Management Of Pancreatic Adenocarcinoma Research Articles

Analyzing the role of TM4SF1 expression in pancreatic adenocarcinoma: understanding prognostic implications and therapeutic opportunities.

Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of TM4SF1 and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities. Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with TM4SF1 emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising BPIFB4, PLEKHN1, CPTP, DVL1, and DDR1 was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels. Lower TM4SF1 expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated TM4SF1 levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation. This study advances understanding of the molecular landscape of PAAD, emphasizing TM4SF1 as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting TM4SF1 and other identified genes in PAAD management.

From Bytes to Best Practices: Tracing ChatGPT-3.5's Evolution and Alignment With the National Comprehensive Cancer Network® Guidelines in Pancreatic Adenocarcinoma Management.

Artificial intelligence continues to play an increasingly important role in modern health care. ChatGPT-3.5 (OpenAI, San Francisco, CA) has gained attention for its potential impact in this domain. To explore the role of ChatGPT-3.5 in guiding clinical decision-making specifically in the context of pancreatic adenocarcinoma and to assess its growth over a period of time. We reviewed the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines for the Management of Pancreatic Adenocarcinoma and formulated a complex clinical question for each decision-making page. ChatGPT-3.5 was queried in a reproducible fashion. We scored answers on the following Likert scale: 5) Correct; 4) Correct, with missing information requiring clarification; 3) Correct, but unable to complete answer; 2) Partially incorrect; 1) Absolutely incorrect. We repeated this protocol at 3-months. Score frequencies were compared, and subgroup analysis was conducted on Correctness (defined as scores 1-2 vs 3-5) and Accuracy (scores 1-3 vs 4-5). In total, 50-pages of the NCCN Guidelines® were analyzed, generating 50 complex clinical questions. On subgroup analysis, the percentage of Acceptable answers improved from 60% to 76%. The score improvement was statistically significant (Mann-Whitney U-test; Mean Rank = 44.52 vs 56.48, P = .027). ChatGPT-3.5 represents an interesting but limited tool for assistance in clinical decision-making. We demonstrate that the platform evolved, and its responses to our standardized questions improved over a relatively short period (3-months). Future research is needed to determine the validity of this tool for this clinical application.

Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a prevalent and aggressive malignancy in the digestive tract, requiring accurate prediction and effective treatment strategies. Recently, the discovery of disulfidptosis, a novel form of programmed cell death characterized by abnormal disulfide accumulation, has sparked interest in its role in PAAD. In this study, we aimed to investigate the involvement of disulfidptosis-related genes (DRGs) in PAAD. Using publicly available databases, we conducted a comprehensive analysis exploring the complex relationships between DRGs and important aspects of PAAD, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we observed significant heterogeneity among different disulfidptosis subclusters and identified specific differentially expressed genes in PAAD. Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration. This study presents exciting opportunities and challenges in unraveling the underlying mechanisms of PAAD prognosis. It also establishes a foundation for personalized cancer care and the development of innovative immunotherapeutic strategies. By shedding light on the role of DRGs, particularly hub genes, we enhance our understanding and management of PAAD.

HKDC1 enhances the proliferation, migration and glycolysis of pancreatic adenocarcinoma and is linked to immune infiltration.

Background: Understanding the molecular mechanisms of pancreatic adenocarcinoma (PAAD) development is vital for treating this disease, as the current prognosis and treatment options are highly discouraging. Objective: This study aimed to examine the involvement of Hexokinase Domain Containing 1 (HKDC1) in the progression of PAAD. Methods: The study utilized bioinformatics techniques to evaluate the relationship between the expression of HKDC1 and clinical characteristics. In vitro experiments were conducted to investigate the molecular mechanisms and biological functions of HKDC1 in PAAD. Results: The findings of this research indicate that the expression of HKDC1 was increased in various types of human cancers, and a significant correlation was observed between elevated HKDC1 expression in PAAD and unfavorable prognosis. According to the findings from univariate and multivariate Cox regression analyses, HKDC1 could potentially serve as a standalone prognostic indicator for individuals diagnosed with PAAD. After performing calculations, we determined that the HKDC1 high-expression group exhibited lower immunologic score and higher ESTIMATE score, indicating a difference in immune infiltration score. In order to validate the expression of HKDC1 in PAAD cell lines, we analyzed the PAAD cell lines through qPCR and protein blotting. The expression of HKDC1 in human PAAD tissues was also detected by western blotting. Additionally, we explored the involvement of HKDC1 in PAAD by conducting experiments such as colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays. In our study, we discovered that disruption of HKDC1 expression in PAAD cell types resulted in a decrease in cell growth rate and inhibited cell movement and invasion. Conclusion: To conclude, our findings indicate that HKDC1 has a significant impact on the tumor microenvironment (TME) of PAAD and could potentially be a promising target for PAAD treatment, offering fresh perspectives on the management of PAAD.

Regret affects the choice between neoadjuvant therapy and upfront surgery for potentially resectable pancreatic cancer

BackgroundWhen treating potentially resectable pancreatic adenocarcinoma, therapeutic decisions are left to the sensibility of treating clinicians who, faced with a decision that post hoc can be proven wrong, may feel a sense of regret that they want to avoid. A regret-based decision model was applied to evaluate attitudes toward neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic adenocarcinoma. MethodsThree clinical scenarios describing high-, intermediate-, and low-risk disease-specific mortality after upfront surgery were presented to 60 respondents (20 oncologists, 20 gastroenterologists, and 20 surgeons). Respondents were asked to report their regret of omission and commission regarding neoadjuvant chemotherapy on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied to analyze respondents’ attitudes toward neoadjuvant therapy. ResultsThe lowest regret of omission was elicited in the low-risk scenario, and the highest regret in the high-risk scenario (P < .001). The regret of the commission was diametrically opposite to the regret of omission (P ≤ .001). The disease-specific threshold mortality at which upfront surgery is favored over the neoadjuvant therapy progressively decreased from the low-risk to the high-risk scenarios (P ≤ .001). The nonsurgeons working in or with lower surgical volume centers (P = .010) and surgeons (P = .018) accepted higher disease-specific mortality after upfront surgery, which resulted in the lower likelihood of adopting neoadjuvant therapy. ConclusionRegret drives decision making in the management of pancreatic adenocarcinoma. Being a surgeon or a specialist working in surgical centers with lower patient volumes reduces the likelihood of recommending neoadjuvant therapy.

Cytotoxic Chemotherapy for Pancreatic Adenocarcinoma in England 2010–2017: Survival Outcomes

AimsCytotoxic chemotherapy is widely used in the management of pancreatic adenocarcinoma as adjuvant treatment after radical surgery and also in advanced disease. The results of randomised trials in selected patient groups provide reliable evidence of comparative treatment efficacy, but studies of population-based observational cohorts provide insight into survival outcomes in routine care. Materials and methodsWe conducted a large population-based observational cohort study of patients, diagnosed during 2010–2017, who received chemotherapy within the National Health Service in England. We considered overall survival and 30-day all-cause mortality risk after chemotherapy. We conducted a literature search to compare these results to published studies. ResultsIn total, 9390 patients were included in the cohort. For 1114 patients treated with radical surgery and chemotherapy with curative intent, overall survival from the start of chemotherapy was 75.8% (95% confidence interval 73.3–78.3) at 1 year and 22.0% (18.6–25.3) at 5 years. For 7468 patients treated with non-curative intent, overall survival was 29.6% (28.6–30.6) at 1 year and 2.0% (1.6–2.4) at 5 years. In both groups, poorer performance status at the start of chemotherapy was strongly associated with poorer survival. The risk of 30-day mortality in patients treated with non-curative intent was 13.6% (12.8–14.5). This was higher in younger patients and those with higher stage disease and a poorer performance status. ConclusionsSurvival in this general population was poorer than that published in randomised trials. This study will aid informed discussion with patients regarding anticipated outcomes in routine clinical care.

Pancreatic Adenocarcinoma: Emerging Systemic Therapy Options

Although we are “winning the war against cancer,” pancreatic malignancies are expected to be the most common cause of cancer-related death by 2040. Several systemic therapies, such as oxaliplatin + irinotecan/fluorouracil/leucovorin (FOLFIRINOX) and gemcitabine + nab-paclitaxel, have shown activity in the adjuvant and neoadjuvant settings. The current NCCN Guidelines reflect the most up-to-date, evidence-based data relating to the evaluation and management of pancreatic adenocarcinoma. They were recently updated to recommend germline testing for any patient with pancreatic cancer and molecular analysis of any metastatic pancreatic tumor.

Endoscopic ultrasound role in pancreatic adenocarcinoma treatment: A review focusing on technical success, safety and efficacy.

The impressive technological advances in recent years have rapidly translated into the shift of endoscopic ultrasound (EUS) from diagnostic modality into an interventional and therapeutic tool. Despite the great advance in its diagnosis, the majority of pancreatic adenocarcinoma cases are inoperable when diagnosed, thus demanding alternative optional therapies. EUS has emerged as an easy, minimally invasive modality targeting this carcinoma with different interventions that have been reported recently. In this review we summarize the evolving role of interventional therapeutic EUS in pancreatic adenocarcinoma management.

Pancreatic Adenocarcinoma: Experience at the National Oncologic Institute of Panama, 2013-2018

Introduction: Pancreatic adenocarcinoma ranks sixth in cancer mortality in Panama. In our country there is no literature that describes pancreatic adenocarcinoma in patients treated at the National Oncologic Institute Nacional (ION). Methods: A descriptive study was carried out from medical records, which included all patients with a diagnosis of pancreatic adenocarcinoma treated at the ION, from January 2013 to December 2018. We describe the sociodemographic and clinical characteristics, referring to the diagnosis, staging and management of pancreatic adenocarcinoma. The tabulation and statistical analysis was carried out with the Microsoft Excel Office 365 © program. Results: 388 files were reviewed, of which 284 met the inclusion criteria. 52% were male and 48% female, the average age was 65 years (± 11.7 years). The most frequent symptoms at the time of diagnosis were abdominal pain (73%) and weight loss (70%). 70% presented in stage IV and only 5% with resectable disease. 21 surgical interventions were performed with a curative intent. The palliative approach was used as initial treatment in 253 patients; 18 patients in radiotherapy, 80 in palliative care unit and 155 in systemic therapy. 28% of the patients were treated without histological confirmation. 27.8% had Ca19-9 values below 37U/mL, 28.5% over 1000 U/mL and 16.5% were not tested. Conclusions: Approximately 50 patients with pancreatic adenocarcinoma are evaluated at the institution per year, and only 5% present with resectable disease. Two thirds of the patients presented with distant metastases at the time of diagnosis, this representing poor prognosis.

Arterial Divestment and Resection in Post-neoadjuvant Pancreatic Adenocarcinoma.

IntroductionThe advent of neoadjuvant therapy in the management of pancreatic adenocarcinoma has significantly improved the prognosis of the disease. Nevertheless, the only chance of long-term disease-free survival in pancreatic cancer is achieved with complete tumor resection, and artery involvement by the tumor is one of the major determinants in its resectability. We aim to evaluate the feasibility of a novel technique, namely, the periarterial divestment, which has allowed surgeons to clear the tumor tissues off the visceral arteries without the need for arterial reconstruction.Materials and methodsIn this single-center, retrospective, descriptive, cross-sectional study done between August 2019 and July 2021, seven consecutive patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC) who underwent neoadjuvant therapy were included. Arterial divestment was performed in six of seven patients and arterial reconstruction was performed in one of the patients. The data on perioperative and the early oncological outcome were recorded.ResultsFive patients underwent periarterial divestment, one underwent sub-adventitial divestment, and one underwent superior mesenteric artery reconstruction due to deeper tumor infiltration into the arterial wall. The intraoperative frozen section of periarterial tissue was positive in three cases and the final histopathological specimen after the divestment showed a positive margin in two of the cases. The clinically significant postoperative pancreatic fistula was noted in two patients, and one patient experienced grade C post-pancreaticoduodenectomy hemorrhage due to a hepatic artery pseudoaneurysm. Four patients, all of whom underwent periarterial divestment, experienced postoperative diarrhea. There were no mortality and the median postoperative hospital stay was seven days.ConclusionThe need for arterial reconstruction in borderline and locally advanced pancreatic cancer can be avoided by using the periarterial divestment technique. Divestment of arteries is technically feasible and can be carried out safely without compromising the patient's oncological outcome. However, further validation of this technique must be done by well-designed studies with a greater sample size.

A new pancreatic adenocarcinoma-derived organoid model of acquired chemoresistance to FOLFIRINOX: First insight of the underlying mechanisms.

Although improvements have been made in the management of pancreatic adenocarcinoma (PDAC) during the past 20 years, the prognosis of this deadly disease remains poor with an overall 5-year survival under 10%. Treatment with FOLFIRINOX, a combined regimen of 5-fluorouracil, irinotecan (SN-38) and oxaliplatin, is nonetheless associated with an excellent initial tumour response and its use has allowed numerous patients to go through surgery while their tumour was initially considered unresectable. These discrepancies between initial tumour response and very low long-term survival are the consequences of rapidly acquired chemoresistance and represent a major therapeutic frontier. To our knowledge, a model of resistance to the combined three drugs has never been described due to the difficulty of modelling the FOLFIRINOX protocol both in vitro and in vivo. Patient-derived tumour organoids (PDO) are the missing link that has long been lacking in the wide range of epithelial cancer models between 2D adherent cultures and in vivo xenografts. In this work we sought to set up a model of PDO with resistance to FOLFIRINOX regimen that we could compare to the paired naive PDO. We first extrapolated physiological concentrations of the three drugs using previous pharmacodynamics studies and bi-compartmental elimination models of oxaliplatin and SN-38. We then treated PaTa-1818x naive PDAC organoids with six cycles of 72 h-FOLFIRINOX treatment followed by 96 h interruption. Thereafter, we systematically compared treated organoids to PaTa-1818x naive organoids in terms of growth, proliferation, viability and expression of genes involved in cancer stemness and aggressiveness. We reproductively obtained resistant organoids FoxR that significantly showed less sensitivity to FOLFORINOX treatment than the PaTa-1818x naive organoids from which they were derived. Our resistant model is representative of the sequential steps of chemoresistance observed in patients in terms of growth arrest (proliferation blockade), residual disease (cell quiescence/dormancy) and relapse. To our knowledge, this is the first genuine in vitro model of resistance to the three drugs in combined therapy. This new PDO model will be a great asset for the discovery of acquired chemoresistance mechanisms, knowledge that is mandatory before offering new therapeutic strategies for pancreatic cancer.

Value of Neoadjuvant Radiation Therapy in the Management of Pancreatic Adenocarcinoma.

Value of Neoadjuvant Radiation Therapy in the Management of Pancreatic Adenocarcinoma.

Role of Radiotherapy in the Management of Pancreatic Adenocarcinoma: Debate and Discordance in Clinical Trials

Pancreatic adenocarcinoma (PAC) is an extremely fatal malignancy with dismal outcome with standard treatment till date. Investigators are constantly in search of optimal treatment approach and radiation therapy (RT) remains in the centre of debate. Human pancreatic cancer cell lines have shown both intrinsic and hypoxia induced radio resistance, and RT has produced conflicting results as well in the various clinical trials. However, most of the American studies continued the use of RT as a potential treatment modality but the European school of thought is widely criticized for their ‘therapeutic nihilism’ towards radiation and faulty clinical trial designs. This article has reviewed the available literature on the evolving role of RT for the management of resectable and borderline resectable PAC and has highlighted the increasing trend towards the use of radiotherapy for both adjuvant and neo adjuvant treatment. With the advent of modern RT techniques, the acute and late toxicities are much less than the earlier time, and therefore augmented RT is expected to produce better clinical outcomes for the patients with pancreatic carcinoma.

Current controversies and advances in the management of pancreatic adenocarcinoma

Pancreatic adenocarcinoma is a lethal disease with a mortality rate that has not significantly improved over decades. This is likely due to several challenges unique to pancreatic cancer. Most patients with pancreatic cancer are diagnosed at a late stage of disease due to the lack of specific symptoms prompting an early investigation. A small subset of patients who are diagnosed at an early stage have a better chance at survival with curative surgical resection, but most patients still succumb to the disease in a few years. The dismal overall prognosis is due to suspected micro-metastasis at an early stage. Due to this reason, there is a recent interest in treating all patients with pancreatic cancers with systemic therapy upfront (including the ones that are surgically resectable). This approach is still not the standard of care due to the lack of robust prospective data available. Recent advancements in treatment regimens of chemotherapy, radiation and immunotherapy have improved the overall short-term survival but the long-term survival still remains poor. Novel approaches in diagnosis and treatment have shown promise in clinical studies but long-term clinical data is lacking. The following manuscript presents an overview of the epidemiology, diagnosis, staging, recent advances, novel approaches and controversies in the management of pancreatic adenocarcinoma.

Neoadjuvant chemoradiation may be associated with improved pathologic response in pancreatic cancer

BackgroundNeoadjuvant therapy is increasingly utilized in the management of pancreatic adenocarcinoma. The type of neoadjuvant therapy and its effect on pathologic response remains understudied. MethodsA retrospective review was performed on patients who underwent neoadjuvant therapy followed by pancreatectomy. Multivariable regressions were used to determine associations between neoadjuvant therapy regimens and pathologic response. ResultsSeventy-five patients with pathologic responses available for review received FOLFIRINOX (61%) or gemcitabine with nab-paclitaxel (39%). Demographics, histologic differentiation, and utilization of chemoradiation were similar between the groups. Multivariable logistic regression demonstrated that chemoradiation was associated with an increased likelihood of a complete or near-complete pathologic response and a decreased rate of lymphovascular invasion and lymph node positivity. Neither chemotherapy regimen nor number of cycles administered were associated with pathologic response. ConclusionsNeoadjuvant chemoradiation may be associated with complete or near-complete pathologic response regardless of chemotherapy regimen in pancreatic cancer patients.

Advances in the Management of Pancreatic Adenocarcinoma

Outcomes in pancreatic cancer are improving. The beneficial effects being achieved with adjuvant and neoadjuvant therapies, and the recent application of molecular profiling, both germline and somatic, are collectively impacting survival. The NCCN Guidelines for Pancreatic Cancer urge clinicians to undertake “agnostic” germline testing for all persons with pancreatic cancer. Fit patients should also be considered for adjuvant therapy with modified FOLFIRINOX (leucovorin, 5-FU, irinotecan, oxaliplatin). Novel therapies that focus on DNA damage repair strategies are proving to be important, but notably several late-stage trials of several other approaches, reported in the last year, proved disappointing.

Benefits of High-Volume Medical Oncology Care for Noncurable Pancreatic Adenocarcinoma: A Population-Based Analysis.

Although pancreatic adenocarcinoma (PA) surgery performed by high-volume (HV) providers yields better outcomes, volume-outcome relationships are unknown for medical oncologists. This study examined variation in practice and outcomes in noncurative management of PA based on medical oncology provider volume. This population-based cohort study linked administrative healthcare datasets and included nonresected PA from 2005 through 2016. The volume of PA consultations per medical oncology provider per year was divided into quintiles, with HV providers (≥16 patients/year) constituting the fifth quintile and low-volume (LV) providers the first to fourth quintiles. Outcomes were receipt of chemotherapy and overall survival (OS). The Brown-Forsythe-Levene (BFL) test for equality of variances was performed to assess outcome variability between provider-volume quintiles. Multivariate regression models were used to examine the association between management by HV provider and outcomes. A total of 7,062 patients with noncurable PA consulted with medical oncology providers. Variability was seen in receipt of chemotherapy and median survival based on provider volume (BFL, P<.001 for both), with superior 1-year OS for HV providers (30.1%; 95% CI, 27.7%-32.4%) compared with LV providers (19.7%; 95% CI, 18.5%-20.6%) (P<.001). After adjustment for age at diagnosis, sex, comorbidity burden, rural residence, income, and diagnosis period, HV provider care was independently associated with higher odds of receiving chemotherapy (odds ratio, 1.19; 95% CI, 1.05-1.34) and with superior OS (hazard ratio, 0.79; 95% CI, 0.74-0.84). Significant variation was seen in noncurative management and outcomes of PA based on provider volume, with management by an HV provider being independently associated with superior OS and higher odds of receiving chemotherapy. This information is important to inform disease care pathways and care organization. Cancer care systems could consider increasing the number of HV providers to reduce variation and improve outcomes.

P-126 - The management of pancreatic adenocarcinoma in a hospitalized-based population (2015-2019)

P-126 - The management of pancreatic adenocarcinoma in a hospitalized-based population (2015-2019)

Provider-volume associated with variable receipt of therapy and outcomes for noncurative pancreas adenocarcinoma: A population-based analysis.

352 Background: While high-volume providers for pancreatic adenocarcinoma (PA) surgery yield better outcomes, variation in practice and the role of provider-volume has not been investigated for systemic therapy. We examined variation in practice and outcomes in the management of non-curative PA, based on medical oncology provider-volume. Methods: We conducted a population based retrospective cohort study of non-resected PA over 2005-2016 by linking administrative healthcare datasets. High-volume (HV) medical-oncology providers were defined as the 5th quintile of number of PA seen per provider per year. Outcomes were receipt of chemotherapy and overall survival (OS). Brown Forsythe Levene (BFL) test for equality of variances assessed outcomes variability between provider-volume quintiles (Q1 to 5). Multivariate regressions examined the association between management by HV provider and receipt of systemic therapy and OS. Results: Of 10,881 non-curative PA patients, 7,062 consulted with medical oncology. Among 341 medical oncology providers, 3% were HV, defined as &gt; 16 patients/year. There was variability in receipt of chemotherapy based on provider-volume, with 44% (IQR: 25-54) for Q1 and 47% (IQR: 43-54) for Q5, and in median survival, with 4.1 months (IQR: 2.7-6.2) for Q1 and 7.5 months (IQR: 6.6-8.0) for Q5. Variability between provider-volume quintiles was significant for receipt of chemotherapy and median survival (both BFL p &lt; 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV provider was independently associated with higher odds of receiving chemotherapy (OR 1.19 [1.05-1.34]), and superior OS (HR 0.79 [0.74-0.84]). Conclusions: There was significant variation in non-curative management and outcomes of PA based on provider-volume. Management by a HV provider was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case-mix. This information is important to inform disease care pathways and care organization. Cancer care systems could consider initiatives to increase the number of HV providers to reduce variation and improve outcomes.

Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes.

This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.