Upper gastrointestinal (UGI) cancers, comprising malignancies of the esophagus, stomach, duodenum, pancreas, liver, biliary tract, and gallbladder, are the second leading cause of cancer-related mortality in the United States and are associated with significant comorbidities. Recent studies show a disproportionate rise in pancreatic and stomach cancer among young adults. This study aims to use a nationwide, population-based cohort to (i) evaluate the trend of all UGI cancer as an aggregate and (ii) examine the role of demographics, histology, and tumor stage in UGI cancer incidence among young adults.

Individuals diagnosed with UGI cancer in the United States from 2001 to 2019 were identified and obtained from the Surveillance, Epidemiology, and End Results-National Program of Cancer Registries database. The primary outcomes were incidence rates of UGI cancer (calculated per 100,000, age-adjusted to the year 2000 US population), stratified by sex and age (< 55 years for young adults and ≥ 55 years for older adults). Trends, annual percentage change, and average annual percentage change were calculated using the parametric method. Sensitivity analysis was performed according to primary site and histology; further analysis examining race and cancer stage was performed in the young adult subgroup.

A total of 2,333,161 patients with UGI cancer were identified. Most cases were male, and 14.3% were < 55 years of age. Incidence of UGI cancer increased most in women younger than 55 years, driven primarily by pancreatic and stomach cancers, as well as neuroendocrine tumor and gastrointestinal stromal tumor histology. African American race and localized tumors and malignancy with distant spread are also contributing to the disparate increase among young women. UGI mortality rates have not changed significantly in young adults.

The overall incidence rate of upper gastrointestinal cancer is increasing significantly in young women compared with men. Increased endoscopic procedures and disparate exposure to risk factors are likely contributing to these trends.

Pancreatic cancer (PC) is the third leading cause of all cancer-related fatalities and accounts for approximately 3% of cancer cases in the United States. PC survival rates are lower in Blacks compared to other races, and this has been attributed to socioeconomic and genetic factors. In this study, we evaluated sociodemographic and genetic characteristics associated with PC incidence and mortality among Blacks. Data from the SEER 22 registries (2000-2020) were used to calculate the incidence rates and relative survival. County mortality rates from 2017 to 2021 were analyzed. Incidence rate ratios based on gender, age, primary disease site, stage, level of education, and poverty were calculated. Survival analysis was conducted using the Kaplan-Meier method. Mutant gene expression was obtained from the MSK-CHORD tumor registry. Overall, 48,606 Black patients were diagnosed with malignant PC between 2000 and 2020: females (53.53%) and males (46.47%). Both males and females experienced a slight increase in Annual Percent Change (APC) of PC incidence (0.24, 95% CI, -0.02-0.53) and (0.22, 95% CI, -0.05-0.51), respectively, from 2000 to 2020. Males aged 55 to 75 years were most frequently affected. Overall incidence risk from 2000-2020 by age was higher in Black males IRR > 1 (1.18, 95% CI, 1.16-1.21). The most common primary PC site for Black males and females was the head of the pancreas, 49.06% and 49.88%, respectively. By staging, distant PC had the highest frequency in Blacks. Poverty level was associated with PC incidence among females and PC mortality among both males and females. Stage was associated with survival among males with localized and regional PC. The 5-year relative survival was less than 11% across combined PC stages for both sexes. Black males had a relatively lower 5-year survival than Black females in localized (31.7 vs. 37.2%) and distant PC (2.6% vs. 2.90%). Mutant KRAS expression was higher in Black males. PC incidence and mortality were significantly higher in Black males. Our analysis points to the importance of poverty alleviation programs that target females are likely to reduce PC incidence. Furthermore, receiving recommended screening for PC and early-stage diagnostics is important to lower PC mortality.

Early-onset pancreatic cancer (EOPC) is usually defined as patients with pancreatic cancer before the age of 50 years, which is relatively rare. However, the research on EOPC is somewhat obscure, and the specific clinical and molecular characteristics of this condition are debated. In this review, we discussed the differences between EOPC and late-onset pancreatic cancer (LOPC) or average-onset pancreatic cancer (AOPC) with a focus on clinical and molecular characteristics, survival outcomes and treatment to promote the diagnosis and treatment of EOPC.

N6-methyladenosine (m6A) is considered the most prevalent RNA epigenetic regulator in cancer. FTO, an m6A demethylase, has been implicated in contributing to the progression of various cancers by up-regulating the expression of multiple oncogenes. However, studies exploring its impact on lipid metabolism in cancer, especially in pNENs, remain scarce. In this study, we demonstrated that FTO was up-regulated in pNENs and played a critical role in tumor growth and lipid metabolism. Mechanistically, we discovered that FTO over-expression increased the expression of APOE in an m6A-IGF2BP2-dependent manner, leading to dysregulation of lipid metabolism. Furthermore, we found APOE could activate the PI3K/AKT/mTOR signaling pathway, thereby enhancing lipid metabolism and proliferative capabilities, by orchestrating the state of FASN ubiquitination. In conclusion, our study reveals the FTO/IGF2BP2/APOE/FASN/mTOR axis as a mechanism underlying aberrant m6A modification in lipid metabolism and provides new insights into the molecular basis for developing therapeutic strategies for pNENs treatment.

This study investigated epidemiologic features of patients with pancreatic cancer in Korea, according to the histologic subtypes.

The Korea Central Cancer Registry data on patients with pancreatic cancer from 1999 to 2019 were reviewed. The 101,446 patients with pancreatic cancer (C25 based on the International Classification of Diseases, 10th revision) were allocated according to the following morphological codes: A, endocrine; B, carcinoma excluding cystic and mucinous; C, cystic or mucinous; D, acinar cell; and E, sarcoma and soft tissue tumor.

The distribution of each pancreatic cancer subtype group in Korea from 1999 to 2019 was as follows: A, n = 3,101 (3.1%); B, n = 95,051 (93.7%); C, n = 2,856 (2.8%); D, n = 299 (0.3%); and E, n = 139 (0.1%). In group B, 49.2% of patients were aged >70 years, and half of them did not receive treatment within 4 months of diagnosis. In addition, only 30.9% of the patients were in the localized and regional stage in which surgical treatment was possible. Pancreatic cancer occurred more frequently in females than in males only in group C. Between 1999 and 2019, the average annual percentage changes in the age-specific incidence rates were positive in groups A (13.9%, P < 0.001), B (1.0%, P < 0.001), and C (6.5%, P = 0.025). Significant improvements in 5-year survival rates over time were observed in subtypes A, B, and C.

The subgroups of pancreatic cancer show different epidemiologic features, including incidences, treatment rates, and prognoses.

Pediatric patients with cancer have limited options to self-manage their health while they are undergoing treatments in the hospital and after they are discharged to their homes. Extended reality (ER) using head-mounted displays has emerged as an immersive method of improving pain and mental health and promoting health-enhancing physical activity among a variety of clinical groups, but there is currently no established protocol for improving both physical and mental health in pediatric cancer rehabilitation.

This phase I, pilot, feasibility randomized controlled trial aims to investigate the potential effects of a 14-week ER program on physical activity participation and indicators of health among pediatric patients with cancer who undergo bone marrow transplantation. An ancillary aim is to evaluate the feasibility of the program through participant engagement.

This study includes a 2-arm parallel group design with a 1-group crossover (the control group will start the intervention after a waiting period). Overall, 16 pediatric patients with cancer undergoing rehabilitation (aged ≥8 years) at a children's hospital will be randomly allocated into one of two groups: (1) an immediate start group that undergoes an ER program in the hospital until discharge and then for 8 weeks at home (total duration of approximately 14 weeks), and (2) a waitlist control group that undergoes usual care in the hospital and for 8 weeks at home, before receiving the 8-week home ER program. The program will include active video gaming with rhythmic music exercises as well as mindfulness-based practices using a high-quality app. Home-based programming will include behavioral coaching calls. Physical activity will be measured daily through step counts using a tri-axial accelerometer. Health outcomes will be measured across time and include global health, measured by the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health Scale Short Form 7+2, and lung function, measured by a forced expiratory volume using a peak flow meter. Feasibility will be evaluated through participant engagement metrics, such as enrollment, dropout, adverse events, and attendance rates. Descriptive statistics will be obtained for all study variables. Outcomes will be modeled using mixed modeling procedures, and changes in means will be estimated with CIs.

The study was funded in February 2024. Recruitment procedures started on June 27, 2024. All data are anticipated to be collected by February 2026. Full trial results are anticipated to be analyzed and submitted for publication by March 2026. The study's anticipated end date is March 31, 2026.

This trial tests an accessible remote program for improving both physical and mental health among pediatric patients with cancer. The knowledge obtained from this study will inform the development of a larger trial.

ClinicalTrials.gov NCT06298357; https://clinicaltrials.gov/study/NCT06298357.

DERR1-10.2196/64879.

Disseminating disease knowledge through concise videos on various platforms is an innovative and efficient approach. However, it remains uncertain whether pancreatic neuroendocrine tumor (pNET)-related videos available on current short video platforms can effectively convey accurate and impactful information to the general public.

Our study aims to extensively analyze the quality of pNET-related videos on TikTok and Bilibili, intending to enhance the development of pNET-related social media content to provide the general public with more comprehensive and suitable avenues for accessing pNET-related information.

A total of 168 qualifying videos pertaining to pNETs were evaluated from the video-sharing platforms Bilibili and TikTok. Initially, the fundamental information conveyed in the videos was documented. Subsequently, we discerned the source and content type of each video. Following that, the Global Quality Scale (GQS) and modified DISCERN (mDISCERN) scale were employed to appraise the educational value and quality of each video. A comparative evaluation was conducted on the videos obtained from these two platforms.

The number of pNET-related videos saw a significant increase since 2020, with 9 videos in 2020, 19 videos in 2021, 29 videos in 2022, and 106 videos in 2023. There were no significant improvements in the mean GQS or mDISCERN scores from 2020 to 2023, which were 3.22 and 3.00 in 2020, 3.33 and 2.94 in 2021, 2.83 and 2.79 in 2022, and 2.78 and 2.94 in 2023, respectively. The average quality scores of the videos on Bilibili and Tiktok were comparable, with GQS and mDISCERN scores of 2.98 on Bilibili versus 2.77 on TikTok and 2.82 on Bilibili versus 3.05 on TikTok, respectively. The source and format of the videos remained independent factors affecting the two quality scores. Videos that were uploaded by professionals (hazard ratio=7.02, P=.002) and recorded in specialized popular science formats (hazard ratio=12.45, P<.001) tended to exhibit superior quality.

This study demonstrates that the number of short videos on pNETs has increased in recent years, but video quality has not improved significantly. This comprehensive analysis shows that the source and format of videos are independent factors affecting video quality, which provides potential measures for improving the quality of short videos.

There is significant variation in inpatient expenditures among physicians and hospitals. This study aimed to characterize the association between variation in physician spending and short-term outcomes among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).

Patients who underwent surgery for PDAC and CRC from 2010 to 2020 were identified using the Surveillance, Epidemiology, and End Result-Medicare-linked database. The cohort was divided into quartiles based on adjusted physician spending, and multivariate models were used to assess the association between physician spending and patient outcomes.

Among 27,596 Medicare beneficiaries, 25,615 (92.8%) underwent surgery for CRC and 1981 (7.2%) underwent surgery for PDAC. Of the variations in spending, 79.9% were due to patient-level factors, 13.3% were due to hospital characteristics, and 6.8% were due to surgeon-level variables. On multivariate analysis, there was no association between physician spending and 30-day readmission (with complications: first quartile [Q1], reference; Q4: odds ratio [OR], 1.10; 95% CI, 0.86-1.41; P = .123; without complications: Q1, reference; Q3, stage IV: OR, 0.97; 95% CI, 0.68-1.40; P = .882) or between physician spending and 30-day mortality (without complications: Q1, reference; Q2, stage I: OR, 1.17; 95% CI, 0.45-3.01; P = .804). However, an increase in physician spending was associated with higher 30-day mortality among patients with complications (Q1, reference; Q4: OR, 2.28; 95% CI, 1.72-3.03; P < .001).

There was more variation in healthcare spending across hospitals than across individual physicians. No consistent association between variation in physician spending and patient outcomes was noted. Wasteful spending can be reduced through targeted interventions aimed at reducing variations at the physician and hospital levels.

Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined.

We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant.

Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01).

Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients.

Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.

We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.

A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).

We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.

This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.

Pancreatic cancer is a prevalent malignant tumor with rising medication resistance and mortality. Due to a dearth of specific and trustworthy biomarkers and therapeutic targets, pancreatic cancer early detection and treatment are still not at their best. Exosomal LncRNAs have been found to be plentiful and persistent within exosomes, and they are capable of functioning whether the exosomes are traveling to close or distant cells. Furthermore, increasing evidence suggests that exosomal LncRNA, identified as an oncogene or tumor suppressor-control the growth, metastasis, and susceptibility of pancreatic cancer to chemotherapy and radiation therapy. Promising prospects for both antitumor targets and diagnostic biomarkers are exosomal LncRNAs. The primary features of exosomal LncRNAs, their biological roles in the onset and progression of pancreatic cancer, and their potential as therapeutic targets and diagnostic molecular markers are outlined in this review.

Tumor-associated macrophages (TAMs) represent a predominant cellular component within the tumor microenvironment (TME) of pancreatic neuroendocrine neoplasms (pNENs). There is a growing body of evidence highlighting the critical role of exosomes in facilitating communication between tumor cells and TAMs, thereby contributing to the establishment of the premetastatic niche. Nonetheless, the specific mechanisms through which exosomes derived from tumor cells influence macrophage polarization under hypoxic conditions in pNENs, and the manner in which these interactions support cancer metastasis, remain largely unexplored. Recognizing the capacity of exosomes to transfer miRNAs that can modify cellular behaviors, our research identified a significant overexpression of miR-4488 in exosomes derived from hypoxic pNEN cells. Furthermore, we observed that macrophages that absorbed circulating exosomal miR-4488 underwent M2-like polarization. Our investigations revealed that miR-4488 promotes M2-like polarization by directly targeting and suppressing RTN3 in macrophages. This suppression of RTN3 enhances fatty acid oxidation and activates the PI3K/AKT/mTOR signaling pathway through the interaction and downregulation of FABP5. Additionally, M2 polarized macrophages contribute to the formation of the premetastatic niche and advance pNENs metastasis by releasing MMP2, thereby establishing a positive feedback loop involving miR-4488, RTN3, FABP5, and MMP2 in pNEN cells. Together, these findings shed light on the role of exosomal miRNAs from hypoxic pNEN cells in mediating interactions between pNEN cells and intrahepatic macrophages, suggesting that miR-4488 holds potential as a valuable biomarker and therapeutic target for pNENs.

To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status.

Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used.

Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes.

Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S.

The aim of this study is to estimate the global burden of pancreatic cancer from 1990 to 2019.

We reconstructed the Global Burden of Diseases (GBD) study results for pancreatic cancer across 204 countries and territories. Our study generated estimates for key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and cost. Linear regression analysis of the natural logarithm of age-standardized outcomes was used to calculate annual percent change.

In 2019, there were a total of 530,296 incident and 442,101 prevalent cases of pancreatic cancer, resulting in 531,107 deaths and 11.5 million DALYs lost. The age-standardized incidence and prevalence of pancreatic cancer has increased from 5.22 (95% CI 4.97-5.40) to 6.57 (CI 6.00-7.09) per 100,000 people per year, and 4.1 (95% CI 3.95-4.26) to 5.4 (CI 4.96-5.87), respectively. This equated to 10 million (95% CI 9.5 to 10.4 million) incident cases of pancreatic cancer. The number of DALYs lost as a result of pancreatic cancer was 225 million years (95% CI 216-234 million years). Mortality from pancreatic cancer increased over the study period from 3.7 (95% CI 3.54-3.83) to 6.9 (95% CI 6.36-7.32). Incidence, prevalence, DALYs, and mortality were higher in countries with a higher socio-demographic index.

Pancreatic cancer is rising around the world and is associated with a high economic burden. Programs aimed at reducing modifiable risk factors are needed.

Endoplasmic reticulum stress (ERS) and unfolded protein response are the critical processes of tumour biology. However, the roles of ERS regulatory genes in pancreatic adenocarcinoma (PAAD) remain elusive. A novel ERS-related risk signature was constructed using the Lasso regression analysis. Its prognostic value, immune effect, metabolic influence, mutational feature and therapeutic correlation were comprehensively analysed through multiple bioinformatic approaches. The biofunctions of KDELR3 and YWHAZ in pancreatic cancer (PC) cells were also investigated through colony formation, Transwell assays, flow cytometric detection and a xenograft model. The upstream miRNA regulatory mechanism of KDELR3 was predicted and validated. ERS risk score was identified as an independent prognostic factor and could improve traditional prognostic model. Meanwhile, it was closely associated with metabolic reprogramming and tumour immune. High ERS risk enhanced glycolysis process and nucleotide metabolism, but was unfavourable for anti-tumour immune response. Moreover, ERS risk score could act as a potential biomarker for predicting the efficacy of ICBs. Overexpression of KDELR3 and YWHAZ stimulated the proliferation, migration and invasion of SW1990 and BxPC-3 cells. Silencing KDELR3 suppressed tumour growth in a xenograft model. miR-137 could weaken the malignant potentials of PC cells through inhibiting KDELR3 (5'-AGCAAUAA-3'). ERS risk score greatly contributed to PAAD clinical assessment. KDELR3 and YWHAZ possessed cancer-promoting capacities, showing promise as a novel treatment target.

Pancreatic cancer has the highest growth in incidence among patients aged ≥80 years. Discharge destination after hospitalization is increasingly recognized as a marker of return to baseline functional status. Our aim was to identify the preoperative and intraoperative predictors of non-home discharge in those aged 80 or older.

The ACS-NSQIP pancreas-targeted database was queried to identify patients aged ≥80 years who underwent pancreatoduodenectomy (PD) from 2014 to 2020. Home discharge (HD) versus non-HD cohorts were compared using univariate logistic regression. Multivariable logistic regression was used to identify predictors of non-HD.

Non-HD was over twice as likely to occur in patients aged ≥80 years than in those aged 65-79 years (p < 0.01). Comorbidity factors significantly associated with non-HD in patients aged ≥80 years included COPD, hypertension, HF, lower preoperative albumin, but not obesity. Non-comorbidity factors included older age, female gender, ASA III-IV, preoperative dependent functional status, and transfer origin before PD.

Individuals ≥80 years have possibly delayed or lower rate of return to baseline functional status following PD compared to those aged 65-79 years. Predictors of non-HD can be identified to facilitate preoperative counseling and discharge planning, thus enhancing care workflow efficiency.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

(1) Background: This study aimed to assess the global burden of pancreatic cancer attributable to a high BMI in 1990-2019. (2) Methods: An ecological study was carried out. Data about deaths and Disability-Adjusted Life Years (DALYs) for pancreatic cancer were extracted from the Global Burden of Disease (GBD) study. The age-standardized rates (ASRs, per 100,000) were presented. In order to determine trends of pancreatic cancer burden, joinpoint regression analysis was used to calculate the average annual percent change (AAPC). (3) Results: The highest ASRs of DALYs of pancreatic cancer were found in the United Arab Emirates (47.5 per 100,000), followed by countries with about 25.0 per 100,000 (such as Hungary, Czechia, and Montenegro). From 1990 to 2019, the ASRs of deaths and DALYs of pancreatic cancer attributable to a high BMI significantly increased (p < 0.001) for both sexes in all ages, and across all SDI quintiles and all GBD regions. The highest fraction of DALYs attributable to a high BMI was found in the United States of America and China (equally about 15.0%), followed by the Russian Federation, India, Germany, and Brazil (about 5.0%, equally). (4) Conclusions: Further analytical epidemiological studies are necessary to elucidate the relationship between pancreatic cancer and a high BMI.

Background and study aims Besides increasing adequacy, rapid on-site evaluation (ROSE) during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) may impact choices and timing of subsequent therapeutic procedures, yet has been unexplored. Patients and methods This was a retrospective evaluation of a prospectively maintained database of a tertiary, academic centre with availability of ROSE and hybrid EUS-ERCP suites. All consecutive patients referred for pathological confirmation of suspected malignancy and jaundice or gastric outlet obstruction (GOO) between Jan-2020 and Sep-2022 were included. Results Of 541 patients with underlying malignancy, 323 (59.7%) required same-session pathological diagnosis (male: 54.8%; age 70 [interquartile range 63-78]; pancreatic cancer: 76.8%, biliary tract adenocarcinoma 16.1%). ROSE adequacy was 96.6%, higher for EUS versus ERCP. Among 302 patients with jaundice, ERCP-guided stenting was successful in 83.1%, but final drainage was completed in 97.4% thanks to 43 EUS-guided biliary drainage procedures. Twenty-one patients with GOO were treated with 15 EUS-gastroenterostomies and six duodenal stents. All 58 therapeutic EUS procedures occurred after adequate ROSE. With ERCP-guided placement of stents, the use of plastic stents was significantly higher among patients with inadequate ROSE (10/11; 90.9%) versus adequate sampling (14/240; 5.8%) P <0.0001; OR 161; 95%CI 19-1352). Median hospital stay for diagnosis and palliation was 3 days (range, 2-7) and median time to chemotherapy was 33 days (range, 24-47). Conclusions Nearly two-thirds of oncological candidates for endoscopic palliation require contemporary pathological diagnosis. ROSE adequacy allows, since the index procedure, state-of-the-art therapeutics standardly restricted to pathologically confirmed malignancies (e.g. uncovered SEMS or therapeutic EUS), potentially reducing hospitalization and time to oncological treatments.

Adjusted prognostic information is important for treatment decisions, especially in elderly patients or survivors of exocrine pancreatic cancer (EPC). This study aims to investigate conditional relative survival (CS) rates and conditional probabilities of death in patients with EPC.

Data of 77,975 individuals diagnosed with EPC between 1999 and 2019 were obtained from the Korea Central Cancer Registry. CS was analyzed across strata including histology groups (ductal adenocarcinoma excluding cystic or mucinous [group I, PDAC] and ductal adenocarcinoma specified as mucinous or cystic adenocarcinoma [group II]), and age.

For PDAC, the overall 5-year relative survival (RS) rate at diagnosis, 3-year CS of 2-year survivors, and 5-year CS of 5-year survivors were 8.5%, 50.1%, and 77.6%, respectively. Overall conditional probabilities of death were 85.2% (≥ 80 years), 73.5% (70-79 years), and 62.0% (60-69 years) in year 1 after diagnosis. Among patients with localized or regional stage who underwent surgery, conditional probabilities of death of ≥ 80, 70-79, and 60-69 years were 37.7%, 32.5%, and 22.6% in the first year, and 26.6%, 27.2%, and 26.0% in year 2 after diagnosis.

Half of patients with EPC who survived for 2 years survived for an additional 3 years. However, 5-year PDAC survivors require follow-up as more than 20% do not survive for a further 5 years. Elderly patients should not be excluded from active treatment for localized or regional-stage PDAC, as the CS of elderly patients who are fit enough to undergo surgery is not inferior to that of younger patients.

Pancreatic neuroendocrine neoplasms (PanNENs) are a group of highly heterogeneous neoplasms originating from the endocrine islet cells of the pancreas with characteristic neuroendocrine differentiation, more than 60% of which represent metastases when diagnosis, causing major tumor-related death. Metabolic alterations have been recognized as one of the hallmarks of tumor metastasis, providing attractive therapeutic targets. However, little is known about the molecular mechanism of metabolic changes regulating PanNEN progression. In this study, we first identified methylmalonic acid (MMA) as an oncometabolite for PanNEN progression, based on serum metabolomics of metastatic PanNEN compared with non-metastatic PanNEN patients. One of the key findings was the potentially novel mechanism of epithelial-mesenchymal transition (EMT) triggered by MMA. Inhibin βA (INHBA) was characterized as a key regulator of MMA-induced PanNEN progression according to transcriptomic analysis, which has been validated in vitro and in vivo. Mechanistically, INHBA was activated by FOXA2, a neuroendocrine (NE) specific transcription factor, which was initiated during MMA-induced progression. In addition, MMA-induced INHBA upregulation activated downstream MITF to regulate EMT-related genes in PanNEN cells. Collectively, these data suggest that activation of INHBA via FOXA2 promotes MITF-mediated EMT during MMA inducing PanNEN progression, which puts forward a novel therapeutic target for PanNENs.

This study aimed to examine the effects of multiple parameters on the incidence of pancreatic cancer. We analyzed data from 1,108,369 individuals in the National Health Insurance Sharing Service Database (NHISS DB; birth to death; 2002 to 2015) and identified 2912 patients with pancreatic cancer. Body mass index, systolic/diastolic blood pressure, and fasting blood glucose and total cholesterol concentrations were lower in women with than without pancreatic cancer (p < 0.01). Fasting blood glucose and total cholesterol concentrations were significantly different between men with and without pancreatic cancer (p < 0.05). In the logistic regression analysis, the total cholesterol concentration (odds ratio (OR), 1.007; 95% confidence interval (CI), 1.005-1.010) was significantly higher in men than women with pancreatic cancer (p < 0.05). Pancreatic cancer rates were highest in men who smoked for 5-9 years or more (OR, 5.332) and in women who smoked for 10-19 years (OR, 18.330). Daily intensive exercise reduced the risk of pancreatic cancer by 56% in men (95% CI, 0.230-0.896). Receiver operating characteristic curve analysis revealed a total cholesterol concentration cut-off point of 188.50 mg/dL (p < 0.05) in men with pancreatic cancer, with a sensitivity and specificity of 53.5% and 54.6%, respectively. For women, the cut-off values for weight and gamma glutamyl transpeptidase concentration were 58.5 kg and 20.50 U/L, respectively. The sex-specific differences in patients with pancreatic cancer identified herein will aid in the development of individualized evidence-based prognostic and preventive programs for the treatment of pancreatic cancer.

Endoscopic ultrasound (EUS) is a main tool in gastroenterology for both diagnosis and exclusion of pancreatic pathology. It allows minimally invasive assessment of various diseases or anatomic variations affecting the pancreas also with the help of new Doppler technologies, elastography, contrast-enhanced imaging including post hoc image processing with quantification analyses, three-dimensional reconstruction, and artificial intelligence. EUS also allows interventional direct access to the pancreatic parenchyma and the retroperitoneal space, to the pancreatic duct, pancreatic masses, cysts, and vascular structures.

This review aimed to summarize new developments of EUS in the field of pancreatology. We highlight the role of EUS in evaluating pancreatic pathology by describing normal anatomic variants like pancreas divisum, pancreatic lipomatosis, pancreatic fibrosis in the elderly and characterizing pancreatic masses, both in the context of chronic pancreatitis and within healthy pancreatic parenchyma. EUS is considered the optimal imaging modality for pancreatic masses of uncertain dignity and allows both cytological diagnosis and histology, which is essential not only for neoplastic conditions but also for tailoring therapy for benign inflammatory conditions.

EUS plays an indispensable role in pancreatology and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas exponentially increased over the last years. The development of computer-aided diagnosis and artificial intelligence algorithms hold the potential to overcome the obstacles associated with interobserver variability and will most likely support decision-making in the management of pancreatic disease.

Pancreatic ductal carcinoma (PDAC) is highly fatal with limited understanding of mechanisms underlying its carcinogenesis. We comprehensively investigated whether lipidomic measures were associated with PDAC in two prospective studies. We measured 904 lipid species and 252 fatty acids across 15 lipid classes in pre-diagnostic serum (up to 24 years) in a PDAC nested-case control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, NCT00002540) with 332 matched case-control sets including 272 having serial blood samples and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC, NCT00342992) with 374 matched case-control sets. Controls were matched to cases by cohort, age, sex, race, and date at blood draw. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) per one-standard deviation increase in log-lipid concentrations within each cohort, and combined ORs using fixed-effects meta-analyses. Forty-three lipid species were associated with PDAC (false discovery rate, FDR ≤ 0.10), including lysophosphatidylcholines (LPC, n = 2), phosphatidylethanolamines (PE, n = 17), triacylglycerols (n = 13), phosphatidylcholines (PC, n = 3), diacylglycerols (n = 4), monoacylglycerols (MAG, n = 2), cholesteryl esters (CE, n = 1), and sphingomyelins (n = 1). LPC(18:2) and PE(O-16:0/18:2) showed significant inverse associations with PDAC at the Bonferroni threshold (P value < 5.5 × 10-5). The fatty acids LPC[18:2], LPC[16:0], PC[15:0], MAG[18:1] and CE[22:0] were significantly associated with PDAC (FDR < 0.10). Similar associations were observed in both cohorts. There was no significant association for the differences between PLCO serial lipidomic measures or heterogeneity by follow-up time overall. Results support that the pre-diagnostic serum lipidome, including 43 lipid species from 8 lipid classes and 5 fatty acids, is associated with PDAC.

Pancreatic neuroendocrine tumor is a rare and heterogeneous entity, and approximately half of the patients harbored liver metastasis when initially diagnosed, whose prognosis is dismal. High-throughput sequencing has largely uncovered the genomic features of pancreatic neuroendocrine tumor, but the genetic alterations in the metastatic cases remain relatively unclear, which we aimed to study.

Pathologically confirmed well-differentiated pancreatic neuroendocrine tumor samples resected in our hospital from 2000 to 2019 were collected. We performed deep sequencing on the exome of 341 tumor-related genes, and compared the differences of genetic alterations between the metastatic and the non-metastatic cases, as well as between the primary and the paired liver metastatic tumors.

Sequencing data of 79 samples from 29 pancreatic neuroendocrine tumor patients were included into analysis. A total of 2,471 somatic variants were identified, 75.5% of which were considered as low-abundance. NOTCH1 was the most frequently mutated gene, altered in 26 (53.1%) pancreatic neuroendocrine tumor samples from 18 (62.1%) patients. Compared with the non-metastatic pancreatic neuroendocrine tumors, the metastatic cases were discovered with more single nucleotide variants and copy number variations, indicating the increased genomic instability. In addition, among the paired metastatic cases, the primary and the metastatic lesions shared limited mutated genes.

Through the targeted deep sequencing, we identified the intratumor, intraindividual, and interindividual heterogeneity in the pancreatic neuroendocrine tumor patients, particularly in the metastatic cases, bringing potential challenges for the current biopsy strategies in guiding clinical treatments.

Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data.

PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults.

A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001).

Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.

A decrease in cancer mortality has been reported in the USA, possibly due to decreased incidence, downstaging and improved survival. The aim of the present study is to estimate the contribution of these factors on the trend in cancer mortality.

Data on incidence, mortality, stage at diagnosis, and overall and stage-specific survival for six common digestive and respiratory cancers (esophagus, stomach, colorectal, liver, pancreas and lung) during 2009-2013 in the USA from the surveillance, epidemiology and end results (SEER) program, was analyzed using generalized linear models separately among men and women.

Our study showed a decrease in mortality for esophageal (-0.09/100 000/year and -0.03/100 000/year), stomach (-0.11/100 000/year and -0.05/100 000/year), colorectal (-0.45/100 000/year and -0.29/100 000/year) and lung cancer (-1.89/100 000/year in men and -0.78/100 000/year in women) in men and women, respectively: for all of them, except lung cancer in women, there was a decrease in the incidence of comparable or greater magnitude; stage distribution and survival also contributed to the decrease in mortality for lung and colorectal cancer. Mortality from pancreatic cancer was stable: an increase in incidence was counterbalanced by an improvement in survival. Mortality from liver cancer increased, driven by an increase in mortality that was not offset by favorable trends in stage distribution and survival.

Trends in mortality were primarily affected by changes in incidence; an increase in the proportion of local stage at diagnosis and improved survival, although evident for some cancers, played a lesser role in mortality trends.

As part of the aging process, fibrotic changes, fatty infiltration, and parenchymal atrophy develop in the pancreas. The pancreatic duct also becomes wider with age. This article provides an overview of the diameter of the pancreatic duct in different age groups and different examination methods. Knowledge of these data is useful to avoid misinterpretations regarding the differential diagnosis of chronic pancreatitis, obstructive tumors, and intraductal papillary mucinous neoplasia (IPMN).

DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC.

Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed.

130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48-9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04-3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13-5.48, p = 0.023) and high post-operative CA 19-9 level (>100 IU/ml) (HR:2.61 95% CI 1.40-4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53.

Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

Pancreatic enzymes assist metabolic digestion, and hormones like insulin and glucagon play a critical role in maintaining our blood sugar levels. A malignant pancreas is incapable of doing its regular functions, which results in a health catastrophe. To date, there is no effective biomarker to detect early-stage pancreatic cancer, which makes pancreatic cancer the cancer with the highest mortality rate of all cancer types. Primarily, mutations of the KRAS, CDKN2A, TP53, and SMAD4 genes are responsible for pancreatic cancer, of which mutations of the KRAS gene are present in more than 80% of pancreatic cancer cases. Accordingly, there is a desperate need to develop effective inhibitors of the proteins that are responsible for the proliferation, propagation, regulation, invasion, angiogenesis, and metastasis of pancreatic cancer. This article discusses the effectiveness and mode of action at the molecular level of a wide range of small molecule inhibitors that include pharmaceutically privileged molecules, compounds under clinical trials, and commercial drugs. Both natural and synthetic small molecule inhibitors have been counted. Anti-pancreatic cancer activity and related benefits of using single and combined therapy have been discussed separately. This article sheds light on the scenario, constraints, and future aspects of various small molecule inhibitors for treating pancreatic cancer-the most dreadful cancer so far.

Organoids are a new type of 3D model for tumor research, which makes up for the shortcomings of cell lines and xenograft models, and promotes the development of personalized precision medicine. Long-term culture, expansion and storage of organoids provide the necessary conditions for the establishment of biobanks. Biobanks standardize the collection and preservation of normal or pathological specimens, as well as related clinical information. The tumor organoid biobank has a good quality control system, which is conducive to the clinical transformation and large-scale application of tumor organoids, such as disease modeling, new drug development and high-throughput drug screening. This article summarized the common tumor types of patient-derived organoid (PDO) biobanks and the necessary information for biobank construction, such as the number of organoids, morphology, success rate of culture and resuscitation, pathological types. In our results, we found that patient-derived tumor organoid (PDTO) biobanks were being established more and more, with the Netherlands, the United States, and China establishing the most. Biobanks of colorectal, pancreas, breast, glioma, and bladder cancers were established more, which reflected the relative maturity of culture techniques for these tumors. In addition, we provided insights on the precautions and future development direction of PDTO biobank building.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor outcomes. Although the management strategies have evolved in recent years, the PDAC 5-year survival rate remains at only 9%; it may become the second leading cause of cancer death in the USA by 2030. Only 15-20% of PDAC patients are eligible to undergo surgery; diagnostic biopsies and individualized treatment present a more significant challenge for the remaining group. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been widely used in the diagnosis of pancreatic masses. With the advancement of this sampling technique, adequate specimens can be obtained from all patients with PDAC in both early and late clinical stages. Recent data suggest that the specimens obtained from EUS-TA might be used to establish viable preclinical models, which conserve the genetic mutation and preserve the heterogeneity of the original tumors. Additionally, any drug sensitivity evident in the EUS-TA-derived preclinical models might predict the clinical response, thus guiding the prospective therapeutic selection. As we move toward the era of precision medicine, this review provides an update on the role of EUS-TA as a method for obtaining genetic material used in preclinical models that can assess and stratify individuals according to their individual cancer biology.

The study aim to investigate whether elderly patients with resectable pancreatic ductal adenocarcinoma (PDAC) could benefit from postoperative chemotherapy.

This study selects the data of PDAC patients who were diagnosed between 2004 and 2014 from the Surveillance, Epidemiology, and End Results program. Median overall survival (mOS) is determined by Kaplan-Meier survival curves. Multivariate logistic regression analysis and hazard ratio are employed to assess the association among potential prognostic factors. Propensity score matching evaluation is used to reduce bias.

In total, there are 11,865 PDAC patients selected from the Surveillance, Epidemiology, and End Results database. Elderly PDAC patients have poor prognoses compared with younger (mOS, 15 vs 21 months). The possible reason might be that the elderly patients are less likely to receive postoperative chemotherapy. After propensity score matching, it is found that, for those who receive postoperative chemotherapy, although the mOS of older group is not as good as that of the younger group (mOS, 20 vs 23 months; 18-month survival rate: 53.4% vs 61.3%), the mOS of older group prolonged by postoperative chemotherapy is similar to that of younger group (9 vs 9 months).

Elderly PDAC patients (≥70 years) might benefit from the currently used postoperative chemotherapy regimens.

Detecting pancreatic cancer at an earlier stage may contribute to an increased survival. Patients with stage I pancreatic cancer have a 5-year survival rate of 36%, while stage IV patients have a 5-year survival rate of 1% in Sweden. Research into novel blood-based biomarkers for pancreatic cancer is highly intensive and innovative, but has yet to result in any routine screening test. The aim of this study was to evaluate the specificity and sensitivity of a hypothetical blood test for pancreatic cancer used for screening purposes and the economic aspects of testing.

A model of a screening test was created, with varying specificity and sensitivity both set at 80%, 85%, 90%, 95% or 99% and applied to selected risk groups. Excessive costs of false positive screening outcomes, QALYs, ICERs and total costs were calculated.

Individuals with family history and genetic mutations associated with pancreatic cancer, new-onset diabetes ≥50 years of age and early symptoms had the highest positive predictive values and ICERs beneath the willingness-to-pay-level of EUR 100,000/QALY. Screening of the general population and smokers resulted in a high rate of false positive cases and extensive extra costs.

General screening for pancreatic cancer is not cost-effective, while screening of certain high-risk groups may be economically justified given the availability of a high-performing blood-based test.

Obesity is a well-established risk factor for pancreatic cancer. Bariatric surgery has demonstrated superior results in terms of weight loss and obesity-related comorbidities compared to medical and behavioral treatments. The aim of this study is to evaluate the effect of bariatric surgery on pancreatic cancer incidence in individuals with obesity.

Individuals with a diagnosis of obesity were retrieved from the French national hospital discharge database. We conducted a cohort study comparing the risk to develop pancreatic cancer in individuals with obesity with and without history of bariatric surgery; the inverse probability of treatment weighting (IPTW) method was performed to assess the uncertainty around the results. Moreover, a subgroup analysis according to age at the time of bariatric surgery was performed to study its impact on the risk of pancreatic cancer. Finally, possible differences depending on the type of bariatric procedure (sleeve gastrectomy vs Roux-en-Y gastric bypass) were also explored.

160,129 (Bariatric Surgery group) and 1,263,804 (control group) patients with 5.2 ± 1.9 and 6.0 ± 1.9 years of follow-up respectively were included. A significant reduced risk to develop pancreatic cancer during follow-up was identified for the bariatric surgery group in the overall population (HR: 0.567). However, this reduced risk was only observed in the 18-50 years group. These results were furtherly confirmed after IPTW analysis. No difference was found between different bariatric procedures.

Bariatric surgery has a protective effect against pancreatic cancer in the 18-50 years population. High-quality prospective studies are needed to confirm these results.

Pancreatic cancer is among the most challenging forms of cancer to treat, owing to its late diagnosis and aggressive nature that reduces the survival rate drastically. Pancreatic cancer diagnosis has been primarily based on imaging, but the current state-of-the-art imaging provides a poor prognosis, thus limiting clinicians' treatment options. The advancement of a cancer diagnosis has been enhanced through the integration of artificial intelligence and imaging modalities to make better clinical decisions. In this review, we examine how AI models can improve the diagnosis of pancreatic cancer using different imaging modalities along with a discussion on the emerging trends in an AI-driven diagnosis, based on cytopathology and serological markers. Ethical concerns regarding the use of these tools have also been discussed.