EPS8L3 promotes pancreatic cancer proliferation and metastasis by activating GSK3B.

Background: We intended to investigate the role and regulatory mechanism of EPS8L3 in increase the development of pancreatic cancer (PC). Methods: In order to analyze the relationship between EPS8L3 level and clinicopathological indicators of PC patients, qRT-PCR was used to detect the expression of EPS8L3 in tumor specimens of 40 PC patients. EPS8L3 knockdown models were then constructed in PC cell lines. Furthermore, the effect of EPS8L3 on PC cell function was analyzed by CCK-8 and Transwell assay. Dual luciferase reporter gene assay and recovery assay were used to further investigate the underlying mechanism. Results: qRT-PCR results indicated that EPS8L3 was highly expressed in PC tissues compared with adjacent ones. At the same time, the incidence of distant metastasis was higher in PC patients with high EPS8L3 level. In vitro analysis such as CCK-8 and Transwell experimentations indicated that knockdown of EPS8L3 markedly inhibited the proliferative and metastatic ability. Bio-informatics together with luciferase report assay proposing that EPS8L3 can target GSK3B. Western Blot results revealed that knockdown of EPS8L3 markedly reduced the GSK3B expression in PC cells, and there was a positively associated between the two in PC cells. In addition, the recovery experimentation proved that EPS8L3 and GSK3B have a mutual regulation effect. Overexpression of GSK3B can reversal the prohibitive effect of EPS8L3 knockdown on the malignant development of PC cells, thereby jointly regulating the occurrence and development of PC. Conclusions: EPS8L3 promotes the development of PC by regulating GSK3B, suggesting that EPS8L3 can be used as a biomarker for early diagnosis and treatment of PC.

Palliative management of a patient with gastric outlet obstruction (GOO) due to caput pancreatic cancer during COVID-19 pandemic

Background: Pancreatic cancer is associated with a poor prognosis and high cancer-related deaths in developed and developing countries because most of the patients are symptomatic until the advanced stage. A small percentage of pancreatic cancer could develop gastric outlet obstruction (GOO) when the tumor causes intestinal obstruction. This case report aimed to highlight the palliative management of GOO due to caput pancreatic cancer. Case presentation: A 48 years-old male was admitted to Dr Soetomo General Academic Hospital in Surabaya during coronavirus disease 2019 (COVID-19) pandemic with complaint of severe heartburn and pain for the last two months with lump around the upper right abdomen. The pain was not related to diet and only slightly relieved by pain relievers and ulcer medication. The patient also complained of nausea and vomiting after eating and drinking with significant weight loss. Unclear borders mass was palpable. The magnetic resonance imaging (MRI) of upper abdomen yielded the mass of head pancreatic that invaded the duodenum, the involvement of the superior mesenteric artery and multiple lymphadenopathies in the paraaortic. Pathology examination confirming the malignant, ductal adenocarcinoma. With other examinations, the patient was diagnosed as GOO due to T4N1M0 head pancreatic cancer. The tumor was unresectable. The patient underwent urgent double bypass biliodigestive laparotomy as part of palliative management. loop gastrojejunostomy, cholecystectomy and choledocujejunostomy Roux en Y was performed. Celiac plexus block was performed to reduce the cancer pain in the patient. Conclusion: This case highlights that the GOO case's selected management depends on the stage disease and evaluation of multidisciplinary involvement even in the COVID-19 pandemic. Therefore, collaboration between surgeons, medical oncologists, gastroentero-hepatologist, radiologists, and supportive and palliative care specialists is required to reduce mortality. © 2023, Sanglah General Hospital. All rights reserved.

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.

Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel.

INTRODUCTION: Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. CASE REPORTS: We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. MANAGEMENT AND OUTCOMES: Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. DISCUSSION: Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.

A National Audit of Pancreatic Enzyme Prescribing in Pancreatic Cancer from 2015 to 2023 in England Using OpenSAFELY-TPP.

OBJECTIVES: Cancer treatments were variably disrupted during the coronavirus disease 2019 (COVID-19) pandemic. UK guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. The aim was to investigate the impact of the COVID-19 pandemic on PERT prescribing to people with unresectable pancreatic cancer and to investigate the national and regional rates from January 2015 to January 2023. DATA SOURCES: With the approval of NHS England, we conducted this study using 24 million electronic health records of people within the OpenSAFELY-TPP research platform. There were 22,860 people diagnosed with pancreatic cancer in the study cohort. We visualized the trends over time and modeled the effect of the COVID-19 pandemic with the interrupted time-series analysis. CONCLUSION: In contrast to many other treatments, prescribing of PERT was not affected during the pandemic. Overall, since 2015, the rates increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in early 2023. There was substantial regional variation, with the highest rates of 50% to 60% in West Midlands. IMPLICATIONS FOR NURSING PRACTICE: In pancreatic cancer, if PERT is prescribed, it is usually initiated in hospitals by clinical nurse specialists and continued after discharge by primary care practitioners. At just under 50% in early 2023, the rates were still below the recommended 100% standard. More research is needed to understand barriers to prescribing of PERT and geographic variation to improve quality of care. Prior work relied on manual audits. With OpenSAFELY, we developed an automated audit that allows for regular updates (https://doi.org/10.53764/rpt.a0b1b51c7a).

Racial, ethnic, and sex-based disparities among high-risk individuals undergoing pancreatic cancer surveillance

Background: The international, multi-center Pancreatic Cancer Early Detection (PRECEDE) Consortium enrolls high-risk individuals (HRIs) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Enrollment began in 2020, and despite challenges related to the COVID-19 pandemic, the PRECEDE Consortium rapidly accrued a large cohort of HRIs. The purpose of this study is to describe the characteristics of this cohort and assess racial, ethnic, and sex-based disparities. Method(s): The PRECEDE Consortium (NCT04970056) is a prospective, multicenter study focused on improving survival from PDAC through early detection. Data from all HRIs who met criteria for PDAC surveillance and enrolled between May 2020 - March 2022 were collected and included in the analysis. Result(s): During the study period, 1299 HRIs enrolled in PRECEDE at 32 centers. HRIs were excluded if enrollment data was incomplete or criteria for PDAC surveillance were not met. Of 1113 who were included, 47.2% met criteria for familial pancreatic cancer (FPC) and 45.4% had a family history of PDAC along with a PV in a PDAC-risk gene (BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). The remainder had familial atypical mole melanoma syndrome (5.7%), Peutz- Jeghers syndrome (1.6%), or hereditary pancreatitis (0.2%). More females than males enrolled (65.9% vs. 33.5%). The distribution of HRIs by race and ethnicity is depicted;the majority identified as white (87.7%). Study participants were primarily from the US (82.7%), the median age was 61 (27-85) and 18.5% had Ashkenazi Jewish ancestry. Nearly all HRIs consented to allow access to imaging data (99.6%), collection of germline DNA (97.7%), and biosample collection (99.5%). There were no race, ethnicity, or sex-based differences in rates of consent for collection of imaging, DNA, or biosamples. Conclusion(s): Enrollment of HRIs in prospective studies of PDAC surveillance is essential for advancing early detection research in PDAC. A distinct advantage of the PRECEDE Consortium for examining enrollment disparities is that recruitment began in 2020, providing a unique and current snapshot of the international PDAC surveillance landscape. Despite the recent attention on addressing disparities in healthcare delivery, significant racial, ethnic, and sex-based disparities persisted in the cohort of HRIs enrolled in the PRECEDE Consortium. Ensuring that the diversity of participants in the PRECEDE Consortium mirrors the communities served by participating centers is crucial. Further examining and addressing the reasons for these disparities is a major focus of the PRECEDE Consortium moving forward.

Comment on "Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression".

The coronavirus disease 2019 (COVID-19) pandemic has become a global burden, further exacerbating the occurrence of risk events in cancer patients. The high risk of death from pancreatic cancer makes it one of the most lethal malignancies. Recently, it was reported in the World Journal of Gastrointestinal Oncology that COVID-19 influences pancreatic cancer progression via the lung-gut-pancreatic axis, and the authors provided insights into the intrinsic crosstalk mechanisms in which the gut microbiota is involved, the characteristics and effects of inflammatory factors, and immunotherapeutic strategies for treating both diseases. Here, we review the latest cutting-edge researches in the field of the lung-gut-pancreatic axis and discuss future perspectives to address the severe survival challenges posed by the COVID-19 pandemic in patients with pancreatic cancer.

The Pancreas in Coronavirus Disease 2019 Infection.

An association between acute pancreatitis (AP) and coronavirus disease 2019 (COVID-19) has been proposed but the mechanisms of pancreatic injury of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the implicative role on the development of AP are not yet fully understood. COVID-19 also imposed major challenges on pancreatic cancer management. We conducted an analysis on the mechanisms of pancreatic injury by SARS-CoV-2 and reviewed published case reports of AP attributed to COVID-19. We also examined the pandemic effect on pancreatic cancer diagnosis and management, including pancreatic surgery.

Telemedicine and Pancreatic Cancer: A Systematic Review.

Introduction: Pancreatic cancer requires a multidisciplinary approach in a high-volume center for all the steps of the diagnostic-therapeutic course. However, the most experienced centers are not evenly distributed throughout the country causing a real "health migration" that involves patients and families with relevant economic, time, and energy costs to bear. The COVID-19 pandemic had a deep impact on surgical and oncological care and the travel limits due to COVID-related restrictions, have delayed the care of cancer patient living far from the referral centers. In this scenario, several telemedicine approaches have been proposed to reduce the distance between clinicians and patients and to allow a fast and effective access to care even for patients distant from referral centers. The aim of the study is to analyze the evidence and describe the current utility of telemedicine tool for patients with pancreatic cancer. Methods: We systematically searched the literature in the following databases: Web of Science, PubMed, Scopus, and MEDLINE. The inclusion criteria were article describing a telemedicine intervention (virtual visits, telephone follow-up/counseling, mobile or online apps, telemonitoring) and focusing on adult patients with pancreatic cancer at any stage of the disease. Results: In total, 846 titles/abstracts were identified. Following quality assessment, the review included 40 studies. Telemedicine has been proposed in multiple clinical settings, demonstrating high levels of patient and health professional satisfaction. Conclusion: Successful telemedicine applications in patients with pancreatic cancer are telerehabilitation and nutritional assessment, remote symptom control, teledischarge after pancreatic surgery, tele-education and medical mentoring regarding pancreatic disease as well as telepathology.

Current status and influencing factors of care burden of pancreatic cancer caregivers under COVID-19.

Objective: To explore the level of care burden and its influencing factors of caregivers of pancreatic cancer patients during hospitalization under the background of COVID-19. Methods: From September 2021 to December 2021, in Jiangsu Province Hospital, the convenience sampling method was used to investigate the care burden level of family caregivers of pancreatic cancer patients, and univariate and multivariate analysis methods were used to analyze the influencing factors. The survey tools included the General Information Questionnaire, the Family Caregiver Care Burden Scale, the Hospital Anxiety and Depression Scale, the Benefit Discovery Rating Scale, and the General Self-Efficacy Scale. Results: A total of 100 subjects were included in this study, of which 45% were male and 55% were older than 50 years. In the Context of COVID-19, the care burden of caregivers of pancreatic cancer patients was at a mild level, and the main influencing factors were family economic status (p < 0.001), anxiety and depression level (p < 0.001) and self-efficacy (p < 0.001). Conclusion: Medical staff should pay attention to the caregivers of pancreatic cancer with a heavy family burden, and pay attention to their anxiety and depression, and take corresponding measures to improve the self-efficacy of the caregivers, so as to reduce the care burden.

The COVID - AGICT study: COVID-19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes.

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. MATERIALS AND METHODS: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. RESULTS: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DISCUSSION: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

A Modified Regimen of 21-day Nab-Paclitaxel Plus Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Real-World Study.

BACKGROUND: It is 1 of the standard treatment options for metastasis pancreatic cancer to receive nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1, 8 and 15 every 28 days. Some patients showed intolerance and inconvenience to this therapeutic regimen. Thus, we conducted this retrospective real-world study to determine the efficacy and tolerability of a modified 21-day nab-paclitaxel plus gemcitabine (nab-P/Gem) regimen for the first-line treatment of locally advanced or metastatic pancreatic cancer. METHODS: Patients with locally advanced and metastatic pancreatic cancer treated with nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 every 21-day at West China Hospital and Shang Jin Hospital of Sichuan University from Mar 2018 to Dec 2021 were reviewed retrospectively. Clinical characteristics of patients were collected. The progression-free survival, overall survival, objective response rate, disease control rate, and toxicity were evaluated. RESULTS: A total of 113 patients who received the modified regimen of 21-day nab-P/Gem chemotherapy were included. The median overall survival was 9.3 months and the median progression-free survival was 4.4 months. The objective response rate and disease control rate were 18.6% and 56.7%, respectively. The median relative dose intensity for this modified regimen was 65%. The adverse events were mild to moderate, and the most common grade 3 or 4 treatment-related adverse events were neutropenia (21%) and leukopenia (16%). CONCLUSIONS: Our study showed that this modified regimen of 21-day nab-P/Gem for locally advanced and metastatic pancreatic cancer had comparable efficacy and tolerable toxicity. This treatment may provide a considerable option for pancreatic cancer patients who desire a modified schedule. The modified regimen of 21-day nab-P/Gem is also an option worth considering during the coronavirus disease 2019 pandemic for minimizing the number of visits and limiting the risk of exposure.

Impact of the COVID-19 Pandemic on the Management and End-of-life Care of Unresectable Pancreatic Cancer.

Objective The coronavirus disease (COVID-19) pandemic has altered the delivery of medical care. The present study evaluated the impact of COVID-19 on the outcomes of unresectable pancreatic cancer (PC) patients who received end-of-life care. Methods We retrospectively compared the management of PC patients during the COVID-19 pandemic (from April 2020 to March 2021) to the preceding year, which was unaffected by the pandemic (from April 2019 to March 2020), based on a prospectively maintained institutional database. Results A total of 178 patients were included in the COVID-19-exposed group and 201 patients were included in the COVID-19-unexposed group. The median overall survival was similar between the groups (exposed vs. unexposed: 12.6 vs. 11.9 months, p = 0.174). Treatment regimens and relative dose intensities and the progression-free survival of GnP (gemcitabine in combination with nab-paclitaxel) and mFOLFIRINOX as first- and second-line chemotherapy did not differ significantly between the two groups. Only 9.0% of patients died at home in the COVID-19-unexposed group, compared to 32.0% in the COVID-19-exposed group (p <0.001). A multivariate analysis revealed that death during the COVID-19 exposed period was independently associated with home death (odds ratio: 4.536, 95% confidence interval: 2.527-8.140, p <0.001). Conclusions While the COVID-19 pandemic did not seem to influence chemotherapeutic treatment for PC patients at our institution, it had a large impact on end-of-life care. These findings may promote discussion about end-of-life care in Japan.

Implementing a database to track patients’ compliance in the high-risk pancreatic cancer clinic

BackgroundPancreatic cancer is projected to become the second leading cause of cancer death in the United States by 2030. Screening of high-risk individuals (HRI’s) using endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI), specifically magnetic resonance cholangiopancreatography (MRCP), saves lives and reduces morbidity and mortality. Screening can detect surgically resectable lesions, which is key to survival since most lesions present as unresectable or metastatic. The specific aims of this project were to address the quality improvement process to track adherence of the patients who participate in the high-risk pancreatic cancer clinic at UMass Memorial Healthcare.MethodsPatients deemed to be high risk according to the Cancer of the Pancreas Screening (CAPS) Consortium Guidelines included having at least one first-degree relative with a diagnosis of pancreatic cancer, a genetic mutation that places them at higher risk for pancreatic cancer, or both are the cohort. The data was collected via EMR using REDCap, a secure web application to analyze high-risk patients’ adherence with yearly screening. The method utilized a quality improvement project design.ResultsResults demonstrated a majority of participants were female, 53% had a first-degree relative with pancreatic cancer, a majority of participants did not carry a genetic mutation while the highest mutation finding included 16 participants (14.4%) with a BRCA 2 gene mutation. A majority of participants, 64.9% (n=72) were non-compliant with screening while 35% (n=39) had yearly screening. Participants who were non-adherent with screening endorsed multiple factors for non-adherence including not believing surveillance was necessary, not qualifying for screening at the time of initial appointment, not receiving reminder phone calls for clinic appointments and surveillance imaging, other health concerns, high insurance deductibles, the COVID pandemic, and high anxiety.ConclusionsMitigation of the reasons for non-adherence is a crucial practice implication. Patient education regarding the importance of long-term yearly screening and teaching patients self-efficacy behaviors may improve screening adherence. Prospectively analyzing compliance will reduce missed care opportunities. Health care policies must be amended to require insurance companies to cover the screening of HRI’s.

Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression.

Pancreatic cancer (PC) is one of the most common causes of cancer-associated death worldwide, with a low rate of 5-year survival. Currently, the pathogenesis of PC is complicated, with no efficient therapy. Coronavirus disease 2019 (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 further exacerbates the challenge of patients with PC. The alteration of gut microbiota caused by COVID-19 infection may impact PC progression in patients via immune regulation. The expression of inflammatory immune mediators such as interleukin (IL)-6, IL-8, and IL-10 has been found to increase in both PC and COVID-19 patients, which is associated with the disease severity and prognostic outcome. Gut microbiome serves as a critical connector between viral infection and PC. It can regulate host systemic immune response and impact the efficacy of immunotherapy. Here, we first demonstrated the features of inflammatory cytokines in both diseases and their impact on disease outcomes. Then, we demonstrated the importance of immunotherapeutic strategies. This includes the immune modulation that targets a single or dual receptors using a single agent or their combinations for the treatment of PC in patients who get infected with COVID-19. Additionally, we explored the possibility of managing the disease by regulating gut microbiome. Overall, modulation of the lung-gut-pancreases axis can boost anti-cancer immunotherapy and reduce adverse prognostic outcomes.

Percutaneous biopsy and drainage of the pancreas.

Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.

It's Time to Shift the Paradigm: Translation and Clinical Application of Non-αvß3 Integrin Targeting Radiopharmaceuticals.

For almost the entire period of the last two decades, translational research in the area of integrin-targeting radiopharmaceuticals was strongly focused on the subtype αvß3, owing to its expression on endothelial cells and its well-established role as a biomarker for, and promoter of, angiogenesis. Despite a large number of translated tracers and clinical studies, a clinical value of αvß3-integrin imaging could not be defined yet. The focus of research has, thus, been moving slowly but steadily towards other integrin subtypes which are involved in a large variety of tumorigenic pathways. Peptidic and non-peptidic radioligands for the integrins α5ß1, αvß6, αvß8, α6ß1, α6ß4, α3ß1, α4ß1, and αMß2 were first synthesized and characterized preclinically. Some of these compounds, targeting the subtypes αvß6, αvß8, and α6ß1/ß4, were subsequently translated into humans during the last few years. αvß6-Integrin has arguably attracted most attention because it is expressed by some of the cancers with the worst prognosis (above all, pancreatic ductal adenocarcinoma), which substantiates a clinical need for the respective theranostic agents. The receptor furthermore represents a biomarker for malignancy and invasiveness of carcinomas, as well as for fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), and probably even for Sars-CoV-2 (COVID-19) related syndromes. Accordingly, the largest number of recent first-in-human applications has been reported for radiolabeled compounds targeting αvß6-integrin. The results indicate a substantial clinical value, which might lead to a paradigm change and trigger the replacement of αvß3 by αvß6 as the most popular integrin in theranostics.

This Week in the Journal

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