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This article constitutes a review of the existing literature on the potential correlation between autosomal dominant polycystic kidney disease (ADPKD) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Additionally, it presents a clinical case where familiarity for both pathologies was observed, derived from the direct experience of our clinic, reinforcing the hypothesis of a possible common pathogenetic pathway. The review focuses on the potential genetic correlation between these two pathologies within the realm of ciliopathies, emphasizing the importance of targeted screening and monitoring strategies to detect pancreatic complications early in patients with ADPKD. Furthermore, it highlights the complexity in the clinical management of these rare conditions and underscores the importance of early diagnosis in optimizing clinical outcomes.

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This article presents updates in the surgical management of non-functional sporadic pancreas neuroendocrine tumors NET, including considerations for assessment of biologic behavior to support decision-making, indications for surgery, and surgical approaches tailored to the unique nature of neuroendocrine tumors.

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Pancreatic ductal adenocarcinoma (PDAC) continues to remain one of the leading causes of cancer-related death. Unlike other malignancies where universal screening is recommended, the same cannot be said for PDAC. The purpose of this study is to review which patients are at high risk of developing PDAC and therefore candidates for screening, methods/frequency of screening, and risk for these groups of patients.

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Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation.

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Pancreatic adenocarcinoma is an aggressive malignancy that often presents with advanced disease. Accurate staging is essential for treatment planning and shared decision-making with patients. Staging laparoscopy is a minimally invasive procedure that can detect radiographically occult metastatic disease. Its routine use with the collection of peritoneal washings in patients with pancreatic cancer remains controversial. We, herein, review the current literature concerning staging laparoscopy and peritoneal washings in patients with pancreatic cancer.

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Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.

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Background: Although CA19-9 is an essential blood biomarker of pancreatic cancer (PC), its sensitivity and specificity are limited for early detection. Methods: We analyzed the serum proprotein convertase subtilisin/kexin type 9 (sPCSK9) in PC patients, benign disease groups (BDG), and healthy controls (HC) by ELISA. Results: Consistently, sPCSK9 was considerably lower in PC patients than in HC (Z = -2.546, P < 0.05), and sPCSK9 in PC patients was statistically significantly higher than in BDG (Z = -5.457, P < 0.001). sPCSK9 was linked to the invasion of lymph nodes (χ2 = 6.846, P < 0.01). According to ROC curves, combining sPCSK9 with CA19-9 could potentially enhance the diagnostic capability of CA19-9 in early-stage PC patients. Furthermore, the low sPCSK9 group (n = 41) exhibited statistically significantly prolonged overall survival compared to the high sPCSK9 group (n = 15), with median survival times of 27 months (95% CI [17.59-36.41]) and 11 months (95% CI [7.21-14.79]), respectively (P = 0.022). Conclusion: The diagnostic performance of CA19-9 for early-stage PC patients could be improved by combining sPCSK9 with CA19-9. Moreover, the higher sPCSK9 group has a significantly shorter overall survival rate.

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BACKGROUND Autoimmune pancreatitis (AIP) is identified as an outlier in the clinical practice of chronic pancreatitis caused by autoimmune system dysfunction. AIP is classified into 3 subtypes: AIP type 1 and AIP type 2, which are both sensitive to corticosteroids, and the recently introduced AIP type 3. CASE REPORT We present a case of a patient who presented with painless obstructive jaundice. Computed tomography (CT) revealed hyperdense gallbladder material, further dilatation of intrahepatic bile ducts, and distention of the bile duct (15 mm). Based on the available clinical data, which were strongly compatible with pancreatic cancer, Whipple surgery was selected as the treatment for this case. The consequent histopathological report revealed areas of pancreatic parenchyma with fibrous connective tissue development and dense inflammatory cell infiltration with lymphocytes and plasmacytes, which showcased IgG4 positivity. The clinical results suggested a diagnosis of AIP type 1, and the patient was referred to his treating physician for further treatment of AIP. Preoperative histological examination of the pancreas, along with evaluation of the radiological and serological features, could have aided in determining the diagnosis of AIP type 1 pancreatitis despite the unique abnormality of this particular case. CONCLUSIONS Given the aforementioned conditions, AIP, even as a rare clinical entity, emerges as a canonical ailment and should be considered a viable possibility in clinical practice since it can exclude the patient from an unnecessary surgery.

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Outcomes from pancreatic ductal adenocarcinoma (PDAC) remain poor and better methods of prognostication and therapeutic approaches are needed. Recent advances in cancer genomics have led to the development of molecular subtypes of PDAC associated with clinical outcomes. Current evidence also suggests that the subtypes have differential response to first-line chemotherapy regimens. PDAC is also characterized by different stroma and immune environments. Further work is needed to confirm the utility of these subtypes to predicting response to different systemic therapies.

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AIMS AND BACKGROUND: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. METHODS: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP-7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. RESULTS: MMP-7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP-7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19-9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). CONCLUSIONS: Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

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BACKGROUND: Grade 3 neuroendocrine tumor (G3 PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC) of the pancreas are considered distinct entities from a biological and prognostic perspective but may have overlapping features complicating a definitive diagnosis. CASE PRESENTATION: A 52-year-old female presented with a pancreatic body mass and liver lesions. Initial biopsies showed variable lower- and higher-grade morphologies and modestly elevated Ki67 proliferation index up to 30%, leading to a diagnosis of G3 PanNET. The patient underwent everolimus treatment followed by surgical resection, revealing a complex tumor with features of both G3 PanNET and PanNEC, including admixed well- and poorly differentiated morphologies, modestly elevated hotspot Ki67 of 28%, retained ATRX/DAXX expression, and loss of RB expression. The final diagnosis rendered was "high-grade neuroendocrine neoplasm" with discussion of both entities in the differential. Post-operatively, the patient remains alive with stable metastases. CONCLUSIONS: This case highlights the diagnostic complexities of distinguishing G3 PanNET and PanNEC even with the support of ancillary immunohistochemical and molecular studies. In addition, such cases raise the possibility that G3 PanNET and PanNEC may lie on a spectrum of disease with potential biological overlap.

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PROBLEM: Pancreatic ductal adenocarcinoma (PDAC) is considered a highly lethal cancer due to its advanced stage diagnosis. The five-year survival rate after diagnosis is less than 10%. However, if diagnosed early, the five-year survival rate can reach up to 70%. Early diagnosis of PDAC can aid treatment and improve survival rates by taking necessary precautions. The challenge is to develop a reliable, data privacy-aware machine learning approach that can accurately diagnose pancreatic cancer with biomarkers. AIM: The study aims to diagnose a patient's pancreatic cancer while ensuring the confidentiality of patient records. In addition, the study aims to guide researchers and clinicians in developing innovative methods for diagnosing pancreatic cancer. METHODS: Machine learning, a branch of artificial intelligence, can identify patterns by analyzing large datasets. The study pre-processed a dataset containing urine biomarkers with operations such as filling in missing values, cleaning outliers, and feature selection. The data was encrypted using the Fernet encryption algorithm to ensure confidentiality. Ten separate machine learning models were applied to predict individuals with PDAC. Performance metrics such as F1 score, recall, precision, and accuracy were used in the modeling process. RESULTS: Among the 590 clinical records analyzed, 199 (33.7%) belonged to patients with pancreatic cancer, 208 (35.3%) to patients with non-cancerous pancreatic disorders (such as benign hepatobiliary disease), and 183 (31%) to healthy individuals. The LGBM algorithm showed the highest efficiency by achieving an accuracy of 98.8%. The accuracy of the other algorithms ranged from 98 to 86%. In order to understand which features are more critical and which data the model is based on, the analysis found that the features "plasma_CA19_9", REG1A, TFF1, and LYVE1 have high importance levels. The LIME analysis also analyzed which features of the model are important in the decision-making process. CONCLUSIONS: This research outlines a data privacy-aware machine learning tool for predicting PDAC. The results show that a promising approach can be presented for clinical application. Future research should expand the dataset and focus on validation by applying it to various populations.

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This study aimed to evaluate the diagnostic efficacy of cell block (CB) and liquid-based cytology (LBC) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic tumors. The study included patients who underwent EUS-FNA for pancreatic tumors between January 2015 and February 2021 and whose cytology samples were both processed for LBC and CB. Data of 390 patients (220 men, mean age: 64.2 ± 11.4 years) were retrospectively analyzed. Of the detected lesions (size: 17-120 mm; mean: 39.9 ± 13.9 mm), 220 (56.4%) were located in the head and uncinate process of the pancreas. Lesions in 339 (86.9%) patients were diagnosed as malignant using CB and/or LBC and suspicious for malignancy in 44 (11.3%) patients. In 7 patients with non-diagnostic (6 cases) or negative for malignancy (1 case) EUS-FNA results using both methods, the diagnosis of malignancy was established via ultrasound-guided percutaneous biopsy. Malignancy was detected in 324 (92.4%), 313 (87.9%), and 298 (87.9%) patients using CB, LBC, and both CB and LBC, respectively. Final diagnosis was obtained in 339 (98%) patients by using CB and/or LBC. The combined use of the both methods exhibited significantly superior diagnostic accuracy compared with CB and LBC alone (P < .001). Liquid-based cytology and CB exhibit high diagnostic accuracy for the detection of pancreatic tumors in patients undergoing EUS-FNA. The combined use of both methods showed a significantly higher diagnostic accuracy than LBC and CB alone.

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BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer. METHODS: A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles. RESULTS: Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients). CONCLUSION: Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.

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Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

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Diagnosis of biliopancreatic cancers by the available serum tumor markers, imaging, and histopathological tissue specimen examination remains a challenge. Circulating cell-free DNA derived from matched pairs of secretin-stimulated duodenal fluid (DF) and plasma from 10 patients with biliopancreatic diseases and 8 control subjects was analyzed using AmpliSeq™ HD technology for Ion Torrent Next-Generation Sequencing to evaluate the potential of liquid biopsy with DF in biliopancreatic cancers. The median cfDNA concentration was greater in DF-derived than in plasma-derived samples. A total of 13 variants were detected: 11 vs. 1 were exclusive for DF relative to the plasma source, and 1 was shared between the two body fluids. According to the four-tier systems, 10 clinical tier-I-II (76.9%), 1 tier-III (7.7%), and 2 tier-IV (15.4%) variants were identified. Notably, the 11 tier-I-III variants were exclusively found in DF-derived cfDNA from five patients with biliopancreatic cancers, and were detected in seven genes (KRAS, TP53, BRAF, CDKN2A, RNF43, GNAS, and PIK3CA); 82% of the tier-I-III variants had a low abundance, with a VAF < 6%. The mutational profiling of DF seems to be a reliable and promising tool for identifying cancer-associated alterations in malignant cancers of the biliopancreatic tract.

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Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

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