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Citrate is a key metabolite of the Krebs cycle that can also be exported in the cytosol, where it performs several functions. In normal cells, citrate sustains protein acetylation, lipid synthesis, gluconeogenesis, insulin secretion, bone tissues formation, spermatozoid mobility, and immune response. Dysregulation of citrate metabolism is implicated in several pathologies, including cancer. Here we discuss how cancer cells use citrate to sustain their proliferation, survival, and metastatic progression. Also, we propose two paradoxically opposite strategies to reduce tumour growth by targeting citrate metabolism in preclinical models. In the first strategy, we propose to administer in the tumor microenvironment a high amount of citrate, which can then act as a glycolysis inhibitor and apoptosis inducer, whereas the other strategy targets citrate transporters to starve cancer cells from citrate. These strategies, effective in several preclinical in vitro and in vivo cancer models, could be exploited in clinics, particularly to increase sensibility to current anti-cancer agents., Competing Interests: Declaration of Competing Interest MEM is an inventor on the Patent Application no. EP15767532.3 and US15/514,255 (status patent pending) “The plasma membrane citrate transporter for use in the diagnosis and treatment of cancer” owned by the University Hospital Regensburg. GZ is an employee and shareholder of Eternygen GmbH. PI, MA and LS have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Adapting therapies and providing personalized care for patients with resectable non-small cell lung cancer represent major challenges. This involves integrating several parameters into the patient's management, not only crude pathologic results, but also a better understanding of the mechanisms involved in tumor progression. Many studies have looked at the impact of host and tumor characteristics and their interactions through inflammatory processes or tumor immune environment. Beyond tumor stage, poor nutrition, sarcopenia and inflammatory state have been identified as independent factors that can directly impact postoperative outcome. The development of Enhanced Recovery After Surgery (ERAS), in which patient becomes the main player in their own management, seems to be an interesting answer since it seems to allow a reduction in postoperative complications, length of stay and indirectly reduction in costs. A broader and more complete vision including morphometric evaluation of the patient, physical performances, inflammatory state and nutritional state would provide additional discriminating information which can predict postoperative outcome and help in adapting therapies in a personalized way., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promote accumulation of oxidative lesions and insufficient repair, subsequently leading to cancer cell death. Due to their more flexible metabolism, healthy cells should be less sensitive, shifting their metabolism to support survival and repair. Interestingly, these regimens might stimulate an acute anticancer immune response, and may be of particular interest in tumors with high glucose uptake on positron emission tomography scan, a phenotype associated with poor survival and resistance to RT. Preclinical studies with ketogenic diets yielded more conflicting results, perhaps because cancer cells can sometimes metabolize fatty acids and/or ketone bodies. Randomized trials are awaited to specify the role of each strategy according to the clinical setting, although more stringent definitions of proposed diet, nutritional status, and consensual criteria for tumor response assessment are needed. In conclusion, dietary interventions during RT could be a simple and medically economical and inexpensive method that may deserve to be tested to improve efficiency of radiation., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Results of bilobectomy for non-small cell lung cancer have rarely been studied., Methods: Retrospective analysis was conducted on patients with non-small cell lung cancer having undergone bilobectomy from January 1999 to June 2012 at our institution. Analysis aimed at determining perioperative mortality and morbidity, and at studying prognostic factors for long-term survival using the 7th TNM classification., Results: A total of 103 patients (85 males; mean age 62 years) underwent upper-middle bilobectomy (n = 54) or lower-middle bilobectomy (n = 49). Histologic examination revealed 51 adenocarcinomas, 43 squamous cell carcinomas and 9 other cell carcinomas. Perioperative mortality was 0.97%. The overall morbidity rate was 71%, whereas the rate of life-threatening complications was 9.6%. Complications were more frequent in men (p = 0.032), in patients with chronic pulmonary obstructive diseases (p = 0.030) and after lower-middle bilobectomy (p = 0.0016). The overall 5-year Kaplan-Meier survival rate was 57.8%. In univariate analysis, factors associated with increased survival were the following: pathologic stage (stage I 74.9%, stage II 64.1%, stage III 28.8%, p = 0.0018); nodal status (N0 vs N1, p = 0.011; N0 vs N2, p = 0.0015; N0 vs N+, p = 0.0008); R status (R0 vs R1, p = 0.0032), and smoking status (past smoker or nonsmoker vs active smoker, p = 0.00054). Multivariate analysis revealed that active smokers (RR = 3.87, CI 95% [1.83 to 8.21]; p = 0.00042) and increasing stage (stage 0: RR=1; stage I: RR = 1.98, CI 95% [1.38 to 2.83]; stage II: RR = 3.90, CI 95% [1.90 to 8.02]; stage III: RR=7.72, CI 95% [2.62 to 22.73]; stage IV: RR = 15.25, CI 95% [3.61 to 64.40]; p = 0.0042) were significantly associated with poorer survival., Conclusions: Bilobectomy can be performed with low mortality, acceptable morbidity and long term survival in accordance with TNM staging., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cancer cells activate glycolysis, glutaminolysis and β-oxidation to promote their biosynthesis. The low activity of pyruvate kinase, reexpressed in its embryonic isoform PKM2, generates a bottleneck at the end of glycolysis, which reorients glucose catabolism towards formation of molecules implied in numerous synthesis: ribose for nucleic acids, glycerol for lipid synthesis, etc. However, a part of glucose is transformed in pyruvate, which also comes from aminoacids catabolism. Due to the inhibition of pyruvate dehydrogenase, pyruvate is preferentially transformed into lactate, either in the presence of oxygen (Warburg effect). Lactate dehydrogenase reaction furnishes lactic acid, which acidifies the tumoral microenvironment, a process which favors the cellular growth and regenerates NAD(+), a crucial cofactor for the functioning of various metabolic pathways (glycolysis, DNA synthesis and repair…). Cancer cells consume a lot of glutamine, which replenish Krebs cycle (coupled with ATP production), and/or furnishes aspartate for nucleotides synthesis. This particular metabolism is sustained by activation of oncogenes (Myc, AKT, etc.) and suppressors inactivation (P53, PTEN…). Like a parasite, cells draw on reserves of the host to supply their own biosynthesis, while they secrete waste products (NO, polyamines, ammonia, lactate…) that promote cellular growth. A "symbiotic" cooperation could be established between tumor cells themselves, and/or with environmental cells, to maximize ATP production in relation with resources and oxygen concentration.

Posterior intrathoracic neurogenic tumors often have an intraforaminal extension. Ten percent have an extension intraspinal and are called "dumbbell tumors." The surgically recommended techniques used to treat these conditions may have been applied too systematically, mainly when the diameter of the foramen was obviously enlarged and the possibility of removing the tumor existed. We report two cases to stress the importance of assessing the size of the intervertebral foramina in planning neurinoma cure.

Background: Superior vena cava syndrome (SVCS) is often seen in the natural history of malignant thoracic diseases. SVCS is characterized by unpleasant symptoms that usually lead to death. The purpose of our study is to show the efficiency of percutaneous stenting in the superior vena cava for relieving SVCS and the possibility of repeated stenting after recurrence., Methods: Twenty patients with SVCS caused by malignant diseases who had one or more stents placed in the superior vena cava or its main tributaries were evaluated., Results: Out of 20 patients, 1 died of myocardial infarction 24 hours after the procedure without any signs of pulmonary embolus, hemorrhage, or malposition of the stent. SVCS was successfully controlled in 94% of patients until death or completion of the study. In 3 patients the procedure was repeated (3 to 20 weeks later) because of the recurrence of symptoms., Conclusions: Percutaneous venous stent placement in the superior vena cava is a simple and effective technique to relieve rapid SVCS caused by malignancies. When recurrence occurs, repeated stenting can be performed successfully.