Pancreatic neuroendocrine neoplasms represent a highly heterogeneous group of malignancies exhibiting a broad spectrum of biological behaviors ranging from indolent to highly aggressive. The formulation of therapeutic strategies requires a comprehensive consideration of patient condition and tumor biological characteristics. Neoadjuvant therapy has demonstrated promising efficacy in tumor downstaging,enhancing R0 resection rates,and improving prognoses across various solid tumors,yet its application in pancreatic neuroendocrine neoplasms remains underexplored with limited clinical evidence. This review systematically examines critical issues in neoadjuvant management of pancreatic neuroendocrine neoplasms based on contemporary guidelines and emerging literature,encompassing patient selection criteria,regimen optimization,response evaluation,and optimal surgical timing. Current challenges persist in standardizing neoadjuvant approaches,necessitating multicenter prospective studies to establish high-level evidence. Future advancements in artificial intelligence and precision medicine hold potential to revolutionize personalized therapeutic paradigms,ultimately improving patient survival outcomes.

Pancreatic neuroendocrine neoplasms represent a highly heterogeneous group of malignancies exhibiting a broad spectrum of biological behaviors ranging from indolent to highly aggressive. The formulation of therapeutic strategies requires a comprehensive consideration of patient condition and tumor biological characteristics. Neoadjuvant therapy has demonstrated promising efficacy in tumor downstaging,enhancing R0 resection rates,and improving prognoses across various solid tumors,yet its application in pancreatic neuroendocrine neoplasms remains underexplored with limited clinical evidence. This review systematically examines critical issues in neoadjuvant management of pancreatic neuroendocrine neoplasms based on contemporary guidelines and emerging literature,encompassing patient selection criteria,regimen optimization,response evaluation,and optimal surgical timing. Current challenges persist in standardizing neoadjuvant approaches,necessitating multicenter prospective studies to establish high-level evidence. Future advancements in artificial intelligence and precision medicine hold potential to revolutionize personalized therapeutic paradigms,ultimately improving patient survival outcomes.

ObjectiveTo investigate the influencing factors for traditional Chinese medicine （TCM） syndromes of primary liver cancer， and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups， and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area （31.81%）， abdominal distension （25.30%）， abdominal pain （15.18%）， and weakness （13.98%）， and the main clinical symptoms included poor appetite （70.84%）， fatigue （69.16%）， pain in the liver area （67.47%）， poor sleep （59.04%）， abdominal distension （53.01%）， and constipation （52.53%）. There were significant differences in TCM syndromes between patients with different sexes， courses of the disease， clinical stages， Child-Pugh classes， presence or absence of intrahepatic and extrahepatic metastasis， and presence or absence of transcatheter arterial chemoembolization （TACE） and radiofrequency ablation （all P<0.05）. The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation （odds ratio ［OR］=2.036， P=0.048） and the syndrome of spleen-kidney Yang deficiency （OR=5.240， P<0.001）； a course of disease of<1 year was a risk factor for damp-heat accumulation （OR=2.837， P=0.004） and syndrome of Qi stagnation and blood stasis （OR=2.317， P=0.021）， but it was a protective factor against syndrome of spleen-kidney Yang deficiency （OR=0.385， P=0.005）； Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency （OR=0.079， P<0.001）； intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency （OR=5.117， P=0.003） and syndrome of spleen-kidney Yang deficiency （OR=3.303， P=0.010）； TACE was a protective factor against liver-kidney Yin deficiency （OR=0.171， P<0.001） and syndrome of spleen-kidney Yang deficiency （OR=0.138， P<0.001）； radiofrequency ablation was a risk factor for damp-heat accumulation （OR=4.408， P<0.001） and liver-kidney Yin deficiency （OR=32.036， P<0.001）. ConclusionSex， course of disease， Child-Pugh class， intrahepatic metastasis， TACE， and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.

Objective:To explore the clinicopathologic features of early-onset pancreatic cancer (EOPC) and its correlation with dyslipidemia and prognostic analysis.Methods:This is a retrospective cohort study. Clinical and pathological data of 455 patients with pancreatic cancer who underwent radical surgery from January 2013 to September 2020 in the Department of Pancreatic Surgery, Qilu Hospital, Shandong University were retrospectively collected. According to the onset age≤50 years, the patients were divided into EOPC group(67 cases) and later-onset pancreatic cancer (LOPC) group(388 cases). There were 48 males and 19 females in the EOPC group, aged (44.4±5.7) years(range: 28.0 to 50.0 years); and 230 males and 158 females in the LOPC group, aged (63.0±7.2)years (range: 51.0 to 86.0 years). EOPC was divided into two groups according to the blood lipid status: dyslipidemia (50 cases) and normal (17 cases). General information, blood lipid data, clinicopathological parameters and follow-up information were collected. χ2 test, Mann-Whitney U test and Logistic regression analysis were used to evaluate the difference or correlation between groups, and Cox regression analysis and Kaplan-Meier survival curve were used to analyze the impact of EOPC and dyslipidemia on the prognosis. Propensity score matching was used to match two groups of patients in a 1∶1 ratio using nearest neighbor matching, with a caliper set at 0.05. Results:Compared with LOPC group, EOPC group with a higher proportion of patients with body mass index ≥24 kg/m 2 (55.8%(24/43) vs. 38.7%(113/292), χ2=4.542 ,P=0.033), dyslipidemia(74.6%(50/67) vs. 57.7%(224/388), χ2=6.808, P=0.009), pancreatic head cancer (73.1% (49/67) vs. 60.0%(231/385), χ2=4.176, P=0.041) and a lower proportion of patients with type 2 diabetes (9.0%(6/67) vs. 24.2%(94/388), χ2=7.771, P=0.005) and hypertension (9.0%(6/67) vs. 33.0%(128/388), χ2=15.885, P<0.01). Compared the proportion of dyslipidemia in the two groups,there was a higher proportion of high density lipoprotein cholesterol(HDL-C) abnormality in the EOPC group (65.7%(44/67) vs. 42.8%(166/388), χ2=12.044, P<0.01), whereas there was no significant difference in other lipid indices. Kaplan-Meier survival curve analysis of dyslipidemia did not have a significant effect on the prognosis of EOPC patients ( P=0.430). The results of further Logistic regression analysis showed that gender( OR=6.445 (95% CI: 1.692 to 24.548), P=0.006) and tumor location ( OR=5.352 (95% CI: 1.374 to 20.846), P=0.016) were independent related factors with serum lipid level in patients with EOPC. Conclusions:Compared with LOPC, EOPC is more likely to be combined with obesity and HDL-C abnormalities, and the proportion of pancreatic head cancer is also higher, but there is no significant difference in prognosis between the two groups. In the EOPC patients, serum lipid level is associated with gender and tumor site, but has no effect on survival.

Objective:To investigate the clinicopathological characteristics and prognosis of pancreatic cancer (PC) patients with fatty pancreas (FP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PC who underwent surgery at Qilu Hospital of Shandong University from January 2013 to January 2022 were collected. There were 85 males and 31 females, aged 60(54,65)years. Observation indicators: (1) clinicopathological characteristics of PC patients with FP; (2) influencing factors for FP in PC patients; (3) prognosis of PC patients with FP. Comparison of count data between groups was conducted using the Pearson chi-square test. Multivariate analysis was conducted using the Logistic regression model. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and Cox proportional hazard model was used for survival analysis.Results:(1) Clinicopathological characteristics of PC patients with FP. Of the 116 PC patients, there were 43 cases with FP and 73 cases without FP. Cases with tumor location at pancreatic head were 36 in PC patients with FP and 46 in PC patients without FP. Cases with tumor location at pancreatic body or tail were 7 in PC patients with FP and 27 in PC patients without FP. Cases with high-density lipoprotein cholesterol ≥1.04 mmol/L were 14 in PC patients with FP and 34 in PC patients without FP. Cases with dyslipidemia were 33 in PC patients with FP and 36 in PC patients without FP. There were significant differences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP ( χ2=5.600, 4.588, 5.165, P<0.05). (2) Influencing factors for FP in PC patients. Results of multivariate analysis showed that no correlation was found between tumor location, high-density lipoprotein cholesterol, plasma lipid and FP in PC patients ( P>0.05). (3) Prognosis of PC patients with FP. Eighty of the 116 PC patients were followed up for 30.8(15.1,57.5)months, with the median overall survival time of 24.0 months. Among them, 54 patients with FP had a median overall survival time of 19.5 months, 26 patients without FP had a median overall survival time of 24.6 months, showing no significant difference in survival between them ( hazard ratio=1.031, P>0.05). Conclusions:There are differ-ences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP, but no correlation is found between the above indicators and FP in PC patients. There is no significant difference in prognosis between patients with and without FP.

Objective:To investigate the clinicopathological characteristics and prognosis of pancreatic cancer (PC) patients with fatty pancreas (FP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PC who underwent surgery at Qilu Hospital of Shandong University from January 2013 to January 2022 were collected. There were 85 males and 31 females, aged 60(54,65)years. Observation indicators: (1) clinicopathological characteristics of PC patients with FP; (2) influencing factors for FP in PC patients; (3) prognosis of PC patients with FP. Comparison of count data between groups was conducted using the Pearson chi-square test. Multivariate analysis was conducted using the Logistic regression model. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and Cox proportional hazard model was used for survival analysis.Results:(1) Clinicopathological characteristics of PC patients with FP. Of the 116 PC patients, there were 43 cases with FP and 73 cases without FP. Cases with tumor location at pancreatic head were 36 in PC patients with FP and 46 in PC patients without FP. Cases with tumor location at pancreatic body or tail were 7 in PC patients with FP and 27 in PC patients without FP. Cases with high-density lipoprotein cholesterol ≥1.04 mmol/L were 14 in PC patients with FP and 34 in PC patients without FP. Cases with dyslipidemia were 33 in PC patients with FP and 36 in PC patients without FP. There were significant differences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP ( χ2=5.600, 4.588, 5.165, P<0.05). (2) Influencing factors for FP in PC patients. Results of multivariate analysis showed that no correlation was found between tumor location, high-density lipoprotein cholesterol, plasma lipid and FP in PC patients ( P>0.05). (3) Prognosis of PC patients with FP. Eighty of the 116 PC patients were followed up for 30.8(15.1,57.5)months, with the median overall survival time of 24.0 months. Among them, 54 patients with FP had a median overall survival time of 19.5 months, 26 patients without FP had a median overall survival time of 24.6 months, showing no significant difference in survival between them ( hazard ratio=1.031, P>0.05). Conclusions:There are differ-ences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP, but no correlation is found between the above indicators and FP in PC patients. There is no significant difference in prognosis between patients with and without FP.

Objective:To explore the clinicopathologic features of early-onset pancreatic cancer (EOPC) and its correlation with dyslipidemia and prognostic analysis.Methods:This is a retrospective cohort study. Clinical and pathological data of 455 patients with pancreatic cancer who underwent radical surgery from January 2013 to September 2020 in the Department of Pancreatic Surgery, Qilu Hospital, Shandong University were retrospectively collected. According to the onset age≤50 years, the patients were divided into EOPC group(67 cases) and later-onset pancreatic cancer (LOPC) group(388 cases). There were 48 males and 19 females in the EOPC group, aged (44.4±5.7) years(range: 28.0 to 50.0 years); and 230 males and 158 females in the LOPC group, aged (63.0±7.2)years (range: 51.0 to 86.0 years). EOPC was divided into two groups according to the blood lipid status: dyslipidemia (50 cases) and normal (17 cases). General information, blood lipid data, clinicopathological parameters and follow-up information were collected. χ2 test, Mann-Whitney U test and Logistic regression analysis were used to evaluate the difference or correlation between groups, and Cox regression analysis and Kaplan-Meier survival curve were used to analyze the impact of EOPC and dyslipidemia on the prognosis. Propensity score matching was used to match two groups of patients in a 1∶1 ratio using nearest neighbor matching, with a caliper set at 0.05. Results:Compared with LOPC group, EOPC group with a higher proportion of patients with body mass index ≥24 kg/m 2 (55.8%(24/43) vs. 38.7%(113/292), χ2=4.542 ,P=0.033), dyslipidemia(74.6%(50/67) vs. 57.7%(224/388), χ2=6.808, P=0.009), pancreatic head cancer (73.1% (49/67) vs. 60.0%(231/385), χ2=4.176, P=0.041) and a lower proportion of patients with type 2 diabetes (9.0%(6/67) vs. 24.2%(94/388), χ2=7.771, P=0.005) and hypertension (9.0%(6/67) vs. 33.0%(128/388), χ2=15.885, P<0.01). Compared the proportion of dyslipidemia in the two groups,there was a higher proportion of high density lipoprotein cholesterol(HDL-C) abnormality in the EOPC group (65.7%(44/67) vs. 42.8%(166/388), χ2=12.044, P<0.01), whereas there was no significant difference in other lipid indices. Kaplan-Meier survival curve analysis of dyslipidemia did not have a significant effect on the prognosis of EOPC patients ( P=0.430). The results of further Logistic regression analysis showed that gender( OR=6.445 (95% CI: 1.692 to 24.548), P=0.006) and tumor location ( OR=5.352 (95% CI: 1.374 to 20.846), P=0.016) were independent related factors with serum lipid level in patients with EOPC. Conclusions:Compared with LOPC, EOPC is more likely to be combined with obesity and HDL-C abnormalities, and the proportion of pancreatic head cancer is also higher, but there is no significant difference in prognosis between the two groups. In the EOPC patients, serum lipid level is associated with gender and tumor site, but has no effect on survival.

An increasing number of studies suggested that the tumor microenvironment exerts a substantial influence on the pathophysiology of pancreatic cancer. As a crucial component of the tumor microenvironment,the tumor stroma plays a pivotal role in the occurrence,development,and chemotherapy resistance of pancreatic cancer. By serving as a proxy for the interaction between tumor cells and the microenvironment,the tumor stroma ratio(TSR) has emerged as a focal point of investigation in recent years. At present,numerous studies show that a low TSR is a protective factor for the prognosis of resectable pancreatic cancer. Additionally, patients with a low TSR are more suitable for the gemcitabine and albumin-bound paclitaxel chemotherapy regimen. But these researches are not conclusive, and there is still a gap between guiding precision treatment. Further research and exploration are required. Integration of artificial intelligence deep learning models into traditional pathological and imaging assessments facilitates precise evaluation of the TSR. It can also enable stratification and precision treatment of pancreatic cancer patients based on this index.

An increasing number of studies suggested that the tumor microenvironment exerts a substantial influence on the pathophysiology of pancreatic cancer. As a crucial component of the tumor microenvironment,the tumor stroma plays a pivotal role in the occurrence,development,and chemotherapy resistance of pancreatic cancer. By serving as a proxy for the interaction between tumor cells and the microenvironment,the tumor stroma ratio(TSR) has emerged as a focal point of investigation in recent years. At present,numerous studies show that a low TSR is a protective factor for the prognosis of resectable pancreatic cancer. Additionally, patients with a low TSR are more suitable for the gemcitabine and albumin-bound paclitaxel chemotherapy regimen. But these researches are not conclusive, and there is still a gap between guiding precision treatment. Further research and exploration are required. Integration of artificial intelligence deep learning models into traditional pathological and imaging assessments facilitates precise evaluation of the TSR. It can also enable stratification and precision treatment of pancreatic cancer patients based on this index.

Pancreatic neuroendocrine neoplasm (pNEN) is highly heterogeneous, and the prognosis varies among tumors of different stages and grades. However, there is lacking high pro-gnostic predictors with sensitivity and specificity. Inflammation plays a pivotal role in the occurrence and development of different tumors, various inflammatory markers such as neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio are of great significance in the diagnosis, treat-ment, and prognosis of tumors. Several studies have demonstrated that inflammatory markers are associated with poor prognosis and can serve as predictive factors for tumor prognosis. The authors summarize recent advances in the researches focused on the prognostic value of inflamma-tory markers in pNEN, in order to provide novel insights for clinical decision-making of pNEN.