Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

SMC3 epigenetic silencing regulates Rab27a expression and drives pancreatic cancer progression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is expected to soon surpass colorectal cancer as a leading cause of cancer mortality in both males and females in the US, only lagging behind lung cancer. The lethality of PDAC is driven by late diagnosis and inefficient therapies. The complex biology of PDAC involves various cellular components, including exosomes that carry molecular information between cells. Thus, recipient cells can be reprogrammed, impacting tumorigenesis. Rab27a is a GTPase responsible for the last step of exosomes biogenesis. Hence, dissecting the mechanisms that regulate the expression of Rab27a and that control exosomes biogenesis can provide fundamental insights into the molecular underpinnings regulating PDAC progression. METHODS: To assess the mechanism that regulates Rab27a expression in PDAC, we used PDAC cell lines. The biological significance of these findings was validated in PDAC genetically engineered mouse models (GEMMs) and human samples. RESULTS: In this work we demonstrate in human PDAC samples and GEMMs that Rab27a expression decreases throughout the development of the disease, and that Rab27a knockout promotes disease progression. What is more, we demonstrate that Rab27a expression is epigenetically regulated in PDAC. Treatment with demethylating agents increases Rab27a expression specifically in human PDAC cell lines. We found that SMC3, a component of the cohesin complex, regulates Rab27a expression in PDAC. SMC3 methylation is present in human PDAC specimens and treatment with demethylating agents increases SMC3 expression in human PDAC cell lines. Most importantly, high levels of SMC3 methylation are associated with a worse prognosis in PDAC. Mechanistically, we identified an enhancer region within the Rab27a gene that recruits SMC3, and modulates Rab27a expression. CONCLUSION: Overall, we dissected a mechanism that regulates Rab27a expression during PDAC progression and impacts disease prognosis.

Quality of life in patients with mild Alzheimer disease: the mediator role of mindfulness and spirituality.

OBJECTIVES: This study examined the mediator role of mindfulness and spirituality in the relationship between psychological morbidity, awareness of the disease, functionality, social support, family satisfaction, and quality of life (QoL) in patients with mild AD. METHOD: The sample consisted of 128 patients who answered the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD), the Hospital Anxiety and Depression Scales (HADS), the Satisfaction with Social Support Scale (SSSS), the Family Satisfaction Scale (FSS), the Spiritual and Religious Attitudes in Dealing with Illness (SpREUK), the Index of Barthel, and the Quality of Life-Alzheimer's Disease (QoL-AD). RESULTS: Mindfulness and spirituality mediated the relationship between functionality, awareness of the disease, family satisfaction and QoL. Psychological morbidity had a direct negative impact on QoL and was negatively associated with awareness of the disease, family satisfaction and social support. Mindfulness was negatively associated with spirituality and the latter was negatively associated with QoL. More social support was associated with greater awareness of the disease and family satisfaction. More functionality, awareness of the disease and family satisfaction contributed to more QoL and this relationship was mediated by mindfulness and spirituality. CONCLUSION: Interventions directed at the promotion of the QoL of patients with mild AD should focus on the promotion of mindfulness skills in AD patients, in addition to the reduction of psychological morbidity and the promotion of functionality, awareness of the disease, family relationships and social support.

Longitudinal changes on the quality of life in caregivers of type 2 diabetes amputee patients.

PURPOSE: To explore changes in the quality of life of caregivers of amputees due to type 2 diabetes ten months after amputation. METHODS: This is a longitudinal study with three moments of evaluation (T1: one month after surgery, T2: 7 months, T3: 10 months). The sample comprised 110, 101, and 84 caregivers of amputated patients with type 2 diabetes. Caregivers answered a Socio-demographic questionnaire; the Self-Assessment Caregiver; the Family Disruption from Illness Scale; and the Short Form Health Survey (SF36). RESULTS: Stress levels were not significantly reflected in changes on mental quality of life over time, except in the caregivers who presented less stress, emphasizing the adverse role of stress when experienced on a continuous basis for ten months on the caregivers' mental well-being. Caregivers presented greater number of physical symptoms at T2 that decreased at T3. CONCLUSIONS: According to the results, in order to promote caregivers' physical and mental quality of life, it would be important to evaluate stress levels especially in patients who presented somatic complaints.

Brief emotional screening in oncology: Specificity and sensitivity of the emotion thermometers in the Portuguese cancer population.

OBJECTIVE: This study aimed to determine the cutoff and the specificity and sensitivity of the Emotion Thermometers (ET) in a Portuguese sample of cancer patients. METHOD: A total of 147 patients (mean age = 49.2; SD = 12.6) completed the ET, the Brief Symptom Inventory (BSI), and the Subjective Experiences of Illness Suffering Inventory. Data were collected in a cancer support institution and in a major hospital in the North of Portugal. RESULT: The optimal cutoff for the Anxiety Thermometer was 5v6 (until 5 and 6 or more), which identified 74% of the BSI-anxiety cases and 70% of noncases. The Depression Thermometer cutoff was 4v5 (until 4 and 5 or more), which identified 85% of BSI-depression cases and 82% of noncases. Cutoff for the Anger Thermometer was 4v5 (until 4 and 5 or more), which identified 83% of BSI-hostility cases and 73% of noncases; for the Distress Thermometer, the optimal cutoff was 4v5 (until 4 and 5 or more), which identified 84% of the suffering cases and 73% of noncases. Finally, for the Help Thermometer, it was 3v4 (until 3 and 4 or more), which helped to identify 93% of the suffering cases and 64% of noncases. SIGNIFICANCE OF RESULTS: Results supported the Portuguese version of the ET as an important screening tool for identifying the emotional distress in cancer patients.

Review: Gastric malignancies: Basic aspects.

Gastric cancer is the third deadliest cancer in the world, and the absolute number of cases is increasing every year due to aging and growing of high-risk populations. This disease is a consequence of the complex interaction of microbial agents, with environmental and host factors, resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways. Despite the advances in our understanding of carcinogenesis, there are still reduced therapeutic options for patients with gastric cancer. In recent years, genomic analyses of gastric tumors have emphasized their molecular heterogeneity. The distinction of gastric cancer molecular subtypes may be a key to identify novel therapeutic targets, to predict patient outcome and response to therapy, and to guide early diagnosis strategies. In this review, we summarize the most recent updates on the relationship between microbial agents and gastric cancer, in particular, Helicobacter pylori, the non-H pylori microbiome, and Epstein-Barr virus. We also highlight the main advances made in the past year regarding the molecular characterization of gastric cancer, especially the signatures with potential clinical utility.

New insights into the inflamed tumor immune microenvironment of gastric cancer with lymphoid stroma: from morphology and digital analysis to gene expression.

BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations. CD3+ and CD8+ T-cell densities were calculated by digital analysis. Fifty-four non-GCLSs were used as control group. RESULTS: GCLSs displayed distinctive clinicopathological features, such as lower pTNM stage (p = 0.02) and better overall survival (p = 0.01). EBV+ or MSI-high phenotype was found in 66.7 and 16.7% cases, respectively. GCLSs harbored a cytotoxic T-cell-inflamed profile, particularly at the invasive front of tumors (p < 0.01) and in EBV+ cases (p = 0.01). EBV+ GCLSs, when compared to EBV- GCLSs, showed higher mRNA expression of genes related to Th1/cytotoxic and immunosuppressive biomarkers. PD-L1 protein expression, observed in neoplastic and immune stromal cells (33.3 and 91.7%, respectively), and PD-L1 amplification (18.8%) were restricted to EBV+/MSI-high tumors and correlated with high values of PD-L1 mRNA expression. CONCLUSIONS: This study shows that GCLS has a distinctive clinico-pathological and molecular profile. Furthermore, through an in-depth study of tumor immune microenvironment-by digital analysis and mRNA expression profiling-it highlights the role of EBV infection in promoting an inflamed tumor microenvironment, with putative therapeutic implications.

Beliefs about medicines as mediators in medication adherence in type 2 diabetes.

AIMS: This study analysed whether beliefs about medicines mediated the relationship between illness representations and medication adherence. BACKGROUND: Adherence to medication is required in diabetes treatment, contributing to decreased blood glycaemic levels. The knowledge and perception of patients about diabetes as well as the beliefs about medicines are considered to be key factors for medication adherence. DESIGN: The study used a cross-sectional design that included 387 patients recently diagnosed with type 2 diabetes. METHODS: Participants were assessed, between 2010 and 2013, and answered the Medication Adherence Scale, the Beliefs about Medicines Questionnaire, and the Brief Illness Perception Questionnaire. RESULTS: The results of the path analysis showed that beliefs about medicines had a mediating role on self-report medication adherence with the exception of beliefs about specific concerns with medicines. Therefore, both general beliefs and specific needs about medicines mediated the relationship between diabetes consequences and self-report medication adherence as well as between treatment control and self-report medication adherence. Needs about medicines mediated the relationship between personal control and self-report medication adherence. CONCLUSION: Health professionals should target beliefs about medicines besides illness representations regarding medication adherence. The current study may help optimize adherence to medication in early-diagnosed type 2 diabetes patients.

Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota.

OBJECTIVE: Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma. DESIGN: The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt. RESULTS: The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins. CONCLUSIONS: Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Gastric cancer: Basic aspects.

Despite major breakthroughs in the field of personalized medicine, gastric cancer (GC) remains a clinically challenging disease, characterized by scarce effective treatment options and the lack of reliable molecular tools for the prediction of patient outcome and response to therapy. The pronounced molecular heterogeneity that dictates the phenotypical aggressiveness of gastric neoplasms severely limits the antitumor efficacy of targeted agents brought to clinical trials, and constitutes a favorable setting for the emergence of refractory tumors exhibiting multidrug resistance. We will review the most recent advances in our understanding of GC biology, which are underlying the development and clinical testing of novel targeted therapeutic agents. We will also emphasize how their efficacy and acquired resistance relate to the aberrant molecular signatures that drive gastric malignancy.

Burden changes in caregivers of patients with type 2 diabetes: A longitudinal study.

AIMS: The aim of this study was to explore changes in the burden of caregivers of patients with type 2 diabetes experiencing lower limb amputation after surgery. BACKGROUND: Literature suggests the burden overload experienced by the caregivers of new amputees is related to an imbalance between the demands and the resources available to these caregivers. DESIGN: The study followed a longitudinal design assessing caregiver burden at 1 (T1), 7 (T2) and 10 (T3) months after the patient's surgery. METHODS: We used a convenience sample of caregivers of patients with type 2 diabetes amputated with recent lower limb amputation. Data were collected in several hospital units over 18 months in 2014-2015. Sample size included at T1, T2 and T3 110, 101 and 84. Participants completed the socio-demographic questionnaire, the Burden Assessment Scale and the Self-Assessment Caregiver Questionnaire scale. RESULTS: Caregivers who received help reported lower levels of burden from at baseline with no variation over time. Those caregivers with high levels of stress showed an increase in burden over time, although these results were not significant. Also, caregivers who did not receive help showed higher levels of burden and stress over time compared with the initial baseline that decreased over time. CONCLUSION: These results highlight the importance of receiving help, in care, especially among caregivers who care for patients who have undergone major amputation.

Quality of life in patients with skin tumors: the mediator role of body image and social support.

OBJECTIVE: This study analyzed the relationships between illness representations, psychological morbidity, family stress, and quality of life and whether these variables were mediated by body image and social support. METHODS: The sample consisted of 106 patients with skin tumors, who answered the following measures: Dermatology Life Quality Index, Illness Perception Questionnaire-Brief, Medical Outcomes Study Social Support Survey, Index of Family Relations, Hospital Anxiety and Depression Scales, and the Body Image Scale. RESULTS: Patients with poor quality of life showed more threatening cognitive and emotional illness representations, less perceived social support, higher psychological morbidity, and higher concern with body image. Body image mediated the relationship between cognitive and comprehension illness representations, family stress, psychological morbidity, and quality of life. Social support mediated the relationship between family stress/psychological morbidity and quality of life. CONCLUSIONS: Psychological intervention should focus on body image and social support, particularly in patients with melanoma, less disease duration, tumors in the face, head or neck, in an active professional status, and with lower education.

Gastric cancer: Basic aspects.

Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.

Gastric cancer pathogenesis.

Gastric cancer (GC) results from a multistep process that is influenced by Helicobacter pylori infection, genetic susceptibility of the host, as well as of other environmental factors. GC results from the accumulation of numerous genetic and epigenetic alterations in oncogenes and tumor suppressor genes, leading to dysregulation of multiple signaling pathways, which disrupt the cell cycle and the balance between cell proliferation and cell death. For this special issue, we have selected to review last year's advances related to three main topics: the cell of origin that initiates malignant growth in GC, the mechanisms of direct genotoxicity induced by H. pylori infection, and the role of aberrantly expressed long noncoding RNAs in GC transformation. The understanding of the molecular basis of GC development is of utmost importance for the identification of novel targets for GC prevention and treatment.

Interleukin-1B signalling leads to increased survival of gastric carcinoma cells through a CREB-C/EBPß-associated mechanism.

BACKGROUND: Polymorphisms in inflammation-related genes have been associated with a risk of gastric carcinoma (GC). However, the biological mechanisms underlying these associations are still elusive. Our objective was to determine whether chronic inflammation-associated IL1Β signalling, as seen in the context of Helicobacter pylori infection, could be linked to gastric carcinogenesis by modulating the behaviour of gastric epithelial cells. METHODS: The effect of IL1B was assessed by studying the expression and activation status of the IL1Β-activated transcription factors C/EBPß and CREB in GC cell lines. Interaction between CREB and C/EBPß was explored through interference RNA, chromatin immunoprecipitation and chemical inhibition. CREB and C/EBPß expression was analysed in 66 samples of primary GC and in normal gastric mucosa. GC cell growth was analysed in vitro by BrdU incorporation and in vivo employing a chicken embryo chorioallantoic membrane model. RESULTS: We found that IL1B regulates the expression/activation status of both C/EBPß and CREB in GC cells through an ERK1/2-dependent mechanism. Our results show that CREB is a direct transactivator of CEBPB, acting as an upstream effector in this regulatory mechanism. Furthermore, we found CREB to be overexpressed in 94 % of GC samples and significantly associated with C/EBPß expression (P < 0.05). Finally, we demonstrated both in vitro and in vivo that CREB can mediate IL1B-induced GC cell proliferation. CONCLUSIONS: Our results support the hypothesis that the effect of chronic inflammation on gastric carcinogenesis, as seen in the context of genetically susceptible individuals infected with Helicobacter pylori, includes the modulation of signalling pathways that regulate survival mechanisms in epithelial cells. IL1B is able to increase the expression/activation status of CREB and its target gene C/EBPß, which are mandatory for GC cell survival. Our results may help inform new strategies for the prevention and treatment of GC, including the control of chronic inflammation.

Partners' representations of diabetes as mediators between patients' representations and adherence to self-care behaviors, in type 2 diabetes.

The purpose of this study was to analyze partners' representations of diabetes as mediators between patients' illness representations and adherence to all self-care behaviors, in recently diagnosed type 2 diabetes (T2DM) patients. The sample included 340 patients and their respective partners. The instruments used were: Revised Summary of Diabetes Self-Care Activities (RSDSCA); Medication Adherence Report Scale (MARS); and the Brief Illness Perception Questionnaire  (Brief-IPQ). A mediational effect of partners' representation of diabetes consequences was found between the same patients' representations and  exercise, foot care, and self-monitoring of blood glucose. Partners' representations of personal and treatment control, were mediators between the same partners' representations and self-monitoring of blood glucose. No partners' representations mediated patients' representation and adherence to medication or diet . This study emphasized partners' representations on patient's adherence to exercise, foot care and monitoring of blood glucose, in recent diagnosed T2DM patients. Interventions to promote adherence in T2DM should promote convergence between patients and partners' diabetes representations. This study provides some evidence for the need to treat T2DM within the dyad to improve adherence, starting after the diagnosis.

Coping and quality of life in patients with skin tumors in the follow-up stage: The mediating role of body image and psychological morbidity.

This study examined the relationships between coping style, body image, psychological morbidity, and quality of life. A total of 58 patients who were diagnosed with skin tumors, had been submitted to surgery, and were in the follow-up phase answered the following instruments: dermatology life quality index (DLQI), hospital anxiety and depression scales (HADS), body image scale (BIS), and the mini mental adjustment to cancer scale (Mini-MAC). The results showed that patients with a higher use of the coping styles of helplessness/hopelessness, anxious preoccupation, and cognitive avoidance reported a worse quality of life. Body image mediated the relationship between the coping styles of anxious preoccupation, helplessness/hopelessness, and quality of life. Psychological morbidity mediated the relationship between helplessness/hopelessness and quality of life. Therefore, even in the follow-up phase, it is important that health professionals are aware of the patient's emotional distress and body image to identify those at a higher risk of having a poorer quality of life.

Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies.

Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.