Diagnosis Of Pancreatic Carcinoma Research Articles

Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct

Dilatation of the main pancreatic duct (MPD) has been a surgical indication for intraductal papillary mucinous neoplasms (IPMNs). Few studies have investigated long-term outcomes of IPMNs with MPD dilatation. Among 3610 patients diagnosed with pancreatic cysts between 1994 and 2021, we identified 2829 IPMN patients, including 282 patients with MPD ≥5 mm, and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma. Utilizing competing risks proportional hazards models, we estimated subdistribution hazard ratios for incidence of pancreatic carcinoma with adjustment for potential confounders. In analyses of short-term outcomes of the 282 patients with MPD dilatation, 72 (26%) patients were diagnosed with pancreatic carcinoma based on surgical or nonsurgical exploration. During long-term follow-up of 168 patients, we documented 24 (14%) patients diagnosed with pancreatic carcinoma (18 with IPMN-derived carcinoma and 6 with concomitant ductal adenocarcinoma). The patients with the MPD= 5-9.9 mm had cumulative incidence rates of pancreatic carcinoma diagnosis of 8.1% (95% confidence interval [CI], 4.3%-13.5%) and 10.0% (95% CI, 5.5%-15.9%) at 2 and 5 years, respectively; and the patients with the MPD ≥10 mm had the corresponding rates of 16.0% (95% CI, 3.6-36.5%) and 33.3% (95% CI, 10.3%-58.8%). The multivariable subdistribution hazard ratios were 2.78 (95% CI, 1.57-4.90) and 7.00 (95% CI, 2.58-19.0) for the MPD= 5-9.9 mm and ≥10 mm (vs <5 mm), respectively. IPMNs with MPD dilatation at baseline were associated with higher prevalence and incidence of pancreatic carcinoma compared with IPMNs with no MPD dilatation.

An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.

TPS771 Background: Curative treatment for potentially resectable (resectable or borderline resectable) pancreatic adenocarcinoma, despite recent advances, leads to only suboptimal outcomes. Recent US national cooperative group trials have demonstrated the safety and feasibility of neoadjuvant chemotherapy (PMID 33475684, PMID 35834226), and also show that the two frontline regimens, FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP), are comparable in this setting. Finally, ability to undergo resection remains the key driver of cure. Therefore, an approach that selects chemotherapy based on early response assessment, to maximize the probability of resection, is likely to improve curative outcomes. Methods: This is a phase II study intended to maximize the probability of surgical resection for pancreatic cancer. Key eligibility requirements include adult patients with a confirmed histopathologic diagnosis of pancreatic carcinoma or adenocarcinoma, an ECOG PS ≤ 1, resectable or borderline resectable disease by central radiology review, no prior therapy for index pancreatic cancer, and adequate bone marrow, liver and kidney function. Treatment includes 4 doses (~ 2 months total treatment time) of FOLFIRINOX (“Chemo1”). After a re-evaluation, using radiologic response, CA19.9 response, and chemotherapy toxicity, patients will either continue with “Chemo1” for another 4 cycles (8 doses) or switch to GnP (“Chemo2”) which will be administered for 4 cycles (12 doses, for ~4 month total treatment time), followed by surgical resection. Primary outcome will measure the proportion of patients undergoing surgical resection using historical dated compared to 32 patients in a current study with a time frame of 16 months. Using historical data, the expected proportion of patients undergoing resection is ~60%. The goal of this study is to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, 32 patients will be needed to demonstrate this difference. Key translational correlatives will include serial circulating tumor DNA assessment and extensive tumor molecular profiling. Clinical trial information: NCT04594772 .

Advancements of molecular imaging and radiomics in pancreatic carcinoma.

Despite the recent progress of medical technology in the diagnosis and treatment of tumors, pancreatic carcinoma remains one of the most malignant tumors, with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation. This paper focuses on the research progress of magnetic resonance imaging, nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma. We also briefly described the achievements of our team in this field, to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Granular cell tumour of the pancreas: a case report and systematic review

PurposeGranular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a patient with GCT, a comprehensive review of available literature was conducted to identify the common diagnostic features associated with GCT.MethodsFollowing a case report identified in our institution, a systematic review was conducted by two authors in accordance with Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA) guidelines. Databases MEDLINE, EMBASE, Scopus, World of Science, and grey literature were searched on August 2021. Inclusion criteria were histopathology diagnosed granular cell tumour of the pancreas.ResultsA 37-year-old male presented with 1 month of abdominal pain and an MRI demonstrating a dilated main pancreatic duct, distal parenchymal atrophy, but no focal lesion. Repeat MRI at 6 months re-demonstrated similar findings and subsequent endoscopic ultrasound was suspicious for main duct IPMN. Following multidisciplinary team discussion, a spleen-preserving distal pancreatectomy was performed. Histopathology demonstrated granular cell tumour with cells diffusely positive for S100 and no malignant transformation.11 case reports were identified in the literature with diagnosis confirmed on tissue histopathology based on positive immunohistochemical staining for S-100 protein. Eight patients presented with gastrointestinal symptoms with abdominal pain the main presenting complaint (50%). 10 patients underwent CT with portal venous contrast and all underwent endoscopic examination. Imaging findings were similar in five studies for EUS which demonstrated a hypoechoic lesion with homogenous appearance. On non-contrast CT GCT was iso-enhancing, and with portal venous contrast demonstrated hypo-enhancement that gradually enhanced on late phases. Pre-operative diagnosis of pancreatic carcinoma was described in six cases based on imaging and biopsy, resulting in progression to surgical resection. Nine patients were managed surgically and no complications identified on follow-up (6–52 months).ConclusionThe currently proposed management pathway includes EUS with biopsy and CT, and surgical resection recommended due to malignancy risk. Improved sample collection with EUS-FNA and microscopic assessment utilising S-100 immunohistochemistry may improve pre-operative diagnosis. Limitations include rare numbers in reported literature and short follow-up not allowing an assessment of GCT’s natural history and malignancy risk. Additional cases would expand the current dataset of GCTs of the pancreas, so that surgical resection may be avoided in the future.

ROLE OF CARBOHYDRATE ANTIGEN (CA19-9) AND CARCINOEMBRYONIC ANTIGEN (CEA) AS A PROGNOSTIC FACTORS IN PANCREATIC CARCINOMA

Objective:To investigate the potential utility of pre-treatment carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) as prognostic indicators to assess prognosis in pancreatic carcinoma. MaterialsandMethods:This retrospective observational study was carried out at the Department of General Surgery Hayatabad Medical Complex Peshawar from July 2017 to June 2022. A total of 70 patients with the diagnosis of pancreaticcarcinoma were enrolled.Allpatientswerehistologicallydiagnosedwithpancreaticcarcinoma. ThelevelsofCA19-9andCEAwereevaluatedbeforetreatment.Allpatientsreceivedeitheranoperation,chemotherapy or chemoradiotherapy (CRT), and patientswho only received supportive care, palliative surgery or othertreatmentswerenotincludedinthestudy.Patients with a history of other malignancies were excluded. Results:A total of 70 patients were included in this study. Age ranged between 25-75 years, with a mean age of 50 years. Included patients were stratified into 2 groups (35 each) in regard to their preoperative CEA &amp; CA 19-9 level. Group 1: (Normal serum level group, CEA level value &lt;5ng/ml &amp; CA19-9 &lt;37 U/ml), Group 2: (Elevated level group ≥5ng/ml &amp; ≥37 U/ml)There were 19(54.3%) males and 16(45.7%) females in group 1 with male to female ratio of 1.18:1 and 18(51.4%) male &amp; 17(48.6%) females in group 2 with male to female ratio 1.05:1. CA 19-9 and CEA were evaluated at initial diagnosis,andthemedianlevelswere37U/mL(range,0.1-20000U/mL) and 3.4 ng/mL (range, 0.04-8566 ng/mL), respectively. Conclusion:Patientswithelevated serum CEA levels at diagnosis demonstrated poor overall survival. Pre-treatment CEA level may predict the prognosis of patients with pancreatic adenocarcinoma.

Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses.

BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.

Pancreatic Cystic Lesions on MRI: What Is The Likelihood of a Present or Future Diagnosis of Pancreatic Carcinoma?

Pancreatic cystic lesions (PCLs) are followed for years due to older and likely biased works demonstrating a strong association with pancreatic carcinoma; more recent data are needed clarifying this relationship. To determine the association between PCLs on MRI and a synchronous or future diagnosis of pancreatic carcinoma. Single-center retrospective cohort. A total of 192 patients (111 female, 58%) with median age 66 years (range 26-87 years) with PCLs on abdominal MRI from 2011 to 2016. 1.5 T and 3T, including T2 WI, T1 WI, diffusion weighted imaging and contrast-enhanced T1 WI. Each PCL was reviewed independently by 2 of 10 fellowship-trained abdominal radiologists. Fukuoka guideline worrisome features and high-risk stigmata were evaluated. Follow-up imaging and clinical notes were reviewed within a system that captures pancreatic carcinoma for the region, for a median follow-up of 67months (interquartile range: 43-88months). Pancreatic carcinoma prevalence and incidence rate for future carcinoma with 95% confidence intervals (95% CI). Fisher exact test, logistic regression with odds ratios (OR) and the Wilcoxon rank-sum test were used to assess PCL morphologic features with the Kolmogorov-Smirnov test used to assess for normality. P < 0.05 defined statistical significance. The prevalence of pancreatic carcinoma on initial MRI showing a PCL was 2.4% (95% CI: 0.9%, 5.2%). Thickened/enhancing cyst wall was associated with pancreatic carcinoma, OR 52 (95% CI: 4.5, 1203). Of 189 patients with a PCL but without pancreatic carcinoma at the time of initial MRI, one developed high-grade dysplasia and none developed invasive carcinoma for an incidence rate of 0.97 (95% CI: 0.02, 5.43) and 0 (95% CI: 0, 3.59) cases per 1000 person-years, respectively. A low percentage of patients with a PCL on MRI had a pancreatic carcinoma at the time of initial evaluation and none developed carcinoma over a median 67months of follow-up. 3 TECHNICAL EFFICACY: 5.

Incidence, risk factors, and evolution of venous thromboembolic events in patients diagnosed with pancreatic carcinoma and treated with chemotherapy on an outpatient basis

BackgroundPancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. Patients and methodsWe conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. ResultsWith a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96–2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21–2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30–2.84; p<0.001). ConclusionsPancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.

LncRNA ZFAS1 Promotes HMGCR mRNA Stabilization via Binding U2AF2 to Modulate Pancreatic Carcinoma Lipometabolism

Being one of the most lethal malignant tumors worldwide, pancreatic carcinoma (PC) shows strong invasiveness and high mortality. In tumorigenesis and progression, the role played by long-chain noncoding RNAs (lncRNAs) cannot be ignored. This article mainly probes into the function of lncRNA ZFAS1 in PC. ZFAS1 expression in PC and normal counterparts retrieved from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) database was analysed by GEPIA2. Its expression profile in clinical specimens and human PC cell strains was quantified using qRT-PCR. Measurements of BxPC-3 cell multiplication and invasiveness employed CCK-8, plate clone formation test, and Transwell chamber assay. ZFAS1's impact on lipid content in BxPC-3 cells was detected. RNA pulldown and RIP assays analyzed the interaction of ZFAS1 with U2AF2 and HMGCR in BxPC-3 cells. Finally, the impacts of U2AF2 and HMGCR on the biological behavior of BxPC-3 were observed. ZFAS1 was kept at a high level in PC tissues versus the normal counterparts. ZFAS1 gene knockout remarkably suppressed PC cell multiplication and invasiveness and decreased the contents of free fatty acids, total cholesterol, triglycerides, and phospholipids. Mechanistically, ZFAS1 stabilized HMGCR mRNA through U2AF2, thus increasing HMGCR expression and promoting PC lipid accumulation. Meanwhile, reduced PC cell viability and invasiveness were observed after downregulating U2AF2 and HMGCR. As an oncogene of PC, ZFAS1 can modulate lipometabolism and stabilize HMGCR mRNA expression by binding with U2AF2 in PC, which is a candidate target for PC diagnosis and treatment.

Papanicolaou society of cytopathology system for reporting pancreaticobiliary cytology: Risk stratification and cytology scope - 2.5-year study.

Objectives:Diagnosis of pancreatic lesions remains a clinical challenge. Early and accurate diagnosis is extremely important for improving the therapeutic usefulness of pancreatic cancers and Endoscopic ultrasonography - fine needle aspiration (EUS-FNA) cytology has come up with this advantage. For current study the authors evaluated the diagnostic accuracy of EUS-FNAC by applying PSC system for reporting pancreaticobiliary cytology and Calculated the malignancy risk associated with the diagnostic categories.Material and Methods:A retrospective study over the period of 2.5 years (April 2017 to Oct 2019) 60 patients in our cohort EUS-FNAC guided unstained fixed and unfixed slides received of pancreatic lesion and were stained with Papanicolau and Giemsa using standard technique and immunocytochemistry, where required Application of Papanicolaou Society of Cytopathology system for reporting pancreaticobiliary cytology Histopathological and clinical follow-up were retrieved.Results:Our study has comparable results with sensitivity, specificity, PPV, and NPV of 92.8%, 100%, 100%, and 92.59%, respectively. Fuurthermore, a diagnostic accuracy of 96.2%. Risk of malignancy is lower for benign and indeterminate category whereas it is higher for suspicious and malignant categories.Conclusion:The application of the new proposed terminology for pancreaticobiliary cytology brings standardization. Final diagnosis can be reached by the multidisciplinary approach of EUS-FNA cytology, cell block preparation, immunocytochemistry, and immunohistochemistry; if required, can be adopted as an alternative approach to biopsy. The present study showed high sensitivity and specificity for EUS-FNA in the diagnosis of pancreatic carcinoma, which may influence the treatment plans of both surgeons and oncologists.

Development and validation of a novel model incorporating MRI-based radiomics signature with clinical biomarkers for distinguishing pancreatic carcinoma from mass-forming chronic pancreatitis

PurposeIt is difficult to make a clear differential diagnosis of pancreatic carcinoma (PC) and mass-forming chronic pancreatitis (MFCP) via conventional examinations. We aimed to develop a novel model incorporating an MRI-based radiomics signature with clinical biomarkers for distinguishing the two lesions. MethodsA total of 102 patients were retrospectively enrolled and randomly divided into the training and validation cohorts. Radiomics features were extracted from four different sequences. Individual imaging modality radiomics signature, multiparametric MRI (mp-MRI) radiomics signature, and a final mixed model based on mp-MRI and clinically independent risk factors were established to discriminate between PC and MFCP. The diagnostic performance of each model and model discrimination were assessed in both the training and validation cohorts. ResultsADC had the best predictive performance among the four individual radiomics models, but there were no significant differences between the pairs of models (all p > 0.05). Six potential radiomics features were finally selected from the 960 texture features to formulate the radiomics score (rad-score) of the mp-MRI model. In addition, the boxplot results of the distributions of rad-scores identified the rad-score as an independent predictive factor for the differentiation of PC and MFCP (p< 0.001). Notably, the nomogram integrating rad-score and clinically independent risk factors had a better diagnostic performance than the mp-MRI and clinical models. These results were further confirmed by the validation group. ConclusionThe mixed model was developed and preliminarily validated to distinguish PC from MFCP, which may benefit the formulation of treatment strategies and nonsurgical procedures.

Peripheral Blood Lymphocyte Percentage May Predict Chemotolerance and Survival in Patients with Advanced Pancreatic Cancer. Association between Adaptive Immunity and Nutritional State.

Simple SummaryAlterations of the immune system that consist of induced inflammation and reduction in blood lymphocytes are a major factor contributing to cancer progression in patients with pancreatic carcinoma (PC). Identification of the percentage of lymphocytes in the Total number of White Blood Cells (L% TWBC) that could be associated with chemotolerance and survival time may be important for predicting treatment efficacy. The aim of this retrospective study was to highlight the best value of L% for predicting chemotolerance (n° of cycles tolerated) and survival beyond 12 months from diagnosis. The study found that L ≥ 29.7% TWBC compared to L < 29.7% predicted chemotolerance (p < 0.0001) and survival at every time point of follow-up: 6 (p = 0.04), 12 (p = 0.0003) and 18 months (p = 0.004) after diagnosis. Simple, rapid, routine laboratory data can be useful to predict treatment tolerance and efficacy in PC patients.Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB > 1500 n°/mm3) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.

Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate.

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also provide an insight to the prognosis. For instance, the loss of SMAD4 is associated with a poor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associated with improved survival.

Tissue harmonic versus contrast-enhanced harmonic endoscopic ultrasonography for the diagnosis of pancreatic tumors: Prospective multicenter study.

This prospective multicenter study aimed to assess and compare the accuracy of tissue harmonic endoscopic ultrasonography (TH-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for differentiating pancreatic carcinoma from other pancreatic tumors. Consecutive patients with solid pancreatic tumors were prospectively enrolled between August 2013 and December 2014. To assess the accuracy of TH-EUS and CH-EUS, we compared four parameters of TH-EUS (fuzzy edge, irregular periphery, hypoechogenicity, and heterogeneous internal echogenicity) and four parameters of CH-EUS (hypoenhancement and heterogeneous enhancement in the early and late phases, respectively) to investigate which parameter of each method was most suitable to diagnose pancreatic carcinomas. Interobserver agreement and the diagnostic ability of pancreatic carcinoma using TH-EUS and CH-EUS were assessed and compared. A total of 204 patients were enrolled. For the diagnosis of pancreatic carcinoma, interobserver agreement by experts and nonexperts was 0.33-0.50 and 0.35-0.50 for TH-EUS, respectively, and 0.72-0.74 and 0.20-0.54 for CH-EUS, respectively. Irregular periphery was the most accurate diagnostic parameter among TH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 95.0%, 42.9%, and 78.9%, respectively. Late phase hypoenhancement was the most accurate diagnostic parameter among CH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 90.8%, 74.6%, and 85.8%, respectively. The accuracy of CH-EUS (late phase hypoenhancement) for diagnosis of pancreatic carcinoma was significantly higher than that of TH-EUS (irregular periphery) (p < 0.001). In comparison with TH-EUS, CH-EUS increased the diagnostic ability and reproducibility for the diagnosis of pancreatic carcinoma. UMIN (000011124).

Extracellular Vesicles as Potential Biomarkers for Early Detection and Diagnosis of Pancreatic Cancer.

Pancreatic carcinoma (PC) is highly metastatic, and it tends to be detected at advanced stages. Identifying and developing biomarkers for early detection of PC is crucial for a potentially curative treatment. Extracellular vesicles (EVs) are bilayer lipid membrane-structured nanovesicles found in various human bodily fluids, and they play important roles in tumor biogenesis and metastasis. Cancer-derived EVs are enriched with DNA, RNA, protein, and lipid, and they have emerged as attractive diagnostic biomarkers for early detection of PC. In this article, we provided an overview of the cell biology of EVs and their isolation and analysis, and their roles in cancer pathogenesis and progression. Multiplatform analyses of plasma-based exosomes for genomic DNA, micro RNA, mRNA, circular RNA, and protein for diagnosis of PC were critically reviewed. Numerous lines of evidence demonstrate that liquid biopsy with analysis of EV-based biomarkers has variable performance for diagnosis of PC. Future investigation is indicated to optimize the methodology for isolating and analyzing EVs and to identify the combination of EV-based biomarkers and other clinical datasets, with the goal of improving the predictive value, sensitivity, and specificity of screening tests for early detection and diagnosis of PC.

MicroRNA-23a acts as an oncogene in pancreatic carcinoma by targeting TFPI-2.

Pancreatic carcinoma (PC) is a rapidly progressive, fatal malignant tumor with the poorest prognosis among all major carcinoma types. MicroRNAs (miRNAs/miRs) have been indicated to be key post-transcriptional regulatory factors, which are involved in cancer development. The present study was designed to investigate the effect of miR-23a on PC cell proliferation, metastasis and apoptosis. The expression of miR-23a was detected in a normal pancreatic ductal epithelial cell line and three PC cell lines, and miR-23a inhibitor or mimics were transfected into the Panc-1 and MiaPaCa2 PC cells. The association between miR-23a and tissue factor pathway inhibitor (TFPI)-2 was examined using a luciferase reporter assay. MTT and flow cytometry assays were used to assess cell viability and apoptosis, respectively. Furthermore, wound-healing, Transwell and Matrigel assays were used to evaluate cell migration and invasion abilities, and the protein expression level of TFPI-2 was determined using western blot analysis. The results of the present study revealed that miR-23a was upregulated in PC cells. Furthermore, TFPI-2 was identified as a downstream target of miR-23a, and TFPI-2 expression was found to be increased following miR-23a knockdown. In addition, functional assays revealed that downregulation of miR-23a decreased PC cell proliferation, migration and invasiveness and promoted cell apoptosis, while miR-23a overexpression exerted the opposite effects. Furthermore, TFPI-2 knockdown rescued the biological effects on PC cells, which were induced by miR-23a knockdown. The results of the present study indicated that miR-23a negatively modulated TFPI-2 expression in vitro and enhanced the malignant phenotypes of PC cells. Therefore, miR-23a may be a potential marker and/or target for the diagnosis and treatment of PC.

The Radiolabeling of a Gly-Sar Dipeptide Derivative with Flourine-18 and Its Use as a Potential Peptide Transporter PET Imaging Agent.

We have developed a novel fluorine-18 radiotracer, dipeptide 1, radiolabeled in two steps from mesylate 3. The initial radiolabeling is achieved in a short reaction time (10 min) and purified through solid-phase extraction (SPE) with modest radiochemical yields (rcy = 10 ± 2%, n = 5) in excellent radiochemical purity (rcp > 99%, n = 5). The de-protection of the tert-butyloxycarbonyl (Boc) and trityl group was achieved with mild heating under acidic conditions to provide 18F-tagged dipeptide 1. Preliminary analysis of 18F-dipeptide 1 was performed to confirm uptake by peptide transporters (PepTs) in human pancreatic carcinoma cell lines Panc1, BxPC3, and ASpc1, which are reported to express the peptide transporter 1 (PepT1). Furthermore, we confirmed in vivo uptake of 18F-dipeptide tracer 1 using microPET/CT in mice harboring subcutaneous flank Panc1, BxPC3, and Aspc1 tumors. In conclusion, we have established the radiolabeling of dipeptide 1 with fluoride-18, and demonstrated its potential as an imaging agent which may have clinical applications for the diagnosis of pancreatic carcinomas.

Imaging of Pancreatic Carcinoma on Multidetector Computed Tomography, A Tertiary Care Experience at Liaquat National Hospital, Karachi

Introduction: Pancreatic cancer is a lethal disease. The mortality rate for pancreatic tumor has changed over the last 20 years. Early diagnosis of pancreatic carcinoma is very important for therapeutic decisions and surgical planning. Contrast enhance CT facilitated the detection of primary tumor and staging. Objective: This study is to evaluate various presentations of pancreatic carcinomas on their initial MDCT (Multidetector Computed Tomography) and to evaluate its resectability and to compare CT features among resectable and non-resectable tumors. Methodology: All the patients underwent multi-phasic CT scan on a 16-slice MDCT. CT findings were analyzed included tumor location, size, enhancement pattern, nodal disease, duct dilatations, vascular involvement and evidence of metastatic disease. Results: Total 63 records of patients examined during 2017 and 2019 meeting the inclusion criteria were reviewed. The average age at time of MDCT examination was 62.51 ± 13.17 years. The disease was more common in males (n=36, 57.1%). Out of 63 pancreatic tumors, 14 (22.22%) tumors were identified as resectable tumors on MDCT examination. Tumor size (p&lt;0.001), peripancreatic nodes (p=0.006), contrast enhancement (p=0.018), vessel involvement (p&lt;0.001), ascites (p=0.006), hepatic metastases (p=0.001) and peripheral organ involvement (p&lt;0.001) were significantly different among resectable and non-resectable tumors. Conclusion: MDCT is an excellent and most commonly used modality for diagnosis and staging of pancreatic carcinoma particularly with a high sensitivity for detection of vascular invasion and metastatic disease.

Value of endoscopy for early diagnosis of pancreatic carcinoma.

Despite recent advances in diagnostic imaging modalities, most cases of pancreatic carcinoma are discovered at an unresectable stage, resulting in poor prognosis. Early diagnosis is essential to ensure curative treatment and improve the prognosis of pancreatic carcinoma. Imaging modalities with high diagnostic ability are necessary for the early diagnosis of pancreatic carcinoma. Endoscopic ultrasonography is a reliable and efficient diagnostic modality because it provides superior spatial resolution and should be incorporated into screening programs in patients at high risk of pancreatic carcinoma. Endoscopy facilitates cytopathological diagnosis based on samples collected via endoscopic ultrasonography-guided fine-needle aspiration and endoscopic retrograde cholangiopancreatography. Cytodiagnosis with endoscopic naso-pancreatic drainage is useful in patients with carcinoma in situ. In this review, we highlight the potential role of endoscopy in the early diagnosis of pancreatic carcinoma. We provide an overview of the endoscopy tools used for the diagnosis of pancreatic carcinoma, discuss the diagnostic ability of these tools for small carcinomas and carcinomas in situ, and propose a strategy for endoscopy-based screening of early pancreatic carcinoma.

How Does Ultrasound Manage Pancreatic Diseases? Ultrasound Findings and Scanning Maneuvers.

As ultrasound (US) is simple and less invasive than other imaging modalities, this technique is widely used for mass screening. However, visualizing the entire pancreas due to complicated anatomy, obesity and overlying gas can be difficult. US plays a key role in the diagnosis of pancreatic carcinoma (PC), of which tumors smaller than 10 mm (TS1a) and pancreatic carcinoma in situ are expected to have good prognosis. To detect these forms of PC, main pancreatic duct (MPD) dilatation (3 mm or more) and pancreatic cysts (5 mm or larger) are US findings of high-risk individuals (HRIs), and these subjects should be observed periodically. Scanning maneuvers are also important for both screening for PC and follow-up of HRIs. As lesions in the groove area and ventral pancreas do not affect the MPD or extrahepatic bile duct, we should pay attention to these areas. Visualization of the tail is also challenging due to gas and stool in the alimentary tract. As the position of the pancreas changes depending on the body posture, and several different body positions should be employed, such as the right lateral decubitus, sitting, and upright positions, rather than only applying strong compression with the transducer. In cases with poor visualization, the liquid-filled stomach method is highly recommended.