Diagnosis Of Pancreatic Adenocarcinoma Research Articles

Scalp Lesion as the First Manifestation of Pancreatic Adenocarcinoma, A Very Rare Case.

Pancreatic adenocarcinoma is one of the most aggressive tumors. Its diagnosis is usually made in locally advanced or metastatic disease and survival is less than one year. The most frequent sites of metastatic involvement are the liver, peritoneum and lungs. Other organs such as the bones or the brain may be affected to a lesser extent. Cutaneous involvement of pancreatic adenocarcinoma is extremely rare with less than 150 cases reported in the literature since 1960. Most cases with cutaneous involvement involve the periumbilical region, in a lesion known as "Sister Mary Joseph's Node". Scalp metastases are very rare and their diagnosis suggests advanced disease and the prognosis will be dismal. It is very important to perform a complete physical examination and a global anamnesis to guide the request for diagnostic tests. Once the diagnosis of pancreatic adenocarcinoma has been made, a global assessment will be necessary, involving different medical specialists, nurses, psychologists and social workers among others. In many cases, supportive care is the mainstay of treatment.

Utilization of Relative Evaluation of Pancreatic Perfusion CT Parameters to Support Appropriate Pancreatic Adenocarcinoma Diagnosis

ObjectivesTo investigate the effect of relative evaluation of perfusion computed tomography (PCT) parameters in the diagnosis of pancreatic adenocarcinoma (PAC). MethodsOf the 117 patients in which PCT was performed (May 2019 to June 2023), 99 patients with mass lesions (MLs), including 50 PAC and 11 patients with mass-forming pancreatitis (MFP), and 15 patients without MLs but with main pancreatic duct (MPD) abnormalities, including 6 PAC and 7 no diagnosis of malignancy (NDM) cases were enrolled in this study. Parameter values were obtained from parametric maps of blood flow (BF), blood volume (BV), and mean transit time (MTT) for the ML and abnormal MPD part (AMP), pancreas and spleen. Diagnostic performance was evaluated based on receiver operating characteristic analysis for absolute values and relative values for pancreas and spleen. ResultsBFML, BVML, BFML/Pancreas, BFML/Spleen, BVML/Pancreas and BVML/Spleen were significantly lower in PAC than MFP cases. Areas under the curve (AUCs) for BFML, BFML/Pancreas, BFML/Spleen were 0.71 (sensitivity, 54%; specificity, 91%), 0.80 (sensitivity, 74%; specificity, 82%) and 0.79 (sensitivity, 68%; specificity. 91%), respectively. The AUCs for BVML, BVML/Pancreas, BVML/Spleen were 0.72 (sensitivity, 48%; specificity, 100%), 0.85 (sensitivity, 76%; specificity, 91%) and 0.87 (sensitivity, 76%; specificity, 91%), respectively, with significantly better diagnostic performance on relative evaluation (P < 0.05). BVAMP/Spleen and MTTAMP/Spleen were significantly higher in PAC than NDM cases, with AUCs of 1 (100% sensitivity and specificity) and 0.91 (sensitivity, 86%; specificity, 100%), respectively. ConclusionsRelative evaluation of PCT parameters is expected to contribute to more appropriate diagnosis of PAC.

Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients.

This study explores the optimization of exocrine pancreatic insufficiency (EPI) management in pancreatic adenocarcinoma patients, focusing on the scientific advancements and technological interventions available to improve patient outcomes, including oral pancreatic enzyme replacement therapy (PERT) and immobilized lipase cartridge (RELiZORB®). This was a prospective Institutional Review Board (IRB)-approved study from October 2019 through to August 2021 at the Louisville Medical Center in collaboration with Norton Healthcare and the University of Louisville Division of Surgical Oncology. Patients with a diagnosis of pancreatic adenocarcinoma (Stage 2 or 3) who underwent oncologic surgical resection were included in this study. Patients were contacted at pre-defined intervals (prior to surgery, before hospital discharge, and 2, 4, 6, and 12 weeks after surgery) to complete nutrition evaluation, EPI assessment, and quality of life questionnaires to identify the severity and frequency of gastrointestinal (GI) symptoms. EPI symptoms were reported in 28 of the 35 total patients studied (80%). Jejunostomy tubes were placed during oncologic surgery in 25 of the 35 total patients studied (71%), and 12 of the 25 patients with a jejunostomy tube utilized enzyme cartridges to manage EPI symptoms while on supplemental tube feeding (48%). EPI symptoms were reported in 8 of the 10 patients without a feeding tube (80%), and their EPI symptoms were managed with PERT alone. EPI interventions, both oral PERT and immobilized cartridges, were associated with a decrease in EPI symptoms after surgery and improved quality of life (QOL). Overall, early optimization of EPI is crucial to enhance overall patient care, return to oncology therapy after surgery, and improve quality of life in pancreatic adenocarcinoma patients.

The additive diagnostic value of cytology in fine needle biopsy of pancreatic adenocarcinoma: A tertiary center experience.

Endoscopic ultrasound guide fine needle biopsy (EUS-FNB) is the main diagnostic tool for pancreatic adenocarcinoma. In most instances, only histology is obtained via FNB, without sending cytological slides. The aim of our study was to assess the additive diagnostic yield of cytology performed through FNB. We conducted a retrospective study of all patients with histological diagnosis of pancreatic adenocarcinoma who were diagnosed by EUS-FNB. Overall, 80 patients were included in the study period. The overall concordance between cytology and histology all FNB needles was 78.2%. Notably, cytological assessment improved the diagnostic yield for malignancy by 12.8%. The overall kappa coefficient correlation between histology and cytology was .501, 95% CI 0.361-0.641. However, the kappa correlation for suspicious of malignancy and malignant was excellent of .872, 95% CI 0.733-1, suggesting that cytology is crucial when histology is inconclusive. Further analysis showed that the Acquire and Sharkcore needles outperformed the Procore needle in term of concordance between cytology and histology (kappa correlation of .527, 95% CI 0.331-0.724, .515, 95% CI 0.265-0.764, and .297, 95% CI -0.051-0.646), respectively. Performing cytology specimen when using FNB improves the diagnostic yield in pancreatic adenocarcinoma.

Venous thromboembolism in patients with pancreatic adenocarcinoma: Disease burden and initiation of ambulatory thromboprophylaxis

Background/ObjectivesAmbulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. MethodsPatients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. ResultsThe cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). ConclusionVTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

Effect of glucose lymphocyte ratio on prognosis in patients operated with the diagnosis of pancreatic adenocarcinoma

Aims: Pancreatic adenocarcinoma is one of the most aggressive cancers, and predicting prognosis and survival clinically is challenging. Prognostic markers, easily accessible and routinely evaluated in diagnostic tests, are frequently seen in the literature for survival prediction. So far, the glucose lymphocyte ratio (GLR) has emerged as an indicator that can assess both metabolic dysregulation and immune response. In this study, the aim was to assess the impact of GLR on prognosis and survival by following patients diagnosed with pancreatic adenocarcinoma who underwent surgery. Methods: Between January 1, 2016, and April 31, 2021, a totalof 58 patients who underwent Whipple procedure due to pancreatic adenocarcinoma at the Department of General Surgery, Hitit University, were included in the study. Demographic characteristics, tumor features, laboratory results, and survival durations of the patients were collected. GLR was determined as a mortality predictor, and estimated survival times associated with GLR were determined using Kaplan-Meier Survival analysis. The optimal GLR value was determined through ROC analysis. Results: During the postoperative period, the average follow-up time for patients was 11.39 months, with the longest follow-up time being 48 months. During this period, 43 patients (74.14%) were deceased, while 15 patients (25.86%) survived. The mean age and ASA scores of deceased patients were significantly higher compared to survivors (p&lt;0.001 and p&lt;0.001, respectively). Glucose levels were significantly higher in the mortality group compared to the survival group (p=0.008). GLR was notably higher in the mortality group (p=0.170; p=0.703; p=0.429; and p=0.031). The GLR value that best distinguished the two groups was found to be 94.6387 with 93.3% specificity and 95.8% positive predictive value. Crossing this threshold increased the mortality risk approximately 4.27 times within one year and increased the overall mortality risk by approximately 15 times (p=0.014 and p=0.002). The estimated life expectancy for patients below the threshold value was calculated to be an average of 20.996 months, whereas for patients above the threshold value, this expectation was calculated to be an average of 4.427 months (p&lt;0.001). Conclusion: We believe that GLR may be helpful in predicting one-year survival and determining overall survival duration in patients undergoing surgery for pancreatic adenocarcinoma.

Intraoperative Frozen Section Evaluation of Pancreatic Specimens and Related Liver Lesions.

Frozen sections are essential in the surgical management of patients, especially those with pancreatic masses, because frozen sections can provide answers intraoperatively and aid in treatment decisions. Pancreas frozen sections are challenging because of the small tissue size, processing artifacts, neoadjuvant treatment effects, and concurrent pancreatitis-like obstructive changes. The authors present a review of intraoperative evaluation of pancreatic specimens. To provide an approach to the diagnosis of pancreatic adenocarcinoma on frozen sections and to discuss commonly encountered pitfalls. Indications for pancreas frozen sections and specific margin evaluation will be discussed. We will also review frozen section diagnosis of subcapsular liver lesions and tumors other than metastases of pancreatic ductal adenocarcinoma. Data sources included a literature review and the personal experiences of the authors. The features for diagnosis of pancreatic adenocarcinoma include disordered architecture, glands at abnormal locations, and atypical cytology. It is important to be aware of the pitfalls and clues on frozen section. The evaluation of resection margins can be challenging, and in the setting of the resection of cystic tumors, the key is the diagnosis of high-grade dysplasia or cancer. Finally, it is vital to remember the differential diagnosis for subcapsular liver lesions because not all lesions will be metastases of adenocarcinomas or bile duct adenomas. Frozen sections remain a useful tool for the intraoperative management of patients with pancreatic tumors.

Evaluation of fine-needle core biopsy specimens for pancreatic ductal adenocarcinoma: Diagnostic utility and helpful histological features.

With the advent of new biopsy devices, fine-needle core biopsy specimens can be obtained from pancreas masses. This study aimed to report the histological spectrum of intrapancreatic adenocarcinoma on fine-needle core biopsy and the accuracy of sampling. We identified 423 SharkCore™ fine-needle core biopsies taken from patients with a high clinical concern for pancreatic adenocarcinoma. For each, we recorded patient age and sex, percentage of diagnostic tissue in each sample and tumour site, size and histological findings. The cases came from 392 patients (193 men, 199 women; mean age 69 years). Median diagnostic tissue amount in the samples was 30%. Common histological findings included desmoplasia (36%), single atypical cells (44%), haphazard glandular growth pattern (68%), nuclear pleomorphism > 4:1 (39%), incomplete gland lumens (18%) and detached atypical epithelial strips (37%). Additional levels were ordered on 143 cases. Final clinical diagnoses associated with the 423 cases were adenocarcinoma (n = 343), pancreatitis (n = 22), intraductal neoplasm or other benign/low-grade process (n = 16) and unknown (n = 42, patients lost to follow-up). Of the adenocarcinoma cases, the diagnosis was established by the evaluated fine-needle core biopsy sample alone in 178, by fine-needle aspiration biopsy alone in 30, by both concurrently in 89 and by subsequent biopsy or resection in 37 cases. Among 68 cases called suspicious on fine-needle core biopsy, 78% ultimately represented adenocarcinoma. Fine-needle core biopsy allows for histological diagnosis of pancreatic adenocarcinoma, using known histological parameters. Common findings include single atypical cells, desmoplasia, haphazard gland growth and nuclear pleomorphism. Cases interpreted as suspicious often represent malignancy.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materialsand methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients hadstage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5)months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. PBT is indicated when the number of metastases is limited to ≤ 4 lesionsand all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.

Highly sensitive serum volatolomic biomarkers for pancreatic cancer diagnosis

The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).

Polycyclic Aromatic Hydrocarbons and Pancreatic Cancer: An Analysis of the Blood Biomarker, r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and Selected Metabolism Gene SNPs.

Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (p-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes [OR = 6.26 (95% CI = 2.83, 14.46)], PheT [1.03 (1.02, 1.05)], very well-done red meat [0.90 (0.83, 0.96)], fruit/vegetable servings [1.35 (1.06, 1.73)], recessive (rs12203582) [4.11 (1.77, 9.91)], recessive (rs56679) [0.2 (0.06, 0.85)], overdominant (rs3784605) [3.14 (1.69, 6.01)], and overdominant (rs721430) [0.39 (0.19, 0.76)]. Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.

Echoendoscopic ultrasound pancreatic adenocarcinoma diagnosis and theranostic approach: should KRAS mutation research be recommended in everyday practice?

The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival. In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed. The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC). A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation. KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC.

A prognostic and immunotherapy effectiveness model for pancreatic adenocarcinoma based on cuproptosis-related lncRNAs signature.

Pancreatic adenocarcinoma (PAAD) results in one of the deadliest solid tumors with discouraging clinical outcomes. Growing evidence suggests that long non-coding RNAs (lncRNAs) play a crucial role in altering the growth, prognosis, migration, and invasion of pancreatic cancer cells. Cuproptosis is a novel type of cell death induced by copper (Cu) and is associated with mitochondrial respiration during the tricarboxylic acid cycle. However, the relationship between lncRNAs related to cuproptosis and PAAD is poorly studied. In this study, we investigated the association between a signature of cuproptosis-related lncRNAs and the diagnosis of PAAD. Genomic data and clinical information were obtained using the TCGA dataset, while cuproptosis-related genes (CRGs) from previous studies. Co-expression analysis was utilized to identify lncRNAs associated with cuproptosis. We developed and verified a prognostic risk model following a classification of patients into high- and low-risk categories. The prediction capacity of the risk model was assessed using a number of methods including Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, nomograms, and principal component analysis (PCA). Furthermore, differentially expressed genes (DEGs) were used to perform functional enrichment analyses, and to examine the behaviors of various risk groups in terms of immune-related activities and medication sensitivity. We identified 7 cuproptosis-related lncRNA signatures, including CASC19, FAM83A-AS1, AC074099.1, AC007292.2, AC026462.3, AL358944.1, and AC009019.1, as overall survival (OS) predictors. OS and progression-free survival (PFS) showed significant differences among patients in different risk groups. Independent prognostic analysis revealed that the cuproptosis-related lncRNA signatures can independently achieve patient prognosis. The risk model demonstrated strong predictive ability for patient outcomes, as evidenced by ROC curves, nomograms, and PCA. Higher tumor mutation burden (TMB) and lower tumor immune dysfunction and exclusion (TIDE) scores were observed in the high-risk group. Additionally, the low-risk group was hypersensitive to 3 anti-cancer medications, whereas the high-risk group was hypersensitive to one. A prognostic risk model with a good predictive ability based on cuproptosis-related lncRNAs was developed, providing a theoretical basis for personalized treatment and immunotherapeutic responses in pancreatic cancer.

The yield of cytology and histology obtained by endoscopic ultrasound-guided fine needle aspiration and biopsy needles in the diagnosis of pancreatic adenocarcinoma.

Endoscopic ultrasound-guided fine needle aspiration and biopsy (EUS-FNA, -FNB) are the mainstay for tissue diagnosis of pancreatic lesions. Traditionally, FNA was performed for obtaining cytology and also histology if available from the puncture. Since their advent, however, FNB needles have been intended mainly to obtain core biopsies for histological specimens. We aimed to assess the yield of cytology obtained via both FNA and FNB needles. A retrospective study was performed including all patients who were diagnosed with pancreatic adenocarcinoma obtained via EUS-FNA/FNB needles. Overall, 227 patients were included. Of them, 85 patients underwent FNB, versus 142 patients who had FNA. The average age in the FNB group was 70.46 ± 11.29 years, versus 71.44 ± 11.80 in the FNA group, P = 0.57. Notably, cytological analysis diagnosed malignancy equally in both groups (69.4% in the FNB group, vs. 65.5% in the FNA group). The compatibility rate of cytology with histology was 76.5% in the FNB group, versus 76.1% in the FNA group (P = 0.69). The agreement level between cytology obtained by FNA and FNB, versus histology obtained by both needles, was moderate (kappa = 0.48, 95% CI 0.39-0.57). Similarly, the agreement level between cytology and histology in the FNB group was moderate as well (kappa = 0.5, 95% CI 0.36-0.64). Cytological assessment yielded an equal performance as compared to histological assessment with both needles. We recommend obtaining cytology specimens in pancreatic solid lesion puncture by FNB needle.

Maintaining early diagnosis of pancreatic adenocarcinoma in Japan: Local resilience against COVID-19

Background and aimsThis study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the “Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. MethodsWe retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. ResultsAmong the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients’ first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). ConclusionsThe pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

The roles of race and social determinants of health in pancreatic adenocarcinoma diagnosis and treatment.

e18565 Background: Pancreatic ductal adenocarcinoma (PDAC) is a significant health crisis in the United States and will soon become the second leading cause of death, despite being the 10th most common cancer. It is also associated with disparities in both incidence and outcomes among racial groups, socioeconomic status (SES), and insurance status.Given the dismal outcomes with advanced stage, early diagnosis is critical. The objective of this study is to evaluate the association of social determinants of health with timeframe to PDAC diagnosis (TPD) at an academic center. Methods: This study was an IRB approved retrospective analysis that utilized chart data from patients that were diagnosed with PDAC at the Georgetown University Lombardi Comprehensive Cancer Center from December 2018 to February 2022. Patient demographics were captured from patient charts. The main outcome of this study was TPD, defined as the number of days that elapsed between first symptom presentation to medical personnel and the date of histologic diagnosis. Secondary outcomes included the frequency of being offered specific cancer treatments. The Kruskal-Willis test was used to evaluate for a difference between median Time to Diagnosis among racial and insurance groups, and the Wilcoxon method used for post-hoc analysis. Results: A total of 200 patients (115 females [57%]; 85 males [43%]) were included in the analysis. There were 111 White (W, 55.5%), 71 African American (AA, 34%), 10 Asian (A, 5%), 3 Hispanic (H, 1.5%) and 5 Unknown (U, 2.5%) patients. AA patients received their diagnosis at a median of 16 [P &lt; 0.0001], and 19 [P = 0.001] days later than W and A patients, respectively. Compared to AA, A patients were more likely to be offered clinical trials (odds ratio [OR], 5.27 [95% CI, 1.19-23.2]). Chemotherapy, surgery, and radiation therapy were offered to patients at similar rates, regardless of their racial group, sex, or insurance status. AA patients presented with unresectable PDAC at higher rates than their counterparts in other racial groups: 66.2% compared to 54% of W and 50% of A patients. There were no statistically significant correlations between health outcome rankings and TPD among patients from Virginia and Maryland. In DC communities with poor health outcome rankings were positively associated with longer TPD, with a Spearman’s correlation coefficient of 0.29 (P &lt; 0.03). Conclusions: This study highlights disparities in TPD among racial groups. Racial groups were offered treatments at similar rates, but AA patients were less likely to be offered clinical trials. Furthermore, geographical locations with lower health outcome ratings experienced longer time to diagnosis. Our findings may inform institutional policymaking and quality measures regarding the allocation of resources to achieve better racial and geographic equities in treatment of patients with PDAC.

Evolution of pancreatic ductal adenocarcinoma diagnosis during the last decade.

670 Background: Pancreatic Ductal Adenocarcinoma (PDAC) has historically been an important diagnostic and therapeutic challenge. The multidisciplinary approach and new diagnostic techniques’ implementation have modified this process. Methods: We conducted a retrospective analysis based on clinical data of patients with PDAC between the years 2010 to 2021, analyzing the diagnosis and initial treatment evolution. Results: 673 patients between 2010-2021 with a suspected diagnosis of pancreatic adenocarcinoma were reviewed. Most of them were metastatic (n=362; 53.8%), followed by locally advanced unresectable (n=166; 24.7%) and resectable or borderline resectable (n=145; 21.5%). Regarding the pathological diagnosis, it was not possible in 62 patients (9.2%), varying over time from 21.2% in 2010-2012 to 1% in 2019-2021 (p&lt;0,0001). Moreover, the number of biopsies has decreased with a mean number of biopsies to obtain a pathological diagnosis of 1.55 (2010-2012) vs 1.31 (2019-2021). During this last period, most of the diagnoses were made by cytological analysis (61.4%; n=121). Specifically in the 2019-2021 patients subgroup, we found that 18 NGS (9,1%) were performed in this period (solid tumor), with 4 patients having actionable mutations (22.2%; 3 KRAS G12C). Germline (g) mutational panels were carried out in 89 patients, finding only 9 positive cases (10.1%), being 3 of them gBRCA1/2 mutated (3,4%). In our study, a decrease in palliative management was evidenced over time. In 2010-2012, 28,8% of patients received exclusively palliative care against 9,6% in 2019-21 (p&lt; 0.0001). An increase in PDAC diagnosis was observed since 2010, 44 patients/year in 2010-12 vs. 66 patients/year in 2019-21 (including COVID-19 pandemic period). All previous results are summarized. Conclusions: The diagnosis of PDAC has changed throughout the last decade, increasing the percentage of patients with a pathological diagnosis without increasing the number of invasive procedures. The number of patients suitable for anti-cancer therapy has also increased among time. In our cohort, the implementation of molecular testing would change the therapeutic approach in more than 20% of patients.[Table: see text]

Patterns of pancreatic enzyme replacement therapy (PERT) use among U.S. patients with pancreatic cancer.

696 Background: PERT is an important but costly and inconsistently used supportive care medication in PC. We sought to characterize patterns of PERT use among U.S. insured patients with PC. Methods: We conducted a retrospective observational analysis of patients with a primary diagnosis of pancreatic adenocarcinoma in the IBM MarketScan national claims database between 2013-2019. We identified pharmacy claims for PERT (Creon, Pancreaze, Pertzye, Viokace, and Zenpep) and classified patients as PERT-users (≥ 1 PERT prescription [Rx]) and non-PERT users. We used descriptive statistics for clinical, demographics, and costs. Multiple logistic regression identified predictors of PERT use. Kaplan-Meier method assessed time from PC diagnosis to first PERT Rx. Results: Of 19,866 patients with PC (median age 62 years, 49% women), 6,918 (35%) were PERT-users. The median follow-up was 11 months (PERT users: 14 months, non-PERT users: 9 months). Overall, 43% of patients received no cancer-directed treatment. PERT-users were more likely to have a history of pancreatitis (acute, odds ratio [OR] = 1.9; chronic, OR = 3.6), and received chemotherapy (OR = 1.2), surgery (OR = 2.3), and radiation (OR = 1.4). Among all PERT-users, the median time from PC diagnosis to first fill was 1.9 months (95% CI: 1.8,2.0). The median time from surgery to first fill was 1.6 months (95% CI: 1.4,1.7). The median number of PERT Rxs was 4; 22% of PERT-users received 1 Rx. A median of 150 days of PERT was supplied across all Rxs per patient. The median (IQR) cost of each PERT Rx was $25 ($0- $50). PERT accounted for 16% of all drug out-of-pocket costs (OOPC) (excluding systemic outpatient cancer-directed treatment), and 7% of all healthcare OOPC. Patients with PERT had significantly higher monthly OOPC on Rxs but lower on all other services, including inpatient and outpatient services (all p &lt; 0.0001). Overall, PERT-users had significantly lower per-patient per-month (PPPM) OOPC vs non-PERT users ($469, vs $520, p &lt; 0.0001). They also had fewer PPPM outpatient (0.7 vs 1.2, p &lt; 0.0001) and ER (0.4 vs 0.5, p &lt; 0.0001) visits. Conclusions: In this national study of insured U.S. adults with PC, only one-third received PERT. Of those receiving PERT, approximately a fifth received just a single Rx. PERT users, despite higher OOP drug spending had reduced overall OOP costs and fewer healthcare visits. These data highlight the need to explore non cost-related reasons for lack of and ways to standardize PERT use.

PDGFRβ targeted innovative imaging probe for pancreatic adenocarcinoma detection

The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, making it one of the most lethal forms of cancer. Early-stage diagnosis and resection of the incipient lesions could increase the 4-year survival rate of PA up to 78%. Platelet-derived growth factor receptor β (PDGFRβ), an oncogenic key regulator for migration, proliferation and angiogenesis of cancer cells, has been proved to be aberrantly expressed in the majority of PA. Herein, by amino acid substitution strategy and surface plasmon resonance (SPR) analysis, we designed a novel PDGFRβ-targeting peptide (YQGX-10) with high affinity (Kd = 227.7 nM) and coupled it with a near-infrared fluorescent (NIRF) dye MPA for precisely detection of PA. Great binding affinity and specificity were displayed in a series of in vitro assays. NIRF imaging experiments demonstrated that the synthesized probe could be highly accumulated in xenograft and orthotopic BxPC-3 tumors and provide favorable tumor contrast in the mice, offering a potential novel approach for the early diagnosis of PA. Moreover, YQGX-10 could visualize tumor boundaries and minor lesions in BxPC-3 xenograft mice, shedding a new light on NIRF-guided tumor resection of PA. In addition, we successfully constructed the radioactive probe 99mTc-HYNIC-YQGX-10 for the diagnosis of PA with high specificity and sensitivity. In summary, the probe warrants further exploration for clinical translation in the early diagnosis and NIRF-guided surgery of PA.

Clinicopathological features, prognostic significance, and associated tumor cell functions of family with sequence similarity 111 member B in pancreatic adenocarcinoma.

Among digestive tract tumors, pancreatic adenocarcinoma (PAAD) has a high degree of malignancy. Therefore, it is important to search for pancreatic adenocarcinoma-related differential genes and new oncogene therapeutic targets for early diagnosis, treatment, and prognosis of pancreatic adenocarcinoma. This study aims to investigate the expression and clinical significance of Family with sequence similarity 111 member B (FAM111B) in PAAD. Bioinformatics was used to analyze the relationship between FAM111B expression and pancreatic adenocarcinoma and to predict its role in related pathways. Tissue microarrays were used to assess the levels of FAM111B in pancreatic cancer tissues by immunohistochemical staining, and the effects of FAM111B expression levels on apoptosis, proliferation, invasion and migration of tumor cells were observed and verified by in vitro cellular assays. FAM111B expression was higher in PAAD tissue than in matched normal tissues (p < 0.05). The expression level of FAM111B, the metastatic status of lymph nodes was an independent prognostic factor for PAAD survival (p < 0.05). Meanwhile, overexpression of FAM111B promoted PAAD cell proliferation, migration, invasion and inhibited PAAD cell apoptosis (p < 0.05). In contrast, knockdown of FAM111B triggered the opposite result (p < 0.05). In the results of GSEA, it was shown that FAM111B may be involved in PAAD progression through p53 signaling pathway, cell cycle, and other signaling pathways (p < 0.05 and FDR q-val <0.25). FAM111B is highly expressed in PAAD tissues and is closely associated with poor prognosis of PAAD. FAM111B significantly promotes the proliferation, invasion, and migration of pancreatic adenocarcinoma cells while it inhibits their apoptosis. FAM111B may be a new biomarker for PAAD. It may provide a new direction for the treatment and diagnosis of PAAD.