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BMJ (Clinical Research Ed.) Feb 2024Chronic pancreatitis results from repeated episodes of pancreatic inflammation and associated fibrosis leading to the loss of functional exocrine and endocrine... (Review)
Review
Chronic pancreatitis results from repeated episodes of pancreatic inflammation and associated fibrosis leading to the loss of functional exocrine and endocrine pancreatic function. The disease is manifested by abdominal pain, deterioration in quality of life, food maldigestion and malabsorption, diabetes, and an increased risk for pancreatic adenocarcinoma. This review summarizes the latest evidence on the diagnosis and management of chronic pancreatitis and its manifestations. In particular, this review discusses advances in understanding of the role of genetic disorders in the mechanisms of the disease and surgical options for patients refractory to medical therapy. Furthermore, clinical trials are under way to develop medical therapeutics.
Topics: Humans; Adenocarcinoma; Quality of Life; Pancreatic Neoplasms; Pancreatitis, Chronic
PubMed: 38408777
DOI: 10.1136/bmj-2023-070920 -
Gastroenterology Oct 2023Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with...
BACKGROUND & AIMS
Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance.
METHODS
International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer.
RESULTS
Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5).
CONCLUSIONS
The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.
Topics: Humans; Pancreatic Intraductal Neoplasms; Carcinoma, Pancreatic Ductal; Retrospective Studies; Pancreatic Neoplasms; Pancreas; Cysts; Pancreatic Ducts
PubMed: 37406887
DOI: 10.1053/j.gastro.2023.06.022 -
Radiographics : a Review Publication of... Nov 2023Pancreatic ductal adenocarcinoma (PDAC) is the most common primary pancreatic malignancy, ranking fourth in cancer-related mortality in the United States. Typically,...
Pancreatic ductal adenocarcinoma (PDAC) is the most common primary pancreatic malignancy, ranking fourth in cancer-related mortality in the United States. Typically, PDAC appears on images as a hypovascular mass with upstream pancreatic duct dilatation and abrupt duct cutoff, distal pancreatic atrophy, and vascular encasement, with metastatic involvement including lymphadenopathy. However, atypical manifestations that may limit detection of the underlying PDAC may also occur. Atypical PDAC features include findings related to associated conditions such as acute or chronic pancreatitis, a mass that is isointense to the parenchyma, multiplicity, diffuse tumor infiltration, associated calcifications, and cystic components. Several neoplastic and inflammatory conditions can mimic PDAC, such as paraduodenal "groove" pancreatitis, autoimmune pancreatitis, focal acute and chronic pancreatitis, neuroendocrine tumors, solid pseudopapillary neoplasms, metastases, and lymphoma. Differentiation of these conditions from PDAC can be challenging due to overlapping CT and MRI features; however, certain findings can help in differentiation. Diffusion-weighted MRI can be helpful but also can be nonspecific. Accurate diagnosis is pivotal for guiding therapeutic planning and potential outcomes in PDAC and avoiding biopsy or surgical treatment of some of these mimics. Biopsy may still be required for diagnosis in some cases. The authors describe the typical and atypical imaging findings of PDAC and features that may help to differentiate PDAC from its mimics. RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Zins in this issue.
Topics: Humans; Diagnosis, Differential; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreatitis, Chronic
PubMed: 37824413
DOI: 10.1148/rg.230054 -
Cell Reports. Medicine Feb 2024Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal... (Observational Study)
Observational Study
Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies; Pancreas; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 38280379
DOI: 10.1016/j.xcrm.2023.101391 -
Radiology Jul 2023Pancreatic cystic lesions (PCLs) are widely prevalent and commonly encountered in abdominal radiology. Some PCLs can be definitively identified at imaging as benign... (Review)
Review
Pancreatic cystic lesions (PCLs) are widely prevalent and commonly encountered in abdominal radiology. Some PCLs can be definitively identified at imaging as benign subtypes or those with malignant potential, while others remain indeterminate. Notably, the degree of malignant potential and natural history of the most common subtype, branch-duct intraductal papillary mucinous neoplasms, are not clearly established. In the work-up of PCLs, patients may further be identified as high-risk individuals who are at elevated risk of pancreatic ductal adenocarcinoma due to familial and genetic factors. This review describes current PCL surveillance and management guidelines and highlights ongoing controversies and future directions to aid radiologists in their daily practice.
Topics: Humans; Pancreatic Cyst; Pancreas; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Radiologists
PubMed: 37489987
DOI: 10.1148/radiol.222778 -
Modern Pathology : An Official Journal... Sep 2023Signet-ring cell (SRC)/poorly cohesive cell carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its...
Signet-ring cell (SRC)/poorly cohesive cell carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathologic and molecular profiles based on a multi-institutional cohort of 20 cases. The molecular profiles were investigated using DNA and RNA sequencing. The clinicopathologic parameters and molecular alterations were analyzed based on survival indices and using a validation/comparative cohort of 480 conventional PDAC patients. The primary findings were as follows: (1) clinicopathologic features: SRC carcinomas are highly aggressive neoplasms with poor prognosis, and the lungs are elective metastatic sites; (2) survival analysis: a higher SRC component was indicative of poorer prognosis. In particular, the most clinically significant threshold of SRC was 80%, showing statistically significant differences in both disease-specific and disease-free survival; (3) genomic profiles: SRC carcinomas are similar to conventional PDAC with the most common alterations affecting the classic PDAC drivers KRAS (70% of cases), TP53 (55%), SMAD4 (25%), and CDKN2A (20%). EGFR alterations, RET::CCDC6 fusion gene, and microsatellite instability (3 different cases, 1 alteration per case) represent novel targets for precision oncology. The occurrence of SMAD4 mutations was associated with poorer prognosis; (4) pancreatic SRC carcinomas are genetically different from gastric SRC carcinomas: CDH1, the classic driver gene of gastric SRC carcinoma, is not altered in pancreatic SRC carcinoma; (5) transcriptome analysis: the cases clustered into 2 groups, one classical/exocrine-like, and the other squamous-like; and (6) SRC carcinoma-derived organoids can be successfully generated, and their cultures preserve the histologic and molecular features of parental SRC carcinoma. Although pancreatic SRC carcinoma shares similarities with conventional PDAC regarding the most important genetic drivers, it also exhibits important differences. A personalized approach for patients with this tumor type should consider the clinical relevance of histologic determination of the SRC component and the presence of potentially actionable molecular targets.
Topics: Humans; Precision Medicine; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Carcinoma, Signet Ring Cell; Genomics; Prognosis
PubMed: 37355152
DOI: 10.1016/j.modpat.2023.100251 -
Bratislavske Lekarske Listy 2024Distal pancreatectomy is a standard surgical procedure for selected benign, premalignant, and malignant lesions localized in the pancreatic body or tail. Surgical...
NTRODUCTION
Distal pancreatectomy is a standard surgical procedure for selected benign, premalignant, and malignant lesions localized in the pancreatic body or tail. Surgical resection remains the only curative option for patients diagnosed with adenocarcinoma of the pancreas.
PATIENTS AND METHODS
Perioperative and postoperative clinical courses were retrospectively assessed in patients, who underwent distal pancreatectomy during the 2011‒2021 period.
RESULTS
During the 2011‒2021 period, a total of 112 distal pancreatectomies were performed. 67 patients (59.8%) underwent laparoscopic distal pancreatectomy, and 45 patients (40.2%) open laparotomy. The conversion was necessary for 13 patients (11.6%). Distal pancreatectomies performed laparoscopically were associated more often with biochemical leak and the development of grade B fistula, on the other hand grade C fistula developed only in patients operated by open laparotomy (LPT). The mean operating time was slightly longer in the laparoscopic group (227.1 min vs 214.6 min). The mean estimated blood loss was significantly higher in the LPT group (540.4 ml vs 191.9 ml). The mean hospitalization time was slightly longer in the LPT group (11.8 days vs 9.3 days). The rates of early reoperations were comparable between both groups (6 vs 5).
CONCLUSION
Laparoscopic techniques are preferred in centers around the world to bring patients benefits by using a minimally invasive approach. These techniques are also preferred in our center, in nearly 60% of all distal pancreatectomies performed during 10 years, but on the other hand, there is a much more careful approach chosen in cases of malignant disease to achieve adequate radicality (Tab.4, Ref. 20).
Topics: Humans; Pancreatectomy; Pancreatic Neoplasms; Retrospective Studies; Pancreas; Laparoscopy; Fistula; Treatment Outcome; Postoperative Complications
PubMed: 38526860
DOI: 10.4149/BLL_2024_36 -
Nature Aug 2023A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting...
A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting the argument that alterations in the gut fungal microbiome (the “mycobiome”), along with the presence of fungal elements within pancreatic tissue (specifically those of the genus , are associated with pancreatic oncogenesis. Upon analyzing the human sequencing data presented in the original manuscript, we found few fungal reads in pancreatic tissue samples and did not identify differences in pancreatic or gut mycobiome composition between healthy and pancreatic ductal adenocarcinoma (PDAC) patients. Our re-analysis of these data does not support an association between an intrinsic pancreatic mycobiome and the development of human PDAC, and illustrates the challenges in analyzing microbiome sequencing data from low biomass samples.
Topics: Humans; Mycobiome; Pancreatic Neoplasms; Pancreas; Carcinogenesis
PubMed: 37532819
DOI: 10.1038/s41586-023-06292-1 -
ELife Oct 2023The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the...
The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the PDAC pathogenesis, however, remains elusive. Here, we demonstrate that Sf3b1 alone is insufficient to induce malignant transformation of the murine pancreas, but that it increases aggressiveness of PDAC if it co-occurs with mutated KRAS and p53. We further show that Sf3b1 already plays a role during early stages of pancreatic tumor progression and reduces the expression of TGF-β1-responsive epithelial-mesenchymal transition (EMT) genes. Moreover, we found that SF3B1 confers resistance to TGF-β1-induced cell death in pancreatic organoids and cell lines, partly mediated through aberrant splicing of . Overall, our findings demonstrate that SF3B1 acts as an oncogenic driver in PDAC, and suggest that it promotes the progression of early stage tumors by impeding the cellular response to tumor suppressive effects of TGF-β.
Topics: Animals; Humans; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Mutation; Pancreatic Ducts; Pancreatic Neoplasms; Phosphoproteins; RNA Splicing Factors; Transcription Factors; Transforming Growth Factor beta1
PubMed: 37823551
DOI: 10.7554/eLife.80683 -
Seminars in Cancer Biology Dec 2023Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic... (Review)
Review
Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic ductal adenocarcinoma (PDAC). Several factors potentially explain the increased risk for the development of PDAC, including obesity-induced chronic inflammation within and outside of the pancreas, development of insulin resistance and metabolic dysfunction, promotion of immune suppression within the pancreas during inflammation, pre- and malignant stages, variations in hormones levels (adiponectin, ghrelin, and leptin) produced from the adipose tissue, and acquisition of somatic mutations in tumor once- and suppressor proteins critical for pancreatic tumorigenesis. In this manuscript, we will explore the broad impact of these obesity-induced risk factors on the development and progression of PDAC, focusing on changes within the tumor microenvironment (TME) as they pertain to prevention, current therapeutic strategies, and future directions for targeting obesity management as they relate to the prevention of pancreatic tumorigenesis.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Obesity; Inflammation; Carcinogenesis; Tumor Microenvironment
PubMed: 37926347
DOI: 10.1016/j.semcancer.2023.11.002