AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical r...AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses.The medical records were retrospectively reviewed and immunohistochemical staining for mucin(MUC) in pancreatic tissues was performed.RESULTS:Univariate analysis showed that the following five variables were closely associated with malignant IPMNs preoperatively:absence of extrapancreatic malignancy;symptoms;tumor size > 4 cm;main pancreaticduct(MPD) size > 7 mm;and lymph node enlargement on preoperative computed tomography(CT).Multivariate analysis revealed that the following two factors were significantly associated with malignant IPMNs preoperatively:MPD size > 7 mm [odds ratio(OR) = 2.50];and lymph node enlargement on preoperative CT(OR = 3.57).No significant differences in the expression of MUC1,MUC2 and MUC5AC were observed between benign and malignant IPMNs.CONCLUSION:MPD size > 7 mm and preoperative lymph node enlargement on CT are useful predictive factors associated with malignancy of IPMNs.展开更多
Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these...Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.展开更多
BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinom...BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.展开更多
BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-...BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.展开更多
BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the hi...BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.展开更多
Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex...Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.展开更多
Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years....Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.展开更多
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 art...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.展开更多
BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most ...BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.展开更多
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 ...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.展开更多
Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is co...Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.展开更多
BACKGROUND Patients with intraductal papillary mucinous neoplasm(IPMN)have an increased risk of pancreatic and extrapancreatic malignancies.Lymphomas are rare extrapancreatic malignancies,and in situ collisions of ear...BACKGROUND Patients with intraductal papillary mucinous neoplasm(IPMN)have an increased risk of pancreatic and extrapancreatic malignancies.Lymphomas are rare extrapancreatic malignancies,and in situ collisions of early gastric cancer and diffuse large B-cell lymphoma(DLBCL)are even rarer.Here,we report the first case of pancreatic cancer comorbid with in situ collision of extrapancreatic malignancies(early gastric cancer and DLBCL)in a follow-up IPMN patient.Furthermore,we have made innovations in the treatment of such cases.CASE SUMMARY An 81-year-old Japanese female diagnosed with IPMN developed elevated carbohydrate antigen(CA)19-9 levels during follow-up.Because her CA19-9 levels continued to rise,endoscopic ultrasound(EUS)was performed and revealed a suspicious lesion at the pancreatic tail.However,lesions in the pancreas were not found by computed tomography,magnetic resonance imaging,or endoscopic retrograde cholangiopancreatography.To make an exact pathological diagnosis,EUS-guided fine needle aspiration was performed.To our supprise,early gastric cancer was found in preoperative gastroscopy.The gastric cancer was completely resected through endoscopic submucosal dissection before postoperative pathology identified early adenocarcinoma collided with DLBCL.Subsequent EUS-guided fine needle aspiration provided pathological support forthe pancreatic cancer diagnosis, and then laparoscopic distal pancreatectomy andsplenectomy were performed. CA19-9 levels returned to normal postoperatively.CONCLUSION Endoscopic submucosal dissection is appropriate for submucosal lymphomas inpatients intoleratant of chemotherapy. EUS can detect small IPMN-relatedpancreatic tumors.展开更多
BACKGROUND Guanine nucleotide-binding protein,alpha stimulating(GNAS)mutations are characteristic of intraductal papillary mucinous neoplasms(IPMNs).Pancreatic ductal adenocarcinomas(PDACs)harboring GNAS mutations ori...BACKGROUND Guanine nucleotide-binding protein,alpha stimulating(GNAS)mutations are characteristic of intraductal papillary mucinous neoplasms(IPMNs).Pancreatic ductal adenocarcinomas(PDACs)harboring GNAS mutations originate in IPMNs.GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions,NESP55,GNASAS,GNASXL,GNAS1A,and GNAS.AIM To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts.METHODS GNAS locus methylation was analyzed in archival pancreatic cyst fluid(PCF)obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific–multiplex ligation dependent probe amplification.Results were normalized and analyzed using Coffalyser.Net software.RESULTS Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied.The final diagnoses were surgical(11)and clinicopathological(41),including 30 benign cysts,14 pre-malignant cyst,and eight malignant cysts.Methylation changes at NESP55,GNASAS,GNAS1A,and especially GNASXL were more frequent in malignant cysts,and NESP55 and GNASAS were useful for diagnosis.A combined variable defined as“GNAS locus methylation changes”was significantly associated with malignancy(6/8 malignant cysts and only 2/20 benign cysts)and improved classification.Hypermethylation in both maternally(NESP55)and paternally(GNASXL)derived promoters was found in 3/3 PDACs.CONCLUSION This is the first study to identify methylation changes in the GNAS locus,improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.展开更多
BACKGROUND Liver metastasis(LM)remains a major cause of cancer-related death in patients with pancreatic cancer(PC)and is associated with a poor prognosis.Therefore,identifying the risk and prognostic factors in PC pa...BACKGROUND Liver metastasis(LM)remains a major cause of cancer-related death in patients with pancreatic cancer(PC)and is associated with a poor prognosis.Therefore,identifying the risk and prognostic factors in PC patients with LM(PCLM)is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients.However,there are limited data on risk and prognostic factors in PCLM patients.AIM To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms.METHODS Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance,Epidemiology,and Results Database.Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode.The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model.The performance of the two nomogram models was evaluated using receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA),and risk subgroup classification.The Kaplan-Meier method with a logrank test was used for survival analysis.RESULTS We enrolled 33459 patients with PC in this study.Of them,11458(34.2%)patients had LM at initial diagnosis.Age at diagnosis,primary site,lymph node metastasis,pathological type,tumor size,and pathological grade were identified as independent risk factors for LM in patients with PC.Age>70 years,adenocarcinoma,poor or anaplastic differentiation,lung metastases,no surgery,and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM.The C-index of diagnostic and prognostic nomograms were 0.731 and 0.753,respectively.The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves,calibration plots,and DCA curves.The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation.CONCLUSION Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention.External validation is required to confirm these results.展开更多
With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms(PCNs) has increased. PCNs comprise a broad dif...With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms(PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound(EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.展开更多
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 ...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.展开更多
Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognize...Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.展开更多
Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanN...Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.展开更多
Objective:Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms(PCN)may help clinicians make better intervention choices and will be essential for individualized treatment.Methods:Pre...Objective:Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms(PCN)may help clinicians make better intervention choices and will be essential for individualized treatment.Methods:Preoperative ultrasound and laboratory examination findings,and demographic characteristics were collected from patients.Multiple logistic regression was used to identify independent risk factors associated with malignant PCN,which were then included in the nomogram and validated with an external cohort.The Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model.Results:Malignant PCN were found in 83(40.7%)and 33(38.7%)of the model and validation cohorts,respectively.Multivariate analysis identified age,tumor location,imaging of tumor boundary,blood type,mean hemoglobin concentration,neutrophil-tolymphocyte ratio,carbohydrate antigen 19-9,and carcinoembryonic antigen as independent risk factors for malignant PCN.The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations.A nomogram score cutoff of 192.5 classified patients as having low vs.high risk of malignant PCN.The model achieved good C-statistics of 0.929(95%CI 0.890–0.968,P<0.05)and 0.951(95%CI 0.903–0.998,P<0.05)in predicting malignancy in the development and validation cohorts,respectively.NRI=0.268;IDI=0.271(P<0.001 for improvement).The DCA curve indicated that our model yielded greater clinical benefits than the comparator model.Conclusions:The nomogram showed excellent performance in predicting malignant PCN and may help surgeons select patients for detailed examination and surgery.The nomogram is freely available at https://wangjunjinnomogram.shinyapps.io/DynNomapp/.展开更多
BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curativ...BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs.However,the indications for LN dissection are still controversial.Over the last decade,minimally invasive surgery such as laparoscopic pancreatic surgery(LPS)has been increasingly performed for pancreatic tumors including PNENs.AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODS From April 2001 to December 2019,92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital.Finally,82 patients were enrolled in this study.Using perioperative factors,we examined the predictive factors for LN metastasis in PNENs.RESULTS Among the 82 patients,the percentage of LN metastasis according to the pathological findings was 12%(10/82 cases).The median tumor size was 12 mm(range:5-90 mm).The median tumor size in the LN-positive group(37 mm)was significantly larger than that in the LN-negative group(12 mm)(P=0.0001).Multivariate analyses revealed that larger tumor size(≥20 mm)was an independent risk factor for LN metastasis(odds ratio 16.8,P=0.0062).In patients with small tumors(≤10 mm),LN metastasis was not found.CONCLUSION Larger tumor size(≥20 mm)is an independent risk factor for LN metastasis in PNENs.In smaller PNENs(≤10 mm),we may be able to choose limited surgery without LN dissection.展开更多
文摘AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses.The medical records were retrospectively reviewed and immunohistochemical staining for mucin(MUC) in pancreatic tissues was performed.RESULTS:Univariate analysis showed that the following five variables were closely associated with malignant IPMNs preoperatively:absence of extrapancreatic malignancy;symptoms;tumor size > 4 cm;main pancreaticduct(MPD) size > 7 mm;and lymph node enlargement on preoperative computed tomography(CT).Multivariate analysis revealed that the following two factors were significantly associated with malignant IPMNs preoperatively:MPD size > 7 mm [odds ratio(OR) = 2.50];and lymph node enlargement on preoperative CT(OR = 3.57).No significant differences in the expression of MUC1,MUC2 and MUC5AC were observed between benign and malignant IPMNs.CONCLUSION:MPD size > 7 mm and preoperative lymph node enlargement on CT are useful predictive factors associated with malignancy of IPMNs.
文摘Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.
基金The study protocol was reviewed and approved by the Institutional Research Committee,Faculty of Medicine,Chulalongkorn University(No.0482/65)registered in the Thai Clinical Trials Registry(TCTR20211109002).
文摘BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.
基金reviewed and approved by the Hospital Pablo Tobón Uribe Institutional Review Board(Approval No.PG-DMD-046-F1).
文摘BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.
基金the National Natural Science Foundation of China,No.82000566Natural Science Foundation of Shandong Province,No.ZR2020QH036 and No.ZR2022MH010.
文摘BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.
文摘Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.
文摘Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.
文摘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.
文摘BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.
文摘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.
基金supported by grants from the National Natural Science Foundation of China (82072693, 81902417 and 82172884)the Scientific Innovation Project of Shanghai Education Commit-tee (2019-01-07-00-07-E00057)+2 种基金Clinical and Scientific Innovation Project of Shanghai Hospital Development Center (SHDC12018109)Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1006A)National Key Research and Development Program of China (2020YFA0803202)。
文摘Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.
基金Supported by“136 Yucai Project”of Ningxia Hui Autonomous Region People’s Hospital Core Talent Training Fund Sponsorship to study in Japan(to Ma YH).
文摘BACKGROUND Patients with intraductal papillary mucinous neoplasm(IPMN)have an increased risk of pancreatic and extrapancreatic malignancies.Lymphomas are rare extrapancreatic malignancies,and in situ collisions of early gastric cancer and diffuse large B-cell lymphoma(DLBCL)are even rarer.Here,we report the first case of pancreatic cancer comorbid with in situ collision of extrapancreatic malignancies(early gastric cancer and DLBCL)in a follow-up IPMN patient.Furthermore,we have made innovations in the treatment of such cases.CASE SUMMARY An 81-year-old Japanese female diagnosed with IPMN developed elevated carbohydrate antigen(CA)19-9 levels during follow-up.Because her CA19-9 levels continued to rise,endoscopic ultrasound(EUS)was performed and revealed a suspicious lesion at the pancreatic tail.However,lesions in the pancreas were not found by computed tomography,magnetic resonance imaging,or endoscopic retrograde cholangiopancreatography.To make an exact pathological diagnosis,EUS-guided fine needle aspiration was performed.To our supprise,early gastric cancer was found in preoperative gastroscopy.The gastric cancer was completely resected through endoscopic submucosal dissection before postoperative pathology identified early adenocarcinoma collided with DLBCL.Subsequent EUS-guided fine needle aspiration provided pathological support forthe pancreatic cancer diagnosis, and then laparoscopic distal pancreatectomy andsplenectomy were performed. CA19-9 levels returned to normal postoperatively.CONCLUSION Endoscopic submucosal dissection is appropriate for submucosal lymphomas inpatients intoleratant of chemotherapy. EUS can detect small IPMN-relatedpancreatic tumors.
基金Supported by a Research Grant from Sociedade Portuguesa de Endoscopia Digestiva in 2018.
文摘BACKGROUND Guanine nucleotide-binding protein,alpha stimulating(GNAS)mutations are characteristic of intraductal papillary mucinous neoplasms(IPMNs).Pancreatic ductal adenocarcinomas(PDACs)harboring GNAS mutations originate in IPMNs.GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions,NESP55,GNASAS,GNASXL,GNAS1A,and GNAS.AIM To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts.METHODS GNAS locus methylation was analyzed in archival pancreatic cyst fluid(PCF)obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific–multiplex ligation dependent probe amplification.Results were normalized and analyzed using Coffalyser.Net software.RESULTS Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied.The final diagnoses were surgical(11)and clinicopathological(41),including 30 benign cysts,14 pre-malignant cyst,and eight malignant cysts.Methylation changes at NESP55,GNASAS,GNAS1A,and especially GNASXL were more frequent in malignant cysts,and NESP55 and GNASAS were useful for diagnosis.A combined variable defined as“GNAS locus methylation changes”was significantly associated with malignancy(6/8 malignant cysts and only 2/20 benign cysts)and improved classification.Hypermethylation in both maternally(NESP55)and paternally(GNASXL)derived promoters was found in 3/3 PDACs.CONCLUSION This is the first study to identify methylation changes in the GNAS locus,improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.
文摘BACKGROUND Liver metastasis(LM)remains a major cause of cancer-related death in patients with pancreatic cancer(PC)and is associated with a poor prognosis.Therefore,identifying the risk and prognostic factors in PC patients with LM(PCLM)is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients.However,there are limited data on risk and prognostic factors in PCLM patients.AIM To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms.METHODS Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance,Epidemiology,and Results Database.Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode.The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model.The performance of the two nomogram models was evaluated using receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA),and risk subgroup classification.The Kaplan-Meier method with a logrank test was used for survival analysis.RESULTS We enrolled 33459 patients with PC in this study.Of them,11458(34.2%)patients had LM at initial diagnosis.Age at diagnosis,primary site,lymph node metastasis,pathological type,tumor size,and pathological grade were identified as independent risk factors for LM in patients with PC.Age>70 years,adenocarcinoma,poor or anaplastic differentiation,lung metastases,no surgery,and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM.The C-index of diagnostic and prognostic nomograms were 0.731 and 0.753,respectively.The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves,calibration plots,and DCA curves.The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation.CONCLUSION Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention.External validation is required to confirm these results.
文摘With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms(PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound(EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.
文摘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.
基金This study was supported by a grant from the Innovation Capability Development Project of Jiangsu Province(No.BM2015004).
文摘Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.
基金Supported by National Key R&D Program of China,No.2019YFB1309704.
文摘Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.
基金supported by the National Natural Science Foundation of China(Grant Nos.82030092,81720108028,and 81802433)the Key Program of Prevention and Treatment of Chronic Diseases of Tianjin(Grant No.17ZXMFSY00010).
文摘Objective:Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms(PCN)may help clinicians make better intervention choices and will be essential for individualized treatment.Methods:Preoperative ultrasound and laboratory examination findings,and demographic characteristics were collected from patients.Multiple logistic regression was used to identify independent risk factors associated with malignant PCN,which were then included in the nomogram and validated with an external cohort.The Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model.Results:Malignant PCN were found in 83(40.7%)and 33(38.7%)of the model and validation cohorts,respectively.Multivariate analysis identified age,tumor location,imaging of tumor boundary,blood type,mean hemoglobin concentration,neutrophil-tolymphocyte ratio,carbohydrate antigen 19-9,and carcinoembryonic antigen as independent risk factors for malignant PCN.The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations.A nomogram score cutoff of 192.5 classified patients as having low vs.high risk of malignant PCN.The model achieved good C-statistics of 0.929(95%CI 0.890–0.968,P<0.05)and 0.951(95%CI 0.903–0.998,P<0.05)in predicting malignancy in the development and validation cohorts,respectively.NRI=0.268;IDI=0.271(P<0.001 for improvement).The DCA curve indicated that our model yielded greater clinical benefits than the comparator model.Conclusions:The nomogram showed excellent performance in predicting malignant PCN and may help surgeons select patients for detailed examination and surgery.The nomogram is freely available at https://wangjunjinnomogram.shinyapps.io/DynNomapp/.
文摘BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs.However,the indications for LN dissection are still controversial.Over the last decade,minimally invasive surgery such as laparoscopic pancreatic surgery(LPS)has been increasingly performed for pancreatic tumors including PNENs.AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODS From April 2001 to December 2019,92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital.Finally,82 patients were enrolled in this study.Using perioperative factors,we examined the predictive factors for LN metastasis in PNENs.RESULTS Among the 82 patients,the percentage of LN metastasis according to the pathological findings was 12%(10/82 cases).The median tumor size was 12 mm(range:5-90 mm).The median tumor size in the LN-positive group(37 mm)was significantly larger than that in the LN-negative group(12 mm)(P=0.0001).Multivariate analyses revealed that larger tumor size(≥20 mm)was an independent risk factor for LN metastasis(odds ratio 16.8,P=0.0062).In patients with small tumors(≤10 mm),LN metastasis was not found.CONCLUSION Larger tumor size(≥20 mm)is an independent risk factor for LN metastasis in PNENs.In smaller PNENs(≤10 mm),we may be able to choose limited surgery without LN dissection.
