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Familial Cancer Apr 2024Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is... (Review)
Review
Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is recommended only for individuals who meet familial/genetic risk criteria. To improve upon current approaches to pancreatic cancer early detection and to expand access, more accurate, inexpensive, and safe biomarkers are needed, but finding them has remained elusive. Newer approaches to early detection, such as using gene tests to personalize biomarker interpretation, and the increasing application of artificial intelligence approaches to integrate complex biomarker data, offer promise that clinically useful biomarkers for early pancreatic cancer detection are on the horizon.
PubMed: 38662265
DOI: 10.1007/s10689-024-00381-4 -
Endoscopy Dec 2024
Topics: Humans; Pancreatic Pseudocyst; Drainage; Child, Preschool; Male; Stents; Endosonography
PubMed: 38657669
DOI: 10.1055/a-2299-2253 -
Zeitschrift Fur Gastroenterologie Apr 2024Mucinous-cystic neoplasms (MCN) account for 10% of all pancreatic cystic lesions. They are found almost exclusively in females. MCN have an ovarian-like stroma and often...
BACKGROUND
Mucinous-cystic neoplasms (MCN) account for 10% of all pancreatic cystic lesions. They are found almost exclusively in females. MCN have an ovarian-like stroma and often estrogen and progesterone receptors. During pregnancy, they can massively increase in size and transform into malignancy.
CASE REPORT
We report on a 29-year-old woman in whom a 35mm cyst in the pancreatic tail had been diagnosed several years ago. After workup the lesions had been classified as a pseudocyst. During pregnancy, the cyst massively increased in size and finally was resected. Histology showed a mucinous-cystic neoplasia with focal malignant transformation.
CONCLUSION
Cystic neoplasms of the pancreas require a differentiated management. While overtreatment should be avoided, malignant transformation always merits consideration - in particular if the cystic lesion is located in the pancreatic tail. Women with suspected MCN or cystic pancreatic lesions of uncertain etiology should be informed about the (rare) risk of a malignant transformation of an MCN and should be closely monitored during pregnancy.
PubMed: 38657617
DOI: 10.1055/a-2239-7898 -
Research Square Apr 2024Biomarkers play a crucial role in advancing precision medicine by enabling more targeted and individualized approaches to diagnosis and treatment. Various biofluids,...
Biomarkers play a crucial role in advancing precision medicine by enabling more targeted and individualized approaches to diagnosis and treatment. Various biofluids, including serum, plasma, cerebrospinal fluid (CSF), saliva, tears, pancreatic cyst fluids, and urine, have been identified as rich sources of potential for the early detection of disease biomarkers in conditions such as cancer, cardiovascular diseases, and neurodegenerative disorders. The analysis of plasma and serum in proteomics research encounters challenges due to their high complexity and the wide dynamic range of protein abundance. These factors impede the sensitivity, coverage, and precision of protein detection when employing mass spectrometry, a widely utilized technology in discovery proteomics. Conventional approaches such as neat plasma workflow are inefficient in accurately quantifying low-abundant proteins, including those associated with tissue leakage, immune response molecules, interleukins, cytokines, and interferons. Moreover, the manual nature of the workflow poses a significant hurdle in conducting large cohort studies. In this study, our focus is on comparing workflows for plasma proteomic profiling to establish a methodology that is not only sensitive and reproducible but also applicable for large cohort studies in biomarker discovery. Our investigation revealed that the SeerProteographXT workflow outperforms other workflows in terms of plasma proteome depth, quantitative accuracy, and reproducibility while offering complete automation of sample preparation. Notably, SeerProteographXT demonstrates versatility by applying it to various types of biofluids. Additionally, the proteins quantified widely cover secretory proteins in peripheral blood, and the pathway analysis enriched with relevant components such as interleukins, tissue necrosis factors, chemokines, and B and T cell receptors provides valuable insights. These proteins, often challenging to quantify in complex biological samples, hold potential as early detection markers for various diseases, thereby contributing to the improvement of patient care quality.
PubMed: 38645164
DOI: 10.21203/rs.3.rs-4193960/v1 -
Cell Calcium Jun 2024When activated by increase in intracellular Ca, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the... (Review)
Review
When activated by increase in intracellular Ca, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the Ca-activated epithelial anion-selective channel that is coexpressed together with the abundant scramblase ANO6 and additional intracellular anoctamins. In salivary and pancreatic glands, ANO1 is tightly packed in the apical membrane and secretes Cl. Epithelia of airways and gut use cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl exit pathway while ANO1 supports Cl secretion mainly by facilitating activation of luminal CFTR and basolateral K channels. Under healthy conditions ANO1 modulates intracellular Ca signals by tethering the endoplasmic reticulum, and except of glands its direct secretory contribution as Cl channel might be small, compared to CFTR. In the kidneys ANO1 supports proximal tubular acid secretion and protein reabsorption and probably helps to excrete HCOin the collecting duct epithelium. However, under pathological conditions as in polycystic kidney disease, ANO1 is strongly upregulated and may cause enhanced proliferation and cyst growth. Under pathological condition, ANO1 and ANO6 are upregulated and operate as secretory channel/phospholipid scramblases, partly by supporting Ca-dependent processes. Much less is known about the role of other epithelial anoctamins whose potential functions are discussed in this review.
Topics: Humans; Animals; Anoctamins; Calcium; Cystic Fibrosis Transmembrane Conductance Regulator; Anoctamin-1
PubMed: 38642428
DOI: 10.1016/j.ceca.2024.102885 -
Journal of Gastroenterology and... Apr 2024
Review
PubMed: 38628139
DOI: 10.1111/jgh.16567 -
Scientific Reports Apr 2024Laparoscopic and robotic surgery is a challenge to the surgeon's hand-eye coordination ability, which requires constant practice. Traditional mentor training is...
Laparoscopic and robotic surgery is a challenge to the surgeon's hand-eye coordination ability, which requires constant practice. Traditional mentor training is gradually shifting to simulation training based on various models. Laparoscopic and robotic bilioenteric anastomosis is an important and difficult operation in hepatobiliary surgery. We constructed and optimized the reusable modular 3D-printed models of choledochal cyst. The aim of this study was to verify the ability of this optimized model to distinguish between surgeons with different levels of proficiency and the benefits of repeated practice. A total of 12 surgeons with different levels participated in the study. Operation completion time and OSATS score were recorded. The model was validated by Likert scale. Surgeons were shown the steps and contents before performing laparoscopic or robotic bilioenteric anastomosis using the model. Surgeons with different levels of experience showed different levels when performing laparoscopic bilioenteric anastomosis on this model. Repeated training can significantly shorten the time of laparoscopic bilioenteric anastomosis and improve the operation scores of surgeons with different levels of experience. At the same time, preliminary results have shown that the performance of surgeons on the domestic robotic platform was basically consistent with their laparoscopic skills. This model may distinguish surgeons with different levels of experience and may improve surgical skills through repeated practice. It is worth noting that in order to draw more reliable conclusions, more subjects should be collected and more experiments should be done in the future.
Topics: Humans; Robotic Surgical Procedures; Choledochal Cyst; Anastomosis, Surgical; Laparoscopy; Clinical Competence; Printing, Three-Dimensional
PubMed: 38627503
DOI: 10.1038/s41598-024-59351-6 -
RoFo : Fortschritte Auf Dem Gebiete Der... Apr 2024The time interval from symptom onset to the diagnosis of chronic pancreatitis (CP) remains disproportionately long today due to nonspecific symptoms and the absence of a...
The time interval from symptom onset to the diagnosis of chronic pancreatitis (CP) remains disproportionately long today due to nonspecific symptoms and the absence of a definitive laboratory marker. Nevertheless, mortality is increased by 3.6 times compared to the general population. Additionally, the risk of developing pancreatic carcinoma is 16 times higher in the presence of CP. According to the current S3 guideline, the morphological staging of CP should be based on the Cambridge Classification for CT/MRCP. Most radiologists morphologically associate CP with Cambridge Stage 4, which is characterized by classic calcifications. The subtle morphologies of earlier Cambridge Stages are often unrecognized, leading to delayed diagnosis. The aim of this study was to diagnose CP at Cambridge Stage 2 as the cause of unexplained upper abdominal discomfort.A retrospective analysis was conducted on 266 patients with unexplained upper abdominal pain who underwent outpatient MRI with MRCP between January 1, 2021, and October 1, 2023. The criteria for Cambridge Stage 2 were evaluated: pancreatic duct in the corpus measuring between 2 and 4 mm, pancreatic hypertrophy, cystic changes < 10 mm, irregularities in the duct, or > 3 pathological side branches. Patients with known tumors or other leading diagnoses, which explained the discomfort, were excluded.25 patients (15 female, 10 male) met the criteria for CP Stage 2 (9%). Ductal dilation between 2 and 4 mm was visible in 21 cases. Pancreatic hypertrophy was observed in six cases. Cystic changes < 10 mm were identified in three cases. Irregularities in the duct ("wavy duct") were diagnosed in 19 patients. Dilation of > 3 side branches was recognized in 17 cases. Lipase levels were additionally determined, with 13 patients showing pathologically elevated levels (> 60 U/l).CP at Cambridge Stage 2 is an important and underestimated diagnosis in patients with unexplained upper abdominal pain in the outpatient setting. Radiologists should pay attention not only to common signs like calcifications, large cysts, or duct strictures but also to subtle changes such as duct irregularities ("wavy duct configuration") and pathologically dilated side branches, which could lead to a significantly earlier diagnosis of CP. Lipase determination may be an additional indication of chronic pancreatitis in this context. · Early-stage Cambridge 2 CP is an important and underestimated diagnosis in patients with unexplained upper abdominal pain in the outpatient setting.. · Radiologists should pay attention to subtle signs of early CP.. · Additional information about lipase levels can be helpful in the diagnostic process..
PubMed: 38626882
DOI: 10.1055/a-2275-0946 -
Journal of the National Comprehensive... Apr 2024Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is...
BACKGROUND
Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.
METHODS
PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound.
RESULTS
A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst.
CONCLUSIONS
PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.
Topics: Humans; Pancreatic Neoplasms; Early Detection of Cancer; Prospective Studies; Adenocarcinoma; Genetic Predisposition to Disease; Magnetic Resonance Imaging
PubMed: 38626807
DOI: 10.6004/jnccn.2023.7097 -
Annals of Surgery Apr 2024We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic...
OBJECTIVE
We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome.
SUMMARY BACKGROUND DATA
Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation.
METHODS
Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings.
RESULTS
Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology.
CONCLUSIONS
Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.
PubMed: 38623754
DOI: 10.1097/SLA.0000000000006299