Pancreatic Carcinoma Patients Research Articles

Prevalence of germline variants in Brazilian pancreatic carcinoma patients

We evaluated the prevalence of pathogenic/likely pathogenic germline variants (PGV) in Brazilian pancreatic adenocarcinoma (PC) patients, that represent a multiethnic population, in a cross-sectional study. We included 192 PC patients unselected for family history of cancer. We evaluated a panel of 113 cancer genes, through genomic DNA sequencing and 46 ancestry-informative markers, through multiplex PCR. The median age was 61 years; 63.5% of the patients presented disease clinical stages III or IV; 8.3% reported personal history of cancer; 4.7% and 16.1% reported first-degree relatives with PC or breast and/or prostate cancer, respectively. Although the main ancestry was European, there was considerable genetic composition admixture. Twelve patients (6.25%) were PGV carriers in PC predisposition genes (ATM, BRCA1, BRCA2, CDKN2A, MSH2, PALB2) and another 25 (13.0%) were PGV carriers in genes with a limited association or not previously associated with PC (ACD, BLM, BRIP1, CHEK2, ERCC4, FANCA, FANCE, FANCM, GALNT12, MITF, MRE11, MUTYH, POLE, RAD51B, RAD51C, RECQL4, SDHA, TERF2IP). The most frequently affected genes were CHEK2, ATM and FANC. In tumor samples from PGV carriers in ACD, BRIP1, MRE11, POLE, SDHA, TERF2IP, which were examined through exome sequencing, the main single base substitutions (SBS) mutational signature was SBS1+5+18, probably associated with age, tobacco smoking and reactive oxygen species. SBS3 associated with homologous repair deficiency was also represented, but on a lower scale. There was no difference in the frequency of PGV carriers between: (a) patients with or without first-degree relatives with cancer; and (b) patients with admixed ancestry versus those with predominantly European ancestry. Furthermore, there was no difference in overall survival between PGV carriers and non-carriers. Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following Pancreaticoduodenectomy. a 10-year before and after study.

Sinistral portal hypertension (SPH) may occurs in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) cofluence resection. This study aimed to evaluate outcomes with the bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients. A total of 81 patients were included. We retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from Jan. 2011 to Dec. 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, we prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from Jan. 2021 to Jan. 2023. In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15). Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.

Early Diagnosis of Cancer of the Pancreas: A Key Step in Improving Survival Rates

Cancer of the pancreas has a lifetime incidence in the United States of 1.6% [1]. It accounts for 3.2% of all new cancers and is the 12th most common cancer. The survival of those diagnosed with cancer of the pancreas is unfortunately poor. The majority of pancreatic carcinoma patients are diagnosed at advanced stages of disease [2]. Only 15-20% of patients are candidates for surgical resection at diagnosis and the 5 year survival is less than 10% [3,4]. It is expected to become the second leading cause of death from cancer within a decade [5]. Cancer of the pancreas is the only common cancer for which early detection is not universally available.

Preoperative plasma fibrinogen and C-reactive protein/albumin ratio as prognostic biomarkers for pancreatic carcinoma.

Pancreatic carcinoma is characterised by high aggressiveness and a bleak prognosis; optimising related treatment decisions depends on the availability of reliable prognostic markers. This study was designed to compare various blood biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin (Alb), plasma fibrinogen (PF), and CRP/Alb in patients with pancreatic carcinoma. Our study retrospectively reviewed 250 patients with pancreatic carcinoma diagnosed between July 2007 and December 2018. The Cutoff Finder application was used to calculate the optimal values of CRP/Alb and PF. The Chi-square test or Fisher's exact test was used to analyse the correlation of CRP/Alb and PF with other clinicopathological factors. Conducting univariate and multivariate analyses allowed further survival analysis of these prognostic factors. Multivariate analysis revealed that, in a cohort of 232 patients with pancreatic ductal adenocarcinoma (PDAC), the PF level exhibited statistical significance for overall survival (hazard ratio (HR) = 0.464; p = 0.023); however, this correlation was not found in the entire group of 250 patients with pancreatic carcinoma. Contrastingly, the CRP/Alb ratio was demonstrated statistical significance in both the entire pancreatic carcinoma cohort (HR = 0.471; p = 0.026) and the PDAC subgroup (HR = 0.484; p = 0.034). CRP/Alb and PF demonstrated a positive association (r=0.489, p<0.001) as indicated by Spearman's rank correlation analysis. Additionally, in 232 PDAC patients, the combination of the CRP/Alb ratio and PF had synergistic effects on prognosis when compared with either the CRP/Alb ratio or the PF concentration alone. PF concentration is a convenient, rapid, and noninvasive biomarker, and its combination with the CRP/Alb ratio could significantly enhance the accuracy of prognosis prediction in pancreatic carcinoma patients, especially those with the most common histological subtype of PDAC.

Impact of Combined Chemotherapy and Targeted Therapy on Pancreatic Neuroendocrine Carcinoma with Liver Metastasis: A Single-Center Modified Nomogram Analysis.

To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients. A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model's feasibility, accuracy, and reliability. Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping. Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.

Upregulated miR-27a-3p Indicates a Poor Prognosis in Pancreatic Carcinoma Patients and Promotes the Angiogenesis and Migration by Epigenetic Silencing of GATA6 and Activating VEGFA/VEGFR2 Signaling Pathway [Retraction

[This retracts the article DOI: 10.2147/OTT.S220621.].

Primary tumor resection enhances the survival of pancreatic neuroendocrine carcinoma patients with liver metastasis under the definition of 2019 WHO classification.

With the update and release of the newest version of WHO classification (2019) for neuroendocrine neoplasm, the clinical features, risk factors of prognosis and the effect of surgical treatment on newly classified pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis were not deeply analyzed. In the present study, we tried to reveal the clinical features, and prognostic factors of pNEC patients with liver metastasis with the newest definition of WHO 2019, and explore whether primary tumor resection (PTR), chemotherapy and radiotherapy affect overall survival (OS) and cancer-specific survival (CSS) in those patients. We collected data from pNEC patients with liver metastasis from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed between 2010 and 2019. We strictly selected pNEC patients according to the 2019 WHO classification criteria. The univariate and multivariate Cox regression analysis were used to determine independent predictors of the survival of these patients. The forest plots map was drawn by R-4.2.2 software to display the results of the multivariate analysis visually. Kaplan-Meier method was used to estimate the OS and CSS. Based on the multivariate analysis outcomes, we established the predictable nomogram model to predict the prognosis of pNEC patients with liver metastasis. The calibration plots were shown to prove the predictive value of the nomogram predictable model. We identified 205 eligible pNEC patients with liver metastasis. According to the multivariable Cox regression analysis in this study, we found that PTR, chemotherapy, primary tumor size and diagnosis to treatment time were independent prognostic factors for both OS and CSS. Kaplan-Meier survival curves demonstrated that PTR and chemotherapy were correlated with increased survival for pNEC patients with liver metastasis. The accuracy of the nomogram model was visually proved by the calibration plot with acceptable predictive performance. Four independent predictors of prognosis in pNEC patients with liver metastasis were identified in this study, including PTR, chemotherapy, tumor size and diagnosis to treatment time. PTR and chemotherapy for pNEC with liver metastasis could lead to a better prognosis, which may provide inspiration for practical clinical guidelines.

Prognostic value of pretreatment skeletal muscle index in pancreatic carcinoma patients: A meta-analysis.

The association between pretreatment skeletal muscle index (SMI) and long-term survival of pancreatic carcinoma patients remains unclear up to now. The PubMed, Web of Science and EMBASE databases were searched up to March 1, 2022 for relevant studies. The primary and secondary outcomes were overall survival and progression-free survival, respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and prognosis of pancreatic carcinoma patients. All statistical analysis was conducted by STATA 15.0 software. Twenty retrospective studies involving 3765 patients were included. The pooled results demonstrated that lower pretreatment SMI was significantly related to poorer overall survival (HR = 1.42, 95% CI: 1.25-1.62, P < .001) and progression-free survival (HR = 1.41, 95% CI: 1.08-1.84, P = .012). Besides subgroup analysis based on the treatment (non-surgery vs surgery) and tumor stage (advanced vs early stage) showed similar results. Pretreatment SMI could serve as a promising and reliable prognostic factor for pancreatic carcinoma patients and lower pretreatment SMI predicted worse prognosis.

Comparison of Diagnostic Yield and Safety of Serial Pancreatic Juice Aspiration Cytologic Examination (SPACE) with Different Indications.

We assessed whether there are differences in the diagnostic yield and safety of serial pancreatic juice aspiration cytologic examination (SPACE) among different indications. We retrospectively analyzed 226 patients who underwent SPACE. They were classified into group A (patients with pancreatic masses, including advanced adenocarcinoma, sclerosing pancreatitis, or autoimmune pancreatitis), group B (suspicious pancreatic carcinoma patients without obvious pancreatic masses, including small pancreatic carcinoma, carcinoma in situ, or benign pancreatic duct stenosis), and group C (intraductal papillary mucinous neoplasm, IPMN). There were 41, 66, and 119 patients, with malignancy diagnosed in 29, 14, and 22 patients, in groups A, B, and C, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69%, 100%, 100%, 57%, and 78% in group A; 79%, 98%, 92%, 94%, and 94% in group B; and 27%, 87%, 32%, 84%, and 76% in group C, respectively. PEP was observed in three (7.3%), three (4.5%), and fifteen (13%) patients in group A, B, and C, respectively (p = 0.20). SPACE is useful and safe in patients with suspicious small pancreatic carcinoma. However, it has limited efficacy and might not be recommended in patients with IPMN because of the high frequency of PEP.

Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells.

Our pre-investigation has revealed that long non-coding RNA (LncRNA) AL137789.1 has the potential to predict the survival of patients with pancreatic carcinoma (PCa). Accordingly, the mechanism underlying the implication of AL137789.1 in PCa is covered in the current study. The non-tumor and paired tumor tissues were collected. Kaplan-Meier curve was employed to estimate the survival of PCa patients with high or low expression of AL137789.1. The proliferation, migration, invasion, and cell cycle of PCa cells were determined, and the cytotoxicity of CD8+ T cells was evaluated as well. Levels of AL137789.1, E-cadherin, N-cadherin, and Vimentin were quantified. According to the experimental results, AL137789.1 was highly expressed in PCa and related to a poor prognosis of patients. Overexpressed AL137789.1 enhanced the proliferation, migration, and invasion of PCa cells, increased the cell population at G2/M and S phases yet decreased that in G0/G1 phase, and diminished the cytotoxicity of CD8+ T cells. Also, overexpressed AL137789.1 elevated levels of N-cadherin and Vimentin, while lessening E-cadherin levels. However, the silencing of AL137789.1 produced contrary effects. Collectively, lncRNA AL137789.1 plays a tumor-promotive role in PCa by enhancing the progression and immune escape.

Electrochemiluminescence imaging of a membrane carcinoembryonic antigen at single tissue sections.

Histopathological molecular testing of tissue sections is an essential step in tumor diagnosis; however, the commonly used immunohistochemical methods have problems such as low specificity and the subjective bias of the observer. Here, we report an electrochemiluminescence (ECL) imaging method to detect a membrane carcinoembryonic antigen (CEA) at the single tissue sections of cancer patients. By permeabilizing the tissue attached to a glassy carbon electrode, Ru(bpy)32+ tagged at the membrane CEA of the tissue could electrochemically react with TPrA in solution to emit ECL that has near-zero background and an extremely high signal-to-background ratio. Using the established ECL method, the expression differences and distribution characteristics of the CEA protein in the carcinoma and paracancerous tissues of pancreatic ductal carcinoma (PDAC) and lung adenocarcinoma (LUAD) patients are investigated. The images reveal that CEA proteins are mostly distributed in the acini and surrounding areas both in PDAC and LUAD tissues. Therefore, the presented approach could be able to provide a new molecular recognition method for the diagnosis of adenocarcinoma and other tumors.

A composite indicator of derived neutrophil-lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors.

There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy. Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit. There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis. The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

Preanalytical Variables in the Analysis of Mitochondrial DNA in Whole Blood and Plasma from Pancreatic Cancer Patients.

Given the crucial role of mitochondria as the main cellular energy provider and its contribution towards tumor growth, chemoresistance, and cancer cell plasticity, mitochondrial DNA (mtDNA) could serve as a relevant biomarker. Thus, the profiling of mtDNA mutations and copy number variations is receiving increasing attention for its possible role in the early diagnosis and monitoring therapies of human cancers. This applies particularly to highly aggressive pancreatic cancer, which is often diagnosed late and is associated with poor prognosis. As current diagnostic procedures are based on imaging, tissue histology, and protein biomarkers with rather low specificity, tumor-derived mtDNA mutations detected from whole blood represents a potential significant leap forward towards early cancer diagnosis. However, for future routine use in clinical settings it is essential that preanalytics related to the characterization of mtDNA in whole blood are thoroughly standardized, controlled, and subject to proper quality assurance, yet this is largely lacking. Therefore, in this study we carried out a comprehensive preanalytical workup comparing different mtDNA extraction methods and testing important preanalytical steps, such as the use of different blood collection tubes, different storage temperatures, length of storage time, and yields in plasma vs. whole blood. To identify analytical and preanalytical differences, all variables were tested in both healthy subjects and pancreatic carcinoma patients. Our results demonstrated a significant difference between cancer patients and healthy subjects for some preanalytical workflows, while other workflows failed to yield statistically significant differences. This underscores the importance of controlling and standardizing preanalytical procedures in the development of clinical assays based on the measurement of mtDNA.

The Efficacy of Imaging in Diagnosing Carcinoma Pancreas and to Assess Respectability after Comparing Them with Per-Operative Findings

Background: Carcinoma pancreas is increasingly being identified by conventional imaging techniques such as ultrasonography (USG), computed tomography (CT) scans, and magnetic resonance imaging (MRI). Imaging also allows for the evaluation of resectability. MRI and CT scans are not generally available in our nation, and most pancreatic carcinomas are too advanced for curative surgical resection when discovered. These are unresectable pancreatic carcinomas (UCP). Objective: In this study our main goal is to evaluate the efficacy of imaging in diagnosing carcinoma pancreas and to assess respectability after comparing them with per-operative findings. Method: This prospective study was done at tertiary medical hospital from January 2021 to January 2022. Where Hospital records of all 150 pancreatic carcinoma patients admitted during the period were retrospectively analyzed. Pre-operatively labeled unresectable carcinoma pancreas patients that underwent laparotomy with histopathological proof during this period were included for the study. Total 150 patients were labeled as ‘unresectable carcinoma. All patients were evaluated by USG and CT scan. MRI was done where USG /CT scan had failed to give any clue about the diagnosis in clinically suspected 8 carcinoma pancreas patients. Results: During the study, majority were belonging to &gt;60 years age group, 65%. USG was able to diagnose 85% with pancreatic cancer followed by CT and MRI scan was able to diagnose 90% and 100% with pancreatic cancer. According to per-operative findings most of the lesions were found at the head of the pancreas, 75%, followed by 16% cases were in body and 9% cases were tail. However, the situation is quite different in USG and CT findings. Where in USG 80% cases were head and In CT it was 70%. Moreover, in MRI it was 78%. According to pre-operative findings ascites was seen in 25% cases, however according to USG it was 18% cases, in CT it was 23%, and in MRI it was 15% cases. USG was able to ......

Abstract 1710: Spatial transcriptomics and multiplexed imaging to explore tumor heterogeneity and immune complexity

Abstract Spatial transcriptomics (ST) and CO-Detection by indEXing (CODEX) are becoming the leading transformative approaches for studying spatially resolved tumor heterogeneity and immune complexity. To explore the application of these two cutting-edge technologies and to further investigate the complexities of tumor microenvironment, we applied 10x Visium Gene Expression platform and Akoya CODEX platform on surgical resections from pancreatic ductal adenocarcinoma (PDAC), breast cancer (BRCA), and clear cell renal carcinoma (ccRCC) patients. A total of 30+ protein markers were screened, verified, and conjugated as CODEX antibodies for the 3 types of cancers. Tumor microenvironment was vividly revealed by a set of cancer markers, immune markers, and stroma cells markers on a single ST slide and a single CODEX image. Notably, the distinct immune microenvironment was observed between tumor nests in the neighborhood in terms of cell types, number of cells, and cell distribution patterns. This work highlights the importance of direct visualization for tumor heterogeneity. It also provides a significant insight for understanding tumor complexity and a promising opportunity to benefit personalized medicine. Citation Format: Siqi Chen, Andrew Shinkle, Yanyan Zhao, Chia-Kuei Mo, Andrew Houston, Preet Lal, John M. Herndon, Ryan C. Fields, William Gillanders, Feng Chen, Li Ding. Spatial transcriptomics and multiplexed imaging to explore tumor heterogeneity and immune complexity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1710.

Prognostic Significance of PNI in Patients With Pancreatic Head Cancer Undergoing Laparoscopic Pancreaticoduodenectomy.

BackgroundRecently, several prognosis indicators based on inflammatory and nutritional factors, such as the neutrophil-to-lymphocyte ratio (NLR), plated-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and prognosis nutritional index (PNI), have been proposed as prognosis factors for several cancers. However, few studies have looked into PNI. The goal of this research was to see if preoperative PNI had any predictive value in patients with pancreatic head cancer who were having a laparoscopic pancreaticoduodenectomy.MethodsFrom February 11, 2018 to May 31, 2019, two hundred and fifty-one pancreatic head carcinoma patients were retrospectively enrolled. The receiver operator characteristic (ROC) curve was used to determine the cut-off value. Patients were divided into two groups: PNI > 45.1 (high PNI group) and PNI < 45.1 (low PNI group), and clinic-pathological data was compared between the two groups. The link between PNI and NLR, PLR, and LMR, and their effect on overall survival. In addition, the factors of postoperative survival were analyzed univariate and multivariate.ResultsPNI, NLR, PLR and LMR cut-off values were 45.1, 3.7,287.2 and 3.6, respectively. Between the two groups of patients, the low PNI group exhibited considerably higher PLR and lower LMR. PNI had a negative correlation with PLR and NLR (r = −0.329, p < 0.001 and r = 0.170, p = 0.014), but a positive correlation with LMR (r = 0.476, p < 0.001). The high PNI group had a considerably greater survival rate than the low PNI group (median survival days, 217 vs. 468, log-rank = 45.92, p < 0.001). PNI < 45.1(HR: 0.357, 95 percent CI, 0.263–0.485, p < 0.001) and LMR <3.6(HR: 0.705, 95 percent CI, 0.528–0.942, p < 0.018) were revealed to be possible predictive variable in univariate analysis. Only PNI <45.1 was found to be an independent predictive factor in multivariate analysis (HR: 0.359, 95%CI,: 0.256–0.502, p < 0.001).ConclusionsOur findings shoe that PNI is linked to a variety of systemic inflammatory response and can be used to predict survival in individuals with pancreatic head cancer.

P-224 Тoxicity and tolerability of the mFOLFIRINOX regimen in young elderly and older elderly patients with pancreatic carcinoma (PC)

Currently, the median age of PC patients is about 70 years. By 2030 nearly 70% of PC are expected to be diagnosed in the elderly. These patients are poorly represented in large clinical trials. Hence, there are limited data about the tolerability and efficacy of mFOLFIRINOX regimen in elderly patients. Methods We retrospectively analyzed the data of patients with PC 60 years and older who were treated with mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, 5FU 2400 mg/m2 for 46h) regimen in our center. Results Between 2010 and 2021 104 patients were included in the analysis. 92 patients were young elderly (60-74 years) and 12 were older elderly (75-90 years). The median age was 68 (range, 60 - 78). mFOLFIRINOX was administered postoperatively, as part of induction therapy in borderline/locally advanced or as palliative chemotherapy in 1, 42 and 61 patients, respectively. All patients had ECOG PS 0-2. Most common all grade and grade 3/4 toxicity were neutropenia (69,2% and 42,3%), febrile neutropenia (5,8%), thrombocytopenia (21,2% and 0,96%), anemia (17,3%), diarrhea (41,3% and 8,7%), nausea/vomiting (58,7% and 3,8%), asthenia (50,9% and 3,8%), neurotoxicity (20,1% and 0,96%). Dose reduction was performed in 45 patients (43.2%), 7 (6.7%) permanently discontinued treatment due to toxicity. The median number of cycles administered was 6 (range, 1 - 17). Primary and secondary G-CSF prophylaxis was used in 23% and 28.8% of patients, respectively. No treatment-related deaths were observed. Of the 104 patients, 12 were older elderly. The median age was 76 years (range 75-78). Dose reduction was required more often than the young elderly (58.3% vs 41,3%), but no patient stopped treatment due to toxicity. Most common all grade and grade 3/4 toxicity in older elderly group were neutropenia (16,7% and 50%), thrombocytopenia 1/2 grade (25%), diarrhea (58,3% and 25%), asthenia (66,7% and 0%). Tolerability didn’t differ between ECOG status. mFOLFIRINOX regimen is tolerable and demonstrates manageable toxicity in selected elderly patients with pancreatic carcinoma. This is a retrospective analysis of older patients with pancreatic adenocarcinoma treated with the mFOLFIRINOX regimen. Ages Eligible for Study: 60 Years and older Sexes Eligible for Study: All Criteria Inclusion Criteria: Histologically-confirmed pancreatic adenocarcinoma No prior chemotherapy for pancreatic cancer. ECOG performance status ≤3 Exclusion Criteria: Prior chemotherapy or any other investigational agents for the treatment of pancreatic cancer Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents. The authors.

The Role of Nonapoptotic Programmed Cell Death — Ferroptosis, Necroptosis, and Pyroptosis — in Pancreatic Ductal Adenocarcinoma Treatment

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, with a dismal 5-year survival rate of less than 10%. It is estimated that approximately 80% of pancreatic ductal carcinoma (PDAC) patients are diagnosed at an advanced or metastatic stage. Hence, most patients are not appropriate candidates for surgical resection and therefore require systemic chemotherapy. However, it has been reported that most patients develop chemoresistance within several months, partly because of antiapoptotic mechanisms. Hence, inducing alternative programmed cell death (PCD), including ferroptosis, necroptosis or pyroptosis, seems to be a promising strategy to overcome antiapoptosis-mediated chemoresistance. In this review, we shed light on the molecular mechanisms of ferroptosis, necroptosis and pyroptosis and suggest several potential strategies (e.g., compounds and nanoparticles [NPs]) that are capable of triggering nonapoptotic PCD to suppress PDAC progression. In conclusion, these strategies might serve as adjuvants in combination with clinical first-line chemotherapies to improve patient survival rates.

Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells.

Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.

Restraint of FAM60A has a cancer-inhibiting role in pancreatic carcinoma via the effects on the Akt/GSK-3β/β-catenin signaling pathway.

Family with sequence similarity 60A (FAM60A) has been reported as a new cancer-related protein that affects the malignant progression of some cancers. However, whether FAM60A plays a part in pancreatic carcinoma is undetermined. This work was designed to examine the impact of FAM60A in pancreatic carcinoma. Abundant expression of FAM60A was observed in the primary tumor tissue of pancreatic carcinoma. Moreover, a high FAM60A level was related to a poor overall survival in pancreatic carcinoma patients. Malignant behaviors of pancreatic carcinoma cells, such as proliferation and invasiveness, were markedly affected by FAM60A depletion. In addition, FAM60A depletion enhanced the drug sensitivity of pancreatic carcinoma cells to gemcitabine. Further study revealed that FAM60A depletion impaired the activities of Akt and β-catenin. Inhibiting the activity of Akt abolished FAM60A-mediated β-catenin activation. Re-expression of β-catenin partially diminished the FAM60A-depletion-mediated cancer suppressive effect in pancreatic carcinoma cells. In vivo experiments demonstrated that FAM60A depletion prohibited the xenograft formation of pancreatic carcinoma cells, with concurrent reductions of Akt and β-catenin activities. Collectively, our findings indicate that FAM60A exerts a cancer-promoting role in pancreatic carcinoma through affection of the Akt/β-catenin pathway. This work indicates that FAM60A acts as a tumor promoter in pancreatic carcinoma and can be utilized as a potential target for anti-pancreatic carcinoma therapy development.