Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data

Background:Pancreatic cysts are common.However,most studies are based on data collected from individual centers.The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions(PCLs)by analyzing large epidemiologic data.Methods:Between January 2007 and December 2018,information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea.Results:The final number of patients with pancreatic cysts was 165277 among the total claims for reimbursement of 855983 associated with PCLs over 12 years.The total number of claims were increased from 19453 in 2007 to 155842 in 2018 and the prevalence increased from 0.04%to 0.23%.For 12 years,2874(1.7%)had pancreatic cancer and 8212(5.0%)underwent surgery,and 36 had surgery for twice(total 8248 pancreatectomy).After ruling out claims from the first 3 years of washout period,the incidence increased from 9891 to 24651 and the crude incidence rate of PCLs expanded from 19.96 per 100000 to 47.77 per 100000.Compared to specific neoplasm codes(D136 or D377),the use of pancreatic cyst code(K862)has been remarkably increased and the most common since 2010.The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012,and decreased to 596 until 2018.The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6%in 2007 to 11.7%in 2018.Conclusions:The incidence of PCLs is rapidly increasing.Among PCLs,indeterminate cyst is increasing outstandingly.A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

Molecular analysis of pancreatic cystic neoplasm in routine clinical practice

BACKGROUND Cystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques.Of these,mucinous cysts are especially relevant due to their risk of malignancy.However,morphological findings are often suboptimal for their differentiation.Endoscopic ultrasound fine-needle aspiration(EUS-FNA)with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts.AIM To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.METHODS An 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted.These cysts included those>15 mm with unclear diagnosis,and a change in follow-up or with concerning features in which results might change clinical management.EUS-FNA with cytological,biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts.The cysts were classified as mucinous and non-mucinous by the combination of morphological,cytological and biochemical analyses when surgery was not performed.Malignancy was defined as cytology positive for malignancy,high-grade dysplasia or invasive carcinoma on surgical specimen,clinical or morphological progression,metastasis or death related to neoplastic complications during the 6-mo follow-up period.Next-generation sequencing results were compared for cyst type and malignancy.RESULTS Of the 36 lesions included,28(82.4%)were classified as mucinous and 6(17.6%)as non-mucinous.Furthermore,5(13.9%)lesions were classified as malignant.The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25(69.4%)pancreatic cysts.The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions.Analysis of KRAS and/or GNAS showed 83.33%[95%confidence interval(CI):63.34-100]sensitivity,60%(95%CI:7.06-100)specificity,88.24%(95%CI:69.98-100)positive predictive value and 50%(95%CI:1.66-98.34)negative predictive value(P=0.086)for the diagnosis of mucinous cystic lesions.Mutations in KRAS and GNAS were found in 2/5(40%)of the lesions classified as non-mucinous,thus recategorizing those lesions as mucinous neoplasms,which would have led to a modification of the follow-up plan in 8%of the cysts in which molecular analysis was successfully performed.All 4(100%)malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS,although they were not related to malignancy(P>0.05).None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance(P>0.05).CONCLUSION Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous.Mutations were not able to detect malignant lesions.

Updates in diagnosis and management of pancreatic cysts

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential.The most common pancreatic cystic neoplasms include serous cystadenoma,mucinous cystic neoplasm and intraductal papillary mucinous neoplasm.Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound(EUS)or surgical resection.Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass,nodule and dilated main pancreatic duct.EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging.Various cyst fluid markers including carcinoembryonic antigen,glucose,amylase,cytology,and DNA markers help distinguish mucinous from nonmucinous cysts.This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery.For presumed low risk cysts,surveillance strategies will be discussed.Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.

Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies

BACKGROUND Recurrent acute pancreatitis(RAP)may be a presenting feature of and an indication for resection of pancreatic cysts,including intra-ductal papillary mucinous neoplasm(IPMN).Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIM To study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODS This retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016.The prevalence of preoperative high-risk cyst features,and of neoplasia was compared between patients with and without RAP.To identify the cause of pancreatitis,all the patients had a detailed history of alcohol,smoking,medications obtained,and had cross-sectional imaging(contrast-enhanced computed tomography/magnetic resonance imaging)and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis.The incidence of RAP post-resection was the primary outcome.RESULTS IPMN accounted for 101 cases(58.7%){[branch duct(BD)59(34.3%),main duct(MD)42](24.4%)}.Twenty-nine(16.9%)presented with RAP(mean 2.2 episodes):15 had BD-IPMN,8 MD-IPMN,5 mucinous cystic neoplasm and 1 serous cystic neoplasm.Malignancy was similar among those with vs without RAP for all patients[6/29(20.7%)vs 24/143(16.8%)]and IPMN patients[6/23(26.1%)vs 23/78(29.5%)],although tended to be higher with RAP in BD-IPMN,[5/15(33.3%)vs 3/44(6.8%),P=0.04].At mean follow-up of 7.2 years,1(3.4%)RAP patient had post-resection RAP.The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02(P<0.0001).CONCLUSION Malignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP.In addition,specific cyst characteristics were not clearly associated with RAP.The incidence of RAP was markedly decreased in almost all patients following cyst resection.

Analysis of clinical characteristics and treatment of pancreatic cystic tumors

Objective： To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms.Methods： This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiologieal and pathological images and surgical recordings, were collected. Results： Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role.

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions:A single-center study

BACKGROUND Currently,there is insufficient data about the accuracy in the diagnosing of pancreatic cystic lesions(PCLs),especially with novel endoscopic techniques such as with direct intracystic micro-forceps biopsy(mFB)and needle-based confocal laser-endomicroscopy(nCLE).AIM To compare the accuracy of endoscopic ultrasound(EUS)and associated techniques for the detection of potentially malignant PCLs:EUS-guided fine needle aspiration(EUS-FNA),contrast-enhanced EUS(CE-EUS),EUS-guided fiberoptic probe cystoscopy(cystoscopy),mFB,and nCLE.METHODS This was a single-center,retrospective study.We identified patients who had undergone EUS,with or without additional diagnostic techniques,and had been diagnosed with PCLs.We determined agreement among malignancy after 24-mo follow-up findings with detection of potentially malignant PCLs via the EUSguided techniques and/or EUS-guided biopsy when available(EUS malignancy detection).RESULTS A total of 129 patients were included, with EUS performed alone in 47/129. In 82/129 patients,EUS procedures were performed with additional EUS-FNA (21/82), CE-EUS (20/82), cystoscopy(27/82), mFB (36/82), nCLE (44/82). Agreement between EUS malignancy detection and the 24-mo follow-up findings was higher when associated with additional diagnostic techniques thanEUS alone [62/82 (75.6%) vs 8/47 (17%);OR 4.35, 95%CI: 2.70-7.37;P < 0.001]. The highestmalignancy detection accuracy was reached when nCLE and direct intracystic mFB were bothperformed, with a sensitivity, specificity, positive predictive value, negative predictive value andobserved agreement of 100%, 89.4%, 77.8%, 100% and 92.3%, respectively (P < 0.001 comparedwith EUS-alone).CONCLUSIONThe combined use of EUS-guided mFB and nCLE improves detection of potentially malignantPCLs compared with EUS-alone, EUS-FNA, CE-EUS or cystoscopy.

Pancreatic cyst dilemma: Between physical and biochemical markers

Physical analysis of the pancreatic cystic lesions(PCLs)fluid as expressed by the rheological behavior(“string sign”)can improve the diagnostic yield and should be integrated in every multimodal PCLs workup.

Successful outcome of retrograde pancreatojejunostomy for chronic pancreatitis and infected pancreatic cysts:A case report

BACKGROUND Chronic pancreatitis occasionally requires surgical treatment that can be performed with various techniques.Often,this type of surgery presents with postoperative complications.We report a case of a successful retrograde pancreatojejunostomy for chronic pancreatitis and infected pancreatic cysts.CASE SUMMARY A 62-year-old male with a 10-year history of chronic pancreatitis presented with epigastric pain for one week and a 20 kg weight loss over one year.Computed tomography showed stones in the pancreas(mainly the head),expansion of the main pancreatic duct,and thinning of the pancreatic parenchyma.Magnetic resonance imaging showed infected pancreatic cysts connected to the stomach with a fistula from the splenic hilum to the caudal portion of the liver’s lateral segment.An endoscopic retrograde pancreatography was performed;the guide wires could not pass through the stones in the pancreas and therefore,drainage of the main pancreatic duct was not achieved.Next,a distal pancreatomy and splenectomy were performed;however,the pancreatic juice in the remaining parenchyma was blocked by the stones.Hence,we performed a retrograde pancreatojejunostomy and Roux-en-Y anastomosis.The patient had no postoperative complications and was discharged from the hospital on postoperative day 14.CONCLUSION A distal pancreatomy,retrograde pancreatojejunostomy,and Roux-en-Y anastomosis could be an effective surgical procedure for intractable chronic pancreatitis.

Endoscopic intramural cystogastrostomy for treatment of peripancreatic fluid collection: A viewpoint from a surgeon

Percutaneous or endoscopic drainage is the initial choice for the treatment of peripancreatic fluid collection in symptomatic patients.Endoscopic transgastric fenestration(ETGF)was first reported for the management of pancreatic pseu-docysts of 20 patients in 2008.From a surgeon’s viewpoint,ETGF is a similar procedure to cystogastrostomy in that they both produce a wide outlet orifice for the drainage of fluid and necrotic debris.ETGF can be performed at least 4 wk after the initial onset of acute pancreatitis and it has a high priority over the surgical approach.However,the surgical approach usually has a better success rate because surgical cystogastrostomy has a wider outlet(>6 cm vs 2 cm)than ETGF.However,percutaneous or endoscopic drainage,ETGF,and surgical approach offer various treatment options for peripancreatic fluid collection patients based on their conditions.

Fine-needle aspiration technique under endoscopic ultrasound guidance:A technical approach for RNA profiling of pancreatic neoplasms

BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma(PDAC)has been a longstanding challenge.The prognosis of patients with PDAC depends on the stage at diagnosis.It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis.Most molecular studies are done using paraffin-embedded blocks;however,the integrity of DNA and RNA is often compromised in this format.Moreover,RNA isolated from human pancreatic tissue samples is generally of low quality,in part,because of the high concentration of endogenous pancreatic RNAse activity present.AIM To assess the potential of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling,including next-generation sequencing(NGS).METHODS Thirty-four EUS-FNA samples were included in this study:PDAC(n=15),chronic pancreatitis(n=5),pancreatic cysts(n=14),mucinous cysts(mucinous cystic neoplasia/intraductal papillary mucinous neoplasia)n=7,serous cystic neoplasms n=5,and pseudocysts n=2.Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy(TTNB).Samples were stored at -80℃ until analysis.RNA purity(A260/230,A260/280 ratios),concentration,and integrity(RIN)were assessed.Real-time polymerase chain reaction was conducted on all samples,and small RNA libraries were prepared from solid mass samples.RESULTS RNA was successfully extracted from 29/34(85%)EUS-FNA samples:100% pancreatic adenocarcinoma samples,100% chronic pancreatitis samples,70% pancreatic fluid cyst samples,and 50%TTNB samples.The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples(n=29)including lowquality RNA specimens.Low concentration and nonoptimal RIN values(no less than 3)of RNA extracted from EUS-FNA samples did not prevent NGS library preparation.The suitability of cyst fluid samples for RNA profiling varied.The quality of RNA extracted from mucinous cyst fluid had a median RIN of 7.7(5.0-8.2),which was compatible with that from solid neoplasms[6.2(0-7.8)],whereas the quality of the RNA extracted from all fluids of serous cystic neoplasms and TTNB samples had a RIN of 0.CONCLUSION The results demonstrate the high potential of EUS-FNA material for RNA profiling of various pancreatic lesions,including low-quality RNA specimens.

Pancreatic intraductal papillary mucinous neoplasms:Current diagnosis and management

Intraductal papillary mucinous neoplasms(IPMNs)represent approximately 1%of all pancreatic neoplasms and 25%of cystic neoplasms.They are divided into three types:main duct-IPMN(MD-IPPMN),branch duct-IPMN(BD-IPMN),and mixed type-IPMN.In this review,diagnostics,including clinical presentation and radiological investigations,were described.Magnetic resonance imaging is the most useful for most IPMNs.Management depends on the type and radiological features of IPMNs.Surgery is recommended for MD-IPMN.For BD-IPMN,management involves surgery or surveillance depending on the tumor size,cyst growth rate,solid components,main duct dilatation,high-grade dysplasia in cytology,the presence of symptoms(jaundice,new-onset diabetes,pancreatitis),and CA 19.9 serum level.The patient’s age and comorbidities should also be taken into consideration.Currently,there are different guidelines regarding the diagnosis and management of IPMNs.In this review,the following guidelines were presented:Sendai International Association of Pancreatology guidelines(2006),American Gastroenterological Association guidelines,revised international consensus Fukuoka guidelines(2012),revised international consensus Fukuoka guidelines(2017),and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas(2018).The Verona Evidence-Based Meeting 2020 was also presented and discussed.

Observation or resection of pancreatic intraductal papillary mucinous neoplasm:An ongoing tug of war

An increasing number of patients are being referred to pancreatic centres around the world due to often incidentally discovered cystic neoplasms of the pancreas.The evaluation and management of pancreatic cystic neoplasms is a controversial topic and with existing guidelines based on a lack of strong evidence there is discordance between centres and guidelines with regard to when to offer surgery and when to favour surveillance.The frequency,duration and modality of surveillance is also controversial as this is resource-consuming and must be balanced against the perceived benefits and risks involved.While there is consensus that the risk of malignancy should be balanced against the lifeexpectancy and comorbidities,the indications for surgery and surveillance strategies vary among the guidelines.Thus,the tug of war between surveillance or resection continues.Here we discuss the recommendations from guidelines with further accumulating data and emerging reports on intraductal papillary mucinous neoplasm in the literature.

Retroperitoneal tumor finally diagnosed as a bronchogenic cyst:A case report and review of literature

BACKGROUND Retroperitoneal bronchogenic cyst(RBC)is an extremely rare developmental abnormality.Most are benign tumors but malignant transformation is possible.Because of their anatomical position,RBCs are easily misdiagnosed as adrenal or pancreatic solid tumors on radiological evaluation.Here,we report a case of RBC,review the literature,and summarize some important features.CASE SUMMARY A 49-year-old woman was incidentally found to have a retroperitoneal tumor during a physical examination.Enhanced computed tomography and laboratory evaluations,including routine blood examination,blood biochemistry,24-h urine 17 ketones,17 hydroxyls,adrenocortical hormone,serum potassium concentration,serum amylase,lipase,and epithelial tumor markers,revealed a moderate density,54 mm×40 mm mass with a clear boundary near the left adrenal gland.The were no abnormalities in the blood and urine values.Because the patient had a history of hypertension and the location of the mass was adjacent to the adrenal gland,it was initially diagnosed as a left adrenal tumor and was resected by retroperitoneal laparoscopy.However,the pathological examination after surgery confirmed it to be a bronchogenic cyst.CONCLUSION Retroperitoneal laparoscopic surgery can be prioritized for symptomatic RBC patients.Conservative treatment is feasible for selected patients.

Artificial intelligence for pancreatic cancer detection: Recent development and future direction

Artificial intelligence(AI)has been increasingly utilized in medical applications,especially in the field of gastroenterology.AI can assist gastroenterologists in imaging-based testing and prediction of clinical diagnosis,for examples,detecting polyps during colonoscopy,identifying small bowel lesions using capsule endoscopy images,and predicting liver diseases based on clinical parameters.With its high mortality rate,pancreatic cancer can highly benefit from AI since the early detection of small lesion is difficult with conventional imaging techniques and current biomarkers.Endoscopic ultrasound(EUS)is a main diagnostic tool with high sensitivity for pancreatic adenocarcinoma and pancreatic cystic lesion.The standard tumor markers have not been effective for diagnosis.There have been recent research studies in AI application in EUS and novel biomarkers to early detect and differentiate malignant pancreatic lesions.The findings are impressive compared to the available traditional methods.Herein,we aim to explore the utility of AI in EUS and novel serum and cyst fluid biomarkers for pancreatic cancer detection.

Role of endoscopic ultrasound in anticancer therapy:Current evidence and future perspectives

The digestive system is one of the most common sites of malignancies in humans.Since gastrointestinal tumors represent a massive global health burden both in terms of morbidity and health care expenditures,scientists continuously develop novel diagnostic and therapeutic methods to ameliorate the detrimental effects of this group of diseases.Apart from the well-established role of the endoscopic ultrasound(EUS)in the diagnostic course of gastrointestinal and hepatobiliary malignancies,we have recently become acquainted with a vast array of its therapeutic possibilities.A multitude of previously established,evidence-based methods that might now be guided by the EUS emerged:Radiofrequency ablation,brachytherapy,fine needle injection,celiac plexus neurolysis,and endoscopic submucosal dissection.In this review we endeavored to provide a comprehensive overview of the role of these methods in different malignancies of the digestive system,primarily in the treatment and symptom control in pancreatic cancer,and additionally in the management of hepatic,gastrointestinal tumors,and pancreatic cysts.

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Pancreatic cancer has a high mortality rate with minimal proven interventions.Intraductal Papillary Mucinous Neoplasms(IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies,successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia(high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include-through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

Solid pseudopapillary neoplasm-diagnostic approach and postsurgical follow up:Three case reports and review of literature

BACKGROUND Solid pseudopapillary neoplasm(SPN)is a rare tumor that was first described by Frantz in 1959.Although this tumor is benign,some may have malignant potential that can be predicted based on demographics,imaging characteristics,and pathologic evaluation.This case series presents 3 SPN cases with discussion on gender differences,preoperative predictors of malignancy,and a suggested algorithm for diagnostic approach as well as post-surgical follow up.CASE SUMMARY Three adult patients in a tertiary hospital found to have SPN,one elderly male and two young females.Each of the cases presented with abdominal pain and were discovered incidentally.Two cases underwent endoscopic ultrasound with immunohistochemical staining(which were consistent with SPN before undergoing surgery),and one case underwent surgery directly after imaging.The average tumor size was 5 cm.Diagnosis was confirmed by histology.Two patients had post-surgical complications requiring intervention.CONCLUSION Demographic and imaging characteristics can be sufficient to establish diagnosis for SPN,while malignant cases require pre-operative evaluation with endoscopic ultrasound fine needle aspiration/fine needle biopsy.

肝胆管类圆虫病表现为食管胃十二指肠镜和超声内镜下的壶腹病变

Strongyloidiasis is an intestinal infection caused by the parasitic nematodes of the Strongyloides species,most commonly Strongyloides stercoralis.We report a case of a 66-year-old immigrant male from Haiti who presented with complaints of diarrhea and an unintentional 80-lb weight loss over the past 5 years.Stool examination was positive for strongyloidiasis.Following albendazole therapy,esophagogastroduodenoscopy(EGD)showed a unique ampullary lesion.Histopathology of the ampullary lesion showed reactive epithelium with Strongyloides larva.In addition,endoscopic ultrasound(EUS)detected a large pancreatic cyst.Both these findings were absent on EGD 5 years previously,prior to the onset of his symptoms.This paper documents a rare case of an ampullary lesion and pancreatic cyst secondary to hepatobiliary strongyloidiasis in a non-Human Immunodeficiency Virus(HIV)patient.We review the epidemiology,life cycle,clinical presentation and treatment of strongyloidiasis.