BACKGROUND AND OBJECTIVE:Migraine oscillates between different states in association with internal homeostatic functions and biological rhythms that become more easily dysregulated in genetically susceptible individuals. Clinical and pre-clinical data on migraine pathophysiology support a primary role of the central nervous system (CNS) through 'dysexcitability' of certain brain networks, and a critical contribution of the peripheral sensory and autonomic signalling from the intracranial meningeal innervation. This review focuses on the most relevant back and forward translational studies devoted to the assessment of CNS dysfunctions involved in primary headaches and discusses the role they play in rendering the brain susceptible to headache states.METHODS AND RESULTS:We collected a body of scientific literature from human and animal investigations that provide a compelling perspective on the anatomical and functional underpinnings of the CNS in migraine and trigeminal autonomic cephalalgias. We focus on medullary, hypothalamic and corticofugal modulation mechanisms that represent strategic neural substrates for elucidating the links between trigeminovascular maladaptive states, migraine triggering and the temporal phenotype of the disease.CONCLUSION:It is argued that a better understanding of homeostatic dysfunctional states appears fundamental and may benefit the development of personalized therapeutic approaches for improving clinical outcomes in primary headache disorders.SIGNIFICANCE:This review focuses on the most relevant back and forward translational studies showing the crucial role of top-down brain modulation in triggering and maintaining primary headache states and how these central dysfunctions may interact with personalized pain management strategies.

The incidence of cancer is increasing, which translates into a higher demand for medical oncology services every day. Work overload and, consequently, the development of burnout is present in up to 50% of medical oncology staff. Aim: The objective of this publication is to expose the current situation and to establish recommendations for the scheduling of the medical activities in medical oncology considering the different types of care delivery and the necessary time for these to improve patient care while protecting the physician wellbeing. Materials and Methods: A review of the national and international literature was carried out regarding the scheduling of medical oncology care, and a web seminar was held with national medical specialists in oncology. Results: We were able to show that there are no standard schedules, and there is a great dispersion in the number of patients treated in the different centers at the national level. Conclusion: The Chilean Society for Medical Oncology considers essential to standardize medical programming in the different oncology services, in order to assure the best care for cancer patients and to protect the medical personnel from work overload.

Spreading depolarization, usually termed cortical spreading depression has been proposed as the pathophysiological substrate of migraine aura and as an endogenous trigger of headache pain. The links between neurovascular coupling and cortical craniofacial nociceptive activities modulated by SD were assessed by combining in vivo local field potential (LFP) recordings in the primary somatosensory cortex (S1) with functional ultrasound imaging of S1 and caudal insular (INS) cortices of anesthetized male rats. A single SD wave triggered in the primary visual cortex elicited an ipsilateral, quadriphasic hemodynamic and electrophysiological response in S1 with an early phase consisting of concomitant increases of relative cerebral blood volume (rCBV) and LFPs. A transient hypoperfusion was then correlated with the beginning of the neuronal silence, followed by a strong increase of rCBV, whereas synaptic activities remained inhibited. LFPs and rCBV recovery period was followed by a progressive increase in S1 and INS baseline activities and facilitation of cortical responses evoked by periorbital cutaneous receptive field stimulation. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks. SIGNIFICANCE STATEMENT A crucial unsolved issue is whether visual aura and migraine headache are parallel or sequential processes. Here, we show that a single spreading depolarization wave triggered from the primary visual cortex is powerful enough to elicit progressive, sustained increases of hemodynamic and sensory responses to percutaneous periorbital noxious stimuli recorded in S1 and insular ophthalmic fields. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks.

Background Gastric cancer is the fifth cause of cancer incidence worldwide. Multidisciplinary approaches that improve the survival are needed. Perioperative chemotherapies show improvement in pathological complete remission (pCR) and overall survival (OS), but less than 50% of the patients completed the chemotherapeutic regimen. The recent 5-fluorouracil, leucovorin, oxaliplatin, docetaxel-4 (FLOT4) study shows OS 50 months and pCR 16.6%, but only 46% of the patients completed pre- and postoperative treatment. This case series report evaluated pCR and safety in patients that received complete preoperative chemotherapeutic with FLOT. Methods Patients received eight cycles FLOT regimen before surgery. Each cycle comprised 50 mg/m2 docetaxel intravenous (iv) on day 1, 85 mg/m2 oxaliplatin iv on day 1, 200 mg/m2 leucovorin iv on day 1 and 2,600 mg/m2 5-fluorouracil iv in a 24-hour infusion on day 1, every 2 weeks. Results Fifty-nine patients were evaluated, 58 patients received preoperative cycles. Thirty-one patients received all eight cycles of preoperative therapy. 65.5% patients presented any major adverse event. Thirty-nine patients underwent surgery. Thirty-three biopsy reports were obtained. Six patients (18.2%) presented pCR, 13 patients (39.4%) had no lymph node involvement. OS was 21.32 months. Patients with histology of signet ring carcinoma cells had a shorter survival than other histologies. Conclusion Total neoadjuvant with FLOT chemotherapy presents an adequate safety profile, a similar pathologic regression rate, and a slightly higher rate of completing treatment to report in perioperative FLOT regimen studies. A prospective clinical study with suitable diagnostic, staging tools and an adequate follow-up may prove total neoadjuvant chemotherapy’s efficacy.

e16007 Background: GC is frequent in Chile, with an incidence of 7.8% and a mortality rate of 11.6% in 2020. Late diagnosis continues to be one of the most important problems, although treatments in advanced stages have experienced important advances in the last 6 years. REGARD and RAINBOW trials showed an increase in median OS when using Ramucirumab alone or in combination with Paclitaxel of 5,2 and 9,4 mths respectively. Although this therapy is not covered by our Public Health Insurance, there are some patients that they can access. Also, there are not too many reports in LATAM pts so we present our local real world data. Methods: We conducted a retrospective study of local data from patients diagnosed with mGC who progressed with standard first-line treatment and were treated with ramucirumab-based regimens from January 2015 to January 2021. Clinical factors were recorded baseline, characteristics of therapy and AE related to toxicity. Toxicity was assessed by CTCAE v5.0 and response to treatment by RECIST 1.1. Results were analyzed by measuring time to progression and survival. Results: The search resulted in 9 pts, 6 men and 3 women between 38 and 72 years (median 59 years). 66% were in ECOG 1 performance status and 33% in ECOG 2, with a median BMI of 23 kg / m2. 33% were smokers and all had some other comorbidity as a medical history. All tumors were adenocarcinomas and 33% had a signet ring cell component on histology. Only one tumor was HER2 +++ and all were MSS (by IHC). The most common first-line treatment received before progression was FOLFOX; 4 to 12 cycles; 8 cycle average. All patients were treated with paclitaxel-ramucirumab as 2L (4 to 19 cycles, mean of 5 cycles). 67% of patients achieved stable disease with the best response. During the follow-up period, 8 patients experienced disease progression in an average of 6.7 months, who switched to 3L with Nivolumab. Relapses during 2L were in the peritoneum and 55% in other sites as well. Only two patients discontinued paclitaxel treatment after 4 cycles due to intolerance and continued to receive Ramucirumab. 44% developed grade 3 toxicities: 50% of them due to taxane-related peripheral neuropathy. Grade 4 or 5 toxicity was not reported. 50% of patients were alive at 6 months of treatment. Conclusions: In our country and LATAM, GC still has a significant medical and socioeconomic burden. Its incidence is still one of the highest in the world, most patients are diagnosed in the metastatic stage and face treatment in deficient PS. In this context, our local real-world data showed consistency with what the literature says, although more data remains to accumulate and describe.

663 Background: Periampullary cancers can originate in the pancreas, duodenum, bile duct or structures of the ampullary complex. The treatment of choice in early stages is pancreatoduodenectomy. The management post-surgery can depend on the histology pattern, and the overall survival can vary in different subgroups. Methods: A retrospective cohort study. We examined patients (pts) with invasive periampullary cancer undergoing pancreatoduodenectomy at the Hospital Clinico Universidad de Chile between 2002 to 2018. We analyzed epidemiological, clinical, surgical, and histological data. OS and the hazard ratio (HR) were established by GraphPad Prism 8.0. Results: Thirty-seven cases were registered. Twenty-two (59%) pts were men. The mean age was 62.5 (43-83 years). The histological subtypes were: 15 pts (40.5%) intestinal group (IN), 20 pts (54%) pancreatobiliary group (PB), 1 pt (2.7%) mixed and 1 pt (2.7%) signet ring cell type. A full concordance between histology and immunohistochemistry (CK20, CK7, CDX2, MUC1, and MUC2) patterns was 66% of the PB group, and 0% of the IN group. The stage IB was most frequent in all of the group (36,4%). The most frequent stages were IB (66,6%) in the IN type and IIIA (46%) in the PB type. The level of Ca19-9 was higher the PB group than IN group (629.7 versus 41.5 U/ml, respectively). Seven pts received postoperative adjuvant treatment such as FOLFOX, capecitabine, and gemcitabine. The median OS was 133,5 months (mo) in the intestinal group and 32,6 mo in PB group (P-value = 0.021). The HR was 0.38 (95% CI of ratio 0.1332 to 1.084). The 5-year OS was 75,2% and 45,7% in the IN and PB group, respectively. Conclusions: Periampullary cancer remains very challenging because it is a rare malignancy and present diverse histological pattern. These factors influence the behavior and OS of the disease. Our results showed clinically and statistically relevant differences in the staging, levels of Ca19-9, and OS of the IN and PB subtypes. Our patients received few post-operatory therapies such as chemotherapy; this factor could influence the OS in the high-risk group. According to our data, a personalized treatment by histological type should consider in this disease.

¿Cómo saber si la información brindada por un postulante durante un proceso de selección de personal es verídica? Paul Ekman, psicólogo pionero en el estudio de las expresiones faciales, vincula las mentiras con las microexpresiones, un tipo de gesto facial sutil, corto y que representa emociones que una persona intenta reprimir. Esta investigación propone el uso de Local Binary Patterns y Support Vector Machines para detectar microexpresiones y clasificarlas a través de la implementación de un sistema que fue probado en la base de datos SAMM y en sujetos de prueba.

Cancer patient care requires a multi-disciplinary approach and multiple medical and ethical considerations. Clinical care during a pandemic health crisis requires prioritising the use of resources for patients with a greater chance of survival, especially in developing countries. The coronavirus disease 2019 crisis has generated new challenges given that cancer patients are normally not prioritised for admission in critical care units. Nevertheless, the development of new cancer drugs and novel adjuvant/neoadjuvant protocols has dramatically improved the prognosis of cancer patients, resulting in a more complex decision-making when prioritising intensive care in pandemic times. In this context, it is essential to establish an effective and transparent communication between the oncology team, critical care, and emergency units to make the best decisions, considering the principles of justice and charity. Concurrently, cancer treatment protocols must be adapted to prioritise according to oncologic response and prognosis. Communication technologies are powerful tools to optimise cancer care during pandemics, and we must adapt quickly to this new scenario of clinical care and teaching. In this new challenging pandemic scenario, multi-disciplinary work and effective communication between clinics, technology, science, and ethics is the key to optimising clinical care of cancer patients.

BACKGROUND: Increased bone resorption is driven by augmented osteoclast activity in pathological states of the bone, including osteoporosis, fracture and metastatic bone cancer. Pain is a frequent co-morbidity in bone pathologies and adequate pain management is necessary for symptomatic relief. Bone cancer is associated with severe skeletal pain and dysregulated bone remodelling, while increased osteoclast activity and bone pain are also observed in osteoporosis and during fracture repair. However, the effects of altered osteoclast activity and bone resorption on nociceptive processing of bone afferents remain unclear.METHODS: This study investigates whether physiologic osteoclasts and resulting changes in bone resorption can induce skeletal pain. We first assessed correlation between changes in bone microarchitecture (through µCT) and skeletal pain using standardized behavioural phenotyping assays in a mouse model of metastatic bone cancer. We then investigated whether increased activity of physiologic osteoclasts, and the associated bone resorption, is sufficient to induce skeletal pain using mouse models of localized and widespread bone resorption following administration of exogenous receptor activator of nuclear factor kappa-B ligand (RANKL).RESULTS: Our data demonstrates that mice with bone cancer exhibit progressive pain behaviours that correlate with increased bone resorption at the tumour site. Systemic RANKL injections enhance osteoclast activity and associated bone resorption, without producing any changes in motor function or pain behaviours at both early and late timepoints.CONCLUSION: These findings suggest that activation of homeostatic osteoclasts alone is not sufficient to induce skeletal pain in mice.SIGNIFICANCE STATEMENT: The role of osteoclasts in peripheral sensitization of sensory neurones is not fully understood. This study reports on the direct link between oestrogen-independent osteoclast activation and skeletal pain. Administration of exogenous receptor activator of nuclear factor kappa-B ligand (RANKL) increases bone resorption, but does not produce pro-nociceptive changes in behavioural pain thresholds. Our data demonstrates that physiologic osteoclasts are not essential for skeletal pain behaviours.© 2020 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®. PMID: 32955748 Funding information This work was supported by: Versus Arthritis, United Kingdom Wellcome Trust, United Kingdom European Commission's Horizon 2020 Research and Innovation Programme - Marie Skłodowska-Curie Grant, Grant ID: 642720

L’aura migraineuse ainsi que le manque d’habituation aux stimuli hétéro-sensoriels suggèrent l’implication du cortex cérébral dans la pathogenèse migraineuse. D’autre part, les signes prémonitoires couramment observés chez les migraineux, tels que les perturbations du cycle veille-sommeil et les modifications de l’humeur, sont liés à une régulation hypothalamique. Nos études effectuées chez le rat ont permis de mettre en évidence plusieurs mécanismes de plasticité dysfonctionnelle au sein du tronc cérébral, de l’hypothalamus et du cortex cérébral à l’origine des céphalées migraineuses et algies vasculaires de la face. Une meilleure connaissance de ces mécanismes constitue un préalable nécessaire pour la mise en œuvre de nouvelles stratégies thérapeutiques dépourvues d’effets secondaires et/ou à visée prophylactique.