Patients with pancreatic surgery have a high incidence of preoperative malnutri-tion, large surgical trauma, and many postoperative complications. The practice of enhanced recovery after surgery is difficult. After nearly 20 years of development, the concept of enhanced recovery after surgery (ERAS) has formed mature guidelines and consensus in pancreatic surgery. However, its application is faced with problems such as large central differences, low level of evidence-based, and insufficient completion of rehabilitation processes. The growth of publications in journals on related topics has stagnated, and the research heat has a trend of ebbing. Based on the literature at home and abroad, the authors analyze the bottleneck of application of enhanced recovery after surgery in pancreatic cancer from the aspects of process management, pre-rehabilitation and nutrition management, and look forward to the future research direction.

Patients with pancreatic surgery have a high incidence of preoperative malnutri-tion, large surgical trauma, and many postoperative complications. The practice of enhanced recovery after surgery is difficult. After nearly 20 years of development, the concept of enhanced recovery after surgery (ERAS) has formed mature guidelines and consensus in pancreatic surgery. However, its application is faced with problems such as large central differences, low level of evidence-based, and insufficient completion of rehabilitation processes. The growth of publications in journals on related topics has stagnated, and the research heat has a trend of ebbing. Based on the literature at home and abroad, the authors analyze the bottleneck of application of enhanced recovery after surgery in pancreatic cancer from the aspects of process management, pre-rehabilitation and nutrition management, and look forward to the future research direction.

Objective:To construct a patient-derived organoid model and clarify its predictive value for the sensitivity of pancreatic cancer chemotherapy drugs.Methods:A total of 42 tissue samples from patients with pancreatic ductal adenocarcinoma who underwent surgery or percutaneous biopsy at Peking University First Hospital from 2020 to 2023 were collected. Pancreatic cancer organoid models were constructed through in vitro culture. These organoid models were treated with five most commonly used pancreatic cancer chemotherapy drugs, namely Gemcitabine, nab-Paclitaxel, 5-Fluorouracil, Oxaliplatin, and Irinotecan, to determine the IC 50. The consistency between the organoid drug sensitivity test results and the patients' chemotherapy sensitivity was determined. Results:Patient-derived pancreatic cancer organoid models achieved an establishment success rate of 73.33%. The organoid model could reproduce the pathological features of the patients' tumor tissues; there were individual differences in the sensitivity to the same chemotherapy drug among organoid models derived from different patients. The sensitivity of patient derived organoids was highly consistent with the actual treatment effect of the corresponding patients was 81%.Conclusion:The drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on patient derived organoids has the potential to guide individualized chemotherapy for pancreatic cancer.

Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

Objective:To construct a patient-derived organoid model and clarify its predictive value for the sensitivity of pancreatic cancer chemotherapy drugs.Methods:A total of 42 tissue samples from patients with pancreatic ductal adenocarcinoma who underwent surgery or percutaneous biopsy at Peking University First Hospital from 2020 to 2023 were collected. Pancreatic cancer organoid models were constructed through in vitro culture. These organoid models were treated with five most commonly used pancreatic cancer chemotherapy drugs, namely Gemcitabine, nab-Paclitaxel, 5-Fluorouracil, Oxaliplatin, and Irinotecan, to determine the IC 50. The consistency between the organoid drug sensitivity test results and the patients' chemotherapy sensitivity was determined. Results:Patient-derived pancreatic cancer organoid models achieved an establishment success rate of 73.33%. The organoid model could reproduce the pathological features of the patients' tumor tissues; there were individual differences in the sensitivity to the same chemotherapy drug among organoid models derived from different patients. The sensitivity of patient derived organoids was highly consistent with the actual treatment effect of the corresponding patients was 81%.Conclusion:The drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on patient derived organoids has the potential to guide individualized chemotherapy for pancreatic cancer.

Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

The special suppressive tumor immune microenvironment is a significant factor in the high postoperative recurrence rate and insensitivity to immunotherapy in pancreatic cancer. Tertiary lymphoid structures (TLSs) are pathologic ectopic lymphoid tissues composed of various immune cells, playing a crucial role in regulating adaptive anti-tumor immune responses. The presence of TLSs in pancreatic cancer tissues signifies better prognosis and immune therapy response. Examining the quantity, location, maturity, and cellular components of TLSs in pancreatic cancer specimens helps predict prognosis and screen potential beneficiaries of immunotherapy. Exploring key factors inducing TLSs formation and elucidating the anti-tumor immune mechanisms of TLSs may provide a new theoretical basis for enhancing the efficacy of pancreatic cancer immunotherapy. The authors summarize the clinical status and hot topics of TLSs in pancreatic cancer applications, and look forward to the research directions of TLSs in the field of pancreatic cancer.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death in the world.Most patients are diagnosed as locally advanced or metastatic disease at initial visit,losing the opportunity of surgery.Conversion therapy aims to give unresectable tumors the opportunity to receive radical surgery through comprehensive treatment.For unresectable pancreatic cancer,chemotherapy based on AG(abraxane+gemcitabine)or FOLFIRINOX(5-fluorouracil+leucovorin+irinotecan+oxaliplatin),radiotherapy combined with chemotherapy as well as other regimens have shown conversion potential.Targeted therapy and immunotherapy have also become new frontiers of conversion therapy for pancreatic cancer.Focusing on new drugs and new regimens,this review has summarized the latest research progress of conversion therapy for pancreatic cancer.

Pancreatic cancer (PC) is a malignant digestive tract tumor with poor prognosis. Most of patients with PC are insensitive to traditional strategies of chemotherapy, targeted therapy and immunotherapy. PC with microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) is rare in clinic, which has distinctive clinicopathological characteristics and better prognosis from conventional PC. Reasonable acquisition of pancreatic tumor biopsy and accurate assessment of MSI-H/dMMR status are helpful for accurate diagnosis of such patients. Individualized treatment strategy based on immunotherapy can significantly improve the prognosis of patients with MSI-H/dMMR PC. Based on relevant literatures of domestic and foreign, the authors discuss the current status and research hotspots of diagnosis and treatment for MSI-H/dMMR PC.