A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer's Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1 beta and IL-6 mRNA in the brain ' s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APP(NL-G-F/NL-G-F) Alzheimer ' s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1b mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer ' s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.

A 56-year-old female was referred to our department with a five-month history of progressive abdominal pain related to physical exertion and copious meals. The pain was located in the mesogastric region and the right flank and remitted when the patient lay in the recumbent position with the knees bent. The patient reported nausea and a weight loss of 12 kg over the previous ten years. She had been diagnosed 18 years previously with hereditary leiomyomatosis and renal cancer and had undergone a hysterectomy and partial nephrectomy.

Currently, among the possible treatments for hepatocel-lular carcinoma there is group of minimally invasive abla-tion techniques with wide clinical acceptance due to their greater efficacy and safety in comparison to traditional therapies, low cost, and no need of being admitted to hospi-tal (outpatient treatment program). Irreversible electroporation is a non-thermal abla tion technique in which electrical fields are used to create nan-opores in the cell membrane that induce tumor cell death.Irreversible electroporation has shown promising results in numerous clinical trials; however, its control on long-term tumor growth and recurrence is inferior in comparison to that of radiofrequency. Combining irreversible electropora-tion with immunological agents may increase its efficacy in the treatment of focal lesions and metastases. In this work, we present an update on IRE including procedure, mecha-nism of action, application as a treatment for HCC, and the improvements that have been made in the past few years.

Background and aims: Magnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain. Material and methods: This project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts. Results: The experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment. Conclusion: The results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1 cm, thus facilitating early diagnosis of metastatic spread.

Radioembolization (RE) with yttrium-90 (Y-90) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six Y-90-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by Y-90 PET/CT. Specifically, the microsphere distribution predicted was compared with the actual Y-90 activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict Y-90-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

Background/Aim. Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of tumor growth. In this work, we show that it is possible to increase the antitumor efficiency of IRE by simmultaneously injecting c-di-GMP, a STING agonist, intratumorally. Materials and Methods. Intratumoral administration of c-di-GMP simultaneously to IRE was evaluated in murine models of melanona (B16.OVA) and hepatocellular carcinoma (PM299L). Results. The combined therapy increased the number of tumor-infiltrating IFN-gamma/TNF-alpha-producing CD4 and CD8 T cells and delayed tumor growth, as compared to the effect observed in groups treated with c-di-GMP or IRE alone. Conclusion. These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.

Moreno Márquez et al. report an association between arcuate ligament syndrome (ALS) and the "nutcracker" phenomenon (compression of the left renal vein). The case illustrates the association between several syndromes, which all involve compression of vascular or gastrointestinal structures: arcuate ligament syndrome, superior mesenteric artery syndrome (SMAS) or Wilkie's syndrome, the "nutcracker" syndrome and May-Thurner syndrome (compression of the left iliac vein).

Purpose To assess the feasibility of performing same-day vascular flow redistribution and Yttrium-90 radioembolization (90Y-RE) for hepatic malignancies. Materials and Methods From November 2015 to February 2019, patients undergoing same-day hepatic flow redistribution during work-up angiography,(99m)Technetium-labeled macroaggregated albumin (Tc-99m-MAA) SPECT/CT and 90Y microsphere-RE, were recruited. Within 18 h following the delivery of 90Y resin microspheres, an 90Y-PET/CT study was performed. According to patients' vascular anatomy, flow redistribution was performed by microcoil embolization of extrahepatic branches (group A), intrahepatic non-tumoral vessels (group B) and intrahepatic tumoral arteries (group C). The accumulation of(99m)Tc-MAA particles and microspheres in the redistributed areas was qualitatively evaluated using a 5-point visual scale (grade 1 = < 25% accumulation; grade 5 = 100% accumulation). Differences in the distribution of microspheres among groups were assessed with Mann-WhitneyUtest. Results Twenty-two patients were treated for primary (n = 17) and secondary (n = 5) hepatic malignancies. The MAA-SPECT/CT showed uptake in all the redistributed areas. Regarding the accumulation of microspheres within the redistributed segments in all the groups, perfusion patterns were classified as 2 in 1 case, 4 in 6 cases and 5 in 15 cases. No statistically significant differences were observed between groups A and B-C (Uvalue = 34,p = 0.32) and between groups B and C (Uvalue = 26,p = 0.7). Mean predicted absorbed doses by the tumoral and normal hepatic tissues were 163.5 +/- 131.2 Gy and 60.4 +/- 69.3 Gy, respectively. Mean total procedure time (from work-up angiography to 90Y delivery) was 401 +/- 0.055 min. Conclusion Performing same-day redistribution of the arterial hepatic flow to the target and 90Y-microsphere delivery is feasible in the treatment of liver tumors. Clinical Trials RegistryNCT03380130.

Objective: To determine the incidence of immune-mediated adverse reactions with and without radiologic manifestations and to correlate them with the response to immunotherapy. Material and methods: We retrospectively included 79 patients with stage IV lung carcinomas (n=24), renal carcinomas (n=11), or melanoma (n=44) treated with immunotherapy. We evaluated the occurrence of immune-mediated adverse reactions, their radiologic manifestations, and the response pattern according to the immune-related response criteria (irRC). We correlated the presence of immune-mediated adverse reactions with the response pattern. Results: Immune-mediated adverse reactions occurred in 27.8%, being most common in patients with melanoma (40.9%). In 59.1% of patients with adverse reactions, there were radiologic manifestations such as pneumonitis, colitis, hypophysitis, thyroiditis, or myocarditis. Pneumonitis was the most common radiologic manifestation of immune-mediated adverse reactions, even in asymptomatic patients. The rate of response to immunotherapy was higher among patients who developed immune-mediated adverse reactions than in those who did not (68.2% vs. 38.6%, respectively, ¿2 5.58; p=0.018). The rate of favorable responses was higher in patients with radiologic manifestations of immune-mediated adverse reactions than in those without radiologic manifestations (84.6% vs. 44.4%, respectively; p=0.023). Conclusions: The presence of immune-mediated adverse reactions is associated with a better response to immunotherapy. The association with a favorable response is even stronger in patients with radiologic manifestations of the immune-mediated adverse reactions.

BACKGROUND: Latero-lateral duodenojejunostomy is the treatment of choice for superior mesenteric artery syndrome (SMAS). The present study analyzes the long-term outcomes in 13 patients undergoing laparoscopic surgery for SMAS. MATERIALS AND METHODS: A retrospective study of 10 females and three males undergoing surgery between 2001 and 2013 was performed. Demographic, clinical and radiologic data and long-term surgical outcomes were recorded. In 12 patients latero-lateral duodenojejunostomy and in one patient distal laparoscopic gastrectomy with Roux-en-Y reconstruction were performed. The median age was 24 years (20-28), and the median duration of symptoms was 24 months (5-24). The most frequent symptoms were abdominal pain (n¿=¿11; 92.3%), nausea and vomiting (n¿=¿10; 77%) and weight loss (n¿=¿9; 69.2%). The median operating time was 98 min (86-138) and hospital stay was 3 days (1-14). RESULTS: No reconversions occurred, and one patient experienced gastric emptying delay in the immediate postoperative period with spontaneous resolution. In four patients, SMAS was associated with severe stenosis of the celiac trunk which was treated in the same operation, and four patients presented stenosis of the left renal vein (the "nutcracker" phenomenon). With a median follow-up of 94 months (SD 65.3), eight patients (61.5%) had excellent results. One patient had a relapse of symptoms 4 years after surgery requiring distal gastrectomy, two patients presented delay in gastric emptying following temporary improvement and one patient experienced no improvement. CONCLUSIONS: Latero-lateral duodenojejunostomy yields good results in SMAS although it requires other gastric motility disorders to be ruled out for appropriate treatment to be established.