To develop a score system including CT features for predicting postoperative early (≤ 1 year) recurrence-free survival (RFS) in resectable pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical resection and assess its performance.

This dual-center, retrospective study included patients with resectable PDAC who underwent radical resection from September 2016 to April 2023. All CT features were independently evaluated by two blinded radiologists. An early recurrence score (ERS) based on CT and clinical features, for predicting early recurrence risk, was developed by Cox regression analysis in the developing cohort, and was validated in the testing and validation cohorts and compared with AJCC TNM staging system.

This study included 210 patients in the development cohort (mean age ± standard deviation, 60 ± 10 years; 129 men), 92 patients in the testing cohort (60 ± 9 years; 60 men), and 31 patients in the validation cohort (62 ± 7 years; 20 men). CA19-9 (hazard ratio [HR], 1.57; p = 0.044), perineural invasion on CT (HR, 1.83; p = 0.037), tumor necrosis (HR, 3.20; p < 0.001), and lymph nodes metastasis on CT (HR, 1.84; p = 0.004) formed the ERS. Its AUC of 0.851 and 0.901, superior to AJCC TNM staging (AUC of 0.630 and 0.534) in the testing and validation cohorts, (p < 0.05), respectively. The high-risk patients predicted by ERS had significantly higher postoperative 1-year recurrence rates than their low-risk counterparts in both the testing cohort (81.4% vs 22.5%, p < 0.001) and the validation cohort (81.2% vs 26.7%, p = 0.003).

The ERS noninvasively predicted early recurrence in resectable PDAC, outperforming the AJCC TNM system.

Question More accurately risk-stratifying PDAC patients would allow for better treatment planning. Findings Perineural invasion on CT, lymph nodes metastasis on CT, tumor necrosis, and CA19-9 were associated with early recurrence of resectable PDAC. Clinical relevance The ERS system showed better predictive performance for early recurrence in resectable PDAC and outperformed the American Joint Commission on Cancer TNM system.

The American Joint Committee on Cancer (AJCC) 8th edition TNM staging manual, which provided ypTNM for patients undergoing neoadjuvant therapy (NAT), has not been comparatively assessed against pTNM for prognosis in pancreatic cancer. This study aimed to compare the prognosis between ypTNM and pTNM stages.

Clinicopathological data from 586 patients who underwent pancreatic cancer surgery at a tertiary center between 2018 and 2022 were analyzed to compare survival outcomes between ypTNM and pTNM stages and identify prognostic factors.

The analysis included 541 patients (100 ypTNM, 441 pTNM). Significant differences in overall survival (OS) were observed among patients stratified by TNM stage (p < 0.001). However, no significant difference in OS was found between the ypTNM and pTNM groups (2-year survival rate (YSR): 76.8% vs. 66.7%, p = 0.094). Subgroup analysis by stage I (82.4% vs. 76.2%, p = 0.577) and II (68.8% vs. 61.6%, p = 0.715), and III (53.0% vs. 49.8%, p = 0.596) revealed similar survival rates. Multivariate analysis identified factors associated with OS: age > 65 years (HR 1.763, p < 0.001), CA19-9 > 150 U/mL (HR 1.439, p = 0.014), preoperative biliary drainage (HR 1.405, p = 0.029), pathologic T2 stage (HR 1.961, p = 0.004) and T3/4 stage (HR 2.830, p < 0.001) versus T0/1 stage, lymphovascular invasion (HR 2.220, p < 0.001), and adjuvant treatment (HR 0.251, p < 0.001).

This study confirms comparable survival outcomes between ypTNM and pTNM stages in surgically resected pancreatic cancer, affirming the applicability of the TNM staging system after NAT. The results highlight the utility of TNM staging in guiding therapeutic decisions for patients undergoing NAT.

To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.

Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP). Fractional β-cell area and islet density were compared among normal pancreas from donors and paraneoplastic tissues from non-diabetes mellitus (NDM) and T3cDM patients. TUNEL staining, RT-qPCR and CCK8 assay were applied to demonstrate the β-cell apoptosis.

Tumor cells, immune cells and fibroblasts could interact with endocrine cells, and apoptotic pathways were activated in endocrine cells of the PP. The PDAC TME was characterized by marked inflammation, sever fibrosis and atrophy. The islets in the PP had lower fractional β-cell area (0.68 ± 0.65% vs. 0.86 ± 1.02%, P = 0.037) and islet density (0.54 ± 0.42 counts/mm2 vs. 0.83 ± 0.90 counts/mm2, P = 0.001) compared to those in the DP. The PDAC TME in T3cDM exerted a more significant impact on the paraneoplastic islets compared to NDM. Moreover, β-cell apoptosis was markedly increased in the PP compared to the DP in PDAC patients without diabetes, particularly in smaller islets. Apoptosis-related genes were highly expressed in INS-1E cells exposed to PANC-1 medium.

Our research revealed that the PDAC TME is usually accompanied by some pathological changes, including inflammation, fibrosis, and atrophy. These pathological changes are related to a reduction in β-cell mass and trigger the development of T3cDM.

To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT).

Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor.

OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs 27.5 months, P  = 0.014; DSS: 63.3 vs 33.0 months, P  = 0.014; RFS: 20.3 vs 11.3 months, P  = 0.028). Multivariate analysis identified adjuvant chemotherapy ( P  = 0.003) as a favorable prognostic factor of OS and tumor budding ( P  = 0.023) as an adverse prognostic factor of DSS.

This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.

Although neurodegenerative diseases are a leading cause of death, little is known about health care utilization and cost during the end-of-life (EoL) period or how it compares with that of other life-limiting conditions. We aimed to describe and compare resource utilization among US Medicare decedents with neurodegenerative diseases with decedents with cancer.

We conducted a retrospective study of Medicare Part A and B beneficiaries with Alzheimer disease (AD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) who died in 2018. Decedents diagnosed with malignant brain tumors or pancreatic cancer served as non-neurodegenerative comparators. Descriptive analyses examined demographic and clinical characteristics in the last year of life. The probabilities and associated costs of emergency department (ED), inpatient, skilled nursing facility (SNF), and hospice utilization during the last 12 and 6 months of life were also compared between persons with neurodegenerative diseases and cancer, adjusting for sociodemographic factors and comorbidity burden.

A total of 1,126,799 Medicare beneficiaries died in 2018, of which 357,926 had a qualifying diagnosis. Persons with neurodegenerative diseases were older and more frequently received Medicaid assistance than persons with brain or pancreatic cancer. In all groups, health care service utilization increased over the last year of life, and total costs were predominantly attributable to inpatient care. In the last 6 months of life, neurologist care was infrequent among patients with neurodegenerative disease (AD: 1.5%; PD: 8.6%; ALS: 32.0%). Persons with neurodegenerative diseases as compared to persons with malignant brain tumors also had greater odds of ED use (AD: adjusted odds ratio [aOR] 1.17, 95% CI 1.11-1.23; PD: aOR 1.18, 95% CI 1.11-1.25; ALS: aOR 1.11, 95% CI 1.01-1.23), lower odds of hospitalization (AD: aOR 0.64, 95% CI 0.60-0.68; PD: aOR 0.65, 95% CI 0.61-0.69; ALS: aOR 0.33, 95% CI 0.30-0.37), and lower odds of hospice enrollment (AD: aOR 0.33, 95% CI 0.31-0.36; PD: aOR 0.33, 95% CI 0.31-0.36; ALS: aOR 0.41, 95% CI 0.36-0.46). The findings were similar in pancreatic cancer.

Persons with neurodegenerative diseases in the United States are more likely to visit the ED and less likely to use inpatient and hospice services at EoL than persons with brain or pancreatic cancer. These group differences may stem from prognostic uncertainty and reflect inadequate EoL care practices, requiring further investigation to ensure more timely palliative care and hospice referrals.

Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy of current therapies, even when PDAC is detected early, underscores the aggressive nature of the disease and the urgent need for more effective treatments. Clinical management of PDAC still relies heavily on a limited repertoire of therapeutic interventions, highlighting a significant gap between research efforts and available treatments. Over 4300 clinical trials have been or are currently investigating different treatment modalities and diagnostic strategies for PDAC, including targeted therapies, immunotherapies, and precision medicine approaches. These trials aim to develop more effective treatments and improve early detection methods through advanced imaging techniques and blood-based biomarkers. This review seeks to categorize and analyze PDAC-related clinical trials across various dimensions to understand why so few chemotherapeutic options are available to patients despite the numerous trials being conducted. This review aims to provide a comprehensive and nuanced understanding of the landscape of PDAC-related clinical trials, with the overarching goal of identifying opportunities to accelerate progress in drug development and improve patient outcomes in the fight against this devastating disease.

In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC.

Retrospective analysis of single-institution data.

The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease.

This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

The value of splenectomy for body localization (≥ 5 cm from spleen hilum) of pancreatic ductal adenocarcinoma (B-PDAC) is uncertain. This study assessed spleen-preserving distal pancreatectomy (SPDP) results for B-PDAC.

This single-center study included patients who underwent SPDP (Warshaw's technique) or distal splenopancreactomy (DSP) for B-PDAC from 2008 to 2019. Propensity score matching was performed to balance SPDP and DSP patients regarding sex, age, American Society of Anesthesiologists (ASA), body mass index (BMI), laparoscopy, pathological features [American Joint Committee on Cancer (AJCC)/tumor node metastasis classification (TNM)], margins, and neoadjuvant/adjuvant therapies.

A total of 129 patients (64 male, median age 68 years, median BMI 24 kg/m2) were enrolled with a median follow-up of 63 months (95% CI 52-96 months), including 59 (46%) SPDP and 70 (54%) DSP patients. A total of 39 SPDP patients were matched to 39 DSP patients. SPDP patients had fewer harvested nodes (19 vs 22; p = 0.038) with a similar number of positive nodes (0 vs 0; p = 0.237). R0 margins were achieved similarly in SPDP and DSP patients (75% vs 71%; p = 0.840). SPDP patients were associated with decreased comprehensive complication index (CCI, 8.7 vs 16.6; p = 0.004), rates of grade B/C postoperative pancreatic fistula (POPF, 14% vs 29%; p = 0.047), and hospital stay (11 vs 16 days; p < 0.001). SPDP patients experienced similar disease-free survival (DFS, 5 years: 38% vs 32%; p = 0.180) and overall survival (OS, 5 years 54% vs 44%; p = 0.710). After matching, SPDP patients remained associated with lower CCI (p = 0.034) and hospital stay (p = 0.028) while not associated with risks of local recurrence (HR 0.85; 95% CI 0.28-2.62; p = 0.781), recurrence (HR 1.04; 95% CI 0.61-1.78; p = 0.888), or death (HR 1.20; 95% CI 0.68-2.11; p = 0.556).

SPDP for B-PDAC is associated with less postoperative morbidity than DSP, without impairing oncological outcomes.

The first wave of coronavirus disease 2019 (COVID-19) pandemic in Spain lasted from middle March to the end of June 2020. Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods. In our centre, we managed patients previously and newly diagnosed with cancer. We established a strategy based on limiting perioperative social contacts, preoperative screening (symptoms and reverse transcription-polymerase chain reaction) and creating separated in-hospital COVID-19-free pathways for non-infected patients. We also adopted some practice modifications (surgery in different facilities, changes in staff and guidelines, using continuously changing personal protective equipment…), that supposed new inconveniences.

To analyse cancer patients with a decision for surgery managed during the first wave, focalizing on outcomes and pandemic-related modifications.

We prospectively included adults with a confirmed diagnosis of colorectal, oesophago-gastric, liver-pancreatic or breast cancer with a decision for surgery, regardless of whether they ultimately underwent surgery. We analysed short-term outcomes [30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection] and outcomes after 3 years (adjuvant therapies, oncological events, death, SARS-CoV-2 infection and vaccination). We also investigated modifications to usual practice.

From 96 included patients, seven didn't receive treatment that period and four never (3 due to COVID-19). Operated patients: 28 colon and 21 rectal cancers; laparoscopy 53.6%/90.0%, mortality 3.57%/0%, major complications 7.04%/25.00%, anastomotic leaks 0%/5.00%, 3-years disease-free survival (DFS) 82.14%/52.4% and overall survival (OS) 78.57%/76.2%. Six liver metastases and six pancreatic cancers: no mortality, one major complication, three grade A/B liver failures, one bile leak; 3-year DFS 0%/33.3% and OS 50.0%/33.3% (liver metastases/pancreatic carcinoma). 5 gastric and 2 oesophageal tumours: mortality 0%/50%, major complications 0%/100%, anastomotic leaks 0%/100%, 3-year DFS and OS 66.67% (gastric carcinoma) and 0% (oesophagus). Twenty breast cancer without deaths/major complications; 3-year OS 100% and DFS 85%. Nobody contracted SARS-CoV-2 postoperatively. COVID-19 pandemic-related changes: 78.2% treated in alternative buildings, 43.8% waited more than 4 weeks, two additional colostomies and fewer laparoscopies.

Some patients lost curative-intent surgery due to COVID-19 pandemic. Despite practice modifications and 43.8% delays higher than 4 weeks, surgery was resumed with minimal changes without impacting outcomes. Clean pathways are essential to continue surgery safely.

It is difficult to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) before radical operation. The purpose of this study was to explore the connection between the diffuse reduction of spleen density on computed tomography (DROSD) and the postoperative prognosis of patients with PDAC.

A total of 160 patients with PDAC who underwent radical surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Cox regression analysis was used to cast the overall survival (OS) and evaluate the prognostic factors. Nomogram was used to forecast the possibility of 1-year, 3-year, and 5-year OS. The prediction accuracy and clinical net benefit are performed by concordance index (C-index), calibration curve, time-dependent receiver operating characteristics (tdROC), and decision curve analysis.

In multivariable Cox analysis, DROSD is independently related to OS. Advanced age, TNM stage, neutrophil/lymphocyte ratio, and severe complications were also independent prognostic factors. The calibration curves of nomogram showed optimal agreement between prediction and observation. The C-index of nomogram is 0.662 (95%CI, 0.606-0.754). The area under tdROC curve for a 3-year OS of nomogram is 0.770.

DROSD is an independent risk factor for an OS of PDAC. We developed a nomogram that combined imaging features, clinicopathological factors, and systemic inflammatory response to provide a personalized risk assessment for patients with PDAC.

Invasive carcinomas arising from premalignant lesions are currently staged by the same criteria as conventional pancreatic ductal adenocarcinoma.

Clinicopathologic information and survival data were extracted through a thorough search of histology codes from National Cancer Database (2006-2016). A total of 723 patients with invasive intraductal papillary mucinous neoplasm and mucinous cystic neoplasm were analyzed.

The median age was 67 years, and 351 patients (48.5%) were male. There were 212 (29.3%), 232 (32.1%), 272 (37.6%), and 7 (1.0%) patients with T1, T2, T3, and T4 classification. Extrapancreatic extension (EPE) was present in 284 (39.3%). Age (HR = 1.504, 95% CI 1.196-1.891), R1 or R2 resection (HR = 1.585, 95% CI 1.175-2.140), and EPE (HR = 1.598, 95% CI 1.209-2.113) were independent prognostic factors for overall survival. Size criteria did not significantly affect survival. The median survival was 115.9 months for patients without EPE, compared to 34.2 months for those with EPE. EPE discriminated survival better than tumor size.

The T classification of the eighth edition AJCC staging system is not adequate for invasive carcinomas associated with premalignant lesions of the pancreas. They merit a separate, dedicated staging system that uses appropriate prognostic factors.

Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer.

A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023.

In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival.

IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Lung adenocarcinoma (LUAD) is a highly lethal malignant tumor. While the involvement of multiple mRNAs in the progression of LUAD is well established, the potential diagnostic value of immune-related mRNAs (irmRNAs) in LUAD remains largely unexplored. In this study, we utilized RNA-seq, clinical data, and immune-related gene information from LUAD patients to identify differentially expressed immune-related mRNAs (DEirmRNAs) and developed a predictive risk model based on specific DEirmRNA pairs closely linked with patient prognosis. We classified patients into high-risk and low-risk groups and analyzed factors such as survival rate, clinical characteristics, gene enrichment, immune cell infiltration, tumor mutation load, and drug susceptibility. We confirmed the expression levels of these DEirmRNAs in tumor tissues using qRT-PCR assay. Our results showed that the low-risk group had a longer survival time and lower tumor mutation burden (TMB) and microsatellite instability (MSI) compared to the high-risk group. The high-risk group also had a significant reduction in the number of certain immune cells and a lower half-maximum inhibitor concentration (IC50). We identified specific DEirmRNA pairs that were up-regulated or down-regulated in tumor tissues compared to adjacent tissues. Our prognostic risk model based on DEirmRNA pairs could be used to predict the prognosis of LUAD patients and provide reference for better treatment.

Pancreatic ductal adenocarcinoma contributes significantly to global cancer-related deaths, featuring only a 10% survival rate over five years. The quest for novel tumor markers is critical to facilitate early diagnosis and tailor treatment strategies for this disease, which is key to improving patient outcomes. In pancreatic ductal adenocarcinoma, these markers have been demonstrated to play a crucial role in early identification, continuous monitoring, and prediction of its prognosis and have led to better patient outcomes. Nowadays, biopsy specimens serve to ascertain diagnosis and determine tumor type. However, liquid biopsies present distinct advantages over conventional biopsy techniques. They offer a noninvasive, easily administered procedure, delivering insights into the tumor's status and facilitating real-time monitoring. Liquid biopsies encompass a variety of elements, such as circulating tumor cells, circulating tumor DNA, extracellular vesicles, microRNAs, circulating RNA, tumor platelets, and tumor endothelial cells. This review aims to provide an overview of the clinical applications of liquid biopsy as a technique in the management of pancreatic cancer.

Hepatic metastasis frequently occurs in patients who have undergone radical pancreatic resection for pancreatic cancer. Besides chemotherapy, various local treatment approaches targeting hepatic lesions have been explored. However, research on radiofrequency ablation (RFA) as a localized therapy for hepatic metastasis is limited. Therefore, we conducted this retrospective study to provide clinical evidence.

This is a single-center, retrospective, cohort study. After radical pancreaticoduodenectomy, 32 patients developed metachronous hepatic metastasis with fewer than 3 lesions, the largest of which was less than 3 cm in diameter. These patients underwent combined treatment with chemotherapy and RFA. After 8 weeks of chemotherapy, patients received RFA for hepatic lesions. Additional chemotherapy was administered, and the patients' tumor status and survival were monitored. The primary endpoint of this study was overall survival (OS). Factors affecting OS were analyzed using the Cox risk model.

Among the 32 patients, the mean OS was 28.4 months. Univariate and multivariate Cox regression analysis revealed that the time (in months) of liver metastasis (HR = 0.04, 95% CI: 0.01 to 0.19; P < 0.001), the number of liver metastases (HR = 7.08, 95% CI: 1.85 to 27.08, P = 0.004), and PD (progressive disease) response to the second round of chemotherapy (HR = 29.50, 95% CI: 1.46 to 597.27; P = 0.027) were independent predictors of poorer survival.

Combined therapy with RFA and chemotherapy is safe in patients with hepatic metastasis after radical pancreaticoduodenectomy. Early recurrence (≤12 months), three liver metastatic lesions, and a poor response to the second round of chemotherapy were associated with poor survival.

Although the concept of extrapancreatic extension (EPEx) was removed in the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system, several studies have supported the prognostic significance of EPEx. This study aimed to investigate the significance of EPEx in pancreatic ductal adenocarcinoma (PDAC) using the National Cancer Database (NCDB).

Data of patients who underwent resection for PDAC between 2006 and 2016 were extracted and analyzed from the NCDB. Cases arising from premalignant lesions, those with metastases, and those treated with neoadjuvant therapy were excluded.

Among 37,634 patients, the median overall survival was 23 months and the 5-year survival rate was 22.7%. The EPEx prevalence was the lowest for T1 stage (63.2%) and increased with each T-stage (T2:83.4%, T3:85.8%). The overall survival was better in EPEx-negative patients than in EPEx-positive patients (median 33.7 vs. 21.5 months; p<0.001). When the T-stages were stratified by EPEx, EPEx-positive patients showed worse survival in all T-stages than EPEx-negative patients. Survival was comparable between T1 EPEx-positive and T2 or T3 EPEx-negative patients (p=0.088 and p=0.178, respectively). Furthermore, T2 and T3 EPEx-negative patients had similar survival to each other (p=0.877), and distinctly superior survival compared to T2 and T3 EPEx-positive patients (p<0.001).

EPEx was an important prognostic factor in the overall cohort and in differentiating between T stages. This study strongly suggests that staging systems should reinstate EPEx and apply it to all T-stages, especially in T1, where EPEx was absent in 36% of patients.

The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies validating these modifications have yielded inconsistent results. The existing TNM staging system in prognostic prediction remains unsatisfactory. The prognosis of PDAC is closely associated with pathological and biological factors. Herein, we propose a new staging system incorporating distant metastasis, postoperative serum levels of CA19-9 and CEA, tumor size, lymph node metastasis, lymphovascular involvement, and perineural invasion to enhance the accuracy of prognosis assessment. The proposed staging system exhibited a strong correlation with both overall survival and recurrence-free survival, effectively stratifying survival into five distinct tiers. Additionally, it had favorable discrimination and calibration. Thus, the proposed staging system demonstrates superior prognostic performance compared to the TNM staging system, and can serve as a valuable complementary tool to address the limitations of TNM staging in prognostication.

Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition.

Data from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database.

The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p < .001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database.

Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.

Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.

A retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.

A total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0-38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.

The addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

It is unclear whether pathological staging is significant prognostically and can inform the delivery of adjuvant therapy after pancreatectomy preceded by neoadjuvant therapy.

This multicentre retrospective study included patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma after neoadjuvant treatment at two Italian centres between 2013 and 2017. T and N status were assigned in accordance with the seventh and eighth editions of the AJCC staging system, as well as according to a modified system with T status definition combining extrapancreatic invasion and tumour size. Patients were then stratified by receipt of adjuvant therapy. Survival analysis and multivariable interaction analysis of adjuvant therapy with pathological parameters were performed. The results were validated in an external cohort from the USA.

The developmental set consisted of 389 patients, with a median survival of 34.6 months. The modified staging system displayed the best prognostic stratification and the highest discrimination (C-index 0.763; 1-, 2- and 3-year time-dependent area under the curve (AUC) 0.746, 0.722, and 0.705; Uno's AUC 0.710). Overall, 67.0 per cent of patients received adjuvant therapy. There was no survival difference by receipt of adjuvant therapy (35.0 versus 36.0 months; P = 0.772). After multivariable adjustment, interaction analysis suggested a benefit of adjuvant therapy for patients with nodal metastases or with tumours larger than 2 cm with extrapancreatic extension, regardless of nodal status. These results were confirmed in the external cohort of 216 patients.

Modified staging with a T status definition combining extrapancreatic invasion and tumour size is associated with better prognostic segregation after postneoadjuvant pancreatectomy. This system allows identification of patients who might benefit from adjuvant therapy.

Pulsed high intensity focused ultrasound (pHIFU) is a non-invasive method that allows to permeabilize pancreatic tumors through inertial cavitation and thereby increase the concentration of systemically administered drug. In this study the tolerability of weekly pHIFU-aided administrations of gemcitabine (gem) and their influence on tumor progression and immune microenvironment were investigated in genetically engineered KrasLSL.G12D/þ; p53R172H/þ; PdxCretg/þ (KPC) mouse model of spontaneously occurring pancreatic tumors. KPC mice were enrolled in the study when the tumor size reached 4-6 mm and treated once a week with either ultrasound-guided pHIFU (1.5 MHz transducer, 1 ms pulses, 1% duty cycle, peak negative pressure 16.5 MPa) followed by administration of gem (n = 9), gem only (n = 5) or no treatment (n = 8). Tumor progression was followed by ultrasound imaging until the study endpoint (tumor size reaching 1 cm), whereupon the excised tumors were analyzed by histology, immunohistochemistry (IHC) and gene expression profiling (Nanostring PanCancer Immune Profiling panel). The pHIFU + gem treatments were well tolerated; the pHIFU-treated region of the tumor turned hypoechoic immediately following treatment in all mice, and this effect persisted throughout the observation period (2-5 weeks) and corresponded to areas of cell death, according to histology and IHC. Enhanced labeling by Granzyme-B was observed within and adjacent to the pHIFU treated area, but not in the non-treated tumor tissue; no difference in CD8 + staining was observed between the treatment groups. Gene expression analysis showed that the pHIFU + gem combination treatment lead to significant downregulation of 162 genes related to immunosuppression, tumorigenesis, and chemoresistance vs gem only treatment.

To elucidate the influence of CXC motif chemokine receptor 4 (CXCR4)-directed imaging on staging and proposed oncologic management in patients with digestive system tumors compared with guideline-appropriate imaging (GAI).

From our PET/CT database, we retrospectively identified 37 patients with advanced digestive system tumors, which had been scheduled for CXCR4-targeted [ 68 Ga]Ga-pentixafor PET/CT for potential theranostic considerations. In all subjects, concurrent GAI was also available. Patients were afflicted with gastroenteropancreatic neuroendocrine neoplasms (21/37 [56.8%]), pancreatic duct adenocarcinoma (6/37 [16.2%]), cholangiocarcinoma (5/37 [13.5%]), hepatocellular carcinoma (4/37 [10.8%]), and colorectal carcinoma (1/37 [2.7%]). Staging results and impact on proposed oncologic management by a board-certified gastroenterologist were compared between GAI and [ 68 Ga]Ga-pentixafor PET/CT.

Relative to GAI, CXCR4-directed PET/CT resulted in staging changes in 14 of 37 patients (37.8%). Upstaging was seen in 1 of 14 patients (7.1%), whereas downstaging was recorded in the remaining 13 of 14 patients (92.9%). Among those, staging changes would not have triggered any changes in oncological management in 4 of 14 (28.6%). For the remaining 10 of 14 patients (71.4%), however, findings on [ 68 Ga]Ga-pentixafor PET/CT would have impacted subsequent clinical algorithm, including the necessity for further diagnostic steps or failure to initiate antitumor therapy.

[ 68 Ga]Ga-pentixafor PET/CT missed tumor lesions in 13 patients with digestive system tumors, which would have led to inappropriate downstaging and clinical treatment of 10 patients. As such, our results do not support a more widespread use of [ 68 Ga]Ga-pentixafor PET/CT for clinical staging in those tumor entities.

Pancreatic cancer is known for its tumor microenvironment (TME), which is rich in stromal and immune cells supporting cancer growth and therapy resistance. In particular, tumor-associated macrophages (TAMs) are known for their angiogenesis- and metastasis-promoting properties, which lead to the failure of conventional therapies for pancreatic cancer. Hence, treatment options targeting TAMs are needed. The C-C chemokine receptor type 4 (CCR4) is critical for immune cell recruitment into the TME, and in this paper we explore the effects of its genetic or immunotherapeutic blockade in pancreatic-cancer-bearing mice. Murine PDA6606 pancreatic cancer cells and murine peritoneal macrophages were used for in vitro migration assays. In vivo, a syngeneic, orthotropic pancreatic cancer model was established. Tumor growth and survival were monitored under prophylactic and therapeutic application of a CCR4 antagonist (AF-399/420/18025) in wildtype (CCR4^wt) and CCR4-knockout (CCR4^-/-) mice. Immune infiltration was monitored in tumor tissue sections and via flow cytometry of lysed tumors. PDA6606 cells induced less migration in CCR4^-/- than in CCR4^wt macrophages in vitro. Pancreatic TAM infiltration was higher, and survival was reduced in CCR4^wt mice compared to CCR4^-/- mice. Antagonizing CCR4 in wildtype mice revealed similar results as in CCR4^-/- mice without antagonization. Prophylactic CCR4 antagonist application in wildtype mice was more efficient than therapeutic antagonization. CCR4 seems to be critically involved in TAM generation and tumor progression in pancreatic cancer. CCR4 blockade may help prolong the relapse-free period after curative surgery in pancreatic cancer and improve prognosis.

This study investigated the long-term results, failure patterns, and prognostic factors of patients with initially inoperable non-metastatic pancreatic cancer (PC) receiving definitive radiotherapy (RT). Between January 2016 and December 2020, a total of 168 non-metastatic PC patients, who were surgically unresectable or medically inoperable, were enrolled to receive definitive RT, with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method with a log-rank test. The cumulative incidence of locoregional and distant progression was estimated using the competing risks model. The Cox proportional-hazards model was used to determine the influence of prognostic variables on OS. With a median follow-up of 20.2 months, the median OS (mOS) and median PFS (mPFS) from diagnosis were 18.0 months [95% confidence interval (CI), 16.5-21.7 months] and 12.3 months (95% CI, 10.2-14.3 months), respectively. The mOS and mPFS from RT were 14.3 months (95% CI, 12.7-18.3 months) and 7.7 months (95% CI, 5.5-12.0 months), respectively. The corresponding 1-year, 2-year, and 3-year OS from diagnosis and RT were 72.1%, 36.6%, and 21.5% as well as 59.0%, 28.8%, and 19.0%, respectively. In a multivariate analysis, stage I-II (p = 0.032), pre-RT CA19-9 ≤ 130 U/mL (p = 0.011), receiving chemotherapy (p = 0.003), and a biologically effective dose (BED₁₀) > 80 Gy (p = 0.014) showed a significant favorable influence on OS. Among the 59 available patients with definite progression sites, the recurrences of local, regional, and distant progression were 33.9% (20/59), 18.6% (11/59), and 59.3% (35/59), respectively. The 1-year and 2-year cumulative incidences of locoregional progression after RT were 19.5% (95% CI, 11.5-27.5%) and 32.8% (95% CI, 20.8-44.8%), respectively. Definitive RT was associated with long-term primary tumor control, resulting in superior survival in patients with inoperable non-metastatic PC. Further prospective randomized trials are warranted to validate our results in these patients.

To validate the 7 th and 8 th editions of the AJCC staging system for patients with invasive carcinomas arising in association with IPMN (IPMN-associated PDAC).

Although several studies have validated AJCC systems in patients with conventional PDAC, their applicability to IPMN-associated PDAC has not been assessed.

Two hundred seventy-five patients who underwent resection for IPMN-associated PDAC between 1996 and 2015 at 3 tertiary centers and had data on the size of the invasive component and lymph node status were identified. Concordance probability estimates (CPE) were calculated and recursive partitioning analysis was employed to identify optimal prognostic cutoffs for T and N.

The CPE for the 7 th and 8 th editions of the AJCC schema were relatively good (0.64 for both) and similar for colloid and tubular subtypes (0.64 for both). The 8 th edition introduced T1a sub-staging and a new distinction between N1 and N2. The utility of the former was confirmed, although the latter did not improve prognostic discrimination. The successful validation of the 8th edition of the AJCC criteria in patients with tubular and colloid subtypes allowed us to compare these patients in early vs late T and N stages which showed that with advanced disease, the prognostic superiority of colloid tumors over their tubular counterparts diminishes.

Our findings support the use of the AJCC 8 th edition in the IPMN-associated PDAC population, but suggest that certain cutoffs may need to be revisited. In advanced AJCC stages, patients with colloid vs tubular subtypes have comparable prognosis.

As the most aggressive tumor, TNM staging does not accurately identify patients with pancreatic cancer who are sensitive to therapy. This study aimed to identify associated risk factors and develop a nomogram to predict survival in pancreatic cancer surgery patients and to select the most appropriate comprehensive treatment regimen. First, the survival difference between radiotherapy and no radiotherapy was calculated based on propensity score matching (PSM). Cox regression was conducted to select the predictors of overall survival (OS). The model was constructed using seven variables: histologic type, grade, T stage, N stage, stage, chemotherapy and radiotherapy. All patients were classified into high- or low-risk groups based on the nomogram. The nomogram model for OS was established and showed good calibration and acceptable discrimination (C-index 0.721). Receiver operating characteristic curve (ROC) and DCA curves showed that nomograms had better predictive performance than TNM stage. Patients were divided into low-risk and high-risk groups according to nomogram scores. Radiotherapy is recommended for high-risk patients but not for low-risk patients. We have established a well-performing nomogram to effectively predict the prognosis of pancreatic cancer patients underlying surgery. The web version of the nomogram https://rockeric.shinyapps.io/DynNomapp/ may contribute to treatment optimization in clinical practice.

A prognostic assessment method with good sensitivity and specificity plays an important role in the treatment of pancreatic cancer patients. Finding a way to evaluate the prognosis of pancreatic cancer is of great significance for the treatment of pancreatic cancer.

In this study, GTEx dataset and TCGA dataset were merged together for differential gene expression analysis. Univariate Cox regression and Lasso regression were used to screen variables in the TCGA dataset. Screening the optimal prognostic assessment model is then performed by gaussian finite mixture model. Receiver operating characteristic (ROC) curves were used as an indicator to assess the predictive ability of the prognostic model, the validation process was performed on the GEO datasets.

Gaussian finite mixture model was then used to build 5-gene signature (ANKRD22, ARNTL2, DSG3, KRT7, PRSS3). Receiver operating characteristic (ROC) curves suggested the 5-gene signature performed well on both the training and validation datasets.

This 5-gene signature performed well on both our chosen training dataset and validation dataset and provided a new way to predict the prognosis of pancreatic cancer patients.

Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis.

The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001).

NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

The 5-year survival of pancreatic cancer (PC) remains low. Murine models may not adequately mimic human PC and can be too small for medical device development. A large-animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine containing KRASG12D and TP53R167H). The oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) into one of the main pancreatic ducts. Resultant tumors were characterized by histology, cytokine expression, exome sequencing and transcriptome analysis. Ten of 14 Oncopigs (71%) had gross tumor within 3 weeks. At necropsy, all of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Oncopigs with injections without Cre recombinase and wild-type pigs with AdCre injection did not show notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity to the molecular signatures and pathways of human PC. Although further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC. This article has an associated First Person interview with the joint first authors of the paper.

We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)-directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI).

Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68 Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68 Ga-FAPI-04 PET/CT.

Compared with GCI, 68 Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%).

In patients affected with digestive system tumors, 68 Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.

Pancreatic cancer (PC) is one of the most fatal malignant tumors, and is commonly diagnosed at an advanced stage with no effective therapy. Metabolism-related genes (MRGs) and immune-related genes (IRGs) play considerable roles in the tumor microenvironment. Therefore, an effective prediction model based on MRGs and IRGs could aid in the prognosis of PC. In this study, differential expression analysis was performed to gain 25 intersectional genes from 857 differentially expressed MRGs (DEMRGs), and 1353 differentially expressed IRGs, from The Cancer Genome Atlas database of PC. Cox and Lasso regression were applied and a five-DEMRGs prognostic model constructed. Survival analysis, ROC values, risk curve and validation analysis showed that the model could independently predict PC prognosis. In addition, the correlation analysis suggested that the five-DEMRGs prognostic model could reflect the status of the immune microenvironment, including Tregs, M1 macrophages and Mast cell resting. Therefore, our study provides new underlying predictive biomarkers and associated immunotherapy targets.

To develop and externally validate a prognosis nomogram based on contrast-enhanced computed tomography (CECT) combined clinical for preoperative prognosis prediction of patients with pancreatic ductal adenocarcinoma (PDAC).

184 patients from Center A with histopathologically confirmed PDAC who underwent CECT were included and allocated to training cohort (n=111) and internal validation cohort (n=28). The radiomic score (Rad - score) for predicting overall survival (OS) was constructed by using the least absolute shrinkage and selection operator (LASSO). Univariate and multivariable Cox regression analysis was used to construct clinic-pathologic features. Finally, a radiomics nomogram incorporating the Rad - score and clinical features was established. External validation was performed using Center B dataset (n = 45). The validation of nomogram was evaluated by calibration curve, Harrell's concordance index (C-index) and decision curve analysis (DCA). The Kaplan-Meier (K-M) method was used for OS analysis.

Univariate and multivariate analysis indicated that Rad - score, preoperative CA 19-9 and postoperative American Joint Committee on Cancer (AJCC) TNM stage were significant prognostic factors. The nomogram based on Rad - score and preoperative CA19-9 was found to exhibit excellent prediction ability: in the training cohort, C-index was superior to that of the preoperative CA19-9 (0.713 vs 0.616, P< 0.001) and AJCC TNM stage (0.713 vs 0.614, P< 0.001); the C-index was also had good performance in the validation cohort compared with CA19-9 (internal validation cohort: 0.694 vs 0.555, P< 0.001; external validation cohort: 0.684 vs 0.607, P< 0.001) and AJCC TNM stage (internal validation cohort: 0.694 vs 0.563, P< 0.001; external validation cohort: 0.684 vs 0.596, P< 0.001). The calibration plot and DCA showed excellent predictive accuracy in the validation cohort.

We established a well-designed nomogram to accurately predict OS of PDAC preoperatively. The nomogram showed a satisfactory prediction effect and was worthy of further evaluation in the future.