PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pancreatic Intraductal Neoplasms”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Intraductal Papillary Squamous Neoplasm (IPSN) of the Pancreas: Histological and Molecular Characterization of a Novel and Distinct Intraductal Cancer Precursor.

We report 6 intraductal papillary squamous neoplasms (IPSNs) of the pancreas, a rare but distinctive tumor whose biological features remain largely unknown. Five cases were investigated using an integrated approach combining histomorphological evaluation, immunohistochemistry, and multiregional molecular profiling through whole-exome DNA sequencing and whole-transcriptome RNA sequencing. Only targeted DNA sequencing was available on a sixth recently diagnosed case. Histologically, the intraductal lesions were characterized by large, confluent papillae with fibrovascular cores lined by multilayered epithelial cells with diffuse squamous differentiation. All cases harbored a concomitant invasive carcinoma. The associated invasive carcinomas consistently included a pancreatic tubular/ductal adenocarcinoma; in 5 cases, a poorly differentiated squamous cell carcinoma was also present, the proportion/features of which met the diagnostic criteria of adenosquamous carcinoma in 2 of them. Genomic analyses revealed that IPSNs and their matched invasive carcinomas shared the majority of somatic alterations, supporting a shared clonal origin for the 2 components. Activating KRAS mutations and biallelic inactivation of CDKN2A were detected in all cases. Recurrent mutations involved members of the SWI/SNF chromatin-remodeling complex and KMT2D. Additionally, FGFR1 and MYC amplifications were identified in 2 distinct cases (1 case each). Molecular alterations restricted to the invasive component involved mediators of the transforming growth factor-β signaling pathway. Transcriptomic profiling demonstrated a basal-like expression pattern in all IPSNs and squamous cell carcinomas, although in 2 cases, the matched pancreatic tubular/ductal adenocarcinoma shifted toward a classical transcriptomic subtype. In conclusion, through integrated histological assessment and multiregional molecular sequencing, we demonstrate that IPSN represents a bona fide precursor of invasive pancreatic cancer, a new addition to the intraductal neoplasms category. This study challenges the current paradigm that pancreatic squamous epithelium plays no role in the initiation of pancreatic carcinogenesis, providing the first evidence of its involvement in early tumorigenic processes and yielding immediate implications for pancreatic tumor classification and biological understanding.

Humans↗
PubMed2025

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression.

To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.

Humans↗
PubMed2024

Comprehensive Assessment of the Intrinsic Pancreatic Microbiome.

OBJECTIVE: To sought comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. BACKGROUND: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intrapancreatic microbial dysbiosis may drive malignant transformation. METHODS: Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n = 20; IPMN, n = 20; PDAC, n = 19) and pancreatic cyst fluid (IPMN, n = 30; serous cystadenomas, n = 10; mucinous cystic neoplasm, n = 10). Assessment of bacterial DNA by quantitative polymerase chain reaction and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium were analyzed to validate findings. RESULTS: Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade and high-grade dysplasia IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in high-grade dysplasia cyst fluid. Decontamination analysis using the Clinical Proteomic Tumor Analysis Consortium database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. CONCLUSIONS: Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.

Humans↗
PubMed2026

Liquid Biopsy Differentiation of Pancreatic Cancer From Non-Cancerous Pancreatic Disease Using Dielectrophoresis-Recovered Nanoparticles Carrying Cell-Free DNA and Protein Biomarkers.

Cancer-derived extracellular vesicle (EV) nanoparticles carry important biomarkers but are difficult to recover from plasma, making EV-based diagnostics a challenge for clinical settings. Here, we demonstrate nanoparticle-based detection of pancreatic cancer using dielectrophoresis (DEP) nanoparticle recovery technology, which purifies nanoparticles from undiluted plasma and quantifies associated biomarkers. We combined both nanoparticle recovery and biomarker quantification on a single device by simultaneously collecting cell-free DNA nanoparticles and EVs followed by on-chip biomarker fluorescent staining for DNA and Glypican-1. Using a blinded cohort, these biomarkers differentiated pancreatic cancer from benign pancreatic diseases, including cysts, pancreatitis, and precancerous low-grade intraductal papillary mucinous neoplasm (IPMN) lesions, with a sensitivity of 0.92, a specificity of 0.83, and an AUC of 0.93. The AUC increased to 0.97 for patients over 50 years old. This is higher than the standard invasive endoscopic ultrasound-guided fine needle aspiration tissue biopsy procedure (AUC 0.79). This study is among the first demonstrating a combined threshold of DNA and protein levels that can distinguish pancreatic cancer from its precursor IPMN lesions. We also demonstrated the detection of early-stage pancreatic cancer and high-grade in situ precancerous lesions. This DEP-based technique shows that multiple types of cancer-derived nanoparticles can be quickly and easily recovered from plasma making it promising for future clinical diagnostics.

Humans↗
PubMed1975

Duodenoscopy and endoscopic retrograde choledochopancreatography: present position in relation to periampullary and pancreatic cancer.

Duodenoscopy and endoscopic retrograde choledochopancreatography represent a major advance in the diagnosis of periampullary and pancreatic lesions. Instruments, techniques and complications are reviewed. A combination of endoscopy and ERCP will yield diagnosis in a high proportion of patients suspected of pancreatic or ampullary carcinomata. Information is obtained which is not only of diagnostic value but is important in the surgical treatment of such patients.

Ampulla of Vater↗
PubMed1977

Experimental pancreatic carcinogenesis. I. Morphogenesis of pancreatic adenocarcinoma in the Syrian golden hamster induced by N-nitroso-bis(2-hydroxypropyl)amine.

In serial sacrifice experiment, outbred male Syrian golden hamsters were treated once weekly for life with subcutaneous injections of N-nitroso-bis(2-hydroxypropyl) amine (DIPN). The pancreas was examined by high resolution light (1-micro sections) and transmission electron microscopy. Early nonspecific changes in all pancreatic epithelial cellular elements were followed by a progressive proliferation of intra- and interlobular duct cells, with the development of multicentric foci of cystic and papillary cystic adenomas, intraductal carcinomas, and invasive ductal neoplasms. These observations were consistent with multistage morphogenesis of pancreatic adenocarcinoma of ductal origin.

Adenocarcinoma↗
PubMed1979

Ductal carcinoma of the pancreas. Rationales for total pancreatectomy.

In order to evaluate total pancreatectomy as a surgical procedure for ductal carcinoma of the pancreas, a histopathological analysis was made on 18 resected specimens with special regard to the pattern of cancer growth in the pancreatic tissue. In five of them there was no lymphatic involvement or extrapancreatic invasion, but cancer extended continuously to the tail along with the pancreatic ducts and reached the end of the ducts in three cases. All 11 patients treated with Whipple's procedure died of recurrence, while of four total pancreatectomized patients, one with continuously invasive cancer to the end of the pancreatic duct has been living more than eight years postoperatively. We believe that total pancreatectomy for this type of "intraductal spreading cancer" without invasion beyond the pancreas is indicated as a radical procedure.

Aged↗
PubMed1977

Pancreatic carcinoma. Survival following detection by ultrasonic scanning.

The survival of 28 patients with pancreatic cancer was studied following initial detection of this malignant neoplasm by ultrasonic scanning. By ultrasound examination, 24 patients had an abnormality, and 21 had a demonstrable mass. Twenty-seven patients are now deceased, and the overall survival ranged from eight days to 24 months (mean, 6.1 months). The results of this study indicate that diagnosis by ultrasonic scanning had no effect on the survival of patients with pancreatic carcinoma.

Adult↗
PubMed1979

Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats.

The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.

Animals↗
PubMed1978

Heterotransplantation into nude mice of pancreatic carcinoma induced by N-bis(2-hydroxypropyl)nitrosamine in hamsters.

Heterotransplantation into nude mice by the subcutaneous (s.c.) and intraperitoneal (i.p.) routes of hamster pancreatic ductal cell carcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) was studied. By s.c. transplantation, tumors occurred in 1 of 4 mice at the first trial, and the tumor incidence was 100% for shorter periods by serial transfer. By i.p. transplantation, the malignant potential of hamster pancreatic ductal cell carcinoma was expressed as intra-abdominal invasive tumors with bloody ascites (carcinomatous peritonitis). Tumors in nude mice basically retained the histology of the original hamster pancreatic ductal cell carcinoma.

Animals↗
PubMed1979

Operative approach to pancreatic carcinoma.

It is apparent that we are dealing with a very lethal disease. It is also apparent that this disease is increasing in frequency. In terms of treatment, it is clear that the survival figures between carcinoma of the pancreas and carcinoma of the common duct, papilla of Vater, or duodenum present great differences. The pancreatic tumors do very poorly by comparison. A comparison of the survival figures following a Whipple resection and following a bypass procedure reveal similar results, except when dealing with a very small pancreatic head lesion or when dealing with a malignancy of the papilla of Vater, lower end of common duct, or duodenum. The latter tumor types do better with a Whipple resection than a bypass. A comparison between total pancreatectomy and a Whipple resection for ductal carcinoma of the pancreatic head reveals better results in terms of length of survival following total pancreatectomy as long as one considers only Stage I or Stage II disease and excludes Stage III disease. A Whipple procedure is advocated for carcinoma of the papilla of Vater, common duct, or duodenum, because survival figures are quite good and many patients escape the need for insulin and pancreatic extract replacement. It is too early to evaluate the survival figures that follow regional pancreatectomy.

Ampulla of Vater↗
PubMed1978

Pancreas cancer -- duct cell adenocarcinoma: survival in relation to site, size, stage and type of therapy.

The records of 508 patients with cancer of the pancreas admitted to Memorial Hospital in New York from 1949 through 1972 were examined. Ten distinctive morphological types were delineated and the pathological features and response to various modes of therapy of the most common type -- duct adenocarcinoma -- were studied in 380 patients. Median survival was related to: the site of the cancer -- it was longer with tumors of the head than those of the body or tail; the size of the tumor -- cancers smaller than 3 cm were associated with over twice the survival of those with large tumors; the stage -- stage I patients had over twice the survival of those of stages II and III; and the type of therapy employed. Actuarial survival rate at one year was: with no specific therapy, 0%; with chemotherapy, 1%; after palliative by-pass surgery, 3%; following radiation therapy, 9%; and after all types of "surative" surgery, 21%. The only survivors at five years were in the "curative" surgery group, but these represented only 1% of all patients. Revolutionary changes in diagnosis and therapy will have to occur if significant increase in survival rate is to be achieved.

Antineoplastic Agents↗
PubMed1975

Morphological patterns of primary nonendocrine human pancreas carcinoma.

The study of histological sections of 406 cases of nonendocrine pancreas carcinoma at Memorial Hospital indicated that morphological patterns of pancreas carcinoma could be delineated as follows: duct cell adenocarcinoma (76%), giant-cell carcinoma (5%), microadenocarcinoma (4%), adenosquamous cancinoma (4%), mucinous adenocarcinoma (2%), anaplastic carcinoma (2%), cystadenocarcinoma (1%), acinar cell carcinoma (1%), carcinoma in childhood (under 1%), unclassified (7%). In 195 cases of patients with pancreas carcinoma, search was made for changes in the pancreas duct epithelium and these were compared to duct epithelium in a control group of 100 pancreases from autopsies of patients with nonpancreatic cancer. The following incidences were found for pancreas cancer and nonpancreatic cancer, respectively: mucous cell hypertrophy, 39 versus 28%; pyloric gland metaplasia, 28 and 17%; epidermoid metaplasia, 6 and 12%; papillary hyperplasia, 42 and 12%; atypical duct hyperplasia, 14% and none; cancinoma in situ in 19% and none in the control group. Mucin in the majority of pancreas cancers suggested that the cell type of origin of the common pancreas cancer is the mucin-producing duct epithelium. The association of atypias and carcinomas in situ in the patients with pancreas carcinoma implies, by analogy to other organs, that there may be a significant latent period between the appearance of carcinoma in situ and the grossly recognizable pancreas cancer.

Adenocarcinoma↗
PubMed1977

Early lesions of pancreatic ductal carcinoma in the hamster model.

Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system.

Animals↗
PubMed1977

Improvement of pancreatic cancer model by modified treatment with N-nitroso-bis (2-oxopropyl) amine.

Comparative studies were conducted in 2 groups of Syrian golden hamsters treated with N-nitroso-bis (2-oxopropyl)amine (BOP) weekly for life (group A) or weekly for 6 weeks (group B), and sacrificed at 2-week intervals. Pancreatic neoplasms developed as early as 8 weeks (group B) and 10 weeks (group A); however, in group B there were fewer, smaller lesions, well-differentiated morphologically. Liver neoplasms occurred only in group A, while gallbladder and kidney tumors were seen in both groups. A lower incidence of pulmonary adenomas was found in group B than in group A, which also had pulmonary carcinomas. The results indicate a further advance in the development of a pancreatic cancer model.

Adenocarcinoma↗