Abstract:Pancreatic cancer has a high malignancy degree, with an overall 5-year survival rate of only about 11%. Although curative surgery may cure pancreatic cancer, only about 15% of pancreatic cancers are resectable at the time of initial diagnosis. Neoadjuvant therapy provides an opportunity of R₀ resection for some locally advanced pancreatic cancers (LAPC) that are initially unresectable. Neoadjuvant therapy for LAPC is a new treatment modality based on the current treatment status, which is gradually being accepted by clinical surgeons. The emergence of neoadjuvant treatment regimens has led to 20% to 61% of LAPC cases being converted to resectable cases after neoadjuvant therapy. Oxaliplatin, irinotecan, fluorouracil, and calcium folinate (FOLFIRINOX) and gemcitabine combined with albumin-bound paclitaxel (AG) significantly increase the surgical resection rate of LAPC and are the preferred first-line neoadjuvant treatment regimen for LAPC. There are still significant differences in the choice of treatment plan, duration, evaluation indicators, and surgical timing for LAPC neoadjuvant therapy among medical centers. For some LAPC patients who do not meet surgical indications due to inadequate tumor reduction after preoperative systemic chemotherapy, combined chemoradiotherapy can be used as initial treatment. For LAPC patients who cannot tolerate systemic chemotherapy, stereotactic body radiation therapy (SBRT) can be used to control local tumor progression. The treatment targets for pancreatic cancer include KRAS, EGFR, PARP, and NTRK, among others. The NCCN guidelines recommend genetic testing for all LAPC patients to guide the best drug treatment plan and participate in clinical trials of new drugs. Pancreatic cancer immunotherapy mainly includes immune checkpoint inhibitors, adoptive T-cell therapy, and tumor vaccines. Pembrolizumab is the only second-line treatment approved by the US Food and Drug Administration for microsatellite-instability-high or mismatch-repair-deficient solid tumors, including pancreatic cancer. Currently, adoptive T-cell therapy is limited to metastatic pancreatic cancer. The GVAX tumor vaccine is in the clinical trial stage. There is a synergistic effect between immunotherapy and certain targeted drugs, such as antiangiogenic factors and tyrosine kinase inhibitors. Future immunotherapy should aim to combine multiple new immunotherapy strategies, as well as cytotoxic drugs and/or local ablation therapy, to target tumor-induced immune escape mechanisms. The main challenge of combination therapy will be drug selection, administration sequence, and dosage. It is worth actively recommending the approach of selecting specific LAPC patients for neoadjuvant therapy followed by surgery. It is difficult to evaluate the resectability of tumors after neoadjuvant therapy through imaging evaluation, as CT cannot accurately distinguish between tumor tissue and fibrous tissue. 18F-FDG PET is more accurate than CT in determining the R₀ resectability of pancreatic cancer, but high-quality evidence is still needed to further confirm this. Other evaluations of the effectiveness of neoadjuvant therapy include a decrease in serum tumor marker levels and improvement in clinical symptoms. Liquid biopsy techniques, including the detection of circulating tumor cells, circulating tumor DNA, and exosomes, have shown potential applications in the determination of micrometastases and the evaluation of neoadjuvant therapy efficacy. Long-term survival rates of LAPC patients who underwent surgical resection after neoadjuvant therapy have been improved. Innovative techniques such as adventitial dissection and autologous small bowel transplantation can assist in surgical resection after neoadjuvant therapy. Here, the authors provide a review and discussion of the current status and progress of neoadjuvant therapy for LAPC.

Abstract:Background and Aims With the development of multidisciplinary treatment modalities and the rise of precision medicine, there is a general consensus that neoadjuvant therapy (NAT) can improve the radical resection rate of non-metastatic pancreatic cancer. However, due to the lack of conclusive randomized controlled trials, its role in resectable and borderline resectable patients is still controversial. Therefore, this study was conducted to compare the effectiveness and safety of surgical resection after NAT versus upfront surgery in resectable or borderline resectable pancreatic cancer patients using a Meta-analysis approach, so as to provide evidence-based reference for clinical practice.Methods Randomized controlled trials (RCTs) on NAT and upfront surgery for resectable or borderline resectable pancreatic cancer were searched from several domestic and international databases. The search time limit was from the establishment of the database to November 29, 2022. Cochrane systematic review method was used to evaluate the included studies, and RevMan 5.4 software was used for Meta-analysis of homogeneous studies.Results A total of 7 RCTs with 938 patients were finaly included. Among them, there were 466 patients in NAT group and 472 patients in upfront surgery group. The results of Meta-analysis showed that compared with upfront surgery group, the NAT group had an increased R₀ resection rate (RR=1.65, 95% CI=1.35-2.02, P<0.000 01), a decreased incidence of positive lymph nodes (RR=0.67, 95% CI=0.52-0.85, P=0.001), and a decreased surgical resection rate (RR=0.91, 95% CI=0.84-0.98, P=0.02), while there was no statistically significant difference in median survival time (MD=4.95, 95% CI=-3.26-13.15, P>0.05) or the incidence of surgical complications (RR=1.19, 95% CI=0.97-1.46, P>0.05).Conclusion For resectable or borderline resectable pancreatic cancer, NAT can increase the R₀ resection rate, reduce the incidence of positive lymph nodes, and decrease the surgical resection rate. Whether NAT can improve the overall survival rate of patients with resectable or borderline resectable pancreatic cancer still needs to be verified by more high-quality multicenter randomized controlled studies.

Abstract:Background and Aims Pancreatic cancer is a highly lethal malignant tumor of the digestive tract, with only about 20% of patients eligible for radical surgical resection, and a 5-year survival rate of less than 6%. Currently, the treatment strategy for pancreatic cancer has gradually transitioned from traditional surgery as the mainstay to a comprehensive multidimensional treatment model based on surgical resection. Neoadjuvant therapy has become the preferred and standard treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). Neoadjuvant chemotherapy is an important component of the multidisciplinary treatment system for pancreatic cancer patients. This study was performed to evaluate the clinical application value of neoadjuvant chemotherapy for pancreatic cancer.Methods The clinical data of 54 patients with pancreatic cancer admitted to the Department of Hepatobiliary and Pancreatic Surgery of Chongqing People's Hospital from April 2020 to August 2021 were retrospectively analyzed. All cases were determined to be BRPC or LAPC by clinical imaging evaluation and relevant biochemical indicators. CT or ultrasound-guided puncture biopsy was performed, and the pathological diagnosis was confirmed as pancreatic ductal adenocarcinoma. Three cycles of neoadjuvant chemotherapy with AG regimen (gemcitabine combined with albumin-bound paclitaxel) were given according to the decision of the multidisciplinary treatment mode. During chemotherapy, changes in imaging, CA19-9, clinical symptoms, and signs were dynamically monitored, and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for systematic efficacy evaluation of surgical resectability.Results The median survival period of 54 patients after neoadjuvant chemotherapy was 12.3 months. Among them, 43 patients (79.63%) had a decrease in CA19-9 after neoadjuvant chemotherapy, with 35 patients (64.81%) having a decrease of more than 50% and 13 patients (24.07%) having their CA19-9 level returned to the normal range. Among the 42 patients with abdominal and/or lumbosacral pain, 29 cases (69.04%) had significant pain relief (NRS pain score ≤ 4) after neoadjuvant chemotherapy. According to the mRECIST criteria, 13 cases (24.07%) had a tumor diameter reduction of >30% and no major vessel invasion after neoadjuvant chemotherapy and were evaluated as resectable pancreatic cancer. R₀ resection was performed for all of them. After surgery, the serum CA19-9 levels of all patients were well controlled. The pathological examination indicated nerve invasion in 7 cases (53.84%), vascular invasion in 4 cases (30.77%), and lymph node metastasis was N0 in 9 cases (69.23%), N1 in 4 cases (30.77%), and N2 in 0 cases. The incidence of postoperative complications was 2 cases (15.38%) of grade B pancreatic fistula, 1 case (7.69%) of delayed gastric emptying, 3 cases (23.07%) of lung infection, and 2 cases (15.38%) of abdominal infection. No intra-abdominal bleeding or bile duct fistula occurred. The 90-day postoperative mortality rate was 0. All the surgically treated patients were alive and had a good quality of life during follow-up period.Conclusion For patients with BRPC or LAPC, neoadjuvant chemotherapy can improve the R₀ resection rate, reduce lymph node metastasis, delay tumor progression, effectively relieve abdominal and/or back pain, improve patient quality of life, prolong overall survival, and improve prognosis.

Abstract:Background and Aims Pancreatic cancer is one of the highly malignant solid tumors, and most patients are diagnosed at the locally advanced or late stage due to the lack of early symptoms. Therefore, exploring preoperative prognostic markers is crucial for making diagnosis and treatment strategies in clinical practice. Currently, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and the postoperative prognosis of pancreatic cancer patients is still controversial. This study was conducted to investigate the association of preoperative NLR with the postoperative survival benefits of pancreatic cancer patients, as well as its prognostic value through a Meta-analysis.Methods The studies concerning the relationship between preoperative NLR values and postoperative overall survival (OS) and disease-free survival (DFS) of pancreatic cancer patients were collected by searching PubMed, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang databases. The search was limited from the inception of the databases to March 31, 2022. Two reviewers independently screened and included the literature, and then extracted data, and assessed the risk of bias in the included studies. Revman 5.4 and Stata 16.0 software were used to combine the hazard ratio (HR) and 95% confidence interval (CI), and the corresponding effect model was selected based on heterogeneity. Sensitivity analysis was performed on the included studies, and the Egger regression test was used to determine if there was significant publication bias in the included literature.Results A total of 25 retrospective studies with 4 796 subjects were included. Of these, 24 articles reported the relationship between NLR and postoperative OS, and 6 articles reported the relationship between NLR and postoperative DFS. The NLR cutoff values and sample sizes in the included retrospective studies were 2.0-5.0 and 28-442, respectively, and the NOS scores of the included studies were between 6-9. Meta-analysis results showed that pancreatic cancer patients with high preoperative NLR levels had significantly shortened postoperative OS (HR=1.24, 95% CI=1.16-1.33, P<0.000 01) and DFS (HR=1.39, 95% CI=1.21-1.60, P<0.000 01). Subgroup analyses based on different NLR cutoff values also showed that high preoperative NLR levels were significantly associated with shortened postoperative OS and DFS (all P<0.05). As revealed by the sensitivity analysis results, the pooled effect sizes for OS and DFS showed no significant changes. Publication bias analysis showed no significant publication bias in the included studies.Conclusion Pancreatic cancer patients with high preoperative NLR levels have shortened postoperative OS and DFS compared to those with low preoperative NLR levels. Preoperative NLR value is a potential biomarker for evaluating the prognosis and survival benefits of pancreatic cancer patients. Due to limitations in the number and quality of studies, further high-quality research is needed to verify the above conclusions.

Abstract:Background and Aims Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy. Due to its insidious onset, early symptoms are often not typical, and it has a strong invasive nature, therefore, the prognosis is poor. With the in-depth study of the molecular pathogenesis of pancreatic cancer, immunotherapy has become a new focus of pancreatic cancer treatment. Bibliometrics is a commonly used method to analyze the literature of a certain field, summarize the trend of the literature intuitively, and predict research hotspots. This article aims to provide direction for subsequent research by analyzing the current status, hotspots, and trends of immunotherapy for pancreatic cancer through bibliometrics and knowledge map visualization.Methods The relevant publications on pancreatic cancer immunotherapy published from the inception to May 2022 were extracted from the Web of Science Core Collection. A bibliometric visualization analysis of countries, institutions, authors, references, and keywords in the publications in this filed was performed using software such as CtieSpace and VOSviewer.Results A total of 2 230 English-language literature related to pancreatic cancer immunotherapy published between 2009 and 2022 were included, and the number of publications has been steadily increasing every year since 2016. These publications had 7 943 co-cited references and 7 365 authors from 884 institutions in 75 countries/regions. The country with the most publications was the United States (n=964), followed by China (n=552). The institution with the most publications was Johns Hopkins University in the United States (n=67) and the MD Anderson Cancer Center at the University of Texas (n=65). The authors with the most publications were Elizabeth M Jaffee (n=41) and Lei Zheng (n=31), both from Johns Hopkins University in the United States. The most cited publication was "Genomic analyses identify molecular subtypes of pancreatic cancer" (n=161), and the timeline of co-cited references showed that clustering "tumor microenvironment" has been a hot topic since 2016. The keyword burst detection revealed the development of the field of pancreatic cancer immunotherapy, with "vaccine" being the initial hot topic, and the focus shifting to "ipilimumab" "checkpoint blockade" "epithelial-mesenchymal transition" "stellate cells" "macrophages" "mismatch repair deficiency" and "tumor microenvironment" in recent years.Conclusion Research related to immunotherapy for pancreatic cancer is showing a sustained upward trend and has become an important research direction for the treatment of pancreatic cancer. Currently, the United States is in an absolute leading position in this research field. Studies have shown that the unique tumor microenvironment may be the main reason for the high malignancy and insensitivity to radiation and chemotherapy of pancreatic cancer, and the underlying mechanisms of the pathogenesis of pancreatic cancer tumor microenvironment are the current focus of research. In addition, research focusing on "epithelial-mesenchymal transition" and "immune checkpoint inhibition" is more common. Existing research indicates that single treatment options have limited effectiveness for the treatment of pancreatic cancer, and immune combination therapy or chemotherapy combined with immunotherapy can further improve the clinical efficacy of pancreatic cancer, which is the trend of future clinical research.

Abstract:Background and Aims Insulinoma is the most common functional neuroendocrine tumor of the pancreas. However, there have been few bibliometric studies on insulinoma. Therefore, this study was conducted to describe the hotspots and trends in insulinoma research over the past 20 years through bibliometric analysis.Methods Publications related to insulinoma between 1999 and 2021 were searched in the Web of Science Core Collection (WoSCC), and the results were imported in plain text format into VOSviewer and CiteSpace software for bibliometric analysis. The data was processed using bibliometric methods to conduct visual analysis of authors, countries, institutions, highly cited works, co-citations, keywords, and references.Results A total of 3 863 publications were retrieved, including 19 310 authors, 3 268 organizations, 83 countries/regions, and 1 005 journals. The literature cited a total of 85 078 articles authored by 55 619 individuals from 7 494 journals. Among them, research on insulinoma was mainly conducted in the United States, with Lernmark A being the most prolific author and the University of Washington being the most significant contributor. The Journal of Biological Chemistry was the main journal for publishing research in the insulinoma field. Keyword analysis showed that the current focus is mainly on "Pancreatic Neuroendocrine Tumor" "ENTS Consensus Guideline" "Marker" "Management" and "Neoplasm" indicating that the focus of insulinoma research has gradually shifted from a simple overview, diagnosis, clinical manifestations, and complications of this disease to the exploration of neuroendocrine tumors as a whole.Conclusions In the past 20 years, the publication output of insulinoma has remained at a highly explosive level. The United States has an unshakable position in this field. In addition, the efficacy of emerging tumor markers and how to develop more rational management modes are likely to become future research hotspots. Our study will help predict the development and trends in the field of insulinoma.

Abstract:Background and Aims Pancreatic cancer is a common malignant digestive system disease that is difficult to diagnose and treat. Most patients have missed the opportunity for surgery at the time of diagnosis. Developing new targets for early diagnosis and treatment of pancreatic cancer is of great significance. Therefore, this study was conducted to screen key genes related to the progression of pancreatic cancer using bioinformatics approach and identify their specific mechanisms that affect tumor progressionMethods The GEO datasets GSE15471, GSE16515, and GSE132956 were selected, and differential gene analysis was performed on these three datasets using the R limma package to identify differentially expressed genes in pancreatic cancer. The Venn diagram was used to determine the intersection of these genes. Metascape was used to perform functional enrichment analysis on the differentially expressed genes, KMPLOT was used to analyze the correlation between these genes and patient survival, and GEPIA was used to validate the differential expressions. The key gene was selected, and its correlation with clinical and pathological information of pancreatic cancer was analyzed using Linkedomics. The biological functions of the interaction factors of the key gene were analyzed using KEGG and GO enrichment analysis. A PPI network was constructed using Cytoscape software to analyze related signaling pathways. The expression of the key gene was subsequently verified in pancreatic cancer tissue samples and cell lines, and cellular functional experiments were conducted to validate its function.Results A total of 177 upregulated genes and 104 downregulated genes were identified in the three GEO datasets. Metascape enrichment analysis revealed that the upregulated genes were enriched in tissue morphogenesis, angiogenesis, cell movement, and cell proliferation, while the downregulated genes were enriched in processes such as metabolism and pancreatic secretion. KMPLOT survival analysis identified six factors (CTTNBP2NL, FGD6, ITGA2, KRT19, S100P, TMPRSS4) that were significantly associated with pancreatic cancer and all of them were risk factors for the survival of pancreatic cancer patients (all P<0.05). GEPIA validation also showed that these genes were significantly upregulated in pancreatic cancer (all P<0.05). Among them, CTTNBP2NL was of unknown function in pancreatic cancer, so it was selected for further study. Clinical correlation analysis showed that CTTNBP2NL was significantly correlated with the N stage of TNM classification in pancreatic cancer and was upregulated with the increase of the stage. PPI analysis revealed 17 proteins that interacted with CTTNBP2NL, and KEGG enrichment analysis found that these proteins were related to the PI3K/Akt and TGF-β pathways. GO enrichment analysis also found that these proteins were related to cell separation and apoptosis. The three GEO datasets showed that CTTNB2NL was highly expressed in pancreatic cancer, and both mRNA and protein expressions of CTTNB2NL were upregulated in pancreatic cancer tissues and cell lines (all P<0.05). Functional experiments showed that in pancreatic cancer cells after CTTNBP2NL silencing, the proliferation, migration and invasion were significantly inhibited while the apoptosis was significantly increased, and meanwhile, the activity of the PI3K/Akt signaling pathway was significantly inhibited (all P<0.05).Conclusions CTTNBP2NL is highly expressed in pancreatic cancer and closely associated with the proliferation, migration, and invasion of pancreatic cancer cells. Its mechanism of action may be related to the activation of the PI3K/Akt signaling pathway. CTTNBP2NL can potentially serve as a prognostic biomarker and diagnostic target for pancreatic cancer.

Abstract:Background and Aims Pancreatic cancer is a highly malignant tumor with a very poor prognosis, with a 5-year survival rate of about 11.5%. Nearly half of the patients have distant metastasis at the time of initial diagnosis, and liver metastasis accounts for 37% to 41.9% of them. Exploring new biomarkers for pancreatic cancer liver metastasis may help improve the treatment efficacy in patients. Therefore, this study was conducted to identify and validate key genes that play a critical role in the process of pancreatic cancer liver metastasis using bioinformatics approaches.Methods The high-throughput sequencing dataset GSE151580 for pancreatic ductal adenocarcinoma (PDAC) was downloaded from the GEO database, which included tissue samples from pancreatic cancer liver metastases and primary lesions. The differentially expressed genes between liver metastasis tissue samples and primary lesion tissue samples were screened using the R language limma package. The GO and KEGG functional enrichment analyses were performed on the differentially expressed genes. The protein-protein interaction networks were constructed using the STRING database, which were then visualized using Cytoscape. The top 10 genes were selected using the CytoHubba plugin based on the MCC topology analysis method, which were considered as the candidate core genes. Finally, the candidate core genes were validated using TCGA, GEPIA, UALCAN, and HPA databases.Results A total of 46 512 genes were included in the analysis, with 491 differentially expressed genes meeting the screening criteria, of which 162 were up-regulated and 329 were down-regulated. After selecting the top 10 genes with the highest MCC scores, validation of the candidate genes showed that the APOB gene was highly expressed in tumor tissues (P<0.05), with its expression product mainly located in the cytoplasm and cell membrane, and showing moderate positive staining in immunohistochemistry. APOB gene mutations were related to patients' M stage, with a higher proportion of M1 patients in the mutation group (P=0.022 1). However, the expression of this gene was not significantly associated with overall survival (OS) or disease-free survival (DFS) of the patients (both P>0.05). In addition, the expression product of the APOA4 gene was also mainly located in the cytoplasm and cell membrane, showing moderate positive staining in immunohistochemistry. APOA4 gene mutations were related to patients' TNM stage, with an earlier TNM stage in the mutation group (P=0.018 3). Patients with low expression of this gene had higher DFS (HR=1.75, P=0.025), but its expression was not related to OS (P>0.05).Conclusion The APOB gene may be associated with liver metastasis of pancreatic cancer and has the potential to serve as a molecular biomarker for early screening of pancreatic cancer liver metastasis. The APOA4 gene is associated with the DFS of pancreatic cancer patients and may become a new molecular biomarker for evaluating patient prognosis, monitoring tumor recurrence, or as a potential target for gene therapy.

Abstract:Background and Aims Secondary hyperparathyroidism (SHPT) is one of the most challenging complications of chronic kidney disease (CKD), characterized by a series of calcium and phosphorus metabolism disorders, osteomalacia, and malabsorption, which severely affects the quality of life of patients. Currently, clinical treatment is unsatisfactory, and no ideal target molecules have been discovered. This study was conducted to identify candidate target molecules for SHPT, so as to provide new targets for its treatment.Methods The specimens of 5 fresh normal parathyroid tissues and 15 SHPT patient parathyroid tissues were collected from the Department of Pathology of Xiangya Hospital between 2017 and 2020. Among them, 2 normal parathyroid tissues and 5 SHPT patient parathyroid tissues were used for RNA transcriptome sequencing to obtain the differentially expressed genes, and the core genes were identified through functional enrichment analysis, PPI network construction and topology algorithms. The expressions of the core genes in the remaining normal parathyroid tissues and SHPT patient parathyroid tissues were validated using qRT-PCR and Western blot, respectively. Immunohistochemical staining was performed to detect the expressions of the core genes in the paraffin sections of 36 SHPT patient parathyroid tissues, and 16 normal parathyroid tissues that were inadvertently resected during thyroid surgery.Results A total of 1 323 differentially expressed genes were identified by RNA sequencing, and 10 key genes were screened through construction of PPI network and topological algorithm. Among them, dipeptidyl peptidase 4 (DPP4) was further validated due to its close association with diabetes. Results of qRT-PCR showed that the mRNA expression level of DPP4 in the parathyroid tissue of SHPT patients was significantly higher than that in normal parathyroid tissue (P=0.005 1); results of Western blot showed that the protein expression level of DPP4 in the parathyroid tissue of SHPT patients was significantly higher than that in normal parathyroid tissue (P=0.006 0); results of immunohistochemical staining showed that the positive rate of DPP4 in the parathyroid tissue of SHPT patients was significantly higher than that in normal parathyroid tissue (P=0.006 9).Conclusion The expression level of DPP4 is significantly upregulated in the parathyroid tissue of patients with SHPT, indicating that DPP4 may be involved in the occurrence and development of SHPT, and may be a potential therapeutic target for drug treatment of SHPT.

Abstract:Background and Aims Patients with severe acute pancreatitis (SAP) have a critical and rapidly progressing condition with many complications. Among them, pancreatic portal hypertension (PPH) is a localized and regional portal hypertension. Some patients with PPH are well compensated and have no obvious clinical symptoms, and only spleen enlargement is found during examination, for whom only conservative internal medicine treatment and regular follow-up are needed. For patients with PPH-related symptoms, splenectomy is currently recommended. However, SAP patients combined with PPH generally have a poor overall condition, with greater inflammatory edema and abdominal infection, splenectomy may increase the risk of infection and bleeding. There is currently a lack of recommendations and consensus on treatment methods for such patients both domestically and abroad. Therefore, this study was performed mainly to investigate the clinical efficacy of partial splenic artery embolization (PSE) in the treatment of symptomatic SAP patients with concomitant PPH, as well as the indications, timing, and procedural methods for treatment.Methods The clinical data of 15 patients with SAP and concomitant PPH admitted to the Center for Severe Pancreatitis of Jinling Hospital Affiliated with Nanjing Medical University from January 2014 to December 2021 were retrospectively summarized. The clinical diagnosis and treatment process and prognosis of the patients undergoing PSE therapy for PPH were analyzed, and the relief of PPH clinical symptoms, results of laboratory blood routine tests and imaging examinations, postoperative complications, and recurrence of PPH symptoms of the patients were observed. Imaging evaluations were performed on 3 d as well as 1, 3, and 6 months after operation, and SF-36 quality of life scale scores were assessed before and 1 year after operation.Results All 15 patients received routine treatment including fluid infusion, anti-infection therapy, and enteral nutrition after admission. The median time from AP onset to PSE surgery varied greatly among the patients, with a median time of 487 d. Clinical symptoms related to PPH included splenomegaly and gastric variceal bleeding. Among the 15 patients, 5 had only splenomegaly, 8 had only variceal bleeding, and 2 had both above symptoms. The median area of splenic embolization was 60%. Of the 7 patients with splenomegaly, the peripheral blood cells in all cases recovered to varying degrees after operation, and the blood cell counts had basically returned to normal at 6 months of follow-up. The symptoms of hematemesis, melena and gastric varices were significantly relieved after operation in the 8 patients with repeat upper gastrointestinal bleeding. Two patients developed splenic abscess, which was treated with antibiotics and percutaneous splenic abscess puncture and drainage, and both patients recovered after treatment and were discharged after tube removal. During the 1-year follow-up period, all 15 patients survived without any recurrence of clinical symptoms or complications. The results of the SF-36 quality of life questionnaire showed that various aspects of the patients' quality of life had significantly improved one year after discharge compared to admission (all P<0.05). The three blood cell series of patients with splenomegaly recovered to normal levels, and patients with a history of gastrointestinal bleeding did not experience the symptoms of hematemesis or black stool again.Conclusion For patients with SAP and symptomatic PPH, PSE is a safe and effective treatment method under the premise of reasonable judgment of surgical indications and timing.

Abstract:Background and Aims Autoimmune pancreatitis (AIP) is a rare form pancreatitis caused by an autoimmune process with an incidence of about 10.1/100 000, and a positive response to steroids. However, it is difficult to distinguish focal AIP from pancreatic cancer, and there have been cases of misdiagnosis as pancreatic cancer leading to surgical treatment. Currently, the pathogenesis of AIP is unclear, and there is still a lack of relevant research. This article reports the diagnosis and treatment process of two cases of type 1 AIP recently admitted to our center, and additionally reviews the relevant literature in order to provide a useful reference for clinical work.Methods The clinical data of two patients with type 1 AIP admitted to the Department of Hepatobiliary and Pancreatic Surgery at the Third Xiangya Hospital of Central South University were retrospectively analyzed, combined with review of the relevant literature. The clinical characteristics and treatment decisions of this disease were analyzed and summarized.Results Both patients were male and presented with obstructive jaundice. Imaging examinations showed a mass in the pancreatic head, which was difficult to distinguish between inflammation and tumor. Case 1 had significantly elevated blood IgG4 level and extrapancreatic organ involvement, and was diagnosed with type 1 AIP. The patient's condition improved after steroid treatment. Case 2 was relatively atypical, with no blood IgG4 elevation or extrapancreatic organ involvement. Pathological examination of the ultrasound-guided fine-needle aspiration biopsy showed chronic inflammation, and further diagnosis and treatment were performed with laparoscopic pancreaticoduodenectomy. During the surgery, the pancreatic head was found to be significantly enlarged, hard in texture, and closely adhered to the surrounding tissues. Postoperative pathology revealed typical lymphoplasmacytic sclerosing pancreatitis (LPSP), and the patient was diagnosed with type 1 AIP. The patient's condition improved after steroid treatment.Conclusion For patients with pancreatic mass suspicious for pancreatic malignancy, the possibility of AIP should always be considered, and immunological markers and other examinations should be perfected. Typical cases are generally easy to diagnose, while atypical cases may require surgical resection before a final diagnosis can be made. For middle-aged and elderly men with normal or slightly elevated tumor markers and negative puncture pathology, the possibility of benign lesions is high, and postoperative pathology should be closely monitored. If the diagnosis of AIP is made, patients should be informed to receive standardized medical treatment as soon as possible.

Abstract:Background and Aims The occurrence of infection during the course of acute pancreatitis (AP) is a major factor leading to high mortality rates in critically ill patients. However, severe infection-related complications often manifest more than 2 weeks after onset, and the positive rate of fluid bacterial culture in the early stages of the disease is low, making early antibiotic use lacking in guidance. Blind prophylactic use of antibiotics may face the risk of fungal and antibiotic-resistant infections, exacerbating the condition. Previous studies have found that bacterial infections already exist in the early stages of the disease, and intestinal flora migrate to the pancreas through various pathways to participate in the occurrence and development of the disease. Fluid bacterial culture may provide reference basis for early antibiotic use, but currently, there are few reports on relevant pathogenic studies. Therefore, this study was performed to seek evidence of early infection in AP through bacterial culture of pancreatic juice, to provide reference for anti-infective treatment of AP.Methods AP patients who underwent bacterial culture of pancreatic juice in the Hepatobiliary Surgery Department of Ningxia Medical University General Hospital from January 1, 2019 to June 30, 2020 were reviewed. The results of bacterial culture and clinical data of patients were recorded and analyzed.Results A total of 156 patients were included in the study, of which 64 (41.03%) had positive fluid bacterial cultures. A total of 94 bacterial strains were cultured, with gram-negative bacteria (58.51%) being the most common, followed by gram-positive bacteria (38.30%) and fungi (3.19%). The distribution and composition of pancreatic fluid bacteria in biliary AP, hyperlipidemic AP, and idiopathic AP were similar. The incidence of complications, APACHE Ⅱ score, and levels of inflammatory markers in patients with positive pancreatic fluid bacterial culture were significantly higher than those in patients with negative culture, and the duration of fever was also significantly longer in the positive culture group than in the negative culture group (all P<0.05). Among the 21 patients who developed infected pancreatic necrosis (IPN) in the later stage, 19 cases had early positive fluid cultures, and 9 IPN patients underwent percutaneous drainage, with a 100% (9/9) consistency between the drainage fluid culture and the early pancreatic fluid culture results. In the population of patients with positive pancreatic fluid bacterial cultures, non-infected patients were significantly older than infected patients, and the proportion of non-infected patients with biliary AP was also significantly higher (both P<0.05). In elderly patients with biliary AP, there was no significant difference in the incidence of complications and levels of inflammatory markers between the positive and negative fluid culture groups (all P>0.05).Conclusion The bacteria in early pancreatic fluid of AP patients are mainly intestinal flora and are related to the severity of the disease. Targeted use of antibiotics may have a positive impact on the outcome, but it should be evaluated and used with caution in elderly patients with biliary AP.

Abstract:Pancreatic cancer is a lethal malignant tumor of the digestive system with a highly invasive nature and difficulty for early diagnosis. Most patients are diagnosed at a late stage, and have no chance of receiving radical surgical resection, for whom, there are also no other effective treatment options, resulting in a poor prognosis. Ferroptosis is a newly discovered iron-dependent programmed cell death characterized by intracellular iron overload, increased lipid peroxidation, and abnormal accumulation of reactive oxygen species. Recent studies have found that ferroptosis plays an important role in inhibiting the growth and proliferation of pancreatic cancer cells and can enhance the efficacy of chemotherapy drugs. So, it is expected to be a potential target for the treatment of pancreatic cancer. In this article, the authors provide an overview of the role of ferroptosis in the occurrence and development as well as treatment of pancreatic cancer.

Abstract:The pathogenesis, early diagnosis, and treatment of pancreatic cancer have always been a hot and important topic of concern in the medical community. In recent years, a number of studies have shown that epigenetics plays an important role in the occurrence and development of tumors, with DNA methylation being the most common form. The development of pancreatic cancer is related to the abnormal activation or inhibition of its related oncogenes or tumor suppressor genes due to changes in DNA methylation levels. DNA methylation may occur before somatic cell mutations and runs through the entire process of tumor development, and therefore, it has been widely studied in the diagnosis, treatment, and prevention of tumors. In this article, the authors provide an overview of the concept and mode of action of DNA methylation, its role in the initiation and progression of pancreatic cancer, and its prospects in the diagnosis and treatment of pancreatic cancer, in order to provide a reference for future research on pancreatic cancer.

Abstract:Alcoholic acute pancreatitis (AAP) is currently the second most severe type of acute pancreatitis (AP) following acute biliary pancreatitis (ABP), with a more serious illness, higher mortality rate, and more severe multiple organ damage. Studies have shown that alcohol increases the risk of development of severe acute pancreatitis (SAP), and AAP is more likely to develop into SAP than ABP. In recent years, AAP-related research has become a hot topic, and obtaining ideal animal models can help in-depth research on the pathogenesis of AAP. However, there is a lack of effective methods for AAP animal model construction at present. Therefore, the authors review the common methods for AAP animal models at home and abroad, so as to provide new ideas for AAP research.

Abstract:Acute pancreatitis (AP) is a condition in which the abnormal activation of pancreatic enzymes in the pancreas leads to digestion of the pancreas itself and surrounding organs, characterized mainly by local pancreatic inflammation, which can cause organ dysfunction and acute abdominal pain in severe cases. In the progression of AP, microcirculatory disturbances can lead to intestinal ischemia and hypoxia, which further causes epithelial damage, limiting the balance of gut flora and affecting the basic immune system. The gut barrier requires a continuous cellular layer and matrix connections. In the pathogenesis of AP, the integrity of this gut barrier is disrupted, which causes gut flora to shift to other organs, a decrease in beneficial bacteria, and further harm to patients, resulting in systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and even death. In recent years, domestic and foreign scholars have paid increasing attention to the improvement of the gut environment to alleviate the development of AP. In the treatment of AP patients, supplementing probiotics can protect and repair the intestinal mucosal barrier of AP patients, while reducing the chance of gut flora translocation and improving gut microecology, which provides new ideas for the treatment of AP.

Abstract:背景与目的 胰腺假性囊肿（PPC）形成是急性胰腺炎（AP）常见的局部并发症，PPC发生胰腺结肠瘘者少见。本文对1例PPC并感染致结肠瘘的临床表现、诊断和内镜干预治疗等进行总结分析。方法 本文回顾分析内镜下治疗AP后PPC并感染致结肠瘘1例患者病例资料，结合国内外相关文献，总结PPC发生胰腺结肠瘘的临床表现、诊断和内镜干预治疗选择。结果 患者为51岁女性，因“上腹痛1 d”就诊。术前CT扫描检查报告：AP征象并假PPC形成。超声内镜下经胃后壁穿刺入胰头部，脓肿腔内放置蕈型覆膜金属支架（LAMS）（10 mm×50 mm），引流通畅，但术后患者反复高热。再次经超声内镜下放置覆膜金属支架、双猪尾支架、经鼻脓肿外引流等方法处理胰腺周围坏死。使用内镜吻合夹闭的技术处置胰腺结肠瘘管，术后完全治愈。结论 内镜技术在治疗胰腺周围感染性坏死及重症急性胰腺炎（SAP）合并结肠瘘中具有创伤小、安全性高、疗效确切的优势。

Abstract:背景与目的 胰腺淋巴上皮囊肿（PLEC）是一种罕见的胰腺囊性病变，其临床表现无明显特异性，术前影像学诊断较为困难，与其他胰腺良恶性病变鉴别有一定难度，其确诊仍然依赖术后病理组织学检查。迄今为止，PLEC作为胰腺良性肿瘤，未出现临床症状的患者多建议保守治疗，出现明显临床症状或与恶性肿瘤鉴别不清者需行外科手术治疗。本文介绍1例PLEC的临床表现、诊断及鉴别诊断要点、临床治疗路径和病理组织学特征；并通过国内外相关文献阅读，总结其临床特征，以期为提高PLEC的诊疗水平提供借鉴和参考。方法 回顾性分析了2021年7月大连医科大学附属大连市中心医院肝胆外科诊治的1例PLEC临床资料。结果 患者为59岁男性，因体检意外发现胰腺肿物入院，增强核磁共振扫描可见胰腺颈部大小为2.6 cm×4.3 cm椭圆形异常信号。通过讨论分析患者临床表现、影像学特征、实验室检查结果等方面资料，认为有手术指征和条件，遂行胰十二指肠切除。手术时间360 min，术中出血50 mL。术后病理组织学检查确诊为PLEC。术后患者未出现出血、胰瘘、感染、胃排空障碍等并发症。术后10 d拔除引流管，术后12 d出院。结论 PLEC是一种罕见的胰腺囊性良性病变，由于其临床表现不典型，术前诊断较为困难。有症状的胰腺囊性病患者通常需要行外科手术完整切除病变组织，对于无法明确PLEC诊断的患者，建议行外科手术治疗，患者术后通常预后良好；无症状者可考虑保守治疗和随访观察。

Abstract:背景与目的 腹内疝是一种罕见的临床疾病，可导致0.6%~5.8%的小肠梗阻。腹内疝分为先天性腹内疝和后天性腹内疝，临床上先天性腹内疝少见且术前诊断困难，且梗阻性腹内疝发病急骤，患者短时间内可出现肠管的缺血绞窄、坏死、穿孔，严重者会出现休克死亡。故对于此类患者早期的诊断及干预治疗是至关重要的。本文报告1例典型的先天性左侧十二指肠旁疝（PDH）的诊治经过，结合文献报道并进行讨论。方法 回顾性分析江苏省苏北人民医院收治的1例先天性左侧PDH患者的临床表现、诊断、鉴别诊断以及治疗措施等临床病历资料，并复习相关国内外文献。结果 患者为49岁男性，因进大量宿食后出现脐周疼痛伴腹胀、恶心、呕吐、肛门停止排气排便入院。全腹部CT平扫结果表现：左上腹局部肠管走行欠规则，肠系膜聚集、增厚伴腹腔渗出，考虑腹内疝。行腹腔镜探查术，术中见左上腹小肠聚集成团，疝入Treitz韧带处的Landzert窝，肠管扩张水肿未坏死，疝环口约8 cm×4 cm大小，还纳复位后以倒刺鱼骨缝合线关闭疝环口。术后确诊左侧PDH。患者恢复良好出院。随访至今患者无腹痛腹胀等不适。结论 先天性PDH其临床症状缺乏特异性，影像学检查诊断较为困难，导致临床误诊率较高。且此病发病急骤，早期的诊断及治疗至关重要，故更加需要医师熟知其症状及影像学表现，一旦怀疑为PDH，应及时行手术探查治疗，解除肠管梗阻，以避免肠管发生绞窄性坏死。