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
Objective: To investigate the significance of abnormal E-cadherin and β-catenin expression in pancreatic intraepithelial neoplasia (PanIN) and pancreatic adenocarcinoma. Methods:Pancreatic samples of 156 cases were r...Objective: To investigate the significance of abnormal E-cadherin and β-catenin expression in pancreatic intraepithelial neoplasia (PanIN) and pancreatic adenocarcinoma. Methods:Pancreatic samples of 156 cases were retrospectively studied from surgery and autopsy in Changhai hospital from January 2001 to December 2003, from which tissue microarray blocks containing 129 PanIN-1A lesions, 104 PanIN-1B lesions, 22 PanIN-2 lesions, 11 PanIN-3 lesions, and 121 pancreatic ductal adenocarcinomas and corresponding paracancerous tissues were constructed. EnVision method of immunohistochemistry was used to detect the E-cadherin and β-catenin expression. The correlation between the abnormal E-cadherin and β-catenin expression and clinicopathological parameters was analysed. Results: The rate of E-cadherin abnormal expression was significant in ductal adenocarcinomas compared with the PanIN lesions and normal ducts(64.5%,32.3%,0%), moreover, the rate of E-cadherin abnormal expression was in relation to differentiation, lymph node metastasis and perineural invasion of pancreatic adenocarcinoma(P<0.05). There was remarkable increase in the E-cadherin cytoplasmic expression in PanIN lesions and ductal adenocarcinomas compared with normal ducts. The rate of β-catenin abnormal expression was found to be related with lymph node metastasis and perineural invasion of pancreatic adenocarcinoma(P<0.05). The expression of β-catenin cytoplasm and/or nucleus was significant in high-grade PanIN lesions and ductal adenocarcinomas compared with low grade PanIN lesions or normal ducts(P<0.05). There was a positive relationship between the E-cadherin and β-catenin expression in PanIN lesions and ductal adenocarcinomas (P<0.01, P<0.05). Conclusion: There is aberration in the expression of the E-cadherin and β-catenin in PanIN lesions and ductal adenocarcinomas, suggesting the E-cadherin and β-catenin changes is not only related with the biological action and prognosis, but also involved in pancreatic carcinogenesis.展开更多
AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential biomarkers.METHO...AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential biomarkers.METHODS:Sixty adult male Sprague Dawley rats were randomized into three groups.The rats had DMBA implanted into their pancreas for one(n=20)or two months(n=20)or assigned to the normal group(n =20).The rats were killed after one or two months,and were evaluated histopathologically.Three tissue samples from each group of rats with either normal pancreas,PanIN(PanIN-2)or PC were examined by 2D-DIGE.The different expression spot features were analyzed by matrix-assisted laser desorption/ionizationtime of flight/time of flight(MALDI-TOF/TOF)tandem mass spectrometry.The expression of enolase 1,a differentially expressed protein,was identified by immu-nohistochemistry.RESULTS:There was significant difference in the proportions of neoplastic changes between the 1-and 2-mogroups(P=0.0488).There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group(P=0.0309).No neoplastic changes were observed in any of the animals in the normal group.Enolase 1,pancreatic ELA3B,necdin,Hbp23,CHD3,hnRNP A2/B1,Rap80,and Gnb2l1 were up-regulated in the PanIN and PC tissues,and CEL,TPT1,NME2,PCK2,an unnamed protein product,and glycine C-acetyltransferase were down-regulated in the PanIN and PC tissues.The immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and humans.CONCLUSION:The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.展开更多
BACKGROUND: Ectopic pancreatic tissue is relatively uncommon, and is characterized as pancreatic tissue with no contact with the normal pancreas, and with its own ductal system and blood supply. It is usually asympto...BACKGROUND: Ectopic pancreatic tissue is relatively uncommon, and is characterized as pancreatic tissue with no contact with the normal pancreas, and with its own ductal system and blood supply. It is usually asymptomatic, and can be incidentally diagnosed by conventional imaging studies. METHOD: A 69-year-old woman with a prior history of bilateral breast carcinoma presented with ectopic pancreatic intraepithelial neoplasia (PanIN) that was identified incidentally in the small bowel during an oncological resection of a synchronous primary pancreatic adenocarcinoma, and renal cell carcinoma. RESULTS: The patient underwent subtotal pancreatectomy with splenectomy, regional lymphadenectomy, radical left nephrectomy, and small bowel resection with primary anastomosis of ectopic PanlN-2. She had an uneventful hospitalization and was discharged home on postoperative day 7. CONCLUSIONS: The occurrence of ectopic PanIN is extremely unusual with only few cases previously reported in the literature. The need for negative margins after surgical resection of ectopic PanIN lesions remains controversial.展开更多
Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancre...Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.展开更多
High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatograph...High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.展开更多
Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse panc...Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.展开更多
BACKGROUND:7,12-dimethylbenzanthracene(DMBA)-induced pancreatic intraepithelial neoplasia(PanIN)and pancreatic cancer in rats provide a classic model for uncovering the molecular mechanisms underlying pancreatic ...BACKGROUND:7,12-dimethylbenzanthracene(DMBA)-induced pancreatic intraepithelial neoplasia(PanIN)and pancreatic cancer in rats provide a classic model for uncovering the molecular mechanisms underlying pancreatic cancer.However,this model has not been characterized genetically,and in particular,the major genetic alterations in the p16 gene are unknown.METHODS: Lesions of PanlN and pancreatic cancer were induced with DMBA implantation in 40 rats, and control pancreatic tissue was obtained from 10 age-matched rats without exposure to DMBA. Pancreatic tissue was harvested three months after DMBA implantation and DNA was extracted. Homozy- gous deletions and point mutations of the pl6 (exons 1 and 2) gene were detected by PCR amplification and direct sequencing. RESULTS: DMBA implantation in the 40 rats induced 26 Pan- INs and 9 carcinomas. The overall frequency of p 16 alterations in the pancreatic tissue of these rats was 42.86% (15/35), and the changes were point mutations, not homozygous deletions. p16 mutations were present in 30.77% (8/26) of the rats with PanIN and 77.78% (7/9) of the rats with carcinoma (P〈0.05). The increasing incidence of p16 alterations was detected in 20.00% (1/5) of PanIN-1, 28.57% (2/7) of PanIN-2 and 35.71% (5/14) of PanIN-3 lesions. CONCLUSION: Our findings indicated that p16 alteration is a common event in the carcinogenesis of this model and that the mutation pattern is analogous to that of human lesions.展开更多
Objective:To study the relationship of high-risk human papilloma virus (HPV) infection with mitogen-activated protein kinase/extracellular signal-regulated kinase 3 (MEKK3) and nuclear factorκB (NF-κB) expression in...Objective:To study the relationship of high-risk human papilloma virus (HPV) infection with mitogen-activated protein kinase/extracellular signal-regulated kinase 3 (MEKK3) and nuclear factorκB (NF-κB) expression in cervical intraepithelial neoplasia tissue.Methods:125 cases of cervical biopsy specimens between May 2013 and March 2016 were collected. The cervical inflammation specimens, cervical intraepithelial neoplasia specimens and cervical cancer specimens were included in inflammation group, CIN group and malignant group respectively. HPV-DNA typing detection kits were used to determine HPV typing, immunohistochemical kits were used to determine MEKK3 and NF-κB protein expression, and fluorescent quantitative PCR kits were used to determine the mRNA expression of MEKK3, NF-κB and downstream molecules.Results: MEKK3 and NF-κB protein expression in high-risk HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05), and MEKK3, NF-κB, Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in high-risk type HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05);Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in tissue with positive MEKK3 and NF-κB expression were significantly higher than those in tissue with negative MEKK3 and NF-κB expression (P<0.05).Conclusions:High-risk HPV infection will increase the expression of proliferation genes Bcl-2, XIAP and Bmi-1 as well as invasion genes TGF-β and Vimentin in cervical intraepithelial neoplasia tissue through MEKK3/NF-κB pathway.展开更多
Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due ...Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.展开更多
Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who...Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.展开更多
AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected...AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.展开更多
Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of s...Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.展开更多
BACKGROUND: High-grade pancreatic intraepithelial neoplasia(Pan IN-3), a precursor of pancreatic ductal adenocarcinoma(PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine t...BACKGROUND: High-grade pancreatic intraepithelial neoplasia(Pan IN-3), a precursor of pancreatic ductal adenocarcinoma(PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms(IPMNs).METHODS: A retrospective review of a tertiary care center pathology database(1/2000-6/2014) was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS: A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74(16.2%) patients who either had PDAC(n=67) or main duct(MD)-IPMN(n=7). Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival(OS) for pancreata with Pan IN-3 lesions was significantly better than those without(OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04). Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death(HR=0.43; 95% CI: 0.23-0.82; P=0.01).CONCLUSIONS: Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.展开更多
BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Curren...BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.展开更多
Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To bet...Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.展开更多
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.
基金Supported by Changhai Hospital Subject ConstructProgram.
文摘Objective: To investigate the significance of abnormal E-cadherin and β-catenin expression in pancreatic intraepithelial neoplasia (PanIN) and pancreatic adenocarcinoma. Methods:Pancreatic samples of 156 cases were retrospectively studied from surgery and autopsy in Changhai hospital from January 2001 to December 2003, from which tissue microarray blocks containing 129 PanIN-1A lesions, 104 PanIN-1B lesions, 22 PanIN-2 lesions, 11 PanIN-3 lesions, and 121 pancreatic ductal adenocarcinomas and corresponding paracancerous tissues were constructed. EnVision method of immunohistochemistry was used to detect the E-cadherin and β-catenin expression. The correlation between the abnormal E-cadherin and β-catenin expression and clinicopathological parameters was analysed. Results: The rate of E-cadherin abnormal expression was significant in ductal adenocarcinomas compared with the PanIN lesions and normal ducts(64.5%,32.3%,0%), moreover, the rate of E-cadherin abnormal expression was in relation to differentiation, lymph node metastasis and perineural invasion of pancreatic adenocarcinoma(P<0.05). There was remarkable increase in the E-cadherin cytoplasmic expression in PanIN lesions and ductal adenocarcinomas compared with normal ducts. The rate of β-catenin abnormal expression was found to be related with lymph node metastasis and perineural invasion of pancreatic adenocarcinoma(P<0.05). The expression of β-catenin cytoplasm and/or nucleus was significant in high-grade PanIN lesions and ductal adenocarcinomas compared with low grade PanIN lesions or normal ducts(P<0.05). There was a positive relationship between the E-cadherin and β-catenin expression in PanIN lesions and ductal adenocarcinomas (P<0.01, P<0.05). Conclusion: There is aberration in the expression of the E-cadherin and β-catenin in PanIN lesions and ductal adenocarcinomas, suggesting the E-cadherin and β-catenin changes is not only related with the biological action and prognosis, but also involved in pancreatic carcinogenesis.
基金Supported by Shanghai Science and Technology Commission, No.06JC14047
文摘AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential biomarkers.METHODS:Sixty adult male Sprague Dawley rats were randomized into three groups.The rats had DMBA implanted into their pancreas for one(n=20)or two months(n=20)or assigned to the normal group(n =20).The rats were killed after one or two months,and were evaluated histopathologically.Three tissue samples from each group of rats with either normal pancreas,PanIN(PanIN-2)or PC were examined by 2D-DIGE.The different expression spot features were analyzed by matrix-assisted laser desorption/ionizationtime of flight/time of flight(MALDI-TOF/TOF)tandem mass spectrometry.The expression of enolase 1,a differentially expressed protein,was identified by immu-nohistochemistry.RESULTS:There was significant difference in the proportions of neoplastic changes between the 1-and 2-mogroups(P=0.0488).There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group(P=0.0309).No neoplastic changes were observed in any of the animals in the normal group.Enolase 1,pancreatic ELA3B,necdin,Hbp23,CHD3,hnRNP A2/B1,Rap80,and Gnb2l1 were up-regulated in the PanIN and PC tissues,and CEL,TPT1,NME2,PCK2,an unnamed protein product,and glycine C-acetyltransferase were down-regulated in the PanIN and PC tissues.The immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and humans.CONCLUSION:The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.
文摘BACKGROUND: Ectopic pancreatic tissue is relatively uncommon, and is characterized as pancreatic tissue with no contact with the normal pancreas, and with its own ductal system and blood supply. It is usually asymptomatic, and can be incidentally diagnosed by conventional imaging studies. METHOD: A 69-year-old woman with a prior history of bilateral breast carcinoma presented with ectopic pancreatic intraepithelial neoplasia (PanIN) that was identified incidentally in the small bowel during an oncological resection of a synchronous primary pancreatic adenocarcinoma, and renal cell carcinoma. RESULTS: The patient underwent subtotal pancreatectomy with splenectomy, regional lymphadenectomy, radical left nephrectomy, and small bowel resection with primary anastomosis of ectopic PanlN-2. She had an uneventful hospitalization and was discharged home on postoperative day 7. CONCLUSIONS: The occurrence of ectopic PanIN is extremely unusual with only few cases previously reported in the literature. The need for negative margins after surgical resection of ectopic PanIN lesions remains controversial.
文摘Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.
文摘High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.
文摘Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.
基金supported by a grant from the National Natural Science Foundation of China(30972903)
文摘BACKGROUND:7,12-dimethylbenzanthracene(DMBA)-induced pancreatic intraepithelial neoplasia(PanIN)and pancreatic cancer in rats provide a classic model for uncovering the molecular mechanisms underlying pancreatic cancer.However,this model has not been characterized genetically,and in particular,the major genetic alterations in the p16 gene are unknown.METHODS: Lesions of PanlN and pancreatic cancer were induced with DMBA implantation in 40 rats, and control pancreatic tissue was obtained from 10 age-matched rats without exposure to DMBA. Pancreatic tissue was harvested three months after DMBA implantation and DNA was extracted. Homozy- gous deletions and point mutations of the pl6 (exons 1 and 2) gene were detected by PCR amplification and direct sequencing. RESULTS: DMBA implantation in the 40 rats induced 26 Pan- INs and 9 carcinomas. The overall frequency of p 16 alterations in the pancreatic tissue of these rats was 42.86% (15/35), and the changes were point mutations, not homozygous deletions. p16 mutations were present in 30.77% (8/26) of the rats with PanIN and 77.78% (7/9) of the rats with carcinoma (P〈0.05). The increasing incidence of p16 alterations was detected in 20.00% (1/5) of PanIN-1, 28.57% (2/7) of PanIN-2 and 35.71% (5/14) of PanIN-3 lesions. CONCLUSION: Our findings indicated that p16 alteration is a common event in the carcinogenesis of this model and that the mutation pattern is analogous to that of human lesions.
文摘Objective:To study the relationship of high-risk human papilloma virus (HPV) infection with mitogen-activated protein kinase/extracellular signal-regulated kinase 3 (MEKK3) and nuclear factorκB (NF-κB) expression in cervical intraepithelial neoplasia tissue.Methods:125 cases of cervical biopsy specimens between May 2013 and March 2016 were collected. The cervical inflammation specimens, cervical intraepithelial neoplasia specimens and cervical cancer specimens were included in inflammation group, CIN group and malignant group respectively. HPV-DNA typing detection kits were used to determine HPV typing, immunohistochemical kits were used to determine MEKK3 and NF-κB protein expression, and fluorescent quantitative PCR kits were used to determine the mRNA expression of MEKK3, NF-κB and downstream molecules.Results: MEKK3 and NF-κB protein expression in high-risk HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05), and MEKK3, NF-κB, Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in high-risk type HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05);Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in tissue with positive MEKK3 and NF-κB expression were significantly higher than those in tissue with negative MEKK3 and NF-κB expression (P<0.05).Conclusions:High-risk HPV infection will increase the expression of proliferation genes Bcl-2, XIAP and Bmi-1 as well as invasion genes TGF-β and Vimentin in cervical intraepithelial neoplasia tissue through MEKK3/NF-κB pathway.
文摘Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.
文摘Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.
文摘AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.
文摘Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.
文摘BACKGROUND: High-grade pancreatic intraepithelial neoplasia(Pan IN-3), a precursor of pancreatic ductal adenocarcinoma(PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms(IPMNs).METHODS: A retrospective review of a tertiary care center pathology database(1/2000-6/2014) was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS: A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74(16.2%) patients who either had PDAC(n=67) or main duct(MD)-IPMN(n=7). Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival(OS) for pancreata with Pan IN-3 lesions was significantly better than those without(OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04). Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death(HR=0.43; 95% CI: 0.23-0.82; P=0.01).CONCLUSIONS: Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.
基金the Science and Research Office of Shandong First Medical University Affiliated Provincial Hospital(approved number SWYX:No.2024-294).
文摘BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.
基金Supported by the Associazione Italiana Ricerca sul Cancro,No.12182Cassini Project
文摘Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.