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.

Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography

BACKGROUND Solid pseudopapillary neoplasms of the pancreas(SPN)share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes(PDAC with cystic changes),which may result in unnecessary surgery.AIM To investigate the value of computed tomography(CT)in differentiation of SPN from PDAC with cystic changes.METHODS This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes,confirmed through pathological diagnosis.Quantitative and qualitative analysis was performed,including assessment of age,sex,tumor size,shape,margin,density,enhancement pattern,CT values of tumors,CT contrast enhancement ratios,“floating cloud sign,”calcification,main pancreatic duct dilatation,pancreatic atrophy,and peripancreatic invasion or distal metastasis.Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes,and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination.RESULTS When compared to PDAC with cystic changes,SPN had a lower age(32 years vs 64 years,P<0.05)and a slightly larger size(5.41 cm vs 3.90 cm,P<0.05).SPN had a higher frequency of“floating cloud sign”and peripancreatic invasion or distal metastasis than PDAC with cystic changes(both P<0.05).No significant difference was found with respect to sex,tumor location,shape,margin,density,main pancreatic duct dilatation,calcification,pancreatic atrophy,enhancement pattern,CT values of tumors,or CT contrast enhancement ratios between the two groups(all P>0.05).The area under the receiver operating characteristic curve of the combination was 0.833(95%confidence interval:0.708-0.957)with 78.6%sensitivity,81.3%specificity,and 80.4%accuracy in differentiation of SPN from PDAC with cystic changes.CONCLUSION A larger tumor size,“floating cloud sign,”and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

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.

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.

Endoscopic techniques for diagnosis and treatment of gastroentero-pancreatic neuroendocrine neoplasms:Where we are

BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-enteropancreatic neuroendocrine neoplasms(GEP-NENs).AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 15 years,using both medical subject heading(MeSH)terms and free-language keywords:gastro-enteropancreatic neuroendocrine neoplasms;endoscopy;ultrasound endoscopy;capsule endoscopy;double-balloon enteroscopy;diagnosis;therapy;staging.RESULTS In the diagnostic setting,endoscopic ultrasonography(EUS)represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric,duodenal and rectal NENs.The diagnosis of small bowel NENs(sbNENs)has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy,which allow for direct visualization of the entire small bowel;however,data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive.From a therapeutic point of view,endoscopic removal is the treatment of choice for the majority of gastric NENs(type 1/2),for well-differentiated localized nonmetastatic duodenal NENs<1 cm,confined to the submucosa layer and for<10 mm,stage T1–T2,rectal NENs.EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs.Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.

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.

Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.

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.

Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

Endoscopic ultrasonography(EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography,computed tomography(CT) and transabdominal ultrasound for recognising early pancreatic tumors.As a diagnostic modality for pancreatic cancer,EUS has proved rates higher than 90%,especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT.Besides,EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer.The complication rate of EUS is as low as 1.1%-3.0%.New technical developments such as elastography and the use of contrast agents have recently been applied to EUS,improving its diagnostic capability.EUS has been found to be superior to the recent multidetector CT for T stagingwith less risk of overstaying in comparison to both CT and magnetic resonance imaging,so that patients are not being ruled out of a potentially beneficial resection.The accuracy for N staging with EUS is 64%-82%.In unresectable cancers,EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block,biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.

A clinical evaluation of serological diagnosis for pancreatic cancer

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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.

Pancreatic tumor:DSA diagnosis and treatment

IM To study the clinical significance of the diagnosis and catheterized interventional treatment of digital subtraction angiography (DSA) for pancreatic tumors.METHODS Ninetytwo patients with pancreatic tumor, 69 males and 23 females, aged from 41 to 70 years (mean 571 years) were diagnosed with DSA. Sixtyone patients with pancreatic cancer were treated with transcatheter celiac and superior mesenteric arterial anticancer agents (MMC 20mg, EADM 40mg and 5FU 20g) infusion (TCSAI).RESULTS The DSA diagnoses were confirmed by operations and pathological examinations, with a coincidence 826% rate of, and a therapeutic effective rate of 426%.CONCLUSION DSA is of diagnostic value for pancreatic tumors, and helpful in understanding the course of the disease, judging the prognosis and selecting the therapeutic regimen, and could improve the chemotherapeutic effect as well..

Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.

Diagnosis and management of autoimmune pancreatitis:Experience from China

AIM： To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis （AIP）. METHODS： In this retrospective study, the data of patients with diagnosed chronic pancreatitis （CP） between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria： （1） diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; （2） characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, y-globulin levels or presence of autoantibodies; （3） response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS： Twenty-five （22 male, 3 female; mean age 54 years, 36-76 years） out of 510 CP patients were diagnosed as AIP, which accounted for 49% （21/43） of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases （72%）, abdominal pain in 11 （44%）, weight loss in 10 （40%）, and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas （18 cases）, strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, theremaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION： AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. The differential diagnosis with high index of suspicion of AIP would improve the diagnostic accuracy for AIR

Survivin:Potential role in diagnosis,prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.

Pathological differential diagnosis of solid-pseudopapillary neoplasm and endocrine tumors of the pancreas

AIM:To investigate differential points of solid-pseudo-papillary neoplasm (SPN) of the pancreas and pancre-atic endocrine tumor (PET).METHODS:Ten cases of SPN and fourteen cases of PET were studied in this retrospective study. Clinical and pathologic features,immunostaining reactions and β-catenin gene mutations were analyzed.RESULTS:The mean age of SPN patients was 25.6 years and these patients had no specific symptoms. The mean diameter of the tumors was 11.0 cm,9/10 cases were cystic or a mixture of solid and cystic structures,and there was hemorrhage and necrosis on the cut surface in 8/10 (80%) cases. Characteristic pseudo-papillary structure and discohesive appearance of the neoplastic cells were observed in all 10 (100%) cases. The results of immunostaining showed that nuclear expression of β-catenin and loss of E-cadherin in all the cases,was only seen in SPN. Molecular studies discov-ered that 9/10 (90%) cases harbored a point mutation of exon 3 in β-catenin gene. On the other hand,the mean age of PET patients was 43.1 years. Eight of 14 cases presented with symptoms caused by hypoglyce-mia,and the other 6 cases presented with symptoms similar to those of SPN. The mean size of the tumors was 2.9 cm,most of the tumors were solid,only 3/14 (21%) were a mixture of solid and cystic structures,and macroscopic hemorrhage and necrosis were much less common (3/14,21%). Histologically,tumor cells were arranged in trabecular,acinar or solid patterns and demonstrated no pseudopapillary structure and discohesive appearance in all 14 (100%) cases. The results of immunostaining and mutation detection were completely different with SPN that membrane and cytoplastic expression of β-catenin without loss of E-cadherin,as well as no mutation in β-catenin gene in all the cases. CONCLUSION:Both macroscopic and microscopic features of SPN are quite characteristic. It is not difficult to distinguish it from PET. If necessary,immunos-taining of β-catenin and E-cadherin is quite helpful to make the differential diagnosis.

Computed tomography in diagnosing vascular invasion in pancreatic and periampullary cancers: a systematic review and meta-analysis

BACKGROUND: Preoperative diagnosis of local vascular invasion is very important to the selection of therapeutic protocols and prediction of the prognosis of pancreatic and periampullary cancers. This meta-analysis was designed to evaluate the accuracy of computed tomography (CT) in diagnosing vascular invasion in patients with pancreatic and periampullary cancers. DATA SOURCES: English-language articles reporting diagnostic accuracy of CT for vascular invasion in pancreatic and periampullary cancers were searched from the MEDLINE and PubMed databases. A meta-analysis was conducted to estimate pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. RESULTS: Data were extracted from 18 studies that met the inclusion criteria. The pooled sensitivity and specificity of CT in diagnosing vascular invasion were 77% and 81%. Since CT technology improved in different periods, in the recent five years (2004-2008) CT has shown a higher diagnostic accuracy, and the pooled sensitivity and specificity increased to 85% and 82%, respectively. Subgroup analysis of CT studies was made to determine the involvement of different vessels, and the pooled sensitivities for the invasion of the venous system, portal vein, and arterial system were 75%, 75%, and 68%, and the pooled specificities were 84%, 91%, and 92%, respectively. For CT imaging with vascular reconstruction, the pooled sensitivity and specificity were 84% and 85%, higher than the estimates in studies without reconstruction. CONCLUSIONS: Developed CT technology with vascular reconstruction is used as an imaging modality for diagnosing vascular invasion at present. Further combined application of various imaging modalities may improve the accuracy of diagnosis, especially for smaller vessel involvement, such as the superior mesenteric vein or artery, which are difficult to demarcate.

Development and controversies of adjuvant therapy for pancreatic cancer

BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

A practical approach to the diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis is a disease characterized by specific pathological features,different from those of other forms of pancreatitis,that responds dramatically to steroid therapy.The pancreatic parenchyma may be diffusely or focally involved with the possibility of a low-density mass being present at imaging,mimicking pancreatic cancer.Clinically,the most relevant problems lie in the diagnosis of autoimmune pancreatitis and in distinguishing autoimmune pancreatitis from pancreatic cancer.Since in the presence of a pancreatic mass the probability of tumour is much higher than that of pancreatitis,the physician should be aware that in focal autoimmune pancreatitis the first step before using steroids is to exclude pancreatic adenocarcinoma.In this review,we briefly analyse the strategies to be followed for a correct diagnosis of autoimmune pancreatitis.

Differentiating intraductal papillary mucinous neoplasms from other pancreatic cystic lesions

Intraductal papillary mucinous neoplasms(IPMN) can be difficult to distinguish from other cystic lesions of the pancreas.To understand better and discuss the current knowledge on this topic,the literature and the institutional experience at a large pancreatic disease center have been reviewed.A combination of preoperative demographic,historical,radiographic,laboratory data,as well as postoperative pathologic analyses can often distinguish IPMN from other lesions in the differential diagnosis.