Background: Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. Aim: To systematically investigate the burden and trend of EOPC based on global populations. Methods: In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100 000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. Results: According to the GBD 2019 estimates, there were 36 852 new cases of EOPC and 32 004 related deaths. East Asia had the highest number of cases, with 11 401 incidences and 10 149 deaths. The ASRs were 0.94 per 100 000 individuals for incidence and 0.81 per 100 000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100 000 <ASRs <2.0 per 100 000), and decreased with further increase in SDI in 2019. Conclusions: The findings offer valuable insights into the global distribution and magnitude of the EOPC burden. The burden is increasing at a rapid pace worldwide, particularly in Asia, and is notably high in central and eastern Europe. This highlights the need for additional preventive control efforts targeting high-risk populations.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a type of lethal gastrointestinal malignancy. It is mainly discovered at, and diagnosed with, an advanced stage of metastasis. As the only potentially curative treatment for PDAC, surgical resection has an uncertain impact on the survival of these patients. As such, we aimed to investigate if patients with metastatic PDAC (mPDAC) benefit from surgery. Methods: Patients with pancreatic cancer in 18 registries of the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were reviewed retrospectively. According to the American Joint Committee on Cancer (AJCC), the eighth edition staging system was utilized. Propensity score matching was applied to strengthen the comparability of the study. The impact of surgery on survival was evaluated by restricted mean survival time (RMST) and Kaplan–Meier analysis. Results: A total of 210 well-matched mPDAC patients were included in the study. The 1 year, 3 year, and 5 year overall survival (OS) of patients undergoing surgery was 34.3%, 15.2%, and 11.0%, respectively. The 1 year, 3 year, and 5 year cancer-specific survival (CSS) of these patients was 36.1%, 19.7%, and 14.2%, respectively. RMST analysis revealed that mPDAC patients with surgery had better OS and CSS than those without (OS: 9.49 months vs. 6.45 months, p < 0.01; CSS: 9.76 months vs. 6.54 months, p < 0.01). Nevertheless, subgroup analysis demonstrated that such statistical significance especially existed in oligometastatic PDAC patients, which refers to those metastases that were limited in number and concentrated to a single organ in this study. Additionally, surgery was identified as a significant predictor for the long-term prognosis of patients (OS: [HR, hazard ratio] = 0.48, 95% CI: 0.36–0.65, p < 0.001; CSS: HR = 0.45, 95% CI: 0.33–0.63, p < 0.001). Lastly, a nomogram was established to predict whether an individual was suitable for surgical treatment in this study. Conclusions: Surgical resection significantly prolonged the long-term prognosis of oligometastatic PDAC patients. Such insights might broaden the management of patients with mPDAC to a large extent. However, a prospective clinical trial should be conducted before a recommendation of surgery in these patients.

Background: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. Methods: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan–Meier analysis and Cox proportional hazards models. Results: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p < 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21–0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. Conclusions: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion.

Background: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. Method: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. Results: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. Conclusions: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference.

Objectives: This study aims to assess the association between adjuvant radiotherapy and the development of second primary malignancies (SPMs) and identify its determinants in patients who have undergone surgical treatment for gastric cancer. Design: Retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) database. Setting: Cohorts (18 registries, 2000–2018, from SEER) were screened for any malignancy that developed after sufficient latency from diagnosis of surgically treated non-metastatic gastric cancer. Participants: 24 777 surgically treated gastric cancer cases were included in the cohort. Among them, 6128 patients underwent adjuvant radiotherapy. Outcome measures: The cumulative incidence of SPMs was estimated using Fine and Gray’s competing risk model and the radiotherapy-correlated risks were calculated using Poisson regression analysis. Results: Among patients with sufficient latency, there was no significant association between radiotherapy and the risk of developing second primary solid malignancies (relative risk=1.05, 95% CI 0.83 to 1.33) or haematological malignancies (relative risk=1.17, 95% CI 0.62 to 2.11). Interestingly, radiotherapy was associated with a reduced cumulative incidence of second lung and bronchus cancer compared with no radiotherapy, with a 15-year incidence of 1.4%–3.17% (p<0.05). Radiotherapy was not associated with a significant increase in standardised incidence ratios of SPMs. Conclusions: Adjuvant radiotherapy was not associated with an increased risk of developing SPMs in surgically treated patients with gastric cancer. Clinical trials are warranted to further verify the findings.

Background: The effectiveness of adjuvant chemotherapy (ACT) in ampullary adenocarcinoma (AA) patients and under what conditions ACT should be applied are not clearly defined.Methods: The study encompassed a series of consecutive AA patients who underwent curative surgical resection. These patients were sourced from the National Cancer Center of China, spanning the years 1998 to 2020, as well as from 12 registries within the Western surveillance, epidemiology, and end results program, covering the period from 2004 to 2017. The quantitative nodal burden was evaluated using the log odds of positive lymph nodes (LODDS). The correlation between ACT and overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), was meticulously evaluated using Cox proportional hazards regression models and tested by interaction analysis.Results: Despite its rarity, a total of 948 and 225 eligible patients were included in the Western cohort and the China cohort, respectively. ACT was not significantly associated with improved long-term survival of unselected AA patients in both the China cohort (OS: P = 0.86, RFS: P = 0.84) and Western cohort (OS: P = 0.11, CSS: P = 0.82). After the quantitative analysis of nodal tumor burden, the study revealed that in patient subgroup with LODDS exceeding -1.4, significantly prolonged survival outcome emerged in patients received ACT (Surgery+ACT VS. Surgery alone, HR: 0.38, 95% CI: 0.19 - 0.75, P = 0.01). The multivariate analysis demonstrated that increasing LODDS was associated with increasing survival benefit from ACT (P for interaction = 0.03), whereas the N classification did not reliably identify patients benefiting from ACT based on statistical test of interaction (P = 0.20).Conclusion: This study emphasizes the potential of LODDS to inform personalized therapeutic decisions in the management of AA.