Cases Of Pancreatic Adenocarcinoma Research Articles

Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma

Objective: To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma. Methods: (1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis. Results: (1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients (HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration (ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 (r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway (P=0.029), the PI3K/Akt pathway (P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration (r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma (ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ²=1.93, P=0.165). Conclusion: FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Detective flow imaging versus contrast-enhanced EUS in solid pancreatic lesions.

Detective flow imaging EUS (DFI-EUS) is a new technology that detects fine vessels and low-flow velocity without contrast agents, used in real time during EUS, with a better resolution compared to usual technologies such as color Doppler and eFLOW. The aim of this study was to compare DFI-EUS with contrast-enhanced EUS (CE-EUS) for the evaluation of vascularization in solid pancreatic lesions. We included patients who had a pancreatic mass visualized by EUS, with recorded images of their assessment in DFI-EUS and CE-EUS techniques and a histological diagnosis confirmed malignant tumors or a minimum of 1-year follow-up for benign lesions. Of the 107 patients included in this retrospective single-center study, the histological diagnosis revealed 69 cases (64.5%) of pancreatic adenocarcinoma, 18 cases (16.8%) of neuroendocrine tumors (NETs), and 10 cases (9.3%) of metastases from nonpancreatic cancers. A smaller proportion (9.4%) exhibited other lesions. As a result, the incidence of intralesional microvascularization was 43.9% with DFI-EUS and 48.6% with CE-EUS, indicating a positive correlation between the 2 techniques (P = 0.0001). Compared to CE-EUS, DFI-EUS exhibited sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 88.5%, 98.2%, 97.9%, and 90%, respectively, for the detection of intralesional vessels. The novel technique DFI-EUS demonstrates a remarkable correlation with CE-EUS, exhibiting high sensitivity and specificity for the assessment of microvascularization in solid pancreatic lesions. This method eliminates the need for a contrast agent, thus carrying no risk of adverse effects.

Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics.

Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.

Resectability rate of pancreatic cancer after neoadjuvant therapy.

e16348 Background: Pancreatic Cancer is one of the leading causes of cancer death in Saudi Arabia. Surgery is the mainstay of treatment in resectable non-metastatic cases. Working on improving the resectability rate to achieve R0 resection is the standard of care. Methods: Unresectable cases of pancreatic adenocarcinoma seen from 2004 till 2018 in three hospitals in Saudi Arabia were reviewed to know the conversion rate from unresectable or borderline resectable to resectable after neoadjuvant chemotherapy and to explore the possible prognostic factors. The characteristics and outcomes of these patients were reviewed, with more attention on the known prognostic factors and their impact on the outcome. Notably, performance status, CA19-9, Neutrophil Lymphocyte Ration (NLR), and Platelet Lymphocyte Ratio (PLR). Overall response to neoadjuvant therapy, R0 resection, relapse free survival and overall survival were all reported. Results: Two hundred seventy-three captured cases of all types of pancreatic tumors from the tumor registry in the years between 2004 and 2018. 39 cases were unresectable or borderline resectable cases. The median age was 60 years (range:29-79), and 25 patients were males. 30 patients had an ECOG PS of 0-1and 6 had an ECOG PS of 2. The head of the pancreas was the primary tumor site in 31 patients and the body or tail was in 8 patients. 21 patients (54%) presented with weight loss ( &gt; 5kg), and 21 patients (54%) presented with obstructive jaundice. Neoadjuvant chemotherapy protocols were FOLFORINOX (13 patients, 33%), Gemcitabine/Capecitabine (10 patients), single agent Gemcitabine (10 patients), and other regimens in 6 patients. The median number of chemotherapy cycles was 6 (range: 1-14). 17 patients had dose reduction. 6 patients had preoperative radiation. Response to chemotherapy: ORR: 36%, SD: 26% and PD: 38% .Surgery was done after neoadjuvant therapy in 12 patients (31%). Only 4 out 12 had confirmed R0. Median Overall Survival (MS) and Progression-Free survival (PFS) in all patients were 30 mo (95% CI: 17.75 - 42.56) and 8 mo (95% CI: 5.65 - 11.89) respectively. MS in the surgery and the non-surgery groups was 30 and 25 mo (p- value = 0.26) respectively. The median PFS in the surgery and the non-surgery groups was 19.6 and 5.8 mo (p- value = 0.008) respectively. Multivariate regression analysis done for the following variables: ECOG PS of 2, elevated CA 199, high NLR &gt; 3, high PLR &gt; 225, weight loss and results showed numerical difference of both MS and PFS with no statistical significance (Type 2 error). Conclusions: The conversion rate from unresectable or borderline resectable to resectable after neoadjuvant therapy is 31% which is consistent with the international data. There is PFS improvement in those who underwent surgery (19.6 mo vs. 5.8 mo) with statistical significance (p:0.008), and there is numerical improvement of MS (30 mo vs. 25 mo) that did not reach statistical significance.

The role of germline BRCA1 & BRCA2 mutations in familial pancreatic cancer: A systematic review and meta-analysis.

Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations. Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist. We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted. Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.

Prolonged length of stay and omission of adjuvant therapy are associated with early mortality after pancreatic adenocarcinoma resection

BackgroundSurgical resection is the preferred treatment for non-metastatic pancreatic adenocarcinoma, but post-resection survival is highly variable. We use the National Cancer Database Participant Use Files to investigate risk factors associated with early mortality (survival less than one year) after pancreatic adenocarcinoma resection. Methods51,345 cases of pancreatic adenocarcinoma were identified. 16,234 had survival between three months and one year (early mortality), and 35,111 had survival greater than one year. Descriptive analyses and multivariate Cox regression models were performed to identify demographic, perioperative, and tumor biology factors associated with early mortality. A sub-analysis subsequently explored the relationship between the length of stay and chemotherapy utilization. ResultsOf the 51,345 cases of pancreatic adenocarcinoma, 16,234 had early mortality. In multivariate models adjusted for demographic, socioeconomic, facility type, tumor characteristics, and hospital risk factors, patients with early mortality also had longer lengths of stay, more unplanned readmissions. They were more likely to receive treatment at non-academic centers. Adjuvant chemotherapy utilization was lower in patients with early mortality, particularly in those with longer lengths of stay. ConclusionReducing the length of stay, decreasing variability across different forms of health insurance, and increasing access to treatment at academic centers may reduce early mortality. Adjuvant chemotherapy is associated with a reduced risk of early mortality but is highly underutilized, especially in patients with prolonged hospital stays. Given that delays in receiving adjuvant chemotherapy were associated with an increased risk of early mortality, interventions to decrease perioperative complications to ensure timely access to adjuvant chemotherapy may improve survival.

Abstract B001: Impedance based biomarker for “smart ROSE” pancreatic cancer detection: Initial results from an ongoing clinical trial with nsCanary

Abstract Pancreatic cancer (PC) accounts for half a million new cases and 4.7% of cancer-related deaths globally in 2020. Endoscopic ultrasound (EUS) guided fine needle biopsies (FNB) are the current standard for confirming suspicious lesions, although their diagnostic accuracy remains below 70% with a non-diagnostic rate of the first procedure as high as 40%. Rapid on-site evaluation (ROSE) was introduced to improve diagnostic accuracy via on-site pathology assessment. However, ROSE availability is often limited due to resource constraints. NovaScan has developed the nsCanary, a ”smart ROSE” device, which uses a bioimpedance spectroscopy biomarker based on the Cole Relaxation Frequency (CRF) to detect cancer in biopsy samples in real-time and on-site. The aim of this study is to present initial results from a clinical trial that validates the nsCanary’s ability to detect PC in biopsy samples. Data were collected with the nsCanary device in an IRB approved double-blind study including a cohort of 44 patients (20 males, 24 females; average age of 63 years; 66% White, 22% African American, 12% Hispanic) undergoing EUS procedures with FNB sampling for suspected PC at the Texas International Endoscopy Center in Houston, TX. The nsCanary is a small desktop instrument that performs spectral bioimpedance analysis to extract the CRF based biomarker in less than 30 seconds without altering the biopsied tissue. A touch panel user interface allows for the user to input information and start the measurement. Obtained biopsy samples were flushed in a disposable strainer in order to drain any excess fluid. A circular disposable electrode, consisting of an interdigitated array with alternating polarities was placed in contact with the sample to perform measurements of complex bioimpedance in the 1 kHz - 10 MHz frequency range. The design of the electrode allows it to sense the signal from samples as small as FNB cores. Samples with CRF value below 1 MHz for every scan were considered noncancerous. Samples with at least one CRF value above 1MHz or absence of CRF reading (i.e., CRF out of range) were considered cancerous. PC assessment provided by nsCanary was validated against histopathology outcomes for each biopsy sample. Pathology results indicated that out of the cancerous lesions observed, there were 7 cases of pancreatic adenocarcinoma, 2 cases of invasive adenocarcinoma, 1 case of ductal adenocarcinoma, and 1 case of metastatic renal cell carcinoma. Findings showed a sensitivity of 81.8%, specificity of 84.8%, PPV of 64.3% and NPV of 93.3% for a total of n=44 patients. The device is low cost, portable, and can be used in the surgical suite without interfering with the standard workflow or affecting the sample for following pathological assessment. The implementation of the nsCanary device into the clinic will adjunctively support the decision-making process by providing immediate feedback on cancer detection and sample adequacy. This will enable endoscopists to diagnose PC on the first biopsy procedure, ultimately facilitating prompt treatment of patients. Citation Format: Federica Dibennardo, Martina Guidetti, Onur Fidaner, Daniel S. Gehrke, Donato Ceres, Margaret C. John, Constantine H. Bovalis, Isaac Raijman, Les Bogdanowicz. Impedance based biomarker for “smart ROSE” pancreatic cancer detection: Initial results from an ongoing clinical trial with nsCanary [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B001.

Obesity Is Associated with Distal Migration of Pancreatic Adenocarcinoma to Body and Tail: A Multi-Center Study.

(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15-17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32-6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association.

Childhood and adulthood passive and active smoking, and the ABO group as risk factors for pancreatic cancer in women.

Active smoking and the A blood group are associated with pancreatic adenocarcinoma (PC) risk. However, potential interactions between those risk factors and the role of passive smoking have been little investigated. We aimed to explore specific and joint associations of passive and active smoking, and effect modification by the ABO blood group in French women. The study included 96,594 women from the E3N prospective cohort, mean age: 49years (SD 6.7). Information on active and passive smoking was reported at inclusion and throughout follow-up. Cases were classified according to the International Classification of Diseases 10. Associations with passive and active smoking and effect modification by the ABO blood group were investigated with multivariable Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI). During a 24-year median follow-up, 346 incident PC cases were identified. Current smoking compared with never and former smoking (HR 1.51 [95% CI 1.08-2.10]), and passive smoking in childhood compared with no childhood exposure (HR 1.47 [95% CI 1.08-2.00]) were associated with increased PC risk, but not passive exposure in adulthood (HR 1.16 [95% CI 0.91-1.47]). Exposure to both passive smoking in childhood and current smoking was associated with a stronger risk (HR 2.80 [95% CI 1.42-5.52]) than exposure to both current smoking and passive smoking only in adulthood (HR 1.68 [95% CI 1.10-2.57]) compared with neither passive nor active smoking. Associations between active smoking and PC risk were strongest in the O or B groups, while associations with passive smoking were strongest in the A or AB blood groups, but the interaction terms were not statistically significant. Both current smoking and passive smoking in childhood were associated with PC risk, with a maximal risk of current smokers exposed to passive smoking during childhood. Possible interactions between blood groups and active or passive smoking must be investigated in a larger series.

Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues.

The three-tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC). The Papanicolaou and May Grunwald Giemsa-stained smears from 116 cases of PACs were graded using the three-tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi-quantitatively. The inter-observer reproducibility in grading was evaluated using Kappa and Kendall's tau-c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau-b. 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter-observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter-observer reproducibility. Cases often show multiple grades in the same tumour.

Liquid Biopsy: A Highly Useful Tool to Decide Personalized Therapy in Veteran Patients with Metastatic Pancreaticobiliary Cancer

Abstract Introduction/Objective Pancreatic cancer is one of the leading causes of death in Veteran patients. Early detection and treatment of the pancreatic cancers are key to the successful management of pancreatic cancer with good patient outcome. The National Comprehensive Cancer Network (NCCN) recommends tumor molecular profiling in all patient cases of unresectable or metastatic pancreatic adenocarcinomas and biliary tract cancers who are candidates for chemotherapy. This testing can be performed using liquid biopsy to obtain this molecular profiling from circulating tumor cells (CTC) to obtain information that may impact treatment. However, the literature of metastatic pancreaticobiliary cancers targeted by liquid biopsies and the mutations found is sparse, particularly for the veteran population. Methods/Case Report A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a Veteran Affairs Medical Center (VAMC) from April 2020 to March 3rd, 2023, to examine those patients with metastatic pancreaticobiliary cancers, specifically pancreatic adenocarcinoma, and cholangiocarcinoma. Information on mutations detected was collected. Results (if a Case Study enter NA) There were a total of 5 patient specimens with a history of metastatic pancreatic adenocarcinoma (4 cases/5) and cholangiocarcinoma (1 case/5). The first liquid biopsy from a patient with a history of metastatic pancreaticobiliary cancer was sent on April 14th, 2020, and the last was sent on November 12th, 2021. TP53 was detected on all the successfully tested pancreatic adenocarcinoma cases. Other mutations detected in the individual pancreatic adenocarcinoma cases were KRAS, TET2 BCOR, DNMT3A, FUBP1, RAD21, and STAG2. The mutations found on the single cholangiocarcinoma case included DNMT3A and TP53. 1 of the 4 cases sent on a patient with pancreatic adenocarcinoma resulted in a sample failure. Conclusion Liquid biopsies provided comprehensive molecular profiling in cases of metastatic pancreatic adenocarcinoma and biliary tract cancer in the veteran population treated at a local VAMC to help decide on personalized therapy, in compliance with the recommendations of the NCCN. The results of this pilot quality assurance study help highlight the potential of liquid biopsies to detect most commonly mutated genes such as KRAS and T53 in pancreatic cancer.

Pancreatic Adenocarcinoma: Real World Evidence of Care Delivery in AccessHope Data.

Pancreatic adenocarcinoma is an aggressive disease and the delivery of comprehensive care to individuals with this cancer is critical to achieve appropriate outcomes. The identification of gaps in care delivery facilitates the design of interventions to optimize care delivery and improve outcomes in this population. AccessHope™ is a growing organization that connects oncology subspecialists with treating providers through contracts with self-insured employers. Data from 94 pancreatic adenocarcinoma cases (August 2019-December 2022) in the AccessHope dataset were used to describe gaps in care delivery. In all but 6% of cases, the subspecialist provided guideline-concordant recommendations anticipated to improve outcomes. Gaps in care were more pronounced in patients with non-metastatic pancreatic cancer. There was a significant deficiency in germline testing regardless of the stage, with only 59% of cases having completed testing. Only 20% of cases were receiving palliative care or other allied support services. There was no difference in observed care gaps between patients receiving care in the community setting vs. those receiving care in the academic setting. There are significant gaps in the care delivered to patients with pancreatic adenocarcinoma. A concurrent subspecialist review has the opportunity to identify and address these gaps in a timely manner.

MiRNAs targeting RAS and their clinical relevance in resected pancreatic adenocarcinoma (PC): Results from a prospective study.

e16314 Background: Pancreatic adenocarcinoma (PC) is one of the big killers with a 5-year disease-free survival (DFS) rate of 19-26% after resection despite adjuvant treatments. KRAS mutations have been reported in approximately 90% of PC cases and, beyond KRAS activation by gene mutations, several miRNAs directly targeting KRAS have been reported to be simultaneously downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes downstream miRNA effectors whose role needs to be elucidated. The aim of this study was to evaluate the expression of candidate miRNAs strictly related to KRAS expression in order to elucidate the prognostic value. Methods: In this single-center observational prospective study we included patients with pathologically confirmed PC, who underwent radical surgery and were referred to the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), between 2015 and 2022. Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. Results: Among 44 patients included in the study, 34.1% were male and 65.9% female (median age 75 years). The majority of cases had the primary tumor located at the head of the pancreas (65.9%) and the pathological stage was pT1-2 in 45.5%, pT3 in 54.5%, pN0 in 22.7%, pN+ in 77.3%. Overall, 63.6% of patients received adjuvant chemotherapy and 69.0% experienced disease recurrence. Twenty-three specimens were adequate for miRNA analysis. A different expression of the three target miRNAs between PC and healthy tissue was observed: miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 had a similar expression in both tissues. miR-143 overexpression was associated with nodal involvement (pN+) at the pathological examination (p = 0.029). Among clinicopathological features, pN+ was associated with shorter DFS (p = 0.009) and overall survival (OS) (p = 0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p = 0.095) and miR-143 (p = 0.092). Among patients receiving a first-line treatment for advanced disease, miR-155 was overexpressed in responders vs non-responders (p = 0.048). Conclusions: miRNA expression is involved in tumorigenesis and metastatic spread in PC. A comprehensive analysis of the miRNA-RAS interplay deserves to be further investigated as a predictor of clinical outcome, especially for miR-143 overexpression which was associated with lymphatic spread and, consequently, poor prognosis.

Is lung involvement a favorable prognostic factor for pancreatic ductal adenocarcinoma with synchronous liver metastases?—A propensity score analysis

ABSTRACT Background For advanced pancreatic cancer, pulmonary metastases (PM) have been considered favorable factors compared to metastases of other sites, but it remains unknown whether the prognosis of patients with synchronous liver and lung metastases is better than that of non-PM. Methods Data was derived from a two-decade cohort and included 932 cases of pancreatic adenocarcinoma with synchronous liver metastases (PACLM). Propensity score matching (PSM) was applied to balance 360 selected cases, grouped into PM (n = 90) and non-PM (n = 270). Overall survival (OS) and survival-related factors were analyzed. Results In PSM-adjusted data, the median OS was 7.3 and 5.8 months, for PM and non-PM, respectively (p = 0.16). Multivariate analysis revealed that male gender, poor performance status, higher hepatic tumor burden, ascites, elevated carbohydrate antigen 19–9, and lactate dehydrogenase were factors of poor survival (p < 0.05). Chemotherapy was the only independent significant factor of favorable prognosis (p < 0.05). Conclusion Although lung involvement was indicated to be a favorable prognostic factor for patients with PACLM in the whole cohort, PM were not associated with better survivals in the subset of cases subjected to PSM adjustment.

A Review on Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of Pancreatic Lesions.

The morbidity associated with pancreatectomies limits surgical options for high-risk patients with pancreatic neoplasms that warrant resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) offers a minimally invasive and potentially definitive means to treat pancreatic neuroendocrine tumors and precancerous pancreatic cystic lesions. In addition, EUS-RFA may play a role in the treatment and palliation of non-surgical cases of pancreatic adenocarcinoma. The efficacy of RFA appears to be further enhanced by systemic immunomodulatory effects. Here, we review current studies on the developing role of EUS-RFA in these pancreatic pathologies.

Adenosquamous carcinoma of the pancreas: two case reports and review of the literature

BackgroundAmong the total reported cases of pancreatic duct adenocarcinomas, around 1–2.9% are adenosquamous carcinomas of the pancreas. Due to limited data, preoperative diagnosis is a great challenge for physicians, and it is usually set post-operational, based on the pathologist report. We operated on two cases of adenosquamous carcinoma of the pancreas, which we present alongside the operation and treatment planning.Case reportA 69-year-old Caucasian female and a 63-year-old Caucasian male presented themselves with jaundice in our department. The abdomen computed tomography and magnetic resonance imaging scans revealed lesions of the pancreas. A pancreas–duodenumectomy was performed in both patients, and the post-operational histology analysis revealed adenosquamous carcinoma of the pancreas head. The patients were discharged in good condition and received further chemotherapy treatment after surgery.ConclusionsTwo case reports of adenosquamous carcinoma of the pancreas are described here, which both underwent surgery resection. The limited available literature on this topic substantially limits the knowledge and guidance on treatment. A summarization of the available literature is attempted, alongside a description of possible fields of future research.

The role of EUS elastography-guided fine needle biopsy in the histological diagnosis of solid pancreatic lesions: a prospective exploratory study

This study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastography-guided fine needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions. EUS-EG images were classified into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the first two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG findings using strain histogram analysis with the histological findings. Fifty-five patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had significantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88 and 92%, respectively (P = 0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no significant differences. In pancreatic adenocarcinoma cases, the proportion of fibrous stroma in the core tissue was significantly correlated with the elasticity of the region. (R2 = 0.1226: P = 0.0022) EUS-EG may reflect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained.Clinical Trial Registry No: UMIN-000033073.

Spot-scanning hadron arc (SHArc) therapy: A proof of concept using single- and multi-ion strategies with helium, carbon, oxygen, and neon ions.

To present particle arc therapy treatments using single and multi-ion therapy optimization strategies with helium (4 He), carbon (12 C), oxygen (16 O), and neon (20 Ne) ion beams. An optimization procedure and workflow were devised for spot-scanning hadron arc therapy (SHArc) treatment planning in the PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system (TPS). Physical and biological beam models were developed for helium, carbon, oxygen, and neon ions via FLUKA MC simulation. SHArc treatments were optimized using both single-ion (12 C, 16 O, or 20 Ne) and multi-ion therapy (16 O+4 He or 20 Ne+4 He) applying variable relative biological effectiveness (RBE) modeling using a modified microdosimetric kinetic model (mMKM) with (α/β)x values of 2, 5, and 3.1Gy, respectively, for glioblastoma, pancreatic adenocarcinoma, and prostate adenocarcinoma patient cases. Dose, effective dose, linear energy transfer (LET), and RBE were computed with the GPU-accelerated dose engine FRoG and dosimetric/biophysical attributes were evaluated in the context of conventional particle and photon-based therapies (e.g., volumetric modulated arc therapy [VMAT]). All SHArc plans met the target optimization goals (3GyRBE) and demonstrated increased target conformity and substantially lower low-dose bath to surrounding normal tissues than VMAT. SHArc plans using a singleion species (12 C, 16 O, or 20 Ne) exhibited favorable LET distributions with the highest-LET components centralized in the target volume, with values ranging from ∼80-170keV/μm, ∼130-220keV/μm, and ∼180-350keV/μm for 12 C, 16 O, or 20 Ne, respectively, exceeding mean target LET of conventional particle therapy (12 C:∼55, 16 O:∼75 20 Ne:∼95keV/μm). Multi-ion therapy with SHArc delivery (SHArcMIT ) provided a similar level of target LET enhancement as SHArc compared to conventional planning, however, with additional benefits of homogenous physical dose and RBE distributions. Here, we demonstrate that arc delivery of light and heavy ion beams, using either a single-ion species (12 C, 16 O, or 20 Ne) or combining two ions in a single fraction (16 O+4 He or 20 Ne+4 He) affords enhanced physical and biological distributions (e.g., LET) compared with conventional delivery with photons or particle beams. SHArc marks the first single- and multi-ion arc therapy treatment optimization approach using light and heavy ions.

Distinguishable Prognostic Signatures and Tumor Immunogenicity Between Pancreatic Head Cancer and Pancreatic Body/Tail Cancer.

BackgroundPancreatic head cancer and pancreatic body/tail cancer are considered to have different clinical presentations and to have altered outcomes.MethodsNinety cases of pancreatic adenocarcinoma (PDAC) from our institution were used as a discovery set and 166 cases of PDAC from the TCGA cohort were used as a validation set. According to the anatomical location, the cases of PDAC were divided into the pancreatic head cancer group and the pancreatic body/tail cancer group. Firstly, the different biological functions of the two groups were assessed by ssGSEA. Meanwhile, ESTIMATE and CIBERSORT were conducted to estimate immune infiltration. Then, a novel anatomical site-related risk score (SRS) model was constructed by LASSO and Cox regression. Survival and time-dependent ROC analysis was used to prove the predictive ability of our model in two cohorts. Subsequently, an integrated survival decision tree and a scoring nomogram were constructed to improve prognostic stratification and predictive accuracy for individual patients. In addition, gseaGO and gseaKEGG pathway analyses were performed on genes in the key module by the R package.ResultsOverall survival and the objective response rate (ORR) of patients with pancreatic body/tail cancer were markedly superior to those with pancreatic head cancer. In addition, distinct immune characteristics and gene patterns were observed between the two groups. Then, we screened 5 biomarkers related to the prognosis of pancreatic cancer and constructed a more powerful novel SRS model to predict prognosis.ConclusionsOur research shed some light on the revelation of gene patterns, immune and mutational landscape characterizations, and their relationships in different PDAC locations.

Sustained Weight Loss, Weight Cycling, and Weight Gain During Adulthood and Pancreatic Cancer Incidence in the Women's Health Initiative.

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women's Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR=1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR=1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR=1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women.