Clinical Diagnosis Of Pancreatic Cancer Research Articles

Ultrasensitive Detection and Separation of Pancreatic Cancer Biomarker CA 19-9 Using a Multiphoton Laser Wave-Mixing Detector Interfaced to Capillary Electrophoresis.

The carbohydrate antigen 19-9 (CA 19-9) is the most commonly used biomarker in the clinical diagnosis of pancreatic cancer. Multiphoton nonlinear laser wave-mixing spectroscopy is presented as an ultrasensitive detection method for CA 19-9. Wave mixing is an optical absorption-based method, and hence, one can detect CA 19-9 without labels in their native form using compact ultraviolet (UV) lasers or labeled samples using a visible laser. The wave-mixing signal exhibits a quadratic dependence on the sample concentration, and hence, it is an ideal sensor to monitor small changes in the sample. Wave mixing has inherent advantages over other absorption-based detection methods, including short optical path length (micrometer-thin samples instead of 1 cm cuvette) and excellent spatial resolution (micrometer probe). Since the laser wave-mixing probe volume is small (picoliter), it is convenient to interface to microfluidics or capillary-based electrophoresis systems to enhance chemical specificity. Our wave-mixing detectors could be configured as portable battery-powered devices suitable for field use. Laser wave-mixing spectroscopy offers enhanced selectivity levels for protein detection when coupled with capillary electrophoresis (CE). We report a concentration detection limit of 0.16 U/mL, and a corresponding mass detection limit of 1.2 × 10-8 U, and these detection limits are better than those of chemiluminescence- or ELISA- based methods.

Adipose tissue and skeletal muscle wasting precede clinical diagnosis of pancreatic cancer

Patients with pancreatic cancer commonly develop weight loss and muscle wasting. Whether adipose tissue and skeletal muscle losses begin before diagnosis and the potential utility of such losses for earlier cancer detection are not well understood. We quantify skeletal muscle and adipose tissue areas from computed tomography (CT) imaging obtained 2 months to 5 years before cancer diagnosis in 714 pancreatic cancer cases and 1748 matched controls. Adipose tissue loss is identified up to 6 months, and skeletal muscle wasting is identified up to 18 months before the clinical diagnosis of pancreatic cancer and is not present in the matched control population. Tissue losses are of similar magnitude in cases diagnosed with localized compared with metastatic disease and are not correlated with at-diagnosis circulating levels of CA19-9. Skeletal muscle wasting occurs in the 1–2 years before pancreatic cancer diagnosis and may signal an upcoming diagnosis of pancreatic cancer.

Interobserver Agreement among Cytopathologists in False-Negative Cases by Cytological Diagnosis with Endoscopic Ultrasound-Guided Fine Needle Aspiration in Solid Pancreatic Lesions

Introduction: Early detection and accurate pathological assessment are critical to improving prognosis of pancreatic cancer. EUS has been widely used in diagnosing pancreatic lesions and can obtain histological diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, comprehensive assessment of the interobserver agreement (IOA) among cytopathologists evaluating EUS-FNA specimens is still limited. Therefore, this study evaluated IOA among cytopathologists for EUS-FNA specimens of solid pancreatic lesions, especially in false-negative cases of cytological diagnosis and analyzed the factors that influence cytological diagnosis of EUS-FNA so as to improve the diagnostic efficiency of EUS-FNA. Methods: We retrieved EUS-FNA samples of pancreatic solid lesions from 2017 to 2021 and collected their clinical/cytological data. Two cytopathologists independently reviewed these cases using a quoted, novel standardized cytology scoring tool. Ultimately, we calculated IOA among cytopathologists and performed a binary logistic regression analysis to evaluate factors influencing the cytological diagnosis of EUS-FNA. Results: 161 patients were included, and 60 cases with a clinical diagnosis of pancreatic cancer but a cytological diagnosis of benign and atypical constituted the false-negative group. IOAs for cytological diagnosis of overall patients and the false-negative group were in perfect/moderate agreement with Kendall’s W values of 0.896 and 0.462, respectively. The number of diagnostic cells in the scoring tool had the highest level of agreement (κ = 0.721) for overall patients. There was at best moderate agreement on other quantity and quality parameters for both all cases and false-negative group. Logistic regression analysis showed the number of diagnostic cells (OR = 6.110, p < 0.05) and amount of blood (OR = 0.320, p < 0.05) could influence cytological diagnosis. Conclusions: The false-negative rate of our study as high as 37.26% (60/161) is mainly related to strict standards of cytopathologists, and their ability to standardize pancreatic cytology is still improving. Suboptimal agreement among cytopathologists for cytological diagnosis and the number of diagnostic cells may be associated with the occurrence of false-negative diagnosis. Further regression analysis confirmed that the number of diagnostic cells and obscuring blood were important factors in cytological diagnosis. Therefore, refinement of cytological diagnostic criteria, standardization of specimen quality evaluation, and training of cytopathologists may improve the agreement of cytopathologists, thus improving the repeatability of cytological diagnosis and reducing the occurrence of false-negative events.

Microbiota dysbiosis in pancreatic cancer: evidence ofassociation and tumorigenesis

<p indent="0mm">Pancreatic cancer is a highly malignant disease with poor diagnosis and treatment. Its morbidity and mortality have recently significantly increased with a low survival rate. The 5-year overall survival rate is less than 1%, and the prognosis is extremely poor. Due to the difficulties and a low rate of early diagnosis, the prognosis of patients with pancreatic cancer after surgery will be greatly improved if early clinical diagnosis of pancreatic cancer is accomplished. There are many common risk factors for pancreatic cancer, such as chronic pancreatitis, diabetes, high-fat diets, obesity, and intestinal disorders. In the 1990s, when the etiology of gastric cancer was studied, <italic>Helicobacter pylori</italic> was found to be the causative factor of gastric cancer, and the correlation between microbiota and tumor pathogenesis provided a new clue for the study of tumor pathogenesis. Several lines of evidence have shown that pancreatic cancer is highly associated with changes in the human microbiota. Thus, in this paper, we review current evidence on the role of human microbiota in pancreatic cancer development and provide a perspective on the application of microbiota modulation in the early diagnosis and effective treatment of pancreatic cancer.

A dual-signaling electrochemical ratiometric strategy combining “signal-off” and “signal-on” approaches for detection of MicroRNAs

A dual-signaling electrochemical ratio metric strategy was developed for detection microRNA-18a based on the duplex-specific nuclease-assisted target recycling and electrochemical atom transfer radical polymerization signal amplification. In the presence of target microRNA, RNA/DNA duplexes are formed, which become the substrate of the duplex-specific nuclease-assisted target recycling. Hence only the DNA strand is cleaved by duplex-specific nuclease enzyme, resulting in the throw away of methylene blue (MB) from the electrode (signal off) accompanied by releasing of target microRNA, which can be recycled in the next hybridization. The remaining piece of capture DNAs on the electrode surface hybridize with the Azide labeled-signal DNAs. “Click reactions” were carried out between 3-Butynyl-2-bromoisobutyrate and Azide to initiate the electrochemical atom transfer radical polymerization reaction. This process could bring a great number of ferrocenylmethyl methacrylate (FMMA) on the surface of electrode (signal on). The IFMMA/IMB value was proportionate to the microRNA-18a concentration and measured by square wave voltammetry.The promising potential of the proposed biosensor in clinical analyses was exhibited by its remarkable features such as strong performance, high specificity, agreeable storage stability, and notable selectivity in real sample evaluation with no pretreatment or amplification. Finally, our biosensing method offers such an application to be used for the early clinical diagnosis of Pancreatic Cancer.

Rapid identification of benign and malignant pancreatic tumors using serum Raman spectroscopy combined with classification algorithms

The survival time of patients with pancreatic tumors is closely related to the type of tumor. To diagnose patients with malignant pancreatic tumors as early as possible in order to improve patient survival, we proposed a new method for the assisted diagnosis of pancreatic tumors. First, we used partial least squares (PLS) to extract the Raman spectrum information of patients with pancreatic tumors. The study extracted ten eigenvalues experimentally. The cumulative variance of the first six PLS components reached 97.045 %, and then the feature information extracted by PLS was classified. This experiment used three classification algorithms: linear discriminant analysis (LDA), support vector machine (SVM), and k-nearest neighbor (KNN). Among them, the cubic kernel of SVM achieved the best classification effect, and its classification accuracy reached 96.4 %. This is the first time that serum Raman spectroscopy has been used to distinguish patients with benign and malignant tumors of the pancreas. The experimental results show that serum Raman spectroscopy may become a new auxiliary method for the clinical diagnosis of pancreatic cancer.

Clinical Diagnosis of Pancreatic Cancer Using Texture Analysis in Endoscopic Ultrasonography

Clinical Diagnosis of Pancreatic Cancer Using Texture Analysis in Endoscopic Ultrasonography

Glycan Motif Profiling Reveals Plasma Sialyl-Lewis X Elevations in Pancreatic Cancers That Are Negative for Sialyl-Lewis A *

The sialyl-Lewis A (sLeA) glycan forms the basis of the CA19-9 assay and is the current best biomarker for pancreatic cancer, but because it is not elevated in ∼25% of pancreatic cancers, it is not useful for early diagnosis. We hypothesized that sLeA-low tumors secrete glycans that are related to sLeA but not detectable by CA19-9 antibodies. We used a method called motif profiling to predict that a structural isomer of sLeA called sialyl-Lewis X (sLeX) is elevated in the plasma of some sLeA-low cancers. We corroborated this prediction in a set of 48 plasma samples and in a blinded set of 200 samples. An antibody sandwich assay formed by the capture and detection of sLeX was elevated in 13 of 69 cancers that were not elevated in sLeA, and a novel hybrid assay of sLeA capture and sLeX detected 24 of 69 sLeA-low cancers. A two-marker panel based on combined sLeA and sLeX detection differentiated 109 pancreatic cancers from 91 benign pancreatic diseases with 79% accuracy (74% sensitivity and 78% specificity), significantly better than sLeA alone, which yielded 68% accuracy (65% sensitivity and 71% specificity). Furthermore, sLeX staining was evident in tumors that do not elevate plasma sLeA, including those with poorly differentiated ductal adenocarcinoma. Thus, glycan-based biomarkers could characterize distinct subgroups of patients. In addition, the combined use of sLeA and sLeX, or related glycans, could lead to a biomarker panel that is useful in the clinical diagnosis of pancreatic cancer. Précis: This paper shows that a structural isomer of the current best biomarker for pancreatic cancer, CA19-9, is elevated in the plasma of patients who are low in CA19-9, potentially enabling more comprehensive detection and classification of pancreatic cancers.

Sa1377 Abnormal MRI Findings Identified Prior to Clinical Diagnosis of Pancreatic Cancer

Sa1377 Abnormal MRI Findings Identified Prior to Clinical Diagnosis of Pancreatic Cancer

Nonneoplastic mimickers of pancreatic neoplasms.

Abstract Context.—A variety of nonneoplastic conditions may form pancreatic masses that mimic carcinoma. Approximately 5% to 10% of pancreatectomies performed with the clinical diagnosis of pancreatic cancer prove on microscopic evaluation to be pseudotumors. Objectives.—To illustrate the clinical and pathologic characteristics of the 2 most frequent pseudotumoral inflammatory conditions, autoimmune pancreatitis and paraduodenal pancreatitis, and describe the criteria that may be useful in the differential diagnosis versus pancreatic carcinoma. Data Sources.—Recent literature and the authors' experience with the clinical and pathologic characteristics of autoimmune pancreatitis and paraduodenal pancreatitis. Conclusions.—The knowledge of the clinical, radiologic, and pathologic findings in both autoimmune pancreatitis and paraduodenal pancreatitis is crucial in making the correct preoperative diagnosis. Autoimmune pancreatitis, which occurs in isolated or syndromic forms, is characterized by a distinctive...

Nonneoplastic Mimickers of Pancreatic Neoplasms

A variety of nonneoplastic conditions may form pancreatic masses that mimic carcinoma. Approximately 5% to 10% of pancreatectomies performed with the clinical diagnosis of pancreatic cancer prove on microscopic evaluation to be pseudotumors. To illustrate the clinical and pathologic characteristics of the 2 most frequent pseudotumoral inflammatory conditions, autoimmune pancreatitis and paraduodenal pancreatitis, and describe the criteria that may be useful in the differential diagnosis versus pancreatic carcinoma. Recent literature and the authors' experience with the clinical and pathologic characteristics of autoimmune pancreatitis and paraduodenal pancreatitis. The knowledge of the clinical, radiologic, and pathologic findings in both autoimmune pancreatitis and paraduodenal pancreatitis is crucial in making the correct preoperative diagnosis. Autoimmune pancreatitis, which occurs in isolated or syndromic forms, is characterized by a distinctive fibroinflammatory process that can either be limited to the pancreas or extend to the biliary tree. Its correct preoperative identification on biopsy material with ancillary immunohistochemical detection of dense immunoglobulin G4-positive plasma cell infiltration is possible and crucial to prevent major surgery and to treat these patients with steroid therapy. Paraduodenal pancreatitis is a special form of chronic pancreatitis that affects young males with a history of alcohol abuse and predominantly involves the duodenal wall in the region of the minor papilla. Pathogenetically, the anatomical and/or functional obstruction of the papilla minor, resulting from an incomplete involution of the intraduodenal dorsal pancreas, associated with alcohol abuse represents the key factor. Endoscopic drainage of the papilla minor, with decompression of the intraduodenal and dorsal pancreas, might be considered in these patients.

Analysis of K-ras gene codon 12 mutation in pancreatic tissue of patients with pancreatic cancer

The aim of this study was to analyze K-ras codon 12 mutation in the pancreatic tissue of Serbian patients with pancreatic cancer and assess whether the given mutation can be used as a molecular marker for this disease. The study was performed on pancreatic tissue samples obtained from 40 patients with clinical diagnosis of pancreatic cancer. The presence of K-ras codon 12 mutation was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our study showed that K-ras mutation is present with a high frequency (66%) in the pancreatic tissue of patients with pancretic cancer.

CHRONIC HELICOBACTER PYLORI INFECTION DOES NOT INCREASE THE RISK TO DEVELOP PANCREATIC CANCER.

Background:Helicobacter (HP) infection is associated with a 4–6 time increased risk of gastric cancer most probably via the effects of chronic inflammation. HP infection leads to atrophic changes in the gastric mucosa and in the long run decreased acid production. Acid is involved in the regulation of pancreatic secretion and HP infection could lead to a disturbed pancreatic secretion. Whether HP infection could be involved in the development of pancreatic cancer has not been fully elucidated. The aim of this study was to investigate the occurrence of HP infection in patients with pancreatic cancer. Methods: A cohort of 33,000 persons in Malmö were examined in a health screening investigation between 1974 and 1992. Blood samples were drawn and serum was stored at −20°C for up to 21 years before analysis. In 2000, 126 cases of pancreatic cancer had been diagnosed in this cohort. Diagnoses were validated through diagnostic records and histology. Serum samples from 87 of the 126 persons that developed pancreatic cancer were identified and 263 serum samples from age, gender and time of sampling matched controls in the same cohort were also obtained. Antibody titers against HP were measured with a regular ELISA Results: The median time between health examination and clinical diagnosis of pancreatic cancer was 12,5 years (0,8–24). The median age of the cases was 60,5 years (45–76). Positive HP serology was seen in 34 of the 87 cases (39,1%) and in 129 of the 263 controls (36,9%). Borderline titers were seen in 9,2% of the cases and 8,9% of the controls. Conclusions: In this relatively young population of pancreatic cancer cases there was no increased incidence of chronic HP infection. Whether HP infection could be a risk factor in an older subgroup of patients with pancreatic cancer will have to await later studies. Totally around 300 incident cases are expected in this cohort with time.

Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis.

Our purpose was to determine whether abdominal CT can detect pancreatic cancer before its clinical diagnosis. Two radiologists interpreted in a blinded manner 62 CT scans in 28 pancreatic cancer patients that were obtained before histologic diagnosis and 89 CT scans in 89 control subjects and noted specific CT findings. The presence of pancreatic cancer was characterized as definite, suspicious, low probability, or normal. The scans of the pancreatic cancer patients were divided into four groups on the basis of the time interval preceding cancer diagnosis (0-2, 2-6, 6-18, or > 18 months), and one scan (closest to 18 months) was selected per patient per time interval. Sensitivity and specificity for pancreatic cancer and interobserver agreement for CT findings were calculated. Radiologists agreed that CT findings definite or suspicious for pancreatic cancer were present in 50% of the scans obtained 2-6 and 6-18 months before the diagnosis of pancreatic cancer (3/6 and 4/8 scans, respectively), but they noted such CT findings in only 7% (1/15) of the scans obtained more than 18 months before diagnosis. Pancreatic duct dilatation and cutoff were early CT findings identified by both radiologists and were associated with near-perfect and substantial interobserver agreement (kappa = 0.84 and 0.76, respectively). Ninety-five percent confidence intervals of specificity for tumor absence ranged from 92% to 100%. CT can detect a significant proportion of asymptomatic incident pancreatic cancers before the clinical diagnosis of pancreatic cancer. CT should be considered in screening at-risk patient populations. Pancreatic duct dilatation and cutoff are early findings associated with the development of pancreatic cancer and can be detected on CT with a high degree of reproducibility.

Frequent multiple c‐ki‐ras oncogene activation in pancreatic juice from patients with benign pancreatic cysts

Background: We detected benign pancreatic cysts in more than half of 12 cases of in situ pancreatic cancer. A few investigators, having detected K‐ras mutation in pancreatic juice before the clinical diagnosis of pancreatic cancer, have suggested that this mutation might be an early event in pancreatic oncogenesis. Therefore, in the present study, we evaluated whether benign pancreatic cysts are a precancerous condition as reflected by K‐ras mutation in pancreatic juice.Methods: Pancreatic juice was collected through endoscopic cannulation of the pancreatic duct. Analysis of the mutations was performed using the polymerase chain reaction–preferential homoduplex formation assay.Results: The frequencies and types of K‐ras point mutations and the rate of multiplicity of K‐ras mutations in patients with benign pancreatic cyst were the same as those with pancreatic cancer.Conclusions: Multiple K‐ras codon 12 mutations in the pancreatic juice of patients with benign pancreatic cysts are present as frequently as those with pancreatic cancer. These results indicate that patients with benign cysts may be at a high‐risk for the development of pancreatic cancer.

Two-dimensional zymography for analysis of proteolytic enzymes in human pure pancreatic juice.

Proteolytic enzymes in human pure pancreatic juice (PPJ), which was collected by cannulating the main pancreatic duct using endoscopy, were investigated by two-dimensional zymography (2-DZ). 2-DZ was carried out by combining isoelectric focusing (IEF) in the first dimension with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the second dimension, using gels containing casein or gelatin as a substrate for the proteolytic enzymes. After electrophoresis, the gels were incubated in Triton X-100 followed by incubation at 37 degrees C in Tris buffer (pH 8.5) containing CaCl2. By staining the gels with Coomassie Brilliant Blue (CBB R-250), proteolytic enzymes were detected as clear spots and zones against a blue background. Proteinase inhibitors, such as a cysteine proteinase inhibitor (E-64), a metalloproteinase inhibitor (EDTA), and a serine proteinase inhibitor (Pefabloc SC), were added to PPJ in order to determine the types of proteinases. In patients with pancreatic cancer, spots of molecular weight (Mr) 70,000 and isoelectric points (pI) 5.3-5.5 were clearly detected on the gels containing casein and gelatin, while these spots were not detected in the PPJ from healthy subjects. The proteolytic activities of these spots were strongly inhibited by EDTA and Pefabloc SC but not E-64. These results suggest that the spots of Mr 70,000 and pI 5.3-5.5 in PPJ of pancreatic cancer might be matrix metalloproteinase 2, which is a candidate for tumor-associated proteinase. 2-DZ proved to be a tool for analysis of proteolytic enzymes in PPJ and for the clinical diagnosis of pancreatic cancer.

A Study of 122 Cases of Pancreatic Cancer Diagnosed by Endoscopic Retrograde CholangiopancreatographvERCP

ERCP is a highly accurate and specific method for evaluating patients with suspected pancreatic disease. Its diagnostic significance of specific pancreatographic signs is of even greater importance.We reviewed 122 cases of pancreatic cancer who were done ERCP, at the Department of Internal Medicine, Yonsei University, College of Medicine between June 1973 and August 1983.The results were as follows: The ages of 122 patients ranged from 27 to 76 with the majority in the 6th and the 7th decades. The male to female ratio was 2.49:1.The success rate of cannulation into the orifice of the duodenal papilla in 122 cases was 97.5% (119/122), and the pancreatic duct was visualized in 91.0% (111/122).Diagnostic accuracy of ERCP in pancreatic cancer was 96.4% (107/111) among cases in whom the pancreatic duct was visualized.By ERCP the most common site of the lesion was head of pancreas (51.4%).According to Fukumoto’s classification, the most common type was obstructive type (65.4%), followed by the stenosing type (29.0%), abnormal branching type (3.7%), and narrowing type (1.9%).According to Takaki’s classification, Type I (obstruction or stenosis of the main pancreatic duct) was most common (85.6%), followed by Type III (pancreatic dilatation) (9.0%), Type IV (normal pancreatic duct) (3.6%), and Type II (obstruction of Wirsung’s duct or Santorini’s duct) (1.9%).Of the 122 cases of pancreatic cancer, the bile duct was visualized in 55 and abnormalities, such as indentation (32.1%), stenosis (42.9%), and obstruction (25.0%) were found in 28. The locations of abnormal findings in the bile duct were distal (50.0%), middle (46.4%), and proximal (3.6%).