Update on Familial Pancreatic Cancer

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new “evidence-based guidelines” is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, “stop surveillance” or “continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma”, for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.

Pancreatic cancer is the world's fourth largest causative factor of mortality with a five year of survival rate. Poor definitive diagnosis can be ascribed to both problematic early detections, which render the significant number of therapies approaches mostly ineffective and cause widespread metastasis, in addition to its unique physiological and pathological traits. There have been ongoing efforts to employ novel approaches to combat pancreatic cancer in an effort to improve the therapeutic efficacy of treatments and reduce their cytotoxic effect. Combining nanotechnology approach with cancer targeting has demonstrated enhanced survival of patients and life quality outcomes, providing a potential remedy for treatment problems. The self-nanoemulsifying drug delivery system is one of the most successful nanotechnology approaches for increasing the oral bioavailability of a medicinal agent, particularly one that is poorly water soluble and hydrophobic drug. The self-nanoemulsifying drug delivery system SNEDDS technique has addressed the various problems like inadequate bioavailability, undesired toxicity, poor absorption, and solubility issues at the site of action in case of chemotherapeutic drugs. This review discusses the conventional therapies of pancreatic cancer as well as current advancements in self-nanoemulsifying drug delivery system in order to address the main issue facing the area of oncology.

Pancreatic cancer (PC) carries a poor prognosis with an overall 5-year survival of less than 10%. Early diagnosis, though cumbersome, is essential to allow complete surgical resection. Therefore, primary and secondary prevention are critical to reduce the incidence and to potentially prevent mortality. Given a relatively low lifetime risk of developing PC, identification of high-risk individuals is crucial to allow identification of pre-malignant lesions and small, localized tumors. Although 85–90% of PC cases are sporadic, we could consider risk stratification for the 5–10% of patients with a family history and the 3–5% of cases due to inherited genetic syndromes. These high-risk populations should be considered for screening and surveillance of PC. MRI/MRCP and EUS are the preferred modalities, due to their high sensitivity in lesion detection. Surveillance should be personalized, considering genetics and family history, and assessment of risk factors that may increase cancer risk. Screening programs should be limited to tertiary referral center, with high-volumes and adequate facilities to manage these patients.

Pancreatic cancer (PC) is a fatal disease that has a 5-year survival rate of less than 9%. It is expected to rank second in cancer-related deaths across the United States by 2030. Out of all the patients only about one-fifth patients are potentially treatable, and treatment options are often palliative. PC's poor prognosis is credited to its difficult early detection and also the tumour microenvironment that restrict therapeutic agents’ mobility. Numerous experimental and clinical research studies have demonstrated excellent therapeutic outcomes when a combination or simultaneous administration of chemotherapeutics is achieved. But even so, these 'combination' therapies frequently result in significant systemic toxicity. Nanoparticle-mediated delivery, particularly micelles, has the loading potential for multiple combinations of chemotherapeutics, thereby improving stability and accessibility, tumour-targeted delivery, and reducing chemotherapy-related adverse effects. As a result, a combinatorial approach can modify survival rates in patients promoting quality of life, and potentially providing a solution to hurdles in therapy. This review outlines the key challenges in treating PC, as well as recent advances in micelle-mediated combination treatments that combine chemotherapeutics and other gene-targeting agents such as siRNA and miRNA.

A set of disorders known collectively as cancers are connected to unnatural cell proliferation. Without any intervention, the illness could worsen, resulting in premature death. A lethal malignant tumor is threatened invasion. Pancreatic cancer (PC) is more frequently found in men and elder persons (60–85 years old). Young individuals are recently being identified with PC more frequently. Being one of the deadliest tumors, it has no earliest symptoms and it can quickly infect nearby tissues and organs. Despite significant advancements in the struggle against the disease, continued, intense efforts are made to promote early detection and treatments. Nanomaterials have gained more attentiveness recently for PC diagnosis and treatment. The most recent information about PC risk, diagnostics, and therapy, as well as the role of polymeric NPs (PNPs) in PC treatment and diagnosis are discussed in this chapter. PNPs synthesis and characterization techniques are also discussed. PNPs have the capability to give improvements in early diagnosis, therapeutic monitoring, and image-guided surgery. Drug delivery using PNP increases tumor targeting penetration, targeted and specific drug delivery, and antitumor activity, enhances the stability and biological uptake of the drugs, and reduces cytotoxicity.

Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis.

Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC.

FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16–63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved.

The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia.

FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.