scholarly journals Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival

2020 ◽  
Vol 29 (3) ◽  
pp. 391-398
Author(s):  
Livia Petrusel ◽  
Maria Bilibou ◽  
Vasile Drug ◽  
Daniel Corneliu Leucuta ◽  
Radu Seicean ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
Neuroendocrine Tumors ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
History Of ◽  
Predictive Role ◽  
New Onset

Background and Aims: Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival. Methods: We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival. Results: 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001). Conclusion: Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

scholarly journals How pancreatic adenocarcinoma might cause diabetes? The role of TGF- β

2021 ◽  
pp. 05-10
Author(s):  
Hanan F. Aly
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
De Novo ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Β Cells ◽  
Selective Depletion ◽  
New Onset

Pancreatic ductal adenocarcinoma (PDAC) is a deadly sickness that stays incurable due to past due diagnosis, which renders any healing intervention challenging. Most PDAC sufferers expand de novo diabetes, which exacerbates their morbidity and mortality. How PDAC triggers diabetes continues to be unfolding. Using a mouse version of KrasG12D-pushed PDAC, which faithfully recapitulates the development of the human sickness, we determined a large and selective depletion of β-cells, taking place very early on the degrees of preneoplastic lesions. Mechanistically, it turned into observed that accelerated TGF beta (TGF-β) signaling throughout PDAC development induced erosion of β-mobileular mass thru apoptosis. Suppressing TGF-β signaling, both pharmacologically thru TGF-β immunoneutralization or genetically thru deletion of Smad4 or TGF-β kind II receptor (TβRII), afforded size able safety in opposition to PDAC-pushed β-mobileular depletion. From a translational perspective, each activation of TGF-β signaling and depletion of β-cells often arise in human PDAC, imparting a mechanistic cause of the pathogenesis of diabetes in PDAC sufferers, and similarly implicating new- onset diabetes as a capability early prognostic marker for PDAC. In this mini review we try to analyze the principle relationships between pancreatic cancer and diabetes and vice versa in addition to the implication of TGF-β signaling as a likely goal for attenuating diabetes in pancreatic most cancers patients.

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Perioperative Morbidity ◽  
Log Rank Test ◽  
Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

Malignant Lesions of the Pancreas

2016 ◽  
Author(s):  
Omer Basar ◽  
Abdurrahman Kadayifci ◽  
William R. Brugge
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neuroendocrine Tumors ◽  
Needle Aspiration ◽  
Ductal Adenocarcinoma ◽  
Key Words Pancreatic Cancer ◽  
Cross Sectional ◽  
Painless Jaundice ◽  
Cross Sectional Imaging ◽  
Malignant Lesions

Malignant lesions of pancreas are the fourth most common cause of cancer death in men and women. The majority of pancreatic cancer results from malignant transformation of the exocrine pancreas, and nearly 90% are ductal adenocarcinomas (pancreatic ductal adenocarcinoma, PDAC). Patients typically present at an advanced stage with a poor prognosis. PDAC is acquired through the accumulation of multiple genetic mutations. The major risk factors for PDAC include age, smoking, chronic pancreatitis, diabetes mellitus (DM), male gender, and African American race. Less commonly, hereditary syndromes may be implicated. The clinical presentation may involve weight loss, abdominal discomfort, and or jaundice. Painless jaundice, depression, and new-onset DM can suggest the diagnosis. Cross-sectional imaging has utility in diagnosis and staging. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is a standard approach to tissue diagnosis. Endoscopic retrograde cholangiopancreaticography with palliative stenting can relieve obstructive jaundice. Surgical resection is the only potentially curative option in the management of PDAC but only a minority of patients are candidates for resection. The prognosis for most patients with pancreatic adenocarcinoma is poor. Less common pancreatic malignant lesions such as neuroendocrine tumors (NETs) have a much more favorable prognosis.   Key words: Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic NETs (PNETs); Pancreatic neuroendocrine tumors

scholarly journals Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers

2012 ◽  
Vol 50 (4) ◽  
Author(s):  
Elad Sharon ◽  
Jingli Zhang ◽  
Kevin Hollevoet ◽  
Seth M. Steinberg ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Pancreatic Disease ◽  
Ductal Adenocarcinoma ◽  
Biliary Carcinoma ◽  
Healthy Donors ◽  
Significant Difference ◽  
Individual Participant ◽  
Pair Wise Comparison

AbstractTumor mesothelin overexpression is present in different malignancies, including the majority of patients with pancreatic or biliary cancers. The objective of this study was to evaluate the use of shed serum mesothelin and megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these cancers.A total of 151 individuals, divided into five groups, were retrospectively analyzed: healthy donors (n=15), patients with benign non-pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF concentrations were measured in serum with the Mesomark™ and Human MPF ELISA, respectively.Mesothelin and MPF concentrations did not significantly differ among the five individual participant groups (p=0.34, p=0.33, respectively), nor did any other combination and pair-wise comparison of the participant groups demonstrated a significant difference in biomarker concentrations. In patients with pancreatic cancer, mesothelin or MPF concentrations were not associated with tumor stage (p=0.87, p=0.48, respectively) or differentiation grade (p=0.73, p=0.52, respectively).Serum mesothelin and MPF concentrations, measured with standard available ELISAs, were not specific for benign or pancreatic disease. Both biomarkers were not elevated in patients with pancreatic or biliary cancers, and consequently do not appear to be useful biomarkers for these malignancies.

Association of BRCA-mutant pancreatic cancer with high tumor mutational burden (TMB) and higher PD-L1 expression.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4133-4133 ◽  
Author(s):  
Andreas Seeber ◽  
Alberto Puccini ◽  
Joanne Xiu ◽  
Richard M. Goldberg ◽  
Axel Grothey ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
Brca Mutation ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Brca Mutations ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Brca2 Mutations

4133 Background: In the U.S. 56,000 Americans are expected to be diagnosed with pancreatic cancer in 2019. Prognosis in pancreatic cancer is poor. Therefore, new treatment strategies are urgently needed to improve survival. BRCA1 and BRCA2 mutations have been described to be the most common genetic mutations involved in familial pancreatic cancer. The optimal treatment regimen to use in BRCA-mutant pancreatic cancer has still to be established. Moreover, no data are available on association of BRCA mutation with immune-associated markerssuch as tumor mutational burden (TMB), microsatellite instability (MSI) or PD-L1 expression. Methods: Tumor samples of 2824 patients with pancreatic ductal adenocarcinoma were analyzed for BRCA mutation by NGS and for other genes (MiSeq on 47 genes, NextSeq on 592 genes) at Caris Life Sciences, Phoenix, AZ. TMB was calculated based on somatic nonsynonymous missense mutations, and MSI was evaluated by NGS of known MSI loci. PD-L1 expression was evaluated using immunohistochemistry. Results: In 4.4% (N = 124) of all pancreatic adenocarcinoma samples BRCA mutations were detected. BRCA2 mutations were more common: 3.1% (N = 89) vs 1.1% BRCA1 mutations (N = 35). BRCA mutations were associated with younger age ( BRCA1: 61 yrs for mutated vs. 64 for wild-type, p = 0.07; BRCA2: 61 yrs vs. 64, p = 0.002; both: p < 0.001). BRCA mutations were associated with higher MSI-H frequency (4.8% vs. 1.2%, p = 0.002), elevated PD-L1 expression (22% vs. 11%, p < 0.001) and higher TMB (mean 8.7 mut/MB vs. 6.5, p < 0.001); the differences remain significant in MSS tumors (p < 0.05). BRCA-mutant pancreatic carcinomas showed a significantly lower mutation frequencies in TP53 (59% vs 73%, p = 0.001), CKDN2A (13% vs 25%, p = 0.006), but higher frequencies in APC (6.5% vs 2.2%), KMT2A (1.9% vs 0.2%), AMER1 (1.9 vs 0.5%) and SETD2 (3.7% vs 0.4%) mutations (p < 0.05 for all comparisons). Conclusions: BRCA mutations are found in a significant subgroup of pancreatic ductal adenocarcinoma and these carcinomas are associated with an immunogenic tumor profile. These data suggest evaluating PARP inhibitors in combination with immunotherapy in patients with BRCA-mutant pancreatic adenocarcinoma especially in tumors that are MSS.

scholarly journals Family History of Cancer and Tobacco Exposure in Index Cases of Pancreatic Ductal Adenocarcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
R. Lochan ◽  
A. K. Daly ◽  
H. L. Reeves ◽  
R. M. Charnley
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Tobacco Exposure ◽  
Degree Relative ◽  
Family History Questionnaire ◽  
Increased Risk ◽  
History Of ◽  
History Of Cancer

Aim. To examine interaction between history of cancer in first-degree relatives and tobacco smoking in index patients of pancreatic adenocarcinoma.Methods. We carried out a case-control involving 113 patients with pancreatic adenocarcinoma and 110 controls over a 12-month period at the Freeman Hospital, Newcastle upon Tyne, UK. They were all administered a detailed tobacco exposure questionnaire and a family history questionnaire. We calculated cumulative tobacco exposure and risk for pancreas cancer.Results. Both smokers (OR 3.01 (95% CI: 1.73 to 5.24)) and those with a family history of malignancy (OR 1.98 (95% CI: 1.15–3.38)) were more likely to develop pancreatic cancer. Having more than one first-degree relative with cancer did not significantly further increase the risk of pancreatic cancer. Amongst pancreatic cancer cases, cumulative tobacco exposure was significantly decreased () in the group of smokers (current and ex-smokers) who had a family history of malignancy [mean (SD): 30.00 (24.77) pack-years versus 44.69 (28.47) pack-years with no such history].Conclusions. Individuals with a family history of malignancy are at an increased risk of pancreatic cancer. Furthermore, individuals with a family history of malignancy and who smoke appear to require a lesser degree of tobacco exposure for the development of pancreatic cancer.

Positive association between Helicobacter pylori infection and pancreatic cancer: A case-control study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16243-e16243
Author(s):  
Steve Otieno ◽  
Amit L Jain ◽  
Omar Mohammed ◽  
Jay R Patel ◽  
John Collyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Helicobacter Pylori ◽  
Pancreatic Adenocarcinoma ◽  
Case Control Study ◽  
Positive Association ◽  
Case Control ◽  
Multivariate Logistic Regression ◽  
History Of ◽  
Control Study

e16243 Background: Pancreatic adenocarcinoma is a malignancy with a very poor prognosis. The 5-year overall survival is about 9%. Helicobacter pylori ( H. pylori) is a known risk factor for gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Whether H.pylori is a risk factor for pancreatic adenocarcinoma is still unclear. Previous observational retrospective studies trying to see if there is an association between H.pylori and pancreatic adenocarcinoma have used serology as a marker for H.pylori infection, but these have yielded mixed results. We seek to probe the association of H.pylori infection and pancreatic adenocarcinoma in a case-control study using histology for H.pylori bacteria from esophagogastroduodenoscopy (EGD) biopsies. Methods: A database for patients diagnosed with pancreatic adenocarcinoma at the Veterans Affairs Medical Center in Memphis, TN, from 1988 to 2018 was analyzed to obtain suitable cases. Pathology was reviewed to confirm the diagnosis and then the charts were reviewed to determine if the patient had undergone an EGD and if biopsies done obtained were tested for H.pylori. H.pylori positivity was determined using Steiner staining of the biopsy samples. 402 charts were reviewed and 51 cases meeting the above criteria were obtained. Controls were obtained by reviewing charts for all EGDs that were tested for H.pylori. Care was taken to make sure patients did not have any history of pancreatobiliary malignancy. 130 matched controls fit the screening criteria. Univariate and multivariate logistic regression analysis was done to analyze the risk factors. Results: Significantly more subjects in the case group (53%) were found to have H.Pylori infection compared to the control group (18%). Risk factors associated with pancreatic cancer in the literature, including age, race, smoking history, obesity, alcohol consumption, chronic pancreatitis, and diabetes, were analyzed using multivariate logistic regression. The results revealed that pancreatic cancer was significantly associated with a positive family history of pancreatic cancer (OR = 11.2, 95%CI 2.8-44.4, p = 0.001) and H.Pylori infection (OR = 5.5), 95%CI 2.4-12.7,p < 0.001). Conclusions: A positive association was found between H.pylori infection and pancreatic adenocarcinoma.

scholarly journals Pancreatic ductal adenocarcinoma in a Moroccan population: analysis of six years experience

2018 ◽  
Vol 5 (5) ◽  
pp. 1628
Author(s):  
Aziz Bazine ◽  
Mohamed Fetohi ◽  
Mehdi Tores ◽  
Rachid Tanz ◽  
Moulay El Hassan Tahiri ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Military Hospital ◽  
Female Ratio ◽  
Family History Of Diabetes ◽  
Moroccan Population ◽  
Duodenal Stent ◽  
History Of

Background: Few studies have been done to investigate pancreatic cancer in Morocco. Therefore, the aim of our study was to describe the epidemiological, clinical and therapeutic features of pancreatic ductal adenocarcinoma in Moroccan population.Methods: Author retrospectively reviewed the medical data of pancreatic ductal adenocarcinoma patients presented to the Medical Oncology Department of the Military Hospital Moulay Ismail in Meknes, Morocco, from January 2011 to December 2016.Results: The study included 67 cases of pancreatic ductal adenocarcinoma. The mean age of patients was 61.24±10.35 years. Male/female ratio was 3.2/1. 20.9% of patients were cigarette smokers, 10.5% alcoholics. 23.9% diabetics, 3.0% with a positive family history of pancreatic cancer and 25.4% with a family history of diabetes mellitus. The main symptoms for consultation were weight loss (68.6%), abdominal pain (64.2%), jaundice (53.7%) and vomiting (25.4%). The tumour was located to the pancreatic head in 71.6% of cases. Stage IV disease was the most common stage representing 47.8% of patients. Biliary and duodenal stent placements were respectively performed in 10.4% and 3.0% of patients. 23.9% of patients underwent curative surgery, 7.5% had palliative surgery and 86.6% received chemotherapy. The median overall survival for the entire cohort was 9.3 months (95% CI 7.2-12.1 months) with a median follow-up of 9.7 months (2-63 months).Conclusions: The data on pancreatic ductal adenocarcinoma in Moroccan population are similar to the epidemiologic literature data. With multimodality treatments, the results in terms of survival benefit seem to be similar to those in Asian and Caucasian populations.

scholarly journals Comprehensive Analysis of Prognostic and Immune Infiltrates for CBX Family in Human Pancreatic Adenocarcinoma

2021 ◽  
Author(s):  
qian li ◽  
lei fu ◽  
Dao yuan wu ◽  
feng ju wang
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Immune Cell ◽  
Tumor Stage ◽  
High Expression ◽  
Malignant Tumours ◽  
Expression Levels ◽  
Logistic Analysis ◽  
Regulation Of Cell Cycle

Abstract Background: Pancreatic adenocarcinoma (PAAD) is one of the common Malignant tumours of the digestive tract worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and play key roles in various biological processes. However, the expression level, biological function and immune infiltration of different E2Fs in PAAD and prognostic roles of various CBX family members in Pancreatic adenocarcinoma (PAAD) remain unclear.Methods: In this study, we used multiple bioinformatics tools including Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TIMER and R Tools to analyze expression levels, prognostic value, genetic alteration, immune cell infiltration and risk factors of CBXs in Pancreatic adenocarcinoma patients. Furthermore, we confirmed the expression of CBX3 on clinic pathological specimens by immunohistochemistry.Results: The expression levels of CBX1/3/5/8 were significantly elevated in PAAD tissues, and the high expression of CBX1/5/6/7 was associated with the tumor stage of patients. Higher mRNA expression of CBX2/6/7 and CBX8 were significantly associated with favorable OS of pancreatic cancer patients, while higher expression of CBX3 was significantly associated with short OS. We verified the high expression of CBX3 in pancreatic cancer tissues on clinicopathological specimens. Multivariate logistic analysis demonstrated that high mRNA expressions of CBX3 and low expression of CBX8 were independent risk factors for shorter survival of pancreatic carcinoma patients. The functions of CBXs and its neighboring proteins are mainly related to negative regulation of cell cycle process, PcG protein complex, histone binding and regulating pluripotency of stem cells signaling pathways. We also found that the expression of CBXs was significantly correlated with immune infiltrates.Conclusions: Our study may provide new insights into the selection of immunotherapeutic targets and prognostic biomarkers and revealed that CBX3/8 may represent a clinically useful biomarker for predicting overall survival in patients with PAAD.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

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