Positron emission tomography complete metabolic response as a favorable prog-nostic predictor in esophageal cancer following neoadjuvant chemotherapy with docetaxel/cis-platin/5-fluorouracil

BACKGROUND 18F-fluorodeoxyglucose-positron emission tomography(PET)/computed tomography is useful in diagnosing lymph node and distant metastases of esophageal cancer.However,its value for predicting survival is controversial.AIM To evaluate the value of PET complete metabolic response(CMR)as a prognostic predictor for esophageal cancer.METHODS Between June 2013 and December 2017,58 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy(NAC)in Oita University were enrolled in this retrospective cohort study.Tumors were clinically staged using fluorodeoxyglucose-PET/computed tomography before and after NAC.After NAC,maximal standardized uptake value≤2.5 was defined as PET-CMR,and maximal standardized uptake value>2.5 was defined as non-PET-CMR.We compared short-term outcomes between the PET-CMR group and non-PET-CMR group and evaluated prognostic factors by univariate and multivariate analyses.RESULTS The PET-CMR group included 22 patients,and the non-PET-CMR group included 36 patients.There were no significant differences in intraoperative and post operative complications between the two groups.Five-year relapse-free survival and overall survival in the PET-CMR group were significantly more favorable than those in the non-PET-CMR group(38.6 mo vs 20.8 mo,P=0.021;42.8 mo vs 25.1 mo,P=0.011,respectively).PET-CMR was a significant prognostic factor in terms of relapse-free survival by univariate analysis(hazard ratio:2.523;95%confidence interval:1.034–7.063;P<0.041).Particularly,PET-computed tomography negative N was an independent prognostic factor of relapse-free survival and overall survival by multivariate analysis.CONCLUSION PET-CMR after NAC is considered a favorable prognostic factor for esophageal cancer.Evaluation by PET-computed tomography could be useful in clinical decision making for esophageal cancer.

Effect of Small-Scale Turbulence on the Growth and Metabolism of Microcystis aeruginosa

Microcystis aeruginosa is a single-celled cyanobacterium, forming large colonies on the surface of freshwater ecosystems during summer, and producing a toxin (microcystin) that in high concentration can be harmful to humans and animals. These toxic effects can be governed by abiotic environmental conditions including water temperature, light, nutrient abundance, and fluid motion. We investigated the effect of small-scale turbulence on the growth and metabolism of Microcystis aeruginosa using field measurements and laboratory bioreactor investigations. The laboratory setup included two underwater speakers, generating a quasi-homogeneous turbulent flow with turbulent kinetic energy dissipation rates up to 10-6 m2/s3, comparable to field values in the lacustrine photic zone. The role of turbulence is quantified by comparing cell number, dissolved oxygen production/uptake, and inorganic carbon uptake in stagnant condition and two sets of experiments with turbulent conditions, quantified by the Taylor micro-scale Reynolds number at Reλ = 15 and Reλ = 33. The results suggest that turbulence mediates the metabolism of Microcystis aeruginosa measured by the net oxygen production, oxygen uptake, and inorganic carbon uptake. Furthermore, small-scale turbulence marginally influenced Microcystis growth rate estimated from cell population concentration (-5% and 11% for Reλ = 33 and Reλ = 15, respectively, as compared to stagnant conditions).

Evaluation of ^(177)Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors

BACKGROUND^177Lu peptide receptor radionuclide therapy(PRRT)is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors.AIM To determine the impact of PRRT on quality of life,radiologic and metabolic response,overall survival,prognostic factors and toxicity.METHODS Thirty-six patients treated with^177Lu-PRRT from 2016 to 2019 were included.The most frequent location of the primary tumor was the gastrointestinal tract(52.8%),pancreas(27.8%),and nongastropancreatic neuroendocrine tumor(11.1%).The liver was the most common site of metastasis(91.7%),followed by distant nodes(50.0%),bone(27.8%),peritoneum(25.0%)and lung(11.1%).Toxicity was evaluated after the administration of each dose.Treatment efficacywas evaluated by two parameters:stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested.RESULTS From 36 patients,55.6%were men,with a median age of 61.1±11.8 years.Regarding previous treatments,55.6%of patients underwent surgery of the primary tumor,100%of patients were treated with long-acting somatostatin analogues,66.7%of patients were treated with everolimus,27.8%of patients were treated with tyrosine kinase inhibitor,and 27.8%of patients were treated with interferon.One patient received radioembolization,three patients received chemoembolization,six patients received chemotherapy.Hematological toxicity was registered in 14 patients(G1-G2:55.5%and G3:3.1%).Other events presented were intestinal suboclusion in 4 cases,cholestasis in 2 cases and carcinoid crisis in 1 case.The median follow-up time was 3 years.Currently,24 patients completed treatment.Nineteen are alive with stable disease,two have disease progression,eight have died,and nine are still receiving treatment.The median overall survival was 12.5 mo(95%confidence interval range:9.8–15.2),being inversely proportional to toxicity in previous treatments(P<0.02),tumor grade(P<0.01)and the presence of bone lesions(P=0.009)and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT(P<0.01),,primary tumor surgery(P=0.03)and metastasis surgery(P=0.045).In a multivariate Cox regression analysis,a high Ki67 index(P=0.003),a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT(P<0.01)and a preceding toxicity in previous treatments(P<0.05)were risk factors to overall survival.CONCLUSION Overall survival was inversely proportional to previous toxicity,tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.

High cholesterol intake remodels cholesterol turnover and energy homeostasis in Nile tilapia(Oreochromis niloticus)

The roles of dietary cholesterol in fish physiology are currently contradictory.The issue reflects the limited studies on the metabolic consequences of cholesterol intake in fish.The present study investigated the metabolic responses to high cholesterol intake in Nile tilapia(Oreochromis niloticus),which were fed with four cholesterol-contained diets(0.8,1.6,2.4 and 3.2%)and a control diet for eight weeks.All fish-fed cholesterol diets showed increased body weight,but accumulated cholesterol(the peak level was in the 1.6%cholesterol group).Then,we selected 1.6%cholesterol and control diets for further analysis.The high cholesterol diet impaired liver function and reduced mitochondria number in fish.Furthermore,high cholesterol intake triggered protective adaptation via(1)inhibiting endogenous cholesterol synthesis,(2)elevating the expression of genes related to cholesterol esterification and efflux,and(3)promoting chenodeoxycholic acid synthesis and efflux.Accordingly,high cholesterol intake reshaped the fish gut microbiome by increasing the abundance of Lactobacillus spp.and Mycobacterium spp.,both of which are involved in cholesterol and/or bile acids catabolism.Moreover,high cholesterol intake inhibited lipid catabolic activities through mitochondrialβ-oxidation,and lysosome-mediated lipophagy,and depressed insulin signaling sensitivity.Protein catabolism was elevated as a compulsory response to maintain energy homeostasis.Therefore,although high cholesterol intake promoted growth,it led to metabolic disorders in fish.For the first time,this study provides evidence for the systemic metabolic response to high cholesterol intake in fish.This knowledge contributes to an understanding of the metabolic syndromes caused by high cholesterol intake or deposition in fish.