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Introduction: To this date, surgery remains the only potentially curative approach in the treatment of pancreatic cancer. To analyse the clinical impact of a structured post-operative follow-up programme, we retrospectively analysed a cohort of resected pancreatic adenocarcinoma patients treated at LMU Munich. Methods: Pancreatic adenocarcinoma patients who underwent resection and presented for regular follow-up visits at our centre between 2002 and 2017 were identified from two existing study cohorts. Diagnosis of recurrences was categorised by timing (within or outside a scheduled follow-up visit) and detection modality (imaging, CA 19-9 increase, or clinical deterioration) and correlated with disease-free survival and overall survival (OS). Results: One hundred and twenty-five patients with resected pancreatic adenocarcinoma were included in this analysis. Median OS in the whole cohort was 21.1 months. Of these 125 patients, 103 (82.4%) patients had a documented relapse. Tumour recurrences detected within a scheduled follow-up visit (n = 86, 83.5%) compared to recurrences becoming apparent at an unplanned visit (n = 17, 16.5%) were associated with a significantly improved OS (median 25.5 vs. 20.2 months, p = 0.019). Compared to patients with recurrence detected by clinical deterioration (n = 4, 3.9%), patients with recurrences detected by imaging or laboratory abnormalities (n = 99, 96.0%) had a longer median OS (24.8 vs. 15.1 months, p = 0.007). Discussion: A structured follow-up after pancreatic ductal adenocarcinoma resection may have an impact on patient outcome. Prospective trials are needed to evaluate the clinical impact of post-operative follow-up programmes. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the predictive impact of extracranial metastatic patterns on course of disease and survival in patients with colorectal cancer (CRC) and brain metastasis (BM). A total of 228 patients (134 male [59%], 94 female [41%]) with histologically proven CRC and BM were classified into different groups according to extracranial metastatic patterns. Time intervals to metastatic events and survival times from initial CRC diagnosis, extracranial and intracranial metastasis were analyzed. Extracranial organs mostly affected were liver (102 of 228 [44.7%]) and lung (96 of 228 [42.1%]). Liver and lung metastases were detected in 31 patients (13.6%). Calculated over the entire course of disease, patients with lung metastasis showed longer overall survival (OS) than patients with liver metastasis or patients without lung metastasis (43.9 vs 34.6 [P =.002] vs 35.0 months [P =.002]). From the date of initial CRC diagnosis, lung metastasis occurred later in CRC history than liver metastasis (24.3 vs 7.5 months). Once lung metastasis was diagnosed, BM occurred faster than in patients with liver metastasis (15.8 vs 26.0 months; Δ 10.2 months). Accordingly, OS from the diagnosis of liver metastasis was longer than from lung metastasis (27.1 vs 19.6 months [P =.08]). Once BM was present, patients with lung metastasis lived longer than patients with liver metastasis (3.8 vs 1.1 months [P =.028]). Shortest survival times in all survival categories analyzed revealed patients with concurrent liver and lung metastasis. Patients with CRC and BM form a heterogeneous cohort where extracranial metastasis to liver or lungs predicts survival. What's new? Brain metastases occur in around 5% of patients with colorectal cancer. These are generally not diagnosed until symptoms arise, and usually after other metastases have been found. Here, the authors evaluated patterns of metastases to the liver, lung, or both, looking for an association with survival. Brain metastasis occurs later in patients with lung metastasis than with liver metastasis, and overall survival is longer in patients with lung than with liver metastasis. This is the first analysis of metastasis patterns and survival in CRC patients, and the authors recommend routine cerebral imaging for CRC patients to detect brain metastases. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of obesity-associated inflammation and immune modulation in gastric carcinogenesis during Helicobacter-induced chronic gastric inflammation. Design C57BL/6 male mice were infected with H felis and placed on a high-fat diet (45% calories from fat). Study animals were analysed for gastric and adipose pathology, inflammatory markers in serum, stomach and adipose tissue, and immune responses in blood, spleen, stomach and adipose tissue. Results H felis-induced gastric carcinogenesis was accelerated in diet-induced obese mice compared with lean controls. Obesity increased bone marrow-derived immature myeloid cells in blood and gastric tissue of H felis-infected mice. Obesity also led to elevations in CD4 T cells, IL-17A, granulocyte macrophage colonystimulating factor, phosphorylated STAT3 and prosurvival gene expression in gastric tissue of H felis-infected mice. Conversely, in adipose tissue of obese mice, H felis infection increased macrophage accumulation and expression of IL-6, C-C motif ligand 7 (CCL7) and leptin. Finally, the combination of obesity and gastric inflammation synergistically increased serum proinflammatory cytokines, including IL-6. Conclusions Here, we have established a model to study the molecular mechanism by which obesity predisposes individuals to gastric cancer. In H felisinfected mice, obesity increased proinflammatory immune responses and accelerated gastric carcinogenesis. Interestingly, gastric inflammation augmented obesity-induced adipose inflammation and production of adipose-derived factors in obese, but not lean, mice. Our findings suggest that obesity accelerates Helicobacter-associated gastric cancer through cytokinemediated cross-talk between inflamed gastric and adipose tissues, augmenting immune responses at both tissue sites, and thereby contributing to a protumorigenic gastric microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: To elucidate the role of angiogenesis as a prognostic signature in gastric cancer, we analyzed the expression level of 36 angiogenesis-related genes (ARGs) from Stomach Adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA). Consensus clustering analysis showed two major angiogenesis-related types: one related to more aggressive clinicopathological characteristics and worse survival, and the other related to lower tumor, lymph node, metastasis (TNM) stage and better outcomes. Our analysis of TCGA with a least absolute shrinkage and selection operator (LASSO) regression model identified 10 genes associated with overall survival in gastric cancer patients. With this gene signature, we computed angiogenesis-related gene signature risk scores for individual cancer patients that predicted overall and disease-free survival, which were further validated in the independent dataset Asian Cancer Research Group (ACRG). Moreover, an overall survival (OS)-related nomogram was established and had better performance in prognosis prediction than TNM stage. Our analysis provides a comprehensive map of ARGs that can be serve as useful biomarkers for gastric cancer. Increasing evidence indicates that angiogenesis is crucial in the development and progression of gastric cancer (GC). This study aimed to develop a prognostic relevant angiogenesis-related gene (ARG) signature and a nomogram. The expression profile of the 36 ARGs and clinical information of 372 GC patients were extracted from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to divide patients into clusters 1 and 2. Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to identify the survival related ARGs and establish prognostic gene signatures, respectively. The Asian Cancer Research Group (ACRG) (n = 300) was used for external validation. Risk score of ARG signatures was calculated, and a prognostic nomogram was developed. Gene set enrichment analysis of the ARG model risk score was performed. Cluster 2 patients had more advanced clinical stage and shorter survival rates. ARG signatures carried prognostic relevance in both cohorts. Moreover, ARG-risk score was proved as an independent prognostic factor. The predictive value of the nomogram incorporating the risk score and clinicopathological features was superior to tumor, lymph node, metastasis (TNM) staging. The high-risk score group was associated with several cancer and metastasis-related pathways. The present study suggests that ARG-based nomogram could serve as effective prognostic biomarkers and allow a more precise risk stratification. [ABSTRACT FROM AUTHOR]

Introduction Venous thromboembolism (VTE) is frequent in advanced pancreatic cancer (APC). Recent studies demonstrated that the Khorana score - an established risk stratification tool for VTE in cancer - performs poorly in identifying pancreatic cancer patients at high risk for VTE. Materials and methods We performed a retrospective cohort study in order to define incidence, treatment and outcome of VTE as well as the performance of VTE risk stratification tools (Khorana score, CONKO score and aPTT ratio) in a “real life” clinical cohort of APC patients undergoing palliative chemotherapy. Results and conclusions One hundred and seventy-two eligible APC patients from our comprehensive cancer center were identified. VTE after start of palliative chemotherapy was diagnosed in 71 patients (41.3%). Most VTE events were asymptomatic ( n = 50, 29.1%) with only 21 symptomatic events (12.2%). On multivariate analysis - including age, performance status and carbohydrate antigen 19-9 (CA 19-9) - symptomatic VTE was an independent risk factor for death (hazard ratio [HR]: 2.22, 95% CI: 1.05–2.60, p < 0.05). Khorana score, CONKO score and aPTT ratio alone were not able to predict the risk for symptomatic VTE. High risk patients could only be identified by using a combination of either Khorana or CONKO score with aPTT ratio (30% vs. 10% symptomatic VTE events in high vs. low risk patients, p < 0.05). The combination of Khorana or CONKO score with aPTT thus may represent a novel risk stratification tool for symptomatic VTE in APC and should further be validated within prospective clinical trials. [ABSTRACT FROM AUTHOR]

Recent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, "precision oncology" also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for "universal genetic testing" in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that "precision oncology" approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary "molecular tumor board", and preferably within clinical trials., Competing Interests: Interessenkonflikt: Holch: Honorare, Reisekosten und / oder Mitgliederschaft in Beratungsgremien (Novartis, Roche);Westphalen: Mitgliedschaft in einem Beratungsgremium (Roche); Heinemann: Honorare (Merck, Amgen, Roche, Sanofi, Baxalta, SIRTEX, Servier); Mitgliedschaft in Beratungsgremien (Merck, Amgen, Roche, Sanofi, Baxalta, SIRTEX, Servier, Lilly, Boehringer, MSD, BMS); Forschungsförderung (Merck, Amgen, Roche, Sanofi, Pfizer, SIRTEX, Boehringer-Ingelheim); Reisekostenunterstützung (Merck, Roche, SIRTEX, Baxalta); Metzeler: Honorare (Novartis), Forschungsförderung (Celgene), Reisekostenunterstützung (Janssen-Cilag). Die übrigen Co-Autoren geben keine relvanten Interessenskonflikte an., (© Georg Thieme Verlag KG Stuttgart · New York.)