Circulating tissue factor-positive extracellular vesicles and their association with thrombosis in different diseases.

Tissue factor (TF) is a procoagulant protein released from activated host cells, such as monocytes, and tumor cells on extracellular vesicles (EVs). TF + EVs are observed in the circulation of patients with various types of diseases. In this review, we will summarize the association between TF + EVs and activation of coagulation and survival in different types of diseases, including cancer, sepsis, and infections with different viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will also discuss the source of TF + EVs in various diseases. EVTF activity is associated with thrombosis in pancreatic cancer patients and coronavirus disease 2019 patients (COVID-19) and with disseminated intravascular coagulation in cancer patients. EVTF activity is also associated with worse survival in patients with cancer and COVID-19. Monocytes are the major sources of TF + EVs in sepsis, and viral infections, such as HIV, Ebola virus, and SARS-CoV-2. In contrast, alveolar epithelial cells are the major source of TF + EVs in bronchoalveolar lavage fluid in COVID-19 and influenza A patients. These studies indicate that EVTF activity could be used as a biomarker to identify patients that have an increased risk of coagulopathy and mortality.

Reversibility of valve regurgitation due to cancer-related non-bacterial thrombotic endocarditis after switching direct oral anticoagulation for heparin.

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition related to a state of hypercoagulability in advanced neoplastic disease. Most of the time, arterial thromboembolic event precedes the diagnosis of NBTE. We report here a case of NBTE responsible for multiple ischaemic strokes, which leads to the diagnosis of metastatic pancreatic adenocarcinoma. Aortic and mitral valvular regurgitations secondary to NBTE appeared within 6 weeks despite therapeutic anticoagulation with direct oral anticoagulant (DOAC) in stroke prevention of paroxysmal atrial fibrillation. Bivalvular regurgitations resolved 8 weeks after therapeutic switch to low-molecular-weight heparin (LMWH) and chemotherapy. DOACs are a possible alternative to LMWH for the prevention of venous thromboembolism in patients with active neoplasia. There is a lack of evidence for a clinical efficiency for the prevention of arterial thromboembolism in NBTE. We propose here a short review of the efficacy of anticoagulant therapy for the prevention of arterial thromboembolism in NBTE.

Outcomes of patients undergoing elective liver and pancreas cancer surgery during the SARS-CoV-2 pandemic: an international, multicentre, prospective cohort study.

BACKGROUND: The effect of SARS-CoV-2 infection upon HPB cancer surgery perioperative outcomes is unclear. Establishing risk is key to individualising treatment pathways. We aimed to identify the mortality rate and complications risk for HPB cancer elective surgery during the pandemic. METHODS: International, prospective, multicentre study of consecutive adult patients undergoing elective HPB cancer operations during the initial SARS-CoV-2 pandemic. Primary outcome was 30-day perioperative mortality. Secondary outcomes included major and surgery-specific 30-day complications. Multilevel cox proportional hazards and logistic regression models estimated association of SARS-CoV-2 and postoperative outcomes. RESULTS: Among 2038 patients (259 hospitals, 49 countries; liver n = 1080; pancreas n = 958) some 6.2%, n = 127, contracted perioperative SARS-CoV-2. Perioperative mortality (9.4%, 12/127 vs 2.6%, 49/1911) and major complications (29.1%, 37/127 vs 13.2%, 253/1911) were higher with SARS-CoV-2 infection, persisting when age, sex and comorbidity were accounted for (HR survival 4.15, 95% CI 1.64 to 10.49; OR major complications 3.41, 95% CI 1.72 to 6.75). SARS-CoV-2 was associated with late postoperative bleeding (11.0% vs 4.2%) and grade B/C postoperative pancreatic fistula (17.9% vs 8.6%). CONCLUSION: SARS-CoV-2 infection was associated with significantly higher perioperative morbidity and mortality. Patients without SARS-CoV-2 had acceptable morbidity and mortality rates, highlighting the need to protect patients to enable safe ongoing surgery.

Case presentation and panel discussion: Nutrition issues in cancer.

Advances in treatment of malignancy including novel pharmacologic therapies and surgical interventions has led to significant improvement in survival. As cancer becomes a chronic disease, nutrition interventions play an increasingly important role in short- and long-term outcomes. The current manuscript presents a case of a 66-year-old male with new diagnosis of pancreatic cancer diagnosed incidentally in the setting of COVID-19. Expert panelists in the field of nutrition discuss optimal strategies for diagnosis of malnutrition along with preoperative, perioperative, and postoperative optimization of nutrition. This discussion focuses on the use of probiotics, immune-modulating nutrition, fish oil, specialized proresolving mediators, and use of enteral and parenteral nutrition support.

DEPEND study protocol: early detection of patients with pancreatic cancer - a pilot study to evaluate the utility of faecal elastase-1 and 13C-mixed triglyceride breath test as screening tools in high-risk individuals.

INTRODUCTION: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the 13C-mixed triglyceride (13C-MTG) breath test) to identify patients with PC that urgently needs imaging studies. METHODS AND ANALYSIS: This prospective pilot (proof of concept) study will be carried out on 25 patients with resectable PC, 10 patients with chronic pancreatitis and 25 healthy volunteers. This study will construct a predictive algorithm for PC, using two tests of pancreatic exocrine function, FE-1 test and the 13C-MTG breath test. Continuous flow isotope ratio mass spectrometry in the 13C-MTG breath test will be used to analyse enriched 13CO2 in exhaled breath samples. The additional predictive benefit of other potential biomarkers of PC will also be considered. Potential biomarkers of PC showing abilities to discriminate between patients with PC from healthy subjects or patients with chronic pancreatitis will be selected by metabolomic analysis. ETHICS AND DISSEMINATION: The study was approved by the North of Scotland Research and Ethics Committee on 1 October 2020 (reference: 20/NS/0105, favourable opinion granted). The results will be disseminated in presentations at academic national/international conferences and publication in peer-review journals.

The Impact of COVID-19 Infection on the Postoperative Outcomes in Pancreatic Cancer Patients.

BACKGROUND/AIM: The aim of this study is to report a case series of three patients who developed postoperative severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection, although the initial tests were negative. PATIENTS AND METHODS: Between April and September 2020, three patients submitted to pancreatoduodenectomy developed SARS-CoV-2 infection; their outcomes were compared to those of a similar group in which the postoperative outcomes were uneventful. RESULTS: There were no significant differences between the two groups in terms of pre- and intraoperative outcomes; however, all of the three cases who developed SARS-CoV-2 infection postoperatively required re-admission in the intensive care unit and a longer hospital in stay. The overall mortality rate was null. CONCLUSION: Patients submitted to pancreatoduodenectomy for pancreatic head cancer who develop SARS-COV-2 infection postoperatively need a more appropriate supportive care; however, the overall mortality does not appear to increase, justifying, in this way, the continuation of programmed oncological of surgeries.

Successful and Safe Reinstitution of Chemotherapy for Pancreatic Cancer after COVID-19.

Cancer patients are regarded as highly vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV)-2. However, little is known regarding how cancer treatments should be restarted for cancer patients after coronavirus disease (COVID)-19. We herein report a pancreatic cancer case in which chemotherapy was able to be reinstituted after COVID-19. The patient was a 67-year-old man diagnosed with pancreatic cancer. On day 7 after first chemotherapy, he was infected with COVID-19. A SARS-CoV-2 test was negative after one month of treatment, and we reinstituted chemotherapy. The patient has received three cycles of chemotherapy without recurrence of COVID-19. It may be feasible to reinstitute chemotherapy for cancer patients after a negative SARS-CoV-2 test.

Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic: an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey.

BACKGROUND: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. METHODS: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. RESULTS: Overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. CONCLUSION: This study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a "new" normal world with screening of patients and staff for COVID-19.