Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge

Diagnosing early-stage pancreatic cancer(PC)remains a clinical challenge.Hence,studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative.This article aims to un-derscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC,thereby improving its management and prognosis.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Artificial intelligence as a noninvasive tool for pancreatic cancer prediction and diagnosis

Pancreatic cancer(PC)has a low incidence rate but a high mortality,with patients often in the advanced stage of the disease at the time of the first diagnosis.If detected,early neoplastic lesions are ideal for surgery,offering the best prognosis.Preneoplastic lesions of the pancreas include pancreatic intraepithelial neoplasia and mucinous cystic neoplasms,with intraductal papillary mucinous neoplasms being the most commonly diagnosed.Our study focused on predicting PC by identifying early signs using noninvasive techniques and artificial intelligence(AI).A systematic English literature search was conducted on the PubMed electronic database and other sources.We obtained a total of 97 studies on the subject of pancreatic neoplasms.The final number of articles included in our study was 44,34 of which focused on the use of AI algorithms in the early diagnosis and prediction of pancreatic lesions.AI algorithms can facilitate diagnosis by analyzing massive amounts of data in a short period of time.Correlations can be made through AI algorithms by expanding image and electronic medical records databases,which can later be used as part of a screening program for the general population.AI-based screening models should involve a combination of biomarkers and medical and imaging data from different sources.This requires large numbers of resources,collaboration between medical practitioners,and investment in medical infrastructures.

Vibrational spectroscopy-are we close to finding a solution for early pancreatic cancer diagnosis?

Pancreatic cancer(PC)is an aggressive and lethal neoplasm,ranking seventh in the world for cancer deaths,with an overall 5-year survival rate of below 10%.The knowledge about PC pathogenesis is rapidly expanding.New aspects of tumor biology,including its molecular and morphological heterogeneity,have been reported to explain the complicated“cross-talk”that occurs between the cancer cells and the tumor stroma or the nature of pancreatic ductal adenocarcinoma-associated neural remodeling.Nevertheless,currently,there are no specific and sensitive diagnosis options for PC.Vibrational spectroscopy(VS)shows a promising role in the development of early diagnosis technology.In this review,we summarize recent reports about improvements in spectroscopic methodologies,briefly explain and highlight the drawbacks of each of them,and discuss available solutions.The important aspects of spectroscopic data evaluation with multivariate analysis and a convolutional neural network methodology are depicted.We conclude by presenting a study design for systemic verification of the VS-based methods in the diagnosis of PC.

Pancreatic cancer,autoimmune or chronic pancreatitis,beyond tissue diagnosis:Collateral imaging and clinical characteristics may differentiate them

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death.Often,the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses,such as autoimmune pancreatitis(AIP)and massforming chronic pancreatitis(MFCP),making its diagnosis challenging.Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications.Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses;however,the diagnostic accuracy is imperfect.Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis.It is not unusual that after a thorough diagnostic evaluation,the clinician is confronted with a pancreatic mass with uncertain diagnosis.In those cases,a re-evaluation must be entertained,preferably by an experienced multispecialty team including radiologists,pathologists,gastroenterologists,and surgeons,looking for disease-specific clinical,imaging,and histological hallmarks or collateral evidence that could favor a specific diagnosis.Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP,PDAC,and MFCP and to highlight those disease-specific clinical,radiological,serological,and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.

Role of artificial intelligence in the characterization of indeterminate pancreatic head mass and its usefulness in preoperative diagnosis

Artificial intelligence(AI)has been used in various fields of day-to-day life and its role in medicine is immense.Understanding of oncology has been improved with the introduction of AI which helps in diagnosis,treatment planning,management,prognosis,and follow-up.It also helps to identify high-risk groups who can be subjected to timely screening for early detection of malignant conditions.It is more important in pancreatic cancer as it is one of the major causes of cancer-related deaths worldwide and there are no specific early features(clinical and radiological)for diagnosis.With improvement in imaging modalities(computed tomography,magnetic resonance imaging,endoscopic ultrasound),most often clinicians were being challenged with lesions that were difficult to diagnose with human competence.AI has been used in various other branches of medicine to differentiate such indeterminate lesions including the thyroid gland,breast,lungs,liver,adrenal gland,kidney,etc.In the case of pancreatic cancer,the role of AI has been explored and is still ongoing.This review article will focus on how AI can be used to diagnose pancreatic cancer early or differentiate it from benign pancreatic lesions,therefore,management can be planned at an earlier stage.

Challenges in diagnosis of pancreatic cancer

Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease.

Detection of serum tumor markers in the diagnosis and treatment of patients with pancreatic cancer

BACKGROUND: Although a variety of tumor markers areavailable for diagnosis of pancreatic cancer, their sensitivityand specificity have not yet been ideal. The aims of thisstudy was to detect a panel of serum tumor markers and toevaluate their significance in the diagnosis and prognosis ofpancreatic cancer patients.METHODS: Eight serum tumor markers including AFP,CEA, CA-50, CA72-4, CA-125, CA153, CA19-9 and CA242were detected in 129 patients with pancreatic cancer by usingchemiluminescence immunoassay, immunofluorescence as-say and immunoradiometric assay, respectively. The levelsof these markers were compared in 99 patients with non-pancreatic malignant tumor, 63 patients with other benigndiseases, and 27 patients with pancreatic cancer after pan-createctomy.RESULTS: Among the 8 tumor markers, CA19-9, CA242,CA-50, and CA72-4 were more sensitive in the diagnosis ofpancreatic cancer. Parallel combined testing could increasethe diagnostic sensitivity to 89.2%, and serial combined exa-mination could increase the diagnostic specificity to 92.3%.The serum tumor markers levels were decreased significant-ly after radical tumor resection.CONCLUSIONS: Serum CA19-9, CA242, CA-50, andCA72-4 are the preferred tumor markers to be used in thediagnosis and follow-up of operated cases of pancreaticcancer. Testing of a panel of multiple serum tumor mark-ers may increase the sensitivity and specificity in the diag-nosis of pancreatic cancer.

Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head

BACKGROUND: The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical significance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head. METHODS: The serum levels of CA19-9, CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated. RESULTS: The AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS: Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 has the best diagnostic ability. Combined measurements can increase the specificity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or specificity alone and the results are more integrated and objective.

Endoscopic ultrasonography guided-fine needle aspirationfor the diagnosis of solid pancreaticobiliary lesions:Clinicalaspects to improve the diagnosis

Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA) has been applied to pancreaticobiliary lesions since the 1990 s and is in widespread use throughout the world today. We used this method to confirm the pathological evidence of the pancreaticobiliary lesions and to perform suitable therapies. Complications of EUS-FNA are quite rare, but some of them are severe. Operators should master conventional EUS observation and experience a minimum of 20-30 cases of supervised EUS-FNA on non-pancreatic and pancreatic lesions before attempting solo EUSFNA. Studies conducted on pancreaticobiliary EUSFNA have focused on selection of suitable instruments(e.g., needle selection) and sampling techniques(e.g., fanning method, suction level, with or without a stylet, optimum number of passes). Today, the diagnostic ability of EUS-FNA is still improving; the detection of pancreatic cancer(PC) currently has a sensitivity of 90%-95% and specificity of 95%-100%. In addition to PC, a variety of rare pancreatic tumors can be discriminated by conducting immunohistochemistry on the FNA materials. A flexible, large caliber needle has been used to obtain a large piece of tissue, which can provide sufficient histological information to be helpful in classifying benign pancreatic lesions. EUSFNA can supply high diagnostic yields even for biliary lesions or peri-pancreaticobiliary lymph nodes. This review focuses on the clinical aspects of EUS-FNA in the pancreaticobiliary field, with the aim of providing information that can enable more accurate and efficient diagnosis.

FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: A meta-analysis

AIM: To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). METHODS: A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using χ 2 test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0.RESULTS: A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively. CONCLUSION: PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer

AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer.

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.

Differential diagnosis of pancreatic cancer by single-shot echo-planar imaging diffusion-weighted imaging

AIM: To investigate the diagnostic ability of single-shot echo-planar imaging(EPI) diffusion-weighted imaging (DWI) to differentiate between malignant and benign pancreatic lesions. METHODS: A computerized search was performed on Pub Med, MEDLINE and EMBASE up to August 2014. Nine studies(10 sets of data) with a total of 304 malignant pancreatic lesions and 188 benign pancreatic lesions were included. The characteristics of each study included the study name, year of publication, magnetic resonance modalities used, patient population, strength of field, pulse time, repetition time, echo time(TE), maximum b factor, mean age, mean body weight, fat suppression, number of benign and malignant lesions, and true positive, true negative, false positive and false negative results. All analyses were performed using Meta-Di Sc and Stata 11.0.RESULTS: The pooled sensitivity and specificity of singleshot EPI DWI were 0.83(95%CI: 0.79-0.87) and 0.77(95%CI: 0.70-0.83), respectively. The positive likelihood ratio and negative likelihood ratio were 5.09(95%CI: 2.19-11.84) and 0.23(95%CI: 0.15-0.36), respectively. The P value for the χ2 heterogeneity for all pooled estimates was < 0.05. From the fitted summary receiver operating characteristic curve, the area under the curve and Q* index were 0.89 and 0.82, respectively. Publication bias was not present(t = 0.58, P = 0.58). Meta-regression analysis indicated that fat suppression, mean age, TE, and maximum b factor were not sources of heterogeneity(all P > 0.05). CONCLUSION: Single-shot EPI DWI is useful to differentiate between malignant and benign pancreatic lesions. Lesion size ≥ 2 cm is the limit for the diagnosis of early lesions.

Advances in early diagnosis and therapy of pancreatic cancer

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database) RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

ERCP and CT diagnosis of pancreas divisum and its relation to etiology of chronic pancreatitis

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Clinical diagnosis and management of pancreatic mucinous cystadenoma and cystadenocarcinoma:Single-center experience with 82 patients

BACKGROUND Mucinous cystic neoplasm(MCN)of the pancreas is characterized by mucinproducing columnar epithelium and dense ovarian-type stroma and at risk for malignant transformation.Early diagnosis and treatment of MCN are particularly important.AIM To investigate the clinical characteristics of and management strategies for pancreatic mucinous cystadenoma(MCA)and mucinous cystadenocarcinoma(MCC).METHODS The clinical and pathological data of 82 patients with pancreatic MCA and MCC who underwent surgical resection at our department between April 2015 and March 2019 were retrospectively analyzed.RESULTS Of the 82 patients included in this study,70 had MCA and 12 had MCC.Tumor size of MCC was larger than that of MCA(P=0.049).Age and serum levels of tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)19-9,and CA12-5 were significantly higher in MCC than in MCA patients(P=0.005,0.026,and 0.037,respectively).MCA tumor size was positively correlated with serum CA19-9 levels(r=0.389,P=0.001).Compared with MCC,MCA had a higher minimally invasive surgery rate(P=0.014).In the MCA group,the rate of major complications was 5.7%and that of clinically relevant pancreatic fistula was 8.6%;the corresponding rates in the MCC group were 16.7%and 16.7%,respectively.CONCLUSION Tumor size,age,and serum CEA,CA19-9,and CA12-5 levels may contribute to management of patients with MCN.Surgical resection is the primary treatment modality for MCC and MCA.

Fine needle aspiration diagnosis of isolated pancreatic tuberculosis: A case report

Tuberculosis(TB) involving the pancreas are uncommon, especially when present in immunocompetent hosts. Pancreatic TB is more frequently associated with miliary TB or widely disseminated disease. Pancreatic TB may present as cystic or solid pancreatic masses, pancreatic abscess or acute or chronic pancreatitis. Majority of the cases are diagnosed after surgical exploration for presumed pancreatic malignancy and preoperative diagnosis is quite difficult. However, improvement in imaging techniques and the resulting imageguided interventions gradually can obviate the need for more invasive diagnostic surgical procedures and expedite the planning of therapy. Herein, we report a rare case of isolated pancreatic TB which presented with pancreatic mass lesion in an immunocompetent host. Diagnosis was made by contrast enhanced computed tomography and guided fine needle aspiration of the pancreatic mass which revealed acid-fast bacillion Ziehl-Neelsen stain. The case was treated successfully with antituberculous drugs. Pancreatic tuberculosis should be considered in the differential diagnosis of a pancreatic mass when the patient is young, residing in the endemic zone of tuberculosis. Every attempt should be made to diagnose the cases to prevent unnecessary operation.

A clinical evaluation of serological diagnosis for pancreatic cancer

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