Risk factors and some aspects of pancreatic cancer prevention

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high‐risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high‐risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis of pancreatic cancer to be applied in the clinic. As the only serum biomarker approved by the United States Food and Drug Administration, carbohydrate antigen 19‐9 (CA19‐9) is not recommended to be used in the early screening of pancreatic cancer because of its limited specificity. Recently, increasing numbers of studies focused on the discovering of novel serum biomarkers and exploring their combination with CA19‐9 in the detection of pancreatic cancer. Besides, the application of liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis are drawing more and more attention. Furthermore, many innovative technologies such as artificial intelligence, computer‐aided diagnosis system, metabolomics technology, ion mobility spectrometry (IMS) associated technologies, and novel nanomaterials have been tested for the early diagnosis of pancreatic cancer and have shown promising prospects. Hence, this review aims to summarize the recent progress in the development of early screening and diagnostic methods, including imaging, pathological examination, serological examination, liquid biopsy, as well as other potential diagnostic strategies for pancreatic cancer.

Early Detection of Pancreatic Cancer: Are We Ready for Prime Time?

Recommendations for a More Organized and Effective Approach to the Early Detection of Pancreatic Cancer From the PRECEDE (Pancreatic Cancer Early Detection) Consortium

Pancreatic cancer has one of the worst prognoses of any type of cancer. Early detection and surgery is the best chance for cure. However, symptoms are typically vague and occur when the cancer is unresectable. Early detection through screening is likely to be the best hope to improve survival. The relatively low incidence of pancreatic cancer and the insensitive screening techniques currently available render this approach expensive and inefficient in the general population. Early detection and screening for pancreatic cancer in the current state should be limited to highrisk patiens. But hereditary factors account about 10% of patients with pancreatic cancer (familial pancreatic cancer, hereditary pancreatitis, Peutz Jeghers syndrom etc.). Continued efforts are needed to discover effective test to identify patients with nonhereditary risk factors who will benefit from screening and also to develop less invasive and more costeffective screening modalities aimed at controlling pancreatic cancer. A combined ap-proach of serum markers, genetic markers and specific imaging studies may prove to be the future of pancreatic screening.

ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations

Desmoplasia of Pancreatic Ductal Adenocarcinoma

Detecting Early Pancreatic Cancer: Problems and Prospects

Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates. Both normal and tumour tissues of the pancreas were previously considered sterile. In recent years, with the development of technologies for high-throughput sequencing, a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi. The intratumour microbiome is being revealed as an influential contributor to carcinogenesis. The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression, diagnosis, and treatment, chemotherapy resistance, and immune response. A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies. This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer, the intratumour localization, the interaction with the tumour microenvironment, and strategies for improving the outcome of pancreatic cancer treatment. Thus, this review offers new perspectives for improving the prognosis of pancreatic cancer.

BackgroundPancreatic cancers of the tail have an especially poor prognosis due to their late detection. An earlier diagnosis depends on a better understanding of the clinical course of the disease; however, much of the current literature focuses on pancreatic head adenocarcinomas owing to their higher incidence. Thus, we add our case report to the current literature of pancreatic tail cancers in the hope of aiding earlier detection. We present an interesting case of a patient who initially presented with innocuous abdominal pain and a single episode of vomiting who was subsequently diagnosed with metastatic pancreatic tail cancer.Case presentationA 56-year-old Hispanic man with a past medical history of alcohol and cocaine abuse was initially evaluated in our clinic after presenting to the emergency department with sudden onset of abdominal pain and one episode of emesis. On further questioning, he stated that he had been experiencing dull, intermittent left back pain for the past 2–3 years. Laboratory tests were performed, which showed that the patient had new-onset diabetes, and imaging revealed a pancreatic tail mass with metastases to the liver. Biopsy confirmed the diagnosis of stage IV metastatic pancreatic tail adenocarcinoma. During follow-up 1 month later, the patient reported that he had been largely asymptomatic since his hospital admission; however, his left back pain had increased in severity. He was then started on a FOLFIRINOX chemotherapy regimen (5-fluorouracil/leucovorin, irinotecan, and oxaliplatin).ConclusionsThere are many pitfalls in the diagnosis of pancreatic cancer, especially pancreatic tail cancer due to its vague symptoms. Thus, pancreatic cancer of the tail often presents late with a very poor prognosis. Because there is currently no widespread screening for pancreatic cancer, it is often difficult for practitioners to identify pancreatic tail cancers. Current research suggests that there is a strong association between new-onset diabetes after the age of 50 and pancreatic cancer, and tumors detected at the onset of diabetes are favorable to resection. Pancreatic cancer has also been shown to be associated with certain risk factors, such as smoking, high body mass index, chronic pancreatitis, and a family history of pancreatic cancer. Thus, when patients with presentations similar to our patient’s with new-onset diabetes after the age of 50, along with vague symptoms such as back or abdominal pain as well as the presence of risk factors, we suggest that it is beneficial for practitioners to maintain a high index of suspicion for pancreatic cancer.

The Hirshberg Foundation for Pancreatic Cancer Research was founded by Agi Hirshberg in 1997, following her husband Ronald Hirshberg’s 8-month, 7-day battle with the disease. (http://www.pancreatic.org/). At the time, the Hirshberg family viewed pancreatic cancer as the ‘‘unknown enemy’’ (http:// www.pancreatic.org/site/c.htJYJ8MPIwE/b.8276835/k.66CB/ Agi_Hirshbergs_Story.htm). In the years since Ronald Hirshberg’s death, Agi Hirshberg has made it her mission to unmask the unknown for others facing the same enemy. When patients present with a new diagnosis of pancreatic cancer, most are already in an advanced stage of the disease. Pancreatic cancer is resistant to most chemotherapeutic agents and radiotherapy. These factors combine to make pancreatic cancer a highly lethal disease, and according to the National Cancer Institute (NCI) 2013 estimates, pancreatic cancer was diagnosed in approximately 45,220 US citizens, and some 38,460 died of the disease. 1 The Annual Report to the Nation on the Status of Cancer, 1975Y2009, shows that overall cancer death rates continued to decline in the United States among both men and women, among all major racial and ethnic groups, and for all of the many common cancer sites, including lung, colon and rectum, female breast, and prostate. However, this trend does not hold true for pancreatic cancer. The report demonstrates that death rates continued to increase during the latest time period (2000 through 2009) for pancreatic cancer. 2 Only about 23% of patients with cancer of the pancreas will still be living 1 year after diagnosis, and only about 4% will survive 5 years. Even for those diagnosed with pancreatic cancer that has not spread to other organs or systems, the overall 5-year survival rate approaches only 15%. The Hirshberg Foundation’s vision is to advance pancreatic cancer research and provide information, resources, and support to pancreatic cancer patients and their families. The mission of the Foundation is as follows: & To find a cure for pancreatic cancer in honor of Ron Hirshberg and the thousands of people who are diagnosed with this disease each year. & To create a premier Pancreatic Cancer Center where all needs of pancreatic cancer patients can be met in one location with the most advanced treatment options. & To be recognized as a patient support reference source for

The relationship between diabetes mellitus (DM) and pancreatic cancer is complex-DM is both a risk factor and early sign of pancreatic cancer. DM is a risk factor for pancreatic cancer because it increases insulin resistance, intrapancreatic concentrations of insulin, and the bioavailability of IGF, subsequently promoting ductal cell proliferation. Accordingly, treatment targeting the insulin/IGF pathway is the focus of many researchers. Antidiabetic drugs modify the risk for pancreatic cancer-metformin's antineoplastic effect being most notable and indicating potential clinical use in pancreatic cancer. New-onset DM can also be the first manifestation of pancreatic cancer. There are several theories for the pathogenesis of DM in pancreatic cancer, the most important being that DM is a paraneoplastic syndrome caused by diabetogenic factors. As a consequence of this intricate relationship, new-onset DM after the age of 50 is considered a red flag for pancreatic cancer, prompting the need for screening in this patient population. Multiple clinical studies are currently underway exploring this matter. A better understanding of the relationship between DM and pancreatic cancer could aid in developing novel screening and treatment strategies for pancreatic cancer. This could ultimately improve the prognosis and quality of life of patients with pancreatic cancer.

Pancreatic cancer is a malignancy of rising prevalence, especially in developed countries where dietary patterns and sedentariness favor its onset. This malady ranks seventh in cancer-related deaths in the world, although it is expected to rank second in the coming years, behind lung cancer. The low survival rate is due to the asymptomatic course of the early stages, which in many cases leads to metastases when becoming evident in advanced stages. In this context, molecular pathology is on the way towards finding new approaches with biomarkers that allow a better prognosis and monitoring of patients. So the present study aims to evaluate a series of molecular biomarkers, PARP1, NOX1, NOX2, eNOS and iNOS, as promising candidates for prognosis and survival by using immunohistochemistry. The analysis performed in 41 patients with pancreatic cancer showed a correlation between a high expression of all these components with a low survival rate, with high statistical power for all. In addition, a 60-month longitudinal surveillance program was managed, accompanied by several clinical parameters. The derivative Kaplan–Meier curves indicated a low cumulative survival rate as well. Ultimately, our research emphasized the value of these molecules as survival-associated biomarkers in pancreatic cancer, offering new gates for clinical management.

Chronic Pancreatitis and Pancreatic Cancer: Prediction and Mechanism

BackgroundPancreatic cancer poses a serious medical problem worldwide. Countries in the Western Pacific Region are facing public health challenges from cancer. This study assesses the time trends of pancreatic cancer mortality in the Western Pacific Region from 1990 to 2019 and predicts its trend to 2044.MethodsMortality data were obtained from the Global Health Data Exchange. We used an age-period-cohort model to estimate age, period and birth cohort effects on pancreatic cancer mortality from 1990 to 2019 by calculating net drift, local drift, age-specific rate, period rate ratio, and cohort rate ratio. We also predict pancreatic cancer mortality to 2044 in Western Pacific countries.ResultsOverall, there were 178,276 (95% uncertain interval: 157,771 to 198,636) pancreatic cancer deaths in the Western Pacific Region in 2019, accounting for 33.6% of all deaths due to pancreatic cancer worldwide. There were significant increases in pancreatic cancer disability-adjusted life years between 1990 and 2019 in the Western Pacific Region, mainly due to population growth and aging. Pancreatic cancer mortality increased with age. The period effect showed an increasing trend of mortality for both sexes over the study period. Compared to the reference period (2000 to 2004), the rate ratio was elevated in both males and females in the period of 2015 to 2019. There was an overall increasing rate ratio from early birth cohorts to recent cohorts. Deaths may continue to increase in the next 25 years in the ten countries, while most countries have seen their age-standardized rate forecasts fall.ConclusionThe mortality of pancreatic cancer is still high in the Western Pacific Region. Countries/territories should focus on pancreatic cancer prevention and early cancer screening in high-risk populations. Specific public health methods and policies aimed at reducing risk factors for pancreatic cancer are also needed.

Pancreatic cancer is a rare but lethal cancer due to its biologically aggressive nature, advanced stage at the time of diagnosis, and poor response to oncologic therapies. The risk of pancreatic cancer is significantly higher to 5% in certain high-risk individuals with inherited genetic susceptibility. Screening for pancreatic cancer in these individuals from high-risk groups can help with the early detection of pancreatic cancer as well as the detection of precursor lesions leading to early surgical resection and improved overall outcomes. The advancements in radiological imaging as well as advanced endoscopic procedures has made a significant impact on the early diagnosis, surveillance, and staging of pancreatic cancer. There is also a significant advancement in the development of biomarkers for the early detection of pancreatic cancer, which has also led to the development of liquid biopsy, allowing for microRNA detection in serum and circulating tumor cells. Various societies and organizations have provided guidelines for pancreatic cancer screening and surveillance in high-risk individuals. In this review, we aim to discuss the hereditary risk factors for developing pancreatic cancer, summarize the screening recommendations by different societies, and discuss the development of novel biomarkers and areas for future research in pancreatic cancer screening for high-risk individuals.