The Diagnostic Value of the CA19-9 and Bilirubin Ratio in Patients with Pancreatic Cancer, Distal Bile Duct Cancer and Benign Periampullary Diseases, a Novel Approach

Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent evidence has shown that the ratio between CA19-9 and bilirubin levels supports diagnostic distinction of benign or malignant hepatopancreaticobiliary diseases. Here, we investigate the diagnostic value of this ratio in PDAC, dCCA and benign diseases of the periampullary region in a novel fashion. To address this aim, we enrolled 265 patients with hepatopancreaticobiliary diseases and constructed four logistic regression models on a subset of patients (n = 232) based on CA19-9, bilirubin and the ratio of both values: CA19-9/(bilirubin−1). Non-linearity was investigated using restricted cubic splines and a final model, the ‘Model Ratio’, based on these three variables was fitted using multivariable fractional polynomials. The performance of this model was consistently superior in terms of discrimination and calibration compared to models based on CA19-9 combined with bilirubin and CA19-9 or bilirubin alone. The ‘Model Ratio’ accurately distinguished between malignant and benign disease (AUC [95% CI], 0.91 [0.86–0.95]), PDAC and benign disease (AUC 0.91 [0.87–0.96]) and PDAC and dCCA (AUC 0.83 [0.74–0.92]) which was confirmed by internal validation using 1000 bootstrap replicates. These findings provide a foundation to improve minimally-invasive diagnostic procedures, ultimately ameliorating effective therapy for PDAC and dCCA.

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Unravelling the Diagnostic Dilemma: A MicroRNA Panel of Circulating MiR-16 and MiR-877 as A Diagnostic Classifier for Distal Bile Duct Tumors

Cancers ◽

10.3390/cancers11081181 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1181 ◽

Cited By ~ 4

Author(s):

Laura L. Meijer ◽

Jisce R. Puik ◽

Tessa Y.S. Le Large ◽

Michal Heger ◽

Frederike Dijk ◽

...

Keyword(s):

Multivariate Logistic Regression Analysis ◽

Pancreatic Head ◽

Roc Curves ◽

Benign Disease ◽

Ductal Adenocarcinoma ◽

Healthy Controls ◽

Diagnostic Dilemma ◽

Distal Cholangiocarcinoma ◽

Discovery Phase ◽

Evaluation Phase

Accurate diagnosis of pancreatic head lesions remains challenging as no minimally invasive biomarkers are available to discriminate distal cholangiocarcinoma (CCA) from pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to identify specific circulating microRNAs (miRNAs) to diagnose distal CCA. In the discovery phase, PCR profiling of 752 miRNAs was performed on fourteen patients with distal CCA and age- and sex-matched healthy controls. Candidate miRNAs were selected for evaluation and validation by RT-qPCR in an independent cohort of distal CCA (N = 24), healthy controls (N = 32), benign diseases (N = 20), and PDAC (N = 24). The optimal diagnostic combination of miRNAs was determined by multivariate logistic regression analysis and evaluated by ROC curves with AUC values. The discovery phase revealed 19 significantly dysregulated miRNAs, of which six were validated in the evaluation phase. The validation phase confirmed downregulated miR-16 in patients with distal CCA compared to benign disease or PDAC (P = 0.048 and P = 0.012), while miR-877 was significantly upregulated (P = 0.003 and P = 0.006). This two-miRNA panel was validated as a CCA-specific profile, discriminating distal CCA from benign disease (AUC = 0.90) and from PDAC (AUC = 0.88). In conclusion, the present study identified a two-miRNA panel of downregulated miR-16 and upregulated miR-877 with promising capability to diagnose patients with distal CCA.

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Thrombospondin-2 as a diagnostic biomarker for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma

Clinical & Translational Oncology ◽

10.1007/s12094-021-02685-8 ◽

2021 ◽

Author(s):

J. Byrling ◽

K. S. Hilmersson ◽

D. Ansari ◽

R. Andersson ◽

B. Andersson

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Area Under The Curve ◽

Diagnostic Value ◽

Ductal Adenocarcinoma ◽

Enzyme Linked Immunosorbent Assay ◽

Histopathological Diagnosis ◽

Diagnostic Biomarker ◽

Serum Samples ◽

Distal Cholangiocarcinoma ◽

Additional Value

Abstract Purpose Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Methods Thrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay. Results Thrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P < 0.001). The diagnostic value of adding thrombospondin-2 to CA 19-9 was larger in early disease stages. Thrombospondin-2 did not provide additional value to CA 19-9 in differentiating the benign disease group; however, heterogeneity was notable in the benign cohort. Three of five patients with autoimmune pancreatitis patients had greatly elevated thrombospondin-2 levels. Thrombospondin-2 levels had no correlation with prognoses. Conclusions Serum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer.

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Formal Psychological Assessment for Autism Spectrum Disorder Diagnosis: A New Methodology to Build An Adaptive Testing System

The Open Psychology Journal ◽

10.2174/1874350101811010112 ◽

2018 ◽

Vol 11 (1) ◽

pp. 112-122

Author(s):

Maria Chiara Pino ◽

Andrea Spoto ◽

Melania Mariano ◽

Umberto Granziol ◽

Sara Peretti ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Psychological Assessment ◽

Clinical Symptoms ◽

Diagnostic Procedures ◽

Autism Diagnostic Observation Schedule ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Effective Interventions ◽

Novel Approach ◽

Future Work

Background:Early identification of Autism Spectrum Disorder (ASD) is of paramount importance in establishing effective interventions. Currently, the accepted gold standard for ASD diagnosis is the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2).Methods:In our research study, we applied a novel approach to the ADOS-2 known as the Formal Psychological Assessment (FPA). The innovation of this methodology comes from the construction of a matrix that allows (1) the identification of the existing relations among items in terms of clinical symptoms and (2) an adaptive assessment of an individual.Objective:The aim of this study was to use a practical application of the FPA on the ADOS-2 and show its potential for psychological assessment of individuals with ASD. Particularly, this research raises some important considerations regarding the evaluation of this population and the authors propose future work to improve the quality of clinical assessment.Results:Our results suggest potential for the application of this new methodology to the ADOS-2 to support clinicians using diagnostic procedures.Conclusion:The use of FPA allows analysis of each item of ADOS’s modules based on the presence/absence of clinical elements. This system allows the identification of the critical areas for each individual and reduces the number of items required for the test.

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A Novel Saliva-Based miRNA Signature for Colorectal Cancer Diagnosis

Journal of Clinical Medicine ◽

10.3390/jcm8122029 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2029 ◽

Cited By ~ 10

Author(s):

Rapado-González ◽

Majem ◽

Álvarez-Castro ◽

Díaz-Peña ◽

Abalo ◽

...

Keyword(s):

Colorectal Cancer ◽

Roc Curves ◽

Diagnostic Value ◽

Healthy Controls ◽

Mirna Signature ◽

Clinical Value ◽

Logistic Regression Models ◽

Non Invasive ◽

Promising Tool ◽

Novel Approach

Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (P < 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (P < 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.

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Cost Effectiveness of Transbronchial Needle Aspiration

Canadian Respiratory Journal ◽

10.1155/1999/508741 ◽

1999 ◽

Vol 6 (4) ◽

pp. 332-335 ◽

Cited By ~ 14

Author(s):

Jennifer A Crocket ◽

Eric YL Wong ◽

Dale C Lien ◽

Khanh Gia Nguyen ◽

Michelle R Chaput ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Diagnostic Procedures ◽

Needle Aspiration ◽

Benign Disease ◽

University Hospital ◽

High Yield ◽

Transbronchial Needle Aspiration ◽

Computed Tomographic ◽

The Cost

OBJECTIVE: To evaluate the yield and cost effectiveness of transbronchial needle aspiration (TBNA) in the assessment of mediastinal and/or hilar lymphadenopathy.DESIGN: Retrospective study.SETTING: A university hospital.POPULATION STUDIED: Ninety-six patients referred for bronchoscopy with computed tomographic evidence of significant mediastinal or hilar adenopathy.RESULTS: Ninety-nine patient records were reviewed. Three patients had two separate bronchoscopy procedures. TBNA was positive in 42 patients (44%) and negative in 54 patients. Of the 42 patients with a positive aspirate, 40 had malignant cytology and two had cells consistent with benign disease. The positive TBNA result altered management in 22 of 40 patients with malignant disease and one of two patients with benign disease, thereby avoiding further diagnostic procedures. The cost of these subsequent procedures was estimated at $27,335. No complications related to TBNA were documented.CONCLUSIONS: TBNA is a high-yield, safe and cost effective procedure for the diagnosis and staging of bronchogenic cancer.

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Intra-pancreatic distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: a common short and long-term prognosis?

Updates in Surgery ◽

10.1007/s13304-021-00981-0 ◽

2021 ◽

Author(s):

Théophile Guilbaud ◽

Edouard Girard ◽

Coralie Lemoine ◽

Ghislain Schlienger ◽

Oyekashopefoluw Alao ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Distal Cholangiocarcinoma ◽

Short And Long Term ◽

Long Term Prognosis

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New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

BMJ Open ◽

10.1136/bmjopen-2020-037267 ◽

2020 ◽

Vol 10 (11) ◽

pp. e037267

Author(s):

Dóra Illés ◽

Emese Ivány ◽

Gábor Holzinger ◽

Klára Kosár ◽

M Gordian Adam ◽

...

Keyword(s):

High Risk ◽

Early Detection ◽

Pancreatic Ductal Adenocarcinoma ◽

Clinical Symptoms ◽

Risk Group ◽

High Risk Group ◽

Ductal Adenocarcinoma ◽

Onset Diabetes ◽

Dismal Prognosis ◽

New Onset

IntroductionPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.Methods and analysisThis is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19–9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.Ethics and disseminationThe study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.Trial registration numberClinicalTrials.gov NCT04164602

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Diagnosis of neuroschistosomiasis by antibody specificity index and semi-quantitative real-time PCR from cerebrospinal fluid and serum

Journal of Medical Microbiology ◽

10.1099/jmm.0.066142-0 ◽

2014 ◽

Vol 63 (2) ◽

pp. 309-312 ◽

Cited By ~ 16

Author(s):

Georg Härter ◽

Hagen Frickmann ◽

Sebastian Zenk ◽

Dominic Wichmann ◽

Bettina Ammann ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Real Time ◽

Real Time Pcr ◽

Clinical Symptoms ◽

Diagnostic Procedures ◽

Lower Limbs ◽

Antibody Specificity ◽

Quantitative Real Time Pcr ◽

Specific Antibodies ◽

Routine Diagnosis

We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia and paraesthesia without pareses. A serum–cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti-Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy.

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Meningiomas Of the Internal Auditory Canal

Neurosurgery ◽

10.1227/01.neu.0000126887.55995.e7 ◽

2004 ◽

Vol 55 (1) ◽

pp. 119-128 ◽

Cited By ~ 36

Author(s):

Makoto Nakamura ◽

Florian Roser ◽

Sharham Mirzai ◽

Cordula Matthies ◽

Peter Vorkapic ◽

...

Keyword(s):

Cerebellopontine Angle ◽

Clinical Symptoms ◽

Management Strategies ◽

Internal Auditory Canal ◽

Signs And Symptoms ◽

Vestibular Schwannomas ◽

Additional Patient ◽

Surgical Removal ◽

Neurosurgical Department ◽

Vestibulocochlear Nerve

Abstract OBJECTIVE: Meningiomas arising primarily within the internal auditory canal (IAC) are notably rare. By far the most common tumors that are encountered in this region are neuromas. We report a series of eight patients with meningiomas of the IAC, analyzing the clinical presentations, surgical management strategies, and clinical outcomes. METHODS: The charts of the patients, including histories and audiograms, imaging studies, surgical records, discharge letters, histological records, and follow-up records, were reviewed. RESULTS: One thousand eight hundred meningiomas were operated on between 1978 and 2002 at the Neurosurgical Department of Nordstadt Hospital. Among them, there were 421 cerebellopontine angle meningiomas; 7 of these (1.7% of cerebellopontine angle meningiomas) were limited to the IAC. One additional patient underwent surgery at the Neurosurgical Department of the International Neuroscience Institute, where a total of 21 cerebellopontine angle meningiomas were treated surgically from 2001 to 2003. As a comparison, the incidence of intrameatal vestibular schwannomas during the same period, 1978 to 2002, was 168 of 2400 (7%). There were five women and three men, and the mean age was 49.3 years (range, 27–59 yr). Most patients had signs and symptoms of vestibulocochlear nerve disturbance at presentation. One patient had sought treatment previously for total hearing loss before surgery. No patient had a facial paresis at presentation. The neuroradiological workup revealed a homogeneously contrast-enhancing tumor on magnetic resonance imaging in all patients with hypointense or isointense signal intensity on T1- and T2-weighted images. Some intrameatal meningiomas showed broad attachment, and some showed a dural tail at the porus. In all patients, the tumor was removed through the lateral suboccipital retrosigmoid approach with drilling of the posterior wall of the IAC. Total removal was achieved in all cases. Severe infiltration of the facial and vestibulocochlear nerve was encountered in two patients. There was no operative mortality. Hearing was preserved in five of seven patients; one patient was deaf before surgery. Postoperative facial weakness was encountered temporarily in one patient. CONCLUSION: Although intrameatal meningiomas are quite rare, they must be considered in the differential diagnosis of intrameatal mass lesions. The clinical symptoms are very similar to those of vestibular schwannomas. A radiological differentiation from vestibular schwannomas is not always possible. Surgical removal of intrameatal meningiomas should aim at wide excision, including involved dura and bone, to prevent recurrences. The variation in the anatomy of the faciocochlear nerve bundle in relation to the tumor has to be kept in mind, and preservation of these structures should be the goal in every case.

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