine triphosphate (ATP), lactate, transaminase levels, and histological injury were determined. Bile production and hemodynamics were monitored continuously. RESULTS: ATP levels recovered substantially following 1-hour of NMP reaching pre-ischemic levels by the end of NMP with no difference between groups. There was no difference in peak aspartate aminotransferase (AST) or in lactate dehydrogenase (LDH). Portal vein resistance was lowest in the 4°C group reaching significance after 2 hours (0.13 CI -0.01,0.277, p = 0.025). Lactate levels recovered promptly with no difference between groups. Comparison to AD groups showed no statistical difference in the abovementioned parameters. On electron microscopy the HTK4°C group had the least edema with mean cell thickness of 2.92µm (p = 0.41) while also having the least sinusoidal dilatation with a mean diameter of 5.36µm (p = 0.04). For AD, the 25°C group had the lowest mean cell thickness at 3.14µm (p = 0.09). CONCLUSIONS: Avoidance of the initial cold flush failed to demonstrate added benefit over standard 4°C HTK in this DCD model of liver perfusion.

Normothermic Ex Vivo Machine Perfusion for Liver Grafts Recovered from Donors after Circulatory Death: A Systematic Review and Meta-Analysis.

As a result of donation after circulatory death liver grafts' poor tolerance to cold storage, there has been increasing research interest in normothermic machine perfusion. This study aims to systematically review the current literature comparing normothermic perfusion to cold storage in donation after circulatory death liver grafts and complete a meta-analysis of published large animal and human studies. A total of nine porcine studies comparing cold storage to normothermic machine perfusion for donation after circulatory death grafts were included for analysis. There was a significant reduction in AST (mean difference -2291 U/L, CI (-3019, -1563); P ≤ 0.00001) and ALT (mean difference -175 U/L, CI (-266, -85); P = 0.0001), for normothermic perfusion relative to static cold storage, with moderate (I2 = 61%) and high (I2 = 96%) heterogeneity, respectively. Total bile production was also significantly higher (mean difference = 174 ml, CI (155, 193); P ≤ 0.00001). Further research focusing on standardization, performance of this technology following periods of cold storage, economic implications, and clinical trial data focused on donation after circulatory death grafts will be helpful to advance this technology toward routine clinical utilization for these grafts.

The Effect of Bariatric Surgery on the Spectrum of Fatty Liver Disease.

Nonalcoholic fatty liver disease is becoming one of the most common causes of liver disease in the western world. The most significant risk factors are obesity and the metabolic syndrome for which bariatric surgery has been shown to be an effective treatment. However, the effects of bariatric surgery on nonalcoholic fatty liver disease, specifically liver fibrosis and cirrhosis, are not well established. We review published bariatric surgery outcomes with respect to nonalcoholic liver disease. On the basis of this review we suggest that bariatric surgery may provide a viable treatment option for the treatment of nonalcoholic fatty liver disease, including patients with fibrosis and compensated cirrhosis, and that this topic should be a target of future investigation.

Impact of the N5-proximal Asn on the thermodynamic and kinetic stability of the semiquinone radical in photolyase.

Flavoproteins can dramatically adjust the thermodynamics and kinetics of electron transfer at their flavin cofactor. A versatile regulatory tool is proton transfer. Here, we demonstrate the significance of proton-coupled electron transfer to redox tuning and semiquinone (sq) stability in photolyases (PLs) and cryptochromes (CRYs). These light-responsive proteins share homologous overall architectures and FAD-binding pockets, yet they have evolved divergent functions that include DNA repair, photomorphogenesis, regulation of circadian rhythm, and magnetoreception. We report the first measurement of both FAD redox potentials for cyclobutane pyrimidine dimer PL (CPD-PL, Anacystis nidulans). These values, E(1)(hq/sq) = -140 mV and E(2)(sq/ox) = -219 mV, where hq is FAD hydroquinone and ox is oxidized FAD, establish that the sq is not thermodynamically stabilized (ΔE = E(2) - E(1) = -79 mV). Results with N386D CPD-PL support our earlier hypothesis of a kinetic barrier to sq oxidation associated with proton transfer. Both E(1) and E(2) are upshifted by ∼ 100 mV in this mutant; replacing the N5-proximal Asn with Asp decreases the driving force for sq oxidation. However, this Asp alleviates the kinetic barrier, presumably by acting as a proton shuttle, because the sq in N386D CPD-PL oxidizes orders of magnitude more rapidly than wild type. These data clearly reveal, as suggested for plant CRYs, that an N5-proximal Asp can switch on proton transfer and modulate sq reactivity. However, the effect is context-dependent. More generally, we propose that PLs and CRYs tune the properties of their N5-proximal residue to adjust the extent of proton transfer, H-bonding patterns, and changes in protein conformation associated with electron transfer at the flavin.