Clinical trial-identified inflammatory biomarkers in breast and pancreatic cancers.

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancer-specific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immune-associated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes.

Challenges in Recruitment and Retention: Leveraging Health-Related Antecedents and Information Carrier Factors to Improve Patient Participation in Pancreatic Cancer Research-A Review Article.

ABSTRACT: Advancements in pancreatic ductal adenocarcinoma (PDAC) prevention, diagnosis, and treatment rely on representative and robust clinical trial participation. Given the severity of PDAC, along with the lack of effective early detection approaches, the need for accessible screening tools and new treatments is dire. Unfortunately, enrollment barriers often result in low participant accrual rates for PDAC studies and illustrate the challenging terrain researchers are facing. Research participation along with access to preventative care has been further impacted by the coronavirus disease 2019 pandemic. In this review, we use the Comprehensive Model for Information Seeking to discuss underexplored factors that influence patient participation in clinical studies. Adequate staffing, flexible scheduling, effective patient and physician communication, and culturally responsive messaging, along with the use of telehealth, can support enrollment objectives. Clinical research studies are a key component of health care, informing medical advancements, and improving outcomes. By leveraging health-related antecedents and information carrier factors, researchers can more effectively address barriers to participation and implement potential evidence-based mitigating strategies. While this work focuses on the PDAC research context, the lessons delineated here are applicable to the wider cancer research setting.

Telemedicine and intraductal papillary mucinous neoplasms: Analysis of a new follow-up strategy during COVID-19 outbreak.

BACKGROUND: The Coronavirus pandemic outbreak in 2019 and the saturation of healthcare system led to an increased use of digital tools for surveillance. In this study we described our experience using telemedicine to follow-up on patients with intraductal papillary mucinous neoplasms during the COVID-19 era and analyze those factors associated to patients' satisfaction. METHODS: This 1-year retrospective observational study enrolled patients with intraductal papillary mucinous neoplasms followed-up by telemedicine during COVID-19 outbreak. Patients with high-risk features needing on-site physical examination or declining remote follow-up were excluded. A 13-question survey was conducted; demographic, geographic, and employment information was collected. Univariate and multivariate analyses were performed to evaluate those factors associated to patients' satisfaction. RESULTS: Out of 287, a total of 177 patients with intraductal papillary mucinous neoplasms were included: the mean age was 69 (44-87) years and the male/female ratio was 0.78. A total of 80 (45.2%) patients had previously experienced abdominal pain. Most patients (85.3%) were satisfied with telemedicine: at univariate analysis, age ≥70 years (P = .007), retirement (P = .001), and absence of previous abdominal pain (P = .05) were significantly associated with patient satisfaction. At multivariate analysis, the absence of previous abdominal pain was the only factor independently associated with patient satisfaction (odds ratio 5.964, 95% confidence interval 2.21-16.11, P < .001). CONCLUSION: Telemedicine allows a new follow-up strategy that can be used in selected patients with intraductal papillary mucinous neoplasms. The absence of previous abdominal pain is associated with patient satisfaction during follow-up. Further studies are needed to evaluate safety of remote follow-up in patients with intraductal papillary mucinous neoplasms.

Varied presentations of pancreatic insulinoma: a case report.

An insulinoma is a rare functional pancreatic neuroendocrine tumour that is usually sporadic and solitary. The hallmark is hypersecretion of insulin, which leads to neuroglycopenia symptoms and uncontrolled sympathoadrenal activity. Neuroendocrine tumours can have a varied presentation, with symptoms often ascribed to a different diagnosis, thus delaying correct diagnosis and treatment. We present the case of a 26-year-old female who had a 3-year delay before diagnosing insulinoma after being initially assessed with epilepsy and schizophrenia. The case report below provides a detailed review of the diagnosis, tumour localization, and surgical interventions implemented for the patient during the COVID-19 pandemic.

Impact of the SARS-CoV-2 pandemic on pancreatic cancer: diagnosis and short-term survival.

INTRODUCTION: The COVID-19 pandemic has delayed medical consultation, possibly leading to the diagnosis of gastrointestinal cancer. The aim of the study was to analyze the impact of SARS-Cov-2 pandemic on new diagnosis and short-term survival of patients with pancreatic cancer (PC). METHODS: All consecutive patients who had a suspected diagnosis of pancreatic lesion before (from March to September 2019) and during COVID 19 pandemic (from March to September 2020). Demographics, clinical and treatment were collected and compared. Short-term survival was assessed. RESULTS: A total of 25 patients (n=13 men) with diagnosis of adenocarcinoma of the pancreas and a median age of 70 years (IQR 62-74) were included. An increase was observed in the number of patients with newly diagnosed PC (n= 12 [19.1%] versus n=13 [20.9%]; P= 0.603). The subgroup analysis revealed a tendency toward a longer diagnosis (11 versus 12 days; P= 0.219) and treatment (28 versus 44; P= 0.375) delay for patients with PC during COVID-19 pandemic. A significant increase was observed for number of cases of advanced stage III and IV (n=4 [30.8%] versus n=7 [53.8%]; P= 0.006). Palliative treatment was the most frequent approach during COVID-19 period. During 1-year follow-up, 6 (50%) and 7 (61.5%) deaths were observed among patients diagnosed before and after COVID-19 (P= 0.449), respectively. CONCLUSIONS: The COVID-19 pandemic has led to delays in diagnosis and treatment in PC, which translates into an advanced staging and a worse prognosis. These data should stimulate health care provider to facilitate procedures for detection pancreatic cancer.

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.

Highly sensitive and portable mRNA detection platform for early cancer detection.

Pancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs' GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).

Gastrointestinal Cancer Stage at Diagnosis Before and During the COVID-19 Pandemic in Japan.

Importance: The COVID-19 pandemic has delayed medical consultations, possibly leading to the diagnosis of gastrointestinal cancer at advanced stages. Objective: To evaluate stage at diagnosis among patients with gastrointestinal cancer in Japan before and during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study included patients in a hospital-based cancer registry who were diagnosed with gastrointestinal cancer (ie, esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers) between January 2016 and December 2020 at 2 tertiary Japanese hospitals. Exposures: The pre-COVID-19 period was defined as January 2017 to February 2020, and the COVID-19 period was defined as March 2020 to December 2020. Main Outcome and Measure: Monthly numbers of patients with newly diagnosed cancer were aggregated, classified by stage, and compared. Results: The study evaluated 5167 patients, including 4218 patients (2825 [67.0%] men; mean [SD] age, 71.3 [10.9] years) in the pre-COVID-19 period and 949 patients (607 [64.0%] men; mean [SD] age, 71.8 [10.7] years) in the COVID-19 period. Comparing the pre-COVID-19 period with the COVID-19 period, significant decreases were observed in the mean (SD) number of patients with newly diagnosed gastric cancer (30.63 [6.62] patients/month vs 22.40 [5.85] patients/month; -26.87% change; P < .001) and colorectal cancer (41.61 [6.81] patients/month vs 36.00 [6.72] patients/month; -13.47% change; P = .03). Significant decreases were also observed in the mean (SD) number of cases of stage I gastric cancer (21.55 [5.66] cases/month vs 13.90 [5.99] cases/month; -35.51% change; P < .001), stage 0 colorectal cancer (10.58 [3.36] cases/month vs 7.10 [4.10] cases/month; -32.89% change; P = .008), and stage I colorectal cancer (10.16 [3.14] cases/month vs 6.70 [2.91] cases/month; -34.04% change; P = .003). No significant increases were observed for esophageal, gastric, pancreatic, liver, or biliary tract cancers. A significant decrease was observed in the mean (SD) number of cases per month of stage II colorectal cancer (7.42 [3.06] cases/month vs 4.80 [1.75] cases/month; -35.32% change; P = .01); a significant increase was observed for the mean (SD) number of cases per month of stage III colorectal cancer (7.18 [2.85] cases/month vs 12.10 [2.42] cases/month; 68.42% change; P < .001). Conclusions and Relevance: In this cohort study of patients in a hospital-based cancer registry form Japan, significantly fewer patients were diagnosed with stage I gastric and colorectal cancers during the COVID-19 pandemic. Thus, the number of screening-detected cancers might have decreased, and colorectal cancer may have been diagnosed at more advanced stages.

Effects of COVID-19 Pandemic on the Treatment of Pancreatic Cancer: A Perspective from Central Europe.

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.

Practical recommendations for the management of patients with gastroenteropancreatic and thoracic (carcinoid) neuroendocrine neoplasms in the COVID-19 era.

Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges.

BRCA testing delay during the COVID-19 pandemic: How to act?

Recently, our lab, part of a referral center in Italy, reported its experience regarding the execution of germline BRCA1/2 (gBRCA) testing during the first months of the coronavirus disease-2019 (COVID-19) pandemic, which highlights a substantial reduction (about 60%) compared with the first 2 months of the current year. This evidence appeared to be a lockdown effect due to extraordinary restriction measures to slow down the spread of SARS-CoV-2. In this study, we aimed to evaluate the overall effects of the ongoing pandemic on gBRCA testing in our institution and to understand how COVID-19 has influenced testing after the complete lockdown (March 8-May 5, 2020). Additionally, we compared this year's trend with trends of the last 3 years to better monitor gBRCA testing progress. This detailed analysis highlights two important findings: (1) gBRCA testing did not increase significantly after the lockdown period (May-October 2020) compared with the lockdown period (March-April 2020), emphasizing that even after the lockdown period testing remained low. (2) Comparing the total tests per year (January-October 2017, 2018, 2019, with 2020), the impact of COVID-19 on gBRCA testing is apparent, with similarities of trends registered in 2017. These evidences reveal a gBRCA testing delay for cancer patients and healthy patients at this moment, and the new era of gBRCA testing in the management of ovarian, breast, pancreas and prostate cancer patients has been seriously questioned due to the COVID-19 pandemic. As consequence, we underline that measures to guarantee oncogenetic testing (e.g., gBRCA testing) along with new diagnostic/clinic strategies are mandatory. For these reasons, several proposals are presented in this study.