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1.
Gastroenterology ; 161(3): 785-791, 2021 09.
Article in English | MEDLINE | ID: covidwho-1626143

ABSTRACT

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.


Subject(s)
Biomedical Research/trends , Pancreatic Neoplasms , Animals , Biomarkers, Tumor/genetics , COVID-19 , Cell Lineage , Diffusion of Innovation , Genetic Predisposition to Disease , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Tumor Microenvironment , Videoconferencing
2.
Cancer Prev Res (Phila) ; 14(11): 1021-1032, 2021 11.
Article in English | MEDLINE | ID: covidwho-1463067

ABSTRACT

Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (https://GENERATEstudy.org) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in BRCA2 (N = 15, 17%), ATM (N = 11, 12%), and CDKN2A (N = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches. PREVENTION RELEVANCE: Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Genetic Predisposition to Disease , Genetic Testing/methods , Germ-Line Mutation , Pancreatic Neoplasms/genetics , Risk Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/therapy , Female , Humans , Male , Middle Aged , Models, Genetic , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Patient Participation , Risk Factors , Surveys and Questionnaires , Telemedicine , Young Adult
3.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1450313

ABSTRACT

Cancer therapy reduces tumor burden via tumor cell death ("debris"), which can accelerate tumor progression via the failure of inflammation resolution. Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacological abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth.


Subject(s)
Eicosanoids/metabolism , Epoxide Hydrolases/biosynthesis , Macrophages/immunology , Neoplasm Metastasis/pathology , Receptors, Prostaglandin E, EP4 Subtype/biosynthesis , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Cell Death/drug effects , Cell Line, Tumor , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Cytokines/metabolism , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Neoplasm Metastasis/prevention & control , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Phagocytosis/immunology , RAW 264.7 Cells
4.
Molecules ; 26(12)2021 Jun 09.
Article in English | MEDLINE | ID: covidwho-1282533

ABSTRACT

Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.


Subject(s)
Deoxyglucose/pharmacology , Garcinia/chemistry , Oils, Volatile/pharmacology , Pancreatic Neoplasms/drug therapy , Apoptosis/drug effects , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Humans , Membrane Potential, Mitochondrial , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Plant Leaves/chemistry
5.
Am J Case Rep ; 22: e930733, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1206459

ABSTRACT

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Hormonal/adverse effects , Blood Glucose Self-Monitoring/adverse effects , Dexamethasone/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/chemically induced , Insulin/adverse effects , Pancreatic Neoplasms/drug therapy , Administration, Intravenous , Aged , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Blood Glucose , COVID-19/drug therapy , Dexamethasone/adverse effects , Female , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Hypoglycemic Agents/adverse effects , Insulin/administration & dosage , Neoplasm Recurrence, Local , Pancreatic Neoplasms/pathology , SARS-CoV-2
6.
Dig Surg ; 38(2): 158-165, 2021.
Article in English | MEDLINE | ID: covidwho-1105564

ABSTRACT

BACKGROUND: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. METHODS: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. RESULTS: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. DISCUSSION/CONCLUSIONS: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.


Subject(s)
COVID-19/prevention & control , Health Services Accessibility/trends , Pancreatectomy/trends , Pancreatic Neoplasms/surgery , Practice Patterns, Physicians'/trends , Aftercare/methods , Aftercare/standards , Aftercare/trends , Attitude of Health Personnel , COVID-19/epidemiology , Europe/epidemiology , Health Care Surveys , Health Services Accessibility/standards , Humans , Infection Control/methods , Infection Control/trends , Neoplasm Staging , Pancreatectomy/standards , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Pandemics , Patient Acceptance of Health Care , Perioperative Care/methods , Perioperative Care/standards , Perioperative Care/trends , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Time-to-Treatment/standards , Time-to-Treatment/trends
7.
Tumori ; 107(6): NP24-NP27, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-992257

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare tumor, accounting for about 1% of all pancreatic exocrine cancers. Consensus on the management of metastatic PACC remains unclear. CASE PRESENTATION: Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. After progression of disease evaluated based on RECIST 1.1, toripalimab and SOX regimen was administered because of PD-L1-positive expression, high tumor mutation burden (TMB), and somatic FANCA deletion in the tumor. Both the primary and metastatic tumor mass shrank significantly after two courses. The patient exhibited sustained partial response for at least six courses with well-controlled toxic effects. Then the treatment had to be stopped for 2 months because of the coronavirus disease 2019 pandemic. Computed tomography scan in March 2020 showed disease progression. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. CONCLUSIONS: We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/metabolism , Biomarkers, Tumor/genetics , Carcinoma, Acinar Cell/drug therapy , Immunotherapy/methods , Mutation , Pancreatic Neoplasms/drug therapy , Aged , Albumins/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/immunology , Carcinoma, Acinar Cell/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Male , Paclitaxel/administration & dosage , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology
8.
Cytopathology ; 31(6): 509-513, 2020 11.
Article in English | MEDLINE | ID: covidwho-639476

ABSTRACT

INTRODUCTION: The dramatic spread of COVID-19 has raised many questions about cytological procedures performed in and out of the laboratories all over the world. METHODS: We report a heterogeneous series of fine needle aspirations performed during the period of phase 1 of the lockdown for the COVID-19 pandemic to describe our experience and measures taken during this period. RESULTS: A total of 48 fine needle aspirations (ultrasound, computed tomography and endoscopic ultrasound guided) were processed and reported. CONCLUSIONS: Pre-existing procedures have been modified to allow healthcare professionals to work safely ensuring patients the necessary assistance with samples suitable for cellularity, fixation and staining for an accurate cytological diagnosis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Lung/pathology , Pancreatic Neoplasms/pathology , Pneumonia, Viral/virology , COVID-19 , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endosonography/methods , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
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