Management Of Pancreatic Cancer Research Articles

Surgical management of pancreatic cancer in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a 5 years retrospective descriptive study

IntroductionThe incidence of Pancreatic cancer is different in different parts of the world. It is a cancer with the worst prognosis of all malignancies. Pancreatic cancer is predominantly a disease of an older population. There are different environmental (modifiable) and non-modifiable risk factors associated with the development of pancreatic cancer. At present, surgical resection is the only potential cure for pancreatic cancer. However, as only 10–20% of the patients have resectable disease at the time of diagnosis. The morbidities associated with surgeries for pancreatic cancers remain high though the post-operative mortality has shown significant reduction in the past few decades. So far, no study has been conducted to investigate pancreatic cancer in Ethiopia.ObjectivesTo assess the clinico-pathologic profile, associated factors, surgical management and short-term outcome of patients with pancreatic cancer in Tikur Anbessa Specialized hospital.MethodsA 5 years retrospective hospital-based cross-sectional study was conducted on 52 patients operated with the diagnosis of pancreatic cancer with either curative or palliative intents. The study period was from April 2016 to July 2021. The data collected includes demographic profile, associated risk factors and comorbidities, clinical presentations, biochemical parameters, pathologic features of the tumors as well as type of treatment offered and short term treatment outcome. The data was analyzed using SPSS version 25.ResultThe mean and median age of patients was 54.1 and 54.5% respectively. Males constitute about 52% the patients. 21% of the patients have potential risk factors; whereas only 10 (19.2%) of the patients had medical comorbidities. Median duration of symptoms at diagnosis was 12 weeks. Abdominal pain (88.5%) was the most common presenting symptom followed by anorexia (80.8%) and significant weight loss (78.8%), while 71.2% of the patients have jaundice. On clinical evaluation, 69.2% were jaundiced, while 34.6% had a palpable gallbladder. More than two third of patients presented with advanced disease. 76.9% of the tumors are located in the head of pancreas. More than three quarters (77%) of the surgeries performed were palliative. Postoperative morbidity and mortality were 19.2% and 3.8% respectively.ConclusionAge at first diagnosis of pancreatic cancer is relatively earlier in our setup. Most patients present with advanced condition, only amenable for palliative measures. The post-operative morbidity and mortality are more or less comparable with similar studies. The need for adjuvant therapy in pancreatic cancer should be emphasized.

Potential Use of Human Mesenchymal Stem Cells (hMSCs) in Pancreatic Damage/Cancer

Pancreatic damage and pancreatic cancer pose significant challenges due to their complex pathogenesis, limited treatment options, and poor prognosis. In recent years, the potential use of human Mesenchymal Stem Cells (hMSCs) has been explored to address these complex pancreatic conditions and develop novel therapeutics. hMSCs, known for their regenerative and immunomodulatory properties, offer a novel therapeutic avenue for repairing damaged tissues and possibly inhibiting cancer progression. This communication discusses current research findings on the application of hMSCs in pancreatic damage and cancer treatment while evaluating hMSC-mediated gene therapy in pancreatic disorders. Moreover, the challenges and considerations associated with hMSC-based therapies and the potential best therapeutic approaches are discussed. Furthermore, the current scientific evidence regarding hMSCs in revolutionizing the management of pancreatic damage and cancer, offering future perspectives for improved therapeutic strategies for patients facing these daunting conditions, is critically discussed.

Role of molecular biology in the management of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS-mutated and KRAS-wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.

Guidelines for holistic integrative management of pancreatic cancer

BackgroundPancreatic cancer ranks 10th in the incidence rate of malignant tumors in male, and 12th in female. Pancreatic cancer is the sixth leading cause of tumor-related deaths in China. It is a devastating malignancy with poor prognosis.MethodsDriven by the concept of "integrated medicine", the China Anti-Cancer Association Committee of Pancreatic Cancer organized relevant experts to complete this guideline.ResultsThis guideline aims to guide the integrated treatment and rehabilitation management of pancreatic cancer in an all-round way based on "Preventing, Screening, Diagnosing, Treating, and Rehabilitating".ConclusionsWe hope that this guideline will provide effective references for clinicians, so as to achieve the best treatment effects for pancreatic cancer patients in China.

The preclinical gap in pancreatic cancer and radiotherapy.

Pancreatic ductal adenocarcinoma is an aggressive malignancy with limited treatment options. Chemotherapy offers little benefit and, although there is some evidence that radiotherapy may improve response, its use in the clinical management of pancreatic cancer remains controversial due to conflicting reports on its survival benefit. There has also been a lack of clinical trials that directly investigate the efficacy of radiotherapy in pancreatic cancer. The limited progress in the development of radiotherapeutic strategies in pancreatic cancer can be attributed, at least in part, to a dearth of preclinical research and our limited understanding of the effects of radiation on the pancreatic tumour microenvironment. In this Perspective, we discuss how insight into the immunosuppressive tumour microenvironment and the complex signalling between tumour and stromal cells following radiation is needed to develop effective radiosensitising strategies for pancreatic cancer. We also highlight that to have the best chance for successful clinical translation, more preclinical research is required in appropriately complex models.

Identification and model construction of survival-associated proteins for pancreatic cancer based on deep learning

Pancreatic cancer (PC) is a malignancy typified by its insidious onset, rapid progression, limited resectability, poor treatment response, and exceedingly dismal prognosis. The transition from precursor lesions to infiltrating malignant tumors in pancreatic cancer is concomitant with the accrual of genetic mutations. The elucidation of proteins linked to the prognosis of pancreatic cancer holds paramount importance in the realm of pancreatic cancer management. Herein, we introduce DeepPCSA, a model tailored for the screening of target proteins and the prediction of survival time, employing both conventional methodologies and deep learning techniques for patient survival analysis. This framework leverages the LASSOCOX regression approach on differentially expressed genes (DEGs) to discern pivotal genes, succeeded by the development of a prognostic model employing convolutional and fully connected layers to prognosticate patient survival duration. Furthermore, we account for covariates such as age, gender, and other pertinent factors for independent prognostic scrutiny, affirming the autonomy of our model as a prognostic determinant. Employing unsupervised clustering methodologies, we delineated two molecular subtypes delineated by disparate biological processes. Ultimately, via drug sensitivity analysis, we delineated the interrelation between survival duration and pharmaceuticals, substantiating the necessity for tailored drug interventions catering to patients of varying risk strata.

New Frontiers in Pancreatic Cancer Management: Current Treatment Options and the Emerging Role of Neoadjuvant Therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer.

TPS5626 Background: Novel treatments are needed for patients with ovarian, pancreatic, and mesonephric-like adenocarcinoma (MLA) that has recurred or progressed after initial treatment, as current standard of care therapies in these settings result in low response rates. Chimeric antigen receptor-transduced natural killer (CAR-NK) cells have emerged as a therapeutic alternative to CAR-T cells, with decreased toxicity and enhanced feasibility as an “off-the-shelf” therapy. TROP2, or trophoblast cell-surface antigen 2, is a transmembrane calcium-signal transducer that is overexpressed in many cancer types and associated with poor clinical outcomes. Recent studies have demonstrated TROP2 as a promising target for adoptive cell therapy in breast and gastric cancers. An intraperitoneal route of adoptive cell therapy delivery may provide superior disease control and decreased toxicity in these target cancers with predisposition for intra-abdominal/peritoneal involvement. Pre-clinical studies have established the efficacy and safety of TROP2 CAR NK cells in ovarian and pancreatic cancers. Methods: This is a phase I/II study of the intraperitoneal delivery of TROP2-CAR/IL-15 transduced cord blood (CB)-NK cells for recurrent/progressive ovarian cancer, pancreatic cancer, and MLA (NCT05922930). Subjects must have disease present in the peritoneal cavity or retroperitoneal lymph nodes and tumors must demonstrate at least 1+ TROP2 expression by immunohistochemistry. The primary endpoints are toxicity rates and defining the recommended phase II dose (RP2D). Key secondary endpoints include treatment efficacy, circulating tumor DNA levels, serial characterization of the immune microenvironment, and patient-reported outcomes. There are four possible dose levels ranging from 8.0x106 to 4.0x109 cells. We will enroll patients from the three disease cohorts using the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose and RP2D, with a maximum sample size of 21. Once the R2PD is chosen, we will enroll up to 10 patients within each disease cohort to further evaluate safety and efficacy. Subjects enrolled will be admitted to the hospital, receive lymphodepleting chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300mg/m2) on days -5 to -3, and will receive a single dose of cryopreserved and thawed intraperitoneal TROP2-CAR/IL15-transduced CB-NK cells on day 0. The dose-limiting toxicity window will be from day 0 until day 28. Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. The first patient on this trial was treated in January 2024. Clinical trial information: NCT0592293 .

Gemcitabine-Phospholipid Complex Loaded Lipid Nanoparticles for Improving Drug Loading, Stability, and Efficacy against Pancreatic Cancer.

This study aims to encapsulate gemcitabine (GEM) using a phospholipid complex (PLC) in lipid nanoparticles (NPs) to achieve several desirable outcomes, including high drug loading, uniform particle size, improved therapeutic efficacy, and reduced toxicities. The successful preparation of GEM-loaded lipid NPs (GEM-NPs) was accomplished using the emulsification-solidification method, following optimization through Box-Behnken design. The size of the GEM-NP was 138.5 ± 6.7 nm, with a low polydispersity index of 0.282 ± 0.078, as measured by a zetasizer and confirmed by transmission electron and atomic force microscopy. GEM-NPs demonstrated sustained release behavior, surpassing the performance of the free GEM and phospholipid complex. Moreover, GEM-NPs exhibited enhanced cytotoxicity, apoptosis, and cell uptake in Panc-2 and Mia PaCa cells compared to the free GEM. The in vivo pharmacokinetics revealed approximately 4-fold higher bioavailability of GEM-NPs in comparison with free GEM. Additionally, the pharmacodynamic evaluation conducted in a DMBA-induced pancreatic cancer model, involving histological examination, serum IL-6 level estimation, and expression of cleaved caspase-3, showed the potential of GEM-NPs in the management of pancreatic cancer. Consequently, the lipid NP-based approach developed in our investigation demonstrates high stability and uniformity and holds promise for enhancing the therapeutic outcomes of GEM.

Updates in Clinical Management of Pancreatic Cancer

Updates in Clinical Management of Pancreatic Cancer

A comprehensive review on phytochemicals in the treatment and prevention of pancreatic cancer: Focusing on their mechanism of action.

Pancreatic cancer develops in the normal tissues of the pancreas from malignant cells. The chance of recovery is not good, and the chance of survival 5 years following diagnosis is quite low. Pancreatic cancer treatment strategies such as radiotherapy and chemotherapy had relatively low success rates. Therefore, the present study aims to explore new therapies for treating pancreatic cancer. The present study searched for information about pancreatic cancer pathophysiology, available treatment options; and their comparative benefits and challenges. Aiming to identify potential alternative therapeutics, this comprehensive review analyzed information from renowned databases such as Scopus, PubMed, and Google Scholar. In recent years, there has been a rise in interest in the possibility that natural compounds could be used as treatments for cancer. Cannabinoids, curcumin, quercetin, resveratrol, and triptolide are some of the anticancer phytochemicals now used to manage pancreatic cancer. The above compounds are utilized by inhibiting or stimulating biological pathways such as apoptosis, autophagy, cell growth inhibition or reduction, oxidative stress, epithelial-mesenchymal transformation, and increased resistance to chemotherapeutic drugs in the management of pancreatic cancer. Right now, surgery is the only therapeutic option for patients with pancreatic cancer. However, most people who get sick have been diagnosed too late to benefit from potentially effective surgery. Alternative medications, like natural compounds and herbal medicines, are promising complementary therapies for pancreatic cancer. Therefore, we recommend large-scale standardized clinical research for the investigation of natural compounds to ensure their consistency and comparability in pancreatic cancer treatment.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic tumors.

Surgery is a cornerstone in the management of pancreatic cancer and precancerous pancreatic lesions. However, many patients are not suitable candidates for surgery at the time of diagnosis for various reasons. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) appears to be a promising treatment option for patients who are ineligible for surgery for management of pancreatic adenocarcinoma (PDAC), and pancreatic neuroendocrine tumors (PNETs), and pancreatic cystic lesions (PCLs). EUS-RFA may serve as an adjunct to chemotherapy or palliative measures for inoperable cases of PDAC. Given its feasibility and efficacy, EUS-RFA has an evolving niche as a minimally invasive and potentially definitive treatment for PNETs and high-risk PCLs such as intraductal papillary mucinous neoplasms (IPMNs). EUS-RFA is a generally well tolerated procedure, with abdominal pain and acute pancreatitis being the most common adverse effects, though the risk can be mitigated through prophylactic measures. There is an increasing body of evidence to support the use of EUS-RFA in managing pancreatic lesions, either as definitive, adjunctive, or palliative treatment, depending on lesion type.

Intraoperative strategies and techniques to achieve surgical radicality in pancreatic cancer

SummaryThe treatment of pancreatic cancer presents a challenging task in surgical oncology, demanding innovative approaches to achieve radical resection and improve patient outcomes. This article provides an overview of state-of-the-art surgical principles and techniques for achieving surgical radicality in localized pancreatic cancer, with a particular emphasis on artery-first approaches, the triangle operation, arterial and venous dissection techniques, including arterial divestment, and the significance of R0 resections with complete lymphadenectomy. By applying these techniques and principles of surgical radicality, surgeons are able to enhance resectability, minimize complications, and potentially extend patient survival in the rapidly evolving field of multimodal pancreatic cancer management.

The role of national population-based registries in pancreatic cancer surgery research.

Research and innovation are critical for advancing the multidisciplinary management of pancreatic cancer. Registry-based studies (RBSs) are a complement to randomized clinical trials (RCTs). Compared with RCTs, RBSs offer cost-effectiveness, larger sample sizes, and representation of real-world clinical practice. National population-based registries (NPBRs) aim to cover the entire national population, and studies based on NPBRs are, compared to non-NPBRs, less prone to selection bias. The last decade has witnessed a dramatic increase in NPBRs in pancreatic cancer surgery, which has undoubtedly added invaluable knowledge to the body of evidence on pancreatic cancer management. However, several methodological shortcomings may compromise the quality of registry-based studies. These include a lack of control over data collection and a lack of reporting on the quality of the source registry or database in terms of validation of coverage and data completeness and accuracy. Furthermore, there is a significant risk of double publication from the most commonly used registries as well as the inclusion of historical data that is not relevant or representative of research questions addressing current practices.

Abstract 486: Paclitaxel nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer with a 5-year survival rate of less than 13% due to the lack of effective diagnostic/therapeutic modalities. Paclitaxel (PTX) has been tested in pancreatic cancer (PanCa) therapy with marginally better clinical outcomes, but remains limited by its poor hemocompatibility, biodistribution, and intracellular accumulation in tumor cells. Gemcitabine (GEM) is the most effective therapy for PanCa. However, it shows only a marginal survival benefit of 6 months. The poor therapy response is attributed to high desmoplasia, unfavorable tumor microenvironment (TME), and excessive recruitment of immune suppressive cells. We have recently engineered a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs), which effectively inhibits pancreatic tumor. In this study, we demonstrate that PPNPs effectively sensitize tumor cells to GEM via attenuation of tumor desmoplasia. Our findings also show that PPNPs synergize GEM therapy response in cell lines and in vivo mouse models. Mechanistically, PPNPs target the TME via inhibition of the sonic hedgehog (SHH) pathway and other oncogenic signaling axis that inhibits bidirectional tumor-stromal cell interaction as determined by qPCR and Western blot analyses. In addition, PPNPs effectively target tumor-associated macrophages (TAM) by repolarizing M2 into M1 phenotype via inhibiting expression of M2 markers and an increase in M1 markers in mouse macrophage cell line RAW264.7. M2 polarization of RAW264.7 cells were induced by culture with IL-4 (20 ng/mL) in the presence of PPNPs or vehicle control. Furthermore, PPNPs effectively increase phagocytic capacity in murine macrophages as determined by phagocytosis assay (Vybrant Phagocytosis Assay Kit). In conclusion, we observed that our novel PPNP nano formulation effectively targets TME, and facilitates GEM uptake by inhibiting the activation of SHH signaling and reprograming the tumor immune surveillance mechanisms. This study suggests that PPNPs have great potential for future clinical use in management of pancreatic cancer. Citation Format: Vivek K. Kashyap, Godwin P. Darkwah, Neeraj Chauhan, Mohammed Sikander, Eswara N. Ghali, Meghana Kolli, Bilal B. Hafeez, Murali M. Yallapu, Subhash C. Chauhan. Paclitaxel nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 486.

Abstract 7170: Pharmacokinetic profiling of Re-Phenformin in vivo: A novel approach in pancreatic cancer therapy

Abstract Phenformin, a biguanide medication, has long been utilized in the treatment of diabetes. Recent research indicates that phenformin may also serve as an effective anticancer agent. This study introduces the synthesis and evaluation of Re tricarbonyl phenformin complex (Re-(CO)3-Phenformin, Re-Phen), as a derivative of Phenformin and novel anticancer agent for pancreatic cancer treatment. Re-Phen was synthesized, purified, and characterized through preparative HPLC, NMR, mass spectrometry, and FT-IR. Subsequent in vitro studies, utilizing the MTS assay, assessed its cytotoxicity against pancreatic cancer cell lines, including Kras* murine PDAC and MiaPaca-2 human PDAC. Notably, Re-Phen exhibited significantly higher cytotoxic effects in MiaPaca-2 cells (IC50= 0.755 mM) and Kras* cells (IC50= 0.410 mM) compared to Phenformin treatment (IC50= 4.02 mM and 2.36 mM, respectively). These results highlight Re-Phen's enhanced anticancer activity, outperforming Phenformin in potency. Further investigation into the pharmacokinetics of Re-Phen involved an in vivo study with rats intravenously administered 2 mg/kg of Re-Phenformin. Blood samples were collected at intervals (10 min to 24 h post-dose) and were analyzed by validated LC-MS/MS. The pharmacokinetic profile of Re-Phen was best described by a 2-compartment model, using Phoenix® WinNonlin (version 8.0), with a particular focus on comparing the profiles of Phenformin and Re-Phen. The study revealed that Re-Phen has a significantly extended half-life compared to Phenformin (9.13 hr vs 2.11 hr), indicating prolonged systemic retention. Additionally, Re-Phen demonstrated an increased area under the curve (AUC), suggesting greater systemic exposure at equivalent dosing (90.55 hr*ng/ml vs 7.13 hr*ng/ml). This could imply enhanced bioavailability or altered metabolic clearance of Re-Phen compared to its parent compound. The two-Compartment of Re-Phe, provide a deeper understanding of its pharmacokinetic characteristics. In conclusion, Re-Phen not only demonstrates superior anticancer efficacy in vitro but also exhibits a more favorable pharmacokinetic profile in vivo. The extended half-life and increased AUC of Re-Phen suggest the potential of offering improved therapeutic efficacy in pancreatic cancer treatment. These promising findings warrant further investigation and could position Re-Phen as a promising therapeutic agent for the pharmacological management of pancreatic cancer. Citation Format: Amir Mohammad Gholizadeh, Lu Dai, Fatima Dagher, Chiyi Xiong, Chun Li, Diana S-L Chow. Pharmacokinetic profiling of Re-Phenformin in vivo: A novel approach in pancreatic cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7170.

Abstract 6959: Acetylcholine potentiates invasion and migration of human pancreatic cancer cells under hypoxia through α7 nAChR-mediated increases in HIF-1α expression

Abstract The most significant nerve-related problem in clinical pancreatic cancer management is perineural invasion (PNI), characterized as the neoplastic invasion of cancer cells into or surrounding the nerves. It is a characteristic feature of pancreatic ductal adenocarcinoma (PDAC) associated with a poor prognosis, tumor recurrence, and emergent pain. However, why PDAC is associated with a higher incidence of PNI remains unclear. HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~1000 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying neurotransmitter acetylcholine (Ach)-potentiated HIF-1α expression and subsequent increase in invasion and migration of human pancreatic cancer cells in hypoxia (2% O2). The expression of various acetylcholine receptors in six types of pancreatic cancer cell lines (MIA-PaCa-2, PANC-1, HPAF-II, Capan-1, AsPC-1, and BxPC-3 cells) was observed using qPCR, and α7 nAChRs was observed to be expressed in all pancreatic cancer cells. Therefore, we chose MIA-PaCa-2 cells, expressing high levels of α7 nAChRs, and HPAF-II cells, expressing low levels of α7 nAChRs, for loss- and gain-of-function studies, respectively. In vitro assays showed that, under hypoxic conditions, Ach caused a concentration-dependent increase in α7 nAChRs-mediated HIF-1α expression, enhancing expression of HIF-1α target genes, and promoting invasion and migration of human pancreatic cancer cells. We further found that Ach increased HIF-1α protein stability in pancreatic cancer cells under hypoxic conditions. This effect was mediated by YAP signaling, as evidenced by the fact that Ach-induced increases in HIF-1α protein stability were blocked by siRNA-mediated knockdown of YAP. Consistent with these findings, an investigation of the relationship between α7 nAChRs and clinicopathological features in pancreatic cancer patients using publicly available datasets showed that high levels of α7 nAChRs are correlated with a poorer prognosis in pancreatic cancer patients. Collectively, these findings identify novel mechanisms by which Ach potentiates invasion and migration of pancreatic cancer cells and provide further evidence that HIF-1α is a potential anticancer target in Ach-associated pancreatic cancer. Citation Format: Yunmi Cho, Eun-Taex Oh, Ha Gyeong Kim, Heon Joo Park. Acetylcholine potentiates invasion and migration of human pancreatic cancer cells under hypoxia through α7 nAChR-mediated increases in HIF-1α expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6959.

Endoscopic Ultrasound-Guided Ablation of Premalignant Pancreatic Cysts and Pancreatic Cancer.

Pancreatic cancer is on the rise and expected to become the second leading cause of cancer-related death by 2030. Up to a one-fifth of pancreatic cancers may arise from mucinous pancreatic cysts, which are frequently present in the general population. Currently, surgical resection is the only curative approach for pancreatic cancer and its cystic precursors. However, only a dismal proportion of patients are eligible for surgery. Therefore, novel treatment approaches to treat pancreatic cancer and precancerous pancreatic cysts are needed. Endoscopic ultrasound (EUS)-guided ablation is an emerging minimally invasive method to treat pancreatic cancer and premalignant pancreatic cysts. Different ablative modalities have been used including alcohol, chemotherapy agents, and radiofrequency ablation. Cumulative data over the past two decades have shown that endoscopic ablation of mucinous pancreatic cysts can lead to cyst resolution in a significant proportion of the treated cysts. Furthermore, novel data are emerging about the ability to endoscopically ablate early and locally advanced pancreatic cancer. In this review, we aim to summarize the available data on the efficacy and safety of the different EUS-ablation modalities for the management of premalignant pancreatic cysts and pancreatic cancer.

Advancements in Pancreatic Cancer Detection: Integrating Biomarkers, Imaging Technologies, and Machine Learning for Early Diagnosis.

Artificial intelligence (AI) has come to play a pivotal role in revolutionizing medical practices, particularly in the field of pancreatic cancer detection and management. As a leading cause of cancer-related deaths, pancreatic cancer warrants innovative approaches due to its typically advanced stage at diagnosis and dismal survival rates. Present detection methods, constrained by limitations in accuracy and efficiency, underscore the necessity for novel solutions. AI-driven methodologies present promising avenues for enhancing early detection and prognosis forecasting. Through the analysis of imaging data, biomarker profiles, and clinical information, AI algorithms excel in discerning subtle abnormalities indicative of pancreatic cancer with remarkable precision. Moreover, machine learning (ML) algorithms facilitate the amalgamation of diverse data sources to optimize patient care. However, despite its huge potential, the implementation of AI in pancreatic cancer detection faces various challenges. Issues such as the scarcity of comprehensive datasets, biases in algorithm development, and concerns regarding data privacy and security necessitate thorough scrutiny. While AI offers immense promise in transforming pancreatic cancer detection and management, ongoing research and collaborative efforts are indispensable in overcoming technical hurdles and ethical dilemmas. This review delves into the evolution of AI, its application in pancreatic cancer detection, and the challenges and ethical considerations inherent in its integration.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines. Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.