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.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in prevalence.Early detection of malignant PCNs is crucial for improving prognosis;however,current diagnostic methods are insufficient for accurately identifying malignant PCNs.Here,we utilized mass spectrometry(MS)-based glycosite-and glycoform-specific glycoproteomics,combined with proteomics,to explore potential cyst fluid diagnostic biomarkers for PCN.The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated,and its characteristics during the malignant transformation of PCN were analyzed.Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN,a group of cyst fluid glycoprotein biomarkers was identified.Through parallel reaction monitoring(PRM)-based targeted glycoproteomic analysis,we validated these chosen glycoprotein biomarkers in a second cohort,ultimately confirming N-glycosylated PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0),CEACAM5(Asn-197,H5N4F0S0)and ATP6V0A4(Asn-367,H6N4F0S0)as promising diagnostic biomarkers for distinguishing malignant PCNs.These glycoprotein biomarkers exhibited robust performance,with an area under the curve ranging from 0.771 to 0.948.In conclusion,we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN.These findings hold significant clinical implications,providing valuable insights for PCN decision-making,and potentially offering therapeutic targets for PCN treatment.

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy

Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for risk prediction value was 2.88, and the cumulative risk curves of each cohort showed significant differences between the high- and low-risk groups. Conclusions: The nomogram could predict and identify the NODM risk population, and provide guidance to physicians in monitoring and controlling blood glucose levels in PBLML patients after DP.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma(PDAC)has poor prognosis due to limited therapeutic options.This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets.We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness.HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4.Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC(log-rank P=0.036;HR=1.60,95%CI=1.03–2.47).We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.Furthermore,Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC(log-rank P=0.022;HR=0.31,95%CI=0.14–0.68)but not in patients with SMAD4-normal PDAC.Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway.These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Value of contrast-enhanced ultrasound combined with percutaneous ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic lesions

Background:Contrast-enhanced ultrasound(CEUS)can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion.This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound(US)-guided fine-needle aspiration(FNA)with or without CEUS assessment.Methods:Clinical,imaging,and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital,with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated.Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy.According to FNA cytology diagnoses,we combined non-diagnostic,neoplastic,and negative cases into a negative category.The positive category included malignant,suspicious,and atypical cases.The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months.The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of US-FNA were evaluated between the two groups.Results:This study enrolled 107 male and 74 female patients(average age:60 years).There were 58 cases in the US group and 123 cases in the CEUS group.No statistically significant differences in age,gender,or lesion size were found between the two groups.The diagnostic accuracy of the CEUS group was 95.1%(117/123),which was higher than the 86.2%(50/58)observed in the US group(P=0.036).The sensitivity,specificity,PPV,and NPV of the CEUS group were increased by 7.5%,16.7%,3.4%,and 18.8%,respectively,compared with the US group.However,the differences of the two groups were not statistically significant.Conclusions:Compared with the conventional US,the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy,especially for some complicated FNA cases.

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.