Staging Of Pancreatic Cancer Research Articles

Screening of pancreatic cancer: Target population, optimal timing and how?

Pancreatic cancer patients usually present at a late stage due to subtle clinical manifestations. One of the most predictive prognostic factors in pancreatic cancer is the pancreatic cancer stage at diagnosis; therefore, early diagnosis is essential. Until now, pancreatic cancer screening has not become a standard practice for the general population due to the low incidence. In current circumstances, targeting individuals with a high risk of pancreatic cancer may be more rational. Several screening modalities for pancreatic cancer have also become debatable topics. Therefore, this article will review current evidence and recommendations regarding pancreatic screening cancer protocol in general and in high-risk populations.

Abstract B040: In silico drug design using KRASG12C as a theranostic target for pancreatic cancer

Abstract Pancreatic cancer is one of the most lethal malignancies worldwide, it often results in therapeutic failure and unfavorable outcome because of the absence of screening strategies, difficulties in tumor early detection due to the lack of specific signs/symptoms and aggressive behavior of the disease. Early detection of this cancer is a challenge with the technology we have, its late detection results in a poor outcome and reduced quality of life for the patient. The treatment success depends on surgical intervention, which is not always possible. Thus, trying to find alterations that occur in the early stages of pancreatic cancer is needed. Taking into consideration that the accumulation of genetic and epigenetic alterations results in a complex and heterogeneous disease, each patient has a unique tumor. The heterogeneity of cancer is not restricted to inter-patient differences but, intra-tumoral heterogeneity contributes to functional properties of tumor cell subclones, including proliferative capacity and progression to aggressive phenotypes such as drug tolerance and metastatic potential. Driver mutations are responsible for malignant transformation and tumor progression across different cancer types. One of the most common driver mutations are those leading to the constitutive activation of KRAS oncogene, a GTPase enzyme responsible for cell proliferation and survival that is frequently mutated in pancreatic cancer. Gain-of-function mutation of KRAS gene leads to a protein constitutively activated, which stimulates the proliferation of tumor cells. The c.34G>T missense mutation (rs121913530) causes the substitution of glycine for cysteine in the encoded protein KRASG12C; this mutation has been related to poorer prognosis and therapy resistance in lung cancer. As KRAS occurs before the progression of pancreatic cancer to invasive carcinoma, it is a promising target for new biomarker development. We design three near-infrared probe-drug conjugate directed to the KRASG12C and to predict in silico the best orientation and conformation of the test compounds bound to the KRAS G12C (PDB code: 6OIM), the PyRx program was used, which uses AutoDock Vina as docking software. Based on these profiles and structures of the compounds, AutoDock Vina infers the possible pharmacological interactions and allows the most promising compounds to be classified according to the studied biological activity, using the empirical score function for this classification. The AMG 510 (established inhibitor) and GDP (endogenous activator) were used as a reference to establish the docking box coordinates. The binding energy of the three compounds predicted by docking was analyzed and classified according to the binding affinity described in Kcal/mol. The tested compounds show an excellent affinity for this protein based on the binding energy results obtained by docking using the crystallized KRAS G12C protein. Therefore, they could be great candidates for further chemical synthesis studies aiming to improve diagnosis, treatment, and patient survival in pancreatic cancer. Citation Format: Barbara M. Barbosa, Allana C. F. Martins, Roberto S. Gomes, Claudia A. Rainho. In silico drug design using KRASG12C as a theranostic target for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B040.

Post-Acute Care Outcomes and Functional Status Changes of Adults with New Cancer Discharged to Skilled Nursing Facilities.

Older hospitalized adults with an existing diagnosis of cancer rarely receive cancer treatment after discharge to a skilled nursing facility (SNF). It is unclear to what degree these outcomes may be driven by cumulative effects of previous cancer treatment and their complications vs an absolute functional threshold from which it is not possible to return. We sought to understand post-acute care outcomes of adults newly diagnosed with cancer and explore functional improvement during their SNF stay. Retrospective cohort study, 2011-2013. Surveillance, Epidemiology, and End Results - Medicare database of patients with new stage II-IV colorectal, pancreatic, bladder, or lung cancer discharged to SNF. Primary outcome was time to death after hospital discharge. Covariates include cancer treatment receipt and hospice use. A Minimum Data Set (MDS)-Activities of Daily Living (ADL) score was calculated to measure changes in ADLs during SNF stay. Patient groups of interest were compared descriptively using means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Logistic regression was used to compare patient groups. A total of 6791 cases were identified. Forty-six percent of patients did not receive treatment or hospice, 25.0% received no treatment but received hospice, 20.8% received treatment but no hospice, and 8.5% received both treatment and hospice. Only 43% of decedents received hospice. Patients who received treatment but not hospice had the best survival. There were limited improvements in MDS-ADL scores in the subset of patients for whom we have complete data. Those with greater functional improvement had improved survival. The majority of patients did not receive future cancer treatment or hospice care prior to death. There was limited improvement in MDS-ADL scores raising concern this population might not benefit from the rehabilitative intent of SNFs.

Semantic Segmentation of Pancreatic Cancer in Endoscopic Ultrasound Images Using Deep Learning Approach.

Simple SummarySurgical therapy is critical to pancreatic cancer survival. The segmentation of pancreatic cancer in endoscopic ultrasonography (EUS) images can provide critical characteristics of the pancreatic cancer for surgical therapy. However, EUS has high operator dependency, and it requires a considerable level of experience and competency to stage pancreatic cancer. Deep learning approaches have been used on EUS images, but there have been no studies on the segmentation of pancreatic cancer. The purpose of this study is to segment pancreatic cancer from EUS images using a neural network model with deep attention features, called DAF-Net. The significance of this study lies in the successful segmentation performance of the pancreatic cancer using the DAF-Net, regardless of the size and location of the cancer, and its usefulness in preoperative planning.Endoscopic ultrasonography (EUS) plays an important role in diagnosing pancreatic cancer. Surgical therapy is critical to pancreatic cancer survival and can be planned properly, with the characteristics of the target cancer determined. The physical characteristics of the pancreatic cancer, such as size, location, and shape, can be determined by semantic segmentation of EUS images. This study proposes a deep learning approach for the segmentation of pancreatic cancer in EUS images. EUS images were acquired from 150 patients diagnosed with pancreatic cancer. A network with deep attention features (DAF-Net) is proposed for pancreatic cancer segmentation using EUS images. The performance of the deep learning models (U-Net, Attention U-Net, and DAF-Net) was evaluated by 5-fold cross-validation. For the evaluation metrics, the Dice similarity coefficient (DSC), intersection over union (IoU), receiver operating characteristic (ROC) curve, and area under the curve (AUC) were chosen. Statistical analysis was performed for different stages and locations of the cancer. DAF-Net demonstrated superior segmentation performance for the DSC, IoU, AUC, sensitivity, specificity, and precision with scores of 82.8%, 72.3%, 92.7%, 89.0%, 98.1%, and 85.1%, respectively. The proposed deep learning approach can provide accurate segmentation of pancreatic cancer in EUS images and can effectively assist in the planning of surgical therapies.

CA19-9 in Combination with Methylated HOXA1 and SST Is Useful to Diagnose Stage I Pancreatic Cancer

Introduction: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. Results: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.

RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients.

We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.

The role of staging laparoscopy in pancreatic adenocarcinoma and its effect on patients’ survival

BackgroundPrompt and accurate staging of pancreatic cancer is essential to distinguish patients to benefit from resection with curative intent and those with unresectable disease. A staging laparoscopy is used preoperatively to identify macroscopic or occult metastases not identified on imaging. This single-institution study aims to evaluate the role of staging laparoscopy in patients with pancreatic adenocarcinoma and its effect on overall survival.MethodClinicopathologic data were evaluated for all patients undergoing staging laparoscopy for pancreatic adenocarcinoma from July 2014 to December 2019. The study identified 155 patients eligible for analysis. All patients were followed for at least 2 years. Clinical backgrounds, survival curves and prognostic factors were investigated.ResultsResectability status among the cohort was 62 (40%) upfront resectable, 53 (34%) borderline resectable and 40 (26%) locally advanced disease. The median age was 69, with 44% male patients. Median CA19-9 value was 125 kU/L, and median CA125 value was 22 kU/L. Staging laparoscopy resulted in upstaging nine (15%) upfront resectable patients, five (9%) borderline resectable patients and ten (25%) locally advanced patients. There was positive cytology in 19 (12%), peritoneal deposits in six (4%) and peritoneal liver deposits in seven (5%) patients. Overall, the number needed to treat (NNT) to avoid an unnecessary laparotomy was eight patients.ConclusionStaging laparoscopy continues to be a valuable investigation of pancreatic adenocarcinoma. In this institution, one in every eight patients undergoing a staging laparoscopy was upstaged to metastatic disease, thus avoiding an unnecessary laparotomy or a non-curative resection.

4D Free-Breathing Sequence For The Study Of Pancreatic Lesions In MRI 3 Tesla

Pancreatic cancer is the fourth leading cause of cancer death in both the United States and Europe. A fundamental role in the characterization, early diagnosis, and staging of pancreatic cancer is played by Magnetic Resonance. An innovative and recently implemented sequence, the 4D Free-Breathing sequence, is demonstrating remarkable efficiency in the characterization of pancreatic lesions, as it allows to obtain images with high temporal resolution on the arterial phase, maintaining high spatial and temporal resolution, with the patient free breathing and with compensation of respiratory movement artifacts. The aim of this study was to analyze the 4D Free-Breathing sequence technique and to evaluate its advantages in terms of image quality and diagnostic value in the characterization of pancreatic lesions. The 4D Free Breathing sequence replaces the acquisition of the classic arterial post-contrast phase obtained with the 3D-THRIVE sequence: after a first acquisition of the k-space data in the non-contrast phase (lasting 58 seconds), multiple arterial subphases, each one lasting about 5 seconds, will be acquired with a complete coverage of the post-contrast phase of about 90 seconds. This sequence exploits the k-space sampling technique called "Stack of Stars", based on a radial sampling in the XY plane. In detail, along the slice phase-encoding direction (kz), uniform Cartesian-grid sampling is maintained. Within each kz-encoded plane, radial data is collected with consecutive views (1 per sequence repetition time TR) rotated by a golden-angle of 111.25°, allowing the sampling of a complete circle, also determining a considerably reduced presence of breath artifacts.

4D Free-Breathing Sequence For The Study Of Pancreatic Lesions In MRI 3 Tesla

Pancreatic cancer is the fourth leading cause of cancer death in both the United States and Europe. A fundamental rolein the characterization, early diagnosis, and staging of pancreatic cancer is played by Magnetic Resonance. An innovative and recently implemented sequence, the 4D Free-Breathing sequence, is demonstrating remarkable efficiencyin the characterization of pancreatic lesions, as it allows to obtain images with high temporal resolution on the arterial phase, maintaining high spatial and temporal resolution, with the patient free breathing and with compensationof respiratory movement artifacts. The aim of this study was to analyze the 4D Free-Breathing sequence techniqueand to evaluate its advantages in terms of image quality and diagnostic value in the characterization of pancreaticlesions. The 4D Free Breathing sequence replaces the acquisition of the classic arterial post-contrast phase obtainedwith the 3D-THRIVE sequence: after a first acquisition of the k-space data in the non-contrast phase (lasting 58seconds), multiple arterial subphases, each one lasting about 5 seconds, will be acquired with a complete coverageof the post-contrast phase of about 90 seconds. This sequence exploits the k-space sampling technique called “Stackof Stars”, based on a radial sampling in the XY plane. In detail, along the slice phase-encoding direction (kz), uniform Cartesian-grid sampling is maintained. Within each kz-encoded plane, radial data is collected with consecutiveviews (1 per sequence repetition time TR) rotated by a golden-angle of 111.25°, allowing the sampling of a completecircle, also determining a considerably reduced presence of breath artifacts. The inclusion of the 4D Free-Breathingsequence in the MRI study protocol of the pancreas, through the rapid and consequential acquisitions of 18 arterialphases, allows to improve the diagnostic information contained in the arterial phase, with free breathing, also innon-compliant patients and with correction of breath artifacts

Diagnostic Performance in Low- and High-Contrast Tasks of an Image-Based Denoising Algorithm Applied to Radiation Dose-Reduced Multiphase Abdominal CT Examinations.

BACKGROUND. Anatomic redundancy between phases can be used to achieve denoising of multiphase CT examinations. A limitation of iterative reconstruction (IR) techniques is that they generally require use of CT projection data. A frequency-split multi-band-filtration algorithm applies denoising to the multiphase CT images themselves. This method does not require knowledge of the acquisition process or integration into the reconstruction system of the scanner, and it can be implemented as a supplement to commercially available IR algorithms. OBJECTIVE. The purpose of the present study is to compare radiologists' performance for low-contrast and high-contrast diagnostic tasks (i.e., tasks for which differences in CT attenuation between the imaging target and its anatomic background are subtle or large, respectively) evaluated on multiphase abdominal CT between routine-dose images and radiation dose-reduced images processed by a frequency-split multiband-filtration denoising algorithm. METHODS. This retrospective single-center study included 47 patients who underwent multiphase contrast-enhanced CT for known or suspected liver metastases (a low-contrast task) and 45 patients who underwent multiphase contrast-enhanced CT for pancreatic cancer staging (a high-contrast task). Radiation dose-reduced images corresponding to dose reduction of 50% or more were created using a validated noise insertion technique and then underwent denoising using the frequency-split multi-band-filtration algorithm. Images were independently evaluated in multiple sessions by different groups of abdominal radiologists for each task (three readers in the low-contrast arm and four readers in the high-contrast arm). The noninferiority of denoised radiation dose-reduced images to routine-dose images was assessed using the jackknife alternative free-response ROC (JAFROC) figure-of-merit (FOM; limit of noninferiority, -0.10) for liver metastases detection and using the Cohen kappa statistic and reader confidence scores (100-point scale) for pancreatic cancer vascular invasion. RESULTS. For liver metastases detection, the JAFROC FOM for denoised radiation dose-reduced images was 0.644 (95% CI, 0.510-0.778), and that for routine-dose images was 0.668 (95% CI, 0.543-0.792; estimated difference, -0.024 [95% CI, -0.084 to 0.037]). Intraobserver agreement for pancreatic cancer vascular invasion was substantial to near perfect when the two image sets were compared (κ = 0.53-1.00); the 95% CIs of all differences in confidence scores between image sets contained zero. CONCLUSION. Multiphase contrast-enhanced abdominal CT images with a radiation dose reduction of 50% or greater that undergo denoising by a frequency-split multiband-filtration algorithm yield performance similar to that of routine-dose images for detection of liver metastases and vascular staging of pancreatic cancer. CLINICAL IMPACT. The image-based denoising algorithm facilitates radiation dose reduction of multiphase examinations for both low- and high-contrast diagnostic tasks without requiring manufacturer-specific hardware or software.

S31 Cole Relaxation Frequency: A Parameter for Pancreatic Cancer Detection

Introduction: Pancreatic cancer (PC) accounts for half a million new cases and 4.7% of the world's cancer-related deaths in 2020. It is considered one of the most lethal malignancies with a global survival rate of only 5%. Innovative imaging and endoscopic techniques are being studied to improve the accuracy of PC detection. Endoscopic ultrasound (EUS) guided tissue acquisition is currently the gold standard for sampling pancreatic masses. EUS guided fine needle biopsy has been considered superior to fine needle aspiration, but both are limited by the subjectivity of endoscopists and invasiveness of the procedure. Nonetheless, at present, there is no standard procedure for PC detection. The Cole Relaxation Frequency (CRF) – a derived electrical bioimpedance signature for cancer detection proposed by NovaScan – has been proven to quantitatively detect cancer in breast, skin, and lung tissues. The aim of this pilot study was to determine if the CRF based NovaScan technology can detect cancer in pancreatic tissues. Methods: CRF was measured with NovaScan technology in multiple locations (Figure A) on the pancreas samples in a cohort of n=26 mice, of which 15 were KPC (model of pancreatic ductal adenocarcinoma), 2 were KC (model of pancreatic neoplasia), and 9 were wild type controls. NovaScan determined cancer presence when the CRF parameter was measured above 1 MHz (Figure:B,C). Outcomes were compared to histopathology results for each of these samples to determine the specificity and sensitivity of the NovaScan device. Results: From histology, 12 KPC pancreases were confirmed as cancerous, 9 controls were confirmed as noncancerous, while 5 pancreases (3 KPC and 2 KC) presented with pancreatic intraepithelial neoplasia (PanIN), a precancerous condition. NovaScan technology identified 4 out of 5 PanIN samples as cancerous. Considering the entire cohort (n=26), specificity and sensitivity were 100% and 94%, respectively. If PanIN samples were excluded, specificity and sensitivity were both 100% (n=21). Conclusion: Future development of NovaScan CRF based technology into a rapid onsite evaluation or an endoscopic device would provide an affordable means for accurate and quantitative PC detection that guides or substitutes pancreatic biopsy acquisition. Identification of malignant precursors indicates the technological capability of NovaScan’s device to detect early stage PCs. Further technology development could allow for the distinction between cancerous and precancerous lesions.Figure 1.: (A) KPC pancreas sample placed on Novascan’s electrode array for a series of spectral bioimpedance measurements. A zoom in of the electrode with a pancreas sample is also shown. White rectangles indicate multiple locations measured across the sample. Spectral impedance scans for a control mouse (B) and a KPC mouse (C). The examination of CRF peak properties was used for cancer identification in pancreas samples. For the control mouse the CRF peaks fall below the threshold of 1 MHz, determining no cancer. For the KPC mouse several scans have CRF peaks above the threshold of 1 MHz, determining cancer presence.

Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer.

Simple SummaryThe 8th edition of the AJCC staging system for pancreatic cancer has been validated for pathological staging; however, its suitability for clinical staging is still uncertain. Clinical staging is important for pancreatic cancer because surgical resection is not suitable for most patients. We validated the prognostic performance and suitability of the current staging system for clinical staging. In our analysis using a prospectively collected pancreatic cancer cohort database, survival difference was not shown between stage IB and IIA, which were divided by the new size-based T3 criterion. Among the patients who received surgery, the pathological stage was more advanced than the clinical stage in 57.3%, mostly due to a false-negative lymph node in clinical staging. These findings suggest that the 8th edition AJCC staging system is not validated for clinical staging and separate criteria more suitable for clinical staging should be established.The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

MAIN EPIDEMIOLOGICAL ASPECTS OF PANCREATIC CANCER IN KAZAKHSTAN

According to GLOBOCAN (2020), pancreatic cancer (PC) is in 12th place among oncopathology in terms of incidence - 4.9 cases per 100,000 population. Most cases of pancreatic cancer are registered in China, the USA, Japan, and Germany. In the structure of mortality among oncological diseases, pancreatic cancer occupies 9th place - 4.5 cases per 100 thousand of the population. According to epidemiological studies, by 2040, a 79.9% increase in mortality from pancreatic cancer is predicted. According to statistics, in the United States, there is an increase in the incidence of cancer in the distal pancreas. In addition, early stages of pancreatic cancer were diagnosed more often and less often - the 4th. One of the trends in the epidemiology of pancreatic cancer is an increase in the incidence of this pathology among young people. Factors contributing to the development of pancreatic cancer in people under 50 years of age are genetic mutations, smoking, and obesity. A retrospective statistical analysis of the epidemiological state of pancreatic cancer in Kazakhstan over 3 years was carried out (standardized WHO World indicators per 100,000 population and intensive indicators of morbidity, mortality, distribution by stage, age, and sex), and regional features of pancreatic cancer were studied.

Investigation of key signaling pathways and appropriate diagnostic biomarkers selection between non-invasive to invasive stages in pancreatic cancer: a computational observation.

Pancreatic cancer is the seventh most lethal cancer in the world. Despite its moderate prevalence, the 5-year survival rate of patients with pancreatic cancer is about 10%. Despite different therapeutic and diagnostic strategies for pancreatic cancer, this cancer is still uncontrollable in the invasive stage and can invade various body organs and cause death. Early detection for pancreatic cancer can be an excellent solution to manage treatment better and increase patients' survival rates. This study aimed to find diagnostic biomarkers between non-invasive to invasive stages of pancreatic cancer in the extracellular matrix to facilitate the early diagnosis of this cancer. Using bioinformatics analysis, we selected the appropriate datasets between non-invasive and invasive pancreatic cancer stages and categorized their genes. Then, we charted and confirmed the signaling pathways, gene ontology, protein relationships, and protein expression levels in the human samples using bioinformatics databases. Cell adhesion and hypoxia signaling pathways were observed in up-regulated genes, different phases of the cell cycle, and metabolic signaling pathways with down-regulated genes between non-invasive and invasive pancreatic cancer stages. For proper diagnostic biomarkers selection, the overexpressed genes that released protein into the extracellular matrix were examined in more detail, with 62 proteins selected and SPARC, THBS2, COL11A1, COL1A1, COL1A2, COL3A1, SERPINH1, PLAU proteins chosen. Bioinformatics analysis can more accurately assess the relationship between molecular mechanisms and key actors in pancreatic cancer invasion and metastasis to facilitate early detection and improve treatment management for patients with pancreatic cancer.

Effect of surgery on the survival of elderly patients with early stage pancreatic cancer: A propensity‐matched analysis

AbstractBackground and objectivesResearch about the effect of surgery in geriatric patients with early stage pancreatic ductal adenocarcinoma (PDAC) is limited, and it remains a subject of much debate. The purpose of this study was to evaluate the role of surgery on the survival of elderly patients with T1‐3N0M0 PDAC and to further investigate the prognosis of these patients undergoing different surgical methods.MethodsPatients aged ≥65 with T1‐3N0M0 PDAC diagnosed in 2004–2016 were collected from the Surveillance, Epidemiology, and End Results database. The imbalance of baseline characteristics was reduced by propensity score matching. We used the log‐rank tests to evaluate overall survival (OS) and cancer‐specific survival (CSS) among different groups. Univariate and multivariate Cox regression analysis was utilized to explore prognostic factors in PDAC.ResultsIn total, 6363 patients were enrolled. After matching, 1110 patients were paired. We found that surgery could provide better survival (p &lt; 0.001). Moreover, compared with those who underwent partial resection or larger resection, patients who underwent local tumor destruction had poorer OS and CSS (p &lt; 0.001). However, no statistically significant survival differences were shown between the partial resection group and the larger resection group (p &lt; 0.001).ConclusionSurgical intervention could confer a survival benefit to elderly patients with early stage PDAC. Additionally, these patients could benefit from more radical operations, and radical operations with reasonable extents are advocated rather than too aggressive methods.

Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from “first contact” interactions in the tumor microenvironment

BackgroundPancreatic cancer is one of the most difficult cancers to detect early and most patients die from complications arising due to distant organ metastases. The lack of bona fide early biomarkers is one of the primary reasons for late diagnosis of pancreatic cancer. It is a multifactorial disease and warrants a novel approach to identify early biomarkers.MethodsIn order to characterize the proteome, Extracellular vesicles (EVs) isolated from different in vitro conditions mimicking tumor-microenvironment interactions between pancreatic cancer epithelial and stromal cells were analyzed using high throughput mass spectrometry. The biological activity of the secreted EVome was analyzed by investigating changes in distant organ metastases and associated early changes in the microbiome. Candidate biomarkers (KIF5B, SFRP2, LOXL2, and MMP3) were selected and validated on a mouse-human hybrid Tissue Microarray (TMA) that was specifically generated for this study. Additionally, a human TMA was used to analyze the expression of KIF5B and SFRP2 in progressive stages of pancreatic cancer.ResultsThe EVome of co-cultured epithelial and stromal cells is different from individual cells with distinct protein compositions. EVs secreted from stromal and cancer cells cultures could not induce significant changes in Pre-Metastatic Niche (PMN) modulation, which was assessed by changes in the distant organ metastases. However, they did induce significant changes in the early microbiome, as indicated by differences in α and β-diversities. KIF5B and SFRP2 show promise for early detection and investigation in progressive pancreatic cancer. These markers are expressed in all stages of pancreatic cancer such as low grade PanINs, advanced cancer, and in liver and soft tissue metastases.ConclusionsProteomic characterization of EVs derived from mimicking conditions of epithelial and stromal cells in the tumor-microenvironment resulted in the identification of several proteins, some for the first time in EVs. These secreted EVs cannot induce changes in distant organ metastases in in vivo models of EV education, but modulate changes in the early murine microbiome. Among all the proteins that were analyzed (MMP3, KIF5B, SFRP2, and LOXL2), KIF5B and SFRP2 show promise as bona fide early pancreatic cancer biomarkers expressed in progressive stages of pancreatic cancer.

New-onset type ii diabetes mellitus in early diagnosis of pancreatic cancer: literature review

The literature data on the connection between type 2 diabetes mellitus (DM) and pancreatic cancer (PC) were analyzed. Early detection of pancreatic cancer remains an unsolved problem of oncology because of absence of pathognomonic symptoms for this disease at the early stages, difficulties in visualizing changes in the pancreas as well as difficulties in differential diagnosis with benign tumors. Fifty nine articles in Russian and English were studied, and the data presented in literature regarding the connection between type 2 diabetes mellitus and early stages of pancreaticic cancer have been analyzed.Resectable pancreatic cancer makes up less than 15 % of the cases during initial medical examination. Currently, the existing methods of diagnostics do not allow solving the problem of early detection of pancreatic cancer it dictates the need to search for a new marker that will improve the early diagnosis of this tumor. According to the results of many studies, there has been detected a connection between the new-onset type 2 diabetes mellitus and early stages of pancreatic cancer. Based on the data published by a number of authors, manifestation of the new-onset type 2 diabetes mellitus in patients over fifty (fasting blood glucose level 7 mmol/L, or a blood glucose sugar level 11,1 mmol/L after performing oral glucose tolerance test, or random blood glucose level 11,1 mmol/L with a typical hyperglycemia signs and symptoms) can serve as an early symptom of pancreatic cancer.&#x0D; Thus, the new-onset type 2 diabetes mellitus in persons aged 50 years or older can potentially be used to identify a group of patients requiring a directional examination for the purpose of early detection of pancreatic cancer. Further studies on this problem could allow us to formulate a special program of early diagnostics of pancreatic cancer.

Development of Chitosan-Coated PLGA-Based Nanoparticles for Improved Oral Olaparib Delivery: In Vitro Characterization, and In Vivo Pharmacokinetic Studies

Olaparib (OLP) is an orally active poly (ADP-ribose) polymerase enzyme inhibitor, approved for treatment for the metastatic stage of prostate, pancreatic, breast and ovarian cancer. Due to its low bioavailability, an increase in dose and frequency is required to achieve therapeutic benefits, which also results in associated toxicity in patients. In the current study, OLP-loaded poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) (OLP-PLGA NPs) and a coating of OLP-PLGA NPs with chitosan (CS) (OLP-CS-PLGA NPs) were prepared successfully in order to improve the dissolution rate and bioavailability. The developed OLP-PLGA NPs were evaluated for hydrodynamic particle size (392 ± 5.3 nm), PDI (0.360 ± 0.03), ZP (−26.9 ± 2.1 mV), EE (71.39 ± 5.5%) and DL (14.86 ± 1.4%), and OLP-CS-PLGA NPs, hydrodynamic particle size (622 ± 9.5 nm), PDI (0.321 ± 0.02), ZP (+36.0 ± 1.7 mV), EE (84.78 ± 6.3%) and DL (11.05 ± 2.6%). The in vitro release profile of both developed NPs showed a sustained release pattern. Moreover, the pharmacokinetics results exhibited a 2.0- and 4.75-fold increase in the bioavailability of OLP-PLGA NPs and OLP-CS-PLGA NPs, respectively, compared to normal OLP suspension. The results revealed that OLP-CS-PLGA NPs could be an effective approach to sustaining and improving the bioavailability of OLP.

Helping Patients Understand Pancreatic Cancer Using Animated Pancreas Patient Education With Visual Formats of Learning.

Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube). A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules. During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was "Understanding Clinical Trials" (n = 182,217), and the most common expert video viewed was "What are the different stages of pancreatic cancer?" (n = 15,357). Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer.

Diagnostic value of multi-detector computed tomography angiography (MDCTA) in assessment of vascular invasion and resectability of pancreatic head cancer

Introduction: pancreatic carcinoma is a common gastrointestinal malignancy. Accurate preoperative imaging helps to avoid unnecessary or unsuccessful surgical procedures and reduce the number of aborted pancreatic resections. MDCT is the most widely available and best validated tool for imaging patients with pancreatic adenocarcinoma. Objective: to evaluate the diagnostic value of resectability and local staging of Pancreatic Head Cancer by MDCTA. Materials and methods: This cross-sectional study was conducted on 20 patients referred to the Diagnostic Radiology and Medical Imaging Department at Tanta University Hospitals presenting with pancreatic head cancer. Results: Patients underwent exploratory laparoscopy or laparatomy with progression to a pancreaticoduodenectomy as deemed resectable in 7 (35%) patients, and 6 (30%) of patients underwent exploratory laparoscopy or laparatomy with progression to Gasterojejunostomy, 4 (20%) of patients underwent ERCP for biliary stenting and 3 (15 %) of patients were inoperable. In the studied patients, 15.4% of resectable by MDCTA found to be unresectable at laparoscopy exploratory with true positive was 100%. The MDCTA imaging sensitivity was 100%, specificity was 71%, NPV was 100% and PPV was 87% with accuracy of 90% to assess for resectability.