Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study

Introduction: The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft after esophageal reconstruction. Clinical judgment is unreliable in determining graft perfusion. Therefore, an objective, validated, and reproducible method is urgently needed. Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an emerging and promising modality. This study's objectives are to evaluate the feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion and to validate ICGA by comparison with hemodynamic parameters, blood and tissue expression of hypoxia-induced markers, and tissue mitochondrial respiration rates. And, second, to evaluate its ability to predict AL in patients after minimally invasive esophagectomy (MIE). Methods: Patients (N = 70) with resectable esophageal cancer will be recruited for standard MIE. ICGA will be performed after graft creation and thoracic pull-up. Dynamic digital images will be obtained starting after intravenous bolus administration of ICG. The resulting images will be subjected to curve analysis and to compartmental analysis based on the adiabatic approximation to tissue homogeneity kinetic model. The calculated perfusion parameters will be compared to intraoperative hemodynamic data to evaluate the effects of patient hemodynamics. To verify whether graft perfusion represents tissue oxygenation, ICGA perfusion parameters will be compared with systemic and serosa lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia-related markers and mitochondrial chain respiratory rate. Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict AL and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses. Discussion: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during MIE, potentially reducing the incidence of AL and its associated severe morbidity and mortality

Near-infrared fluorescence guided esophageal reconstructive surgery : a systematic review

BACKGROUND: After an esophagectomy, the stomach is most commonly used to restore continuity of the upper gastrointestinal tract. These esophago-gastric anastomoses are prone to serious complications such as leakage associated with high morbidity and mortality. Graft perfusion is considered to be an important predictor for anastomotic integrity. Based on the current literature we believe Indocyanine green fluorescence angiography (ICGA) is an easy assessment tool for gastric tube (GT) perfusion, and it might predict anastomotic leakage (AL). AIM: To evaluate feasibility and effectiveness of ICGA in GT perfusion assessment and as a predictor of AL. METHODS: This study was designed according to the PRISMA guidelines and registered in the PROSPERO database. PubMed and EMBASE were independently searched by 2 reviewers for studies presenting data on intraoperative ICGA GT perfusion assessment during esophago-gastric reconstruction after esophagectomy. Relevant outcomes such as feasibility, complications, intraoperative surgical changes based on ICGA findings, quantification attempts, anatomical data and the impact of ICGA on postoperative anastomotic complications, were collected by 2 independent researchers. The quality of the included articles was assessed based on the Methodological Index for Non-Randomized Studies. The 19 included studies presented data on 1192 esophagectomy patients, in 758 patients ICGA was used perioperative to guide esophageal reconstruction. RESULTS: The 19 included studies for qualitative analyses all described ICGA as a safe and easy method to evaluate gastric graft perfusion. AL occurred in 13.8% of the entire cohort, 10% in the ICG guided group and 20.6% in the control group (P < 0.001). When poorly perfused cases are excluded from the analyses, the difference in AL was even larger (AL well-perfused group 6.3% vs control group 20.5%, P < 0.001). The AL rate in the group with an altered surgical plan based on the ICG image was 6.5%, similar to the well perfused group (6.3%) and significantly less than the poorly perfused group (47.8%) (P < 0.001), suggesting that the technique is able to identify and alter a potential bad outcome. CONCLUSION: ICGA is a safe, feasible and promising method for perfusion assessment. The lower AL rate in the well perfused group suggest that a good fluorescent signal predicts a good outcome

Litter mixture interactions at the level of plant functional types are additive.

It is very difficult to estimate litter decomposition rates in natural ecosystems because litters of many species are mixed and idiosyncratic interactions occur among those litters. A way to tackle this problem is to investigate litter mixing effects not at the species level but at the level of Plant Functional Types (PFTs). We tested the hypothesis that at the PFT level positive and negative interactions balance each other, causing an overall additive effect (no significant interactions among PFTs). Thereto, we used litter of four PFTs from a temperate peatland in which random draws were taken from the litter species pool of each PFT for every combination of 2, 3, and 4 PFTs. Decomposition rates clearly differed among the 4 PFTs (Sphagnum spp. < graminoids = N-fixing tree < forbs) and showed little variation within the PFTs (notably for the Sphagnum mosses and the graminoids). Significant positive interactions (4 out of 11) in the PFT mixtures were only found after 20 weeks and in all these combinations Sphagnum was involved. After 36 and 56 weeks of incubation interactions were not significantly different from zero. However, standard deviations were larger than the means, indicating that positive and negative interactions balanced each other. Thus, when litter mixture interactions are considered at the PFT level the interactions are additive. From this we conclude that for estimating litter decomposition rates at the ecosystem level, it is sufficient to use the weighted (by litter production) average decomposition rates of the contributing PFTs. © 2009 The Author(s)

Neighbour identity hardly affects litter-mixture effects on decomposition rates of New Zealand forest species.

The mass loss of litter mixtures is often different than expected based on the mass loss of the component species. We investigated if the identity of neighbour species affects these litter-mixing effects. To achieve this, we compared decomposition rates in monoculture and in all possible two-species combinations of eight tree species, widely differing in litter chemistry, set out in two contrasting New Zealand forest types. Litter from the mixed-species litter bags was separated into its component species, which allowed us to quantify the importance of litter-mixing effects and neighbour identity, relative to the effects of species identity, litter chemistry and litter incubation environment. Controlling factors on litter decomposition rate decreased in importance in the order: species identity (litter quality) >> forest type >> neighbour species. Species identity had the strongest influence on decomposition rate. Interspecific differences in initial litter lignin concentration explained a large proportion of the interspecific differences in litter decomposition rate. Litter mass loss was higher and litter-mixture effects were stronger on the younger, more fertile alluvial soils than on the older, less-fertile marine terrace soils. Litter-mixture effects only shifted percentage mass loss within the range of 1.5%. There was no evidence that certain litter mixtures consistently showed interactive effects. Contrary to common theory, adding a relatively fast-decomposing species generally slowed down the decomposition of the slower decomposing species in the mixture. This study shows that: (1) species identity, litter chemistry and forest type are quantitatively the most important drivers of litter decomposition in a New Zealand rain forest; (2) litter-mixture effects—although statistically significant—are far less important and hardly depend on the identity and the chemical characteristics of the neighbour species; (3) additive effects predominate in this ecosystem, so that mass dynamics of the mixtures can be predicted from the monocultures

Susceptibility of Pancreatic Beta Cells to Fatty Acids Is Regulated by LXR/PPARα-Dependent Stearoyl-Coenzyme A Desaturase

Chronically elevated levels of fatty acids-FA can cause beta cell death in vitro. Beta cells vary in their individual susceptibility to FA-toxicity. Rat beta cells were previously shown to better resist FA-toxicity in conditions that increased triglyceride formation or mitochondrial and peroxisomal FA-oxidation, possibly reducing cytoplasmic levels of toxic FA-moieties. We now show that stearoyl-CoA desaturase-SCD is involved in this cytoprotective mechanism through its ability to transfer saturated FA into monounsaturated FA that are incorporated in lipids. In purified beta cells, SCD expression was induced by LXR- and PPARα-agonists, which were found to protect rat, mouse and human beta cells against palmitate toxicity. When their SCD was inhibited or silenced, the agonist-induced protection was also suppressed. A correlation between beta cell-SCD expression and susceptibility to palmitate was also found in beta cell preparations isolated from different rodent models. In mice with LXR-deletion (LXRβ-/- and LXRαβ-/-), beta cells presented a reduced SCD-expression as well as an increased susceptibility to palmitate-toxicity, which could not be counteracted by LXR or PPARα agonists. In Zucker fatty rats and in rats treated with the LXR-agonist TO1317, beta cells show an increased SCD-expression and lower palmitate-toxicity. In the normal rat beta cell population, the subpopulation with lower metabolic responsiveness to glucose exhibits a lower SCD1 expression and a higher susceptibility to palmitate toxicity. These data demonstrate that the beta cell susceptibility to saturated fatty acids can be reduced by stearoyl-coA desaturase, which upon stimulation by LXR and PPARα agonists favors their desaturation and subsequent incorporation in neutral lipids

Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide

Glioblastoma patients undergoing treatment with surgery followed by radiation and temozolomide chemotherapy often develop a state of immunosuppression and are at risk for opportunistic infections and reactivation of hepatitis and herpes viruses. We report the case of a 48-year-old glioblastoma patient who developed acute cholestatic hepatitis with hepatic failure during adjuvant treatment with temozolomide and the integrin inhibitor cilengitide. A viral hepatitis was excluded and valproic acid treatment was stopped. Upon normalisation of the liver tests, temozolomide treatment was resumed without perturbation of the liver tests. Valproic acid related idiosyncratic drug induced hepatotoxicity should be considered as a differential diagnosis in glioblastoma patients undergoing adjuvant therapy

Multiple focal nodular hyperplasia

Focal nodular hyperplasia (FNH) is a benign lesion of the liver which usually presents with one or two localizations. We report a patient with history of resection of a biliary cyst, and who had been taking oral contraceptives for the past 18 years, who had multiple localizations of FNH (more than 30 lesions). The largest lesion measured 10.5 x 11 x 12 cm. The imaging characteristics of our patient were atypical. A central scar could be demonstrated only in the largest lesion, in an eccentric location. In the other lesions, no scar formations could be detected. Futhermore, imaging characteristics suggested that several of the lesions contained fat. This was confirmed by biopsy. The patient had an associated inflammatory syndrome which could not be otherwise explained. The patient was advised to stop taking the oral contraceptives. Follow-up after 2 years showed that the lesions were unchanged; the inflammatory syndrome persisted. Multiple localizations of FNH are very rare. Sometimes they are associated with malformations in other organs (vascular malformations and neoplasia,mostly of the brain). Often they occur as isolated cases, however. Usuary their prognosis seems to be good