[Interpretation of the surgical treatment of pancreatic cancer of the 2024 edition of the NCCN guidelines].

Pancreatic cancer is a highly malignant tumor in the digestive system, and radical surgery is the only possible means to cure pancreatic cancer at present. In the past decade, pancreatic surgery has been developing rapidly, with various new technologies and concepts emerging, among which the use of minimally invasive techniques and the popularization of neoadjuvant therapy concepts are the most notable. At the same time, the surgical treatment of pancreatic cancer still has a long way to go, and many problems need to be solved urgently. This article introduces the surgical treatment of pancreatic cancer in the 2024 edition of the NCCN guidelines, focusing on minimally invasive and open surgical treatments, expanded lymph node dissection, combined vascular resection and reconstruction, surgical treatment of pancreatic neck cancer and neoadjuvant therapy, and briefly discussing the unresolved issues.

[Research progress on HEG1 in cardiovascular generation and tumor development].

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.

[Progress and reflection of conversion therapy for locally advanced pancreatic cancer].

With the improvement of nonsurgical treatment in pancreatic cancer, the increasing accuracy of subclassification of anatomy, and the continuous refinement of surgical resection techniques, more and more locally advanced pancreatic cancer(LAPC) patients have the opportunity to undergo conversion surgery and achieve survival benefits,which has attracted the attention of scholars in this field. Despite the numerous prospective clinical studies conducted, there is still a lack of high-level evidence-based medical evidence in terms of conversion treatment strategies, efficacy evaluation, surgical timing and survival prognosis, and there are not yet specific quantitative standards and guiding principles for conversion treatment for these patients in clinical practice, and the indications for surgical resection rely more on the experience of each center or surgeon, lacking consistency. Therefore,the indicators for the evaluation of the efficacy of conversion treatment in patients with LAPC were summarized to reflect on the different modes of conversion treatment and clinical outcomes currently being explored, expecting to provide more accurate recommendations and guidance for the clinic.

[Minimally invasive enucleation for benign and low-grade malignant pancreatic tumors: an analysis of 60 cases].

Objective: To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation. Methods: The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group(n=25) and laparoscopic group(n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results: All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm,t=-2.825,P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ²=2.289,P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index(OR=1.285,95%CI:1.053 to 1.569,P=0.014),the larger diameter of the tumor(OR=3.703,95%CI:1.465 to 9.360,P=0.006) and intraoperative pancreatic duct repair(OR=7.889,95%CI:1.471 to 42.296,P=0.016) were independent risk factors,whereas robotic surgery(OR=0.168,95%CI:0.036 to 0.796,P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions: Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

[The diagnosis and treatment of G3 neuroendocrine tumors according to the new NCCN guideline].

Gastrointestinal pancreas (GEP) is the most common site of neuroendocrine neoplasms (NENs). In 2019, the World Health Organization (WHO) classification for GEP NET was updated to include a new category of well-differentiated high-grade (Ki 67>20%) GEP-NET G3, distinct from high-grade poorly differentiated neuroendocrine carcinoma (NEC). As a new category, NET G3 are considered a molecularly, radiologically, and prognostically distinct entity compared to NEC and NET G1/G2. The management of NET G3 remains a challenge awaiting future trials taking into consideration the unique characteristics of this new category. The latest NCCN clinical guidelines of neuroendocrine and adrenal tumors firstly gave the recommendation of diagnosis and treatment of G3 NET separately from NEC and G1/G2 NET. Hereon,we aim to summarize the management of G3 NET in combination with the new NCCN guidelines and the current evidences.

[Efficacy of conversion therapy and direct surgical resection in patients with metastatic pancreatic neuroendocrine tumors].

Objective: To explore the prognosis of Chinese patients with metastatic pancreatic neuroendocrine tumor (PanNET) treated with conversion therapy and surgical resection. Methods: The pathological data and prognostic information was retrospectively collected of patients with metastatic PanNET treated in Fudan University Shanghai cancer center from January 2010 to May 2021, and propensity score matching was used to analyze the prognosis difference between conversion treatment followed surgery and direct surgery. Results: There were 58 males and 43 females in 101 patients with metastatic PanNET. The age raged from 18 to 74 years, with a median age of 51 years. A total of 88 patients received primary tumor with liver metastases resection, 1 receied of primary tumor resection and 12 received primary tumor resection and combined organs or extrahepatic metastases. Multivariate analysis showed that R2(HR=1.943,95%CI:1.262-2.990,P=0.003)resection and G3(HR=1.876,95%CI:1.001-3.516,P=0.05) were independent risk factors for postoperative progression of metastatic patients. There were 63 patients (62.4%) who had received direct surgery, and 38 patients (37.6%) who had received preoperative conversion therapy. The conversion therapy had a higher proportion of T3/T4 stage (68.1% vs 39.7%, P=0.007), resection with combined organs/extrahepatic metastasis (26.3% vs 9.5%, P=0.005) and R2 resection (71.1% vs 42.9%, P=0.005). The median progression-free survival (mPFS) between conversion therapy and direct surgery had no statistically significant, but after the propensity score matching the mPFS of the conversion therapy group was significantly longer than direct surgery group (HR=0.442,95%CI:0.207-0.943,P=0.027). Conclusions: Conversion therapy for partially metastatic PanNET is better than that of direct surgery. Radical resection and grade are independent prognostic factors for metastatic PanNET after resection.

[Effect of laparoscopic surgery for pancreatic cancer after neoadjuvant chemotherapy].

Objective: To evaluate the safety and feasibility of laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer. Methods: Clinical data of 8 patients underwent laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer at Fudan University Shanghai Cancer Center from September 2019 to June 2020 were reviewed retrospectively. There were 5 males and 3 females,aged from 47 to 72 years old. All patients underwent abdominal enhanced CT and PET-CT before operation to accurately evaluate the tumor stage and exclude distant metastasis. Results: Neoadjuvant chemotherapy with AG regimen(gemcitabine 1 000 mg/m2 and albumin bound paclitaxel 125 mg/m2) was received for 2 to 6 cycles before surgery. All 8 patients successfully completed the operation,including 5 cases of pancreaticoduodenectomy,2 cases of radical antegrade modular pancreatosplenectomy(RAMPS),and 1 case of total pancreatectomy. No conversion to laparotomy or laparoscopic assisted surgery. The operation time was 240 to 450 minutes,the blood loss was 100 to 500 ml,the postoperative length of stay was 10 to 16 days. During the follow-up period up to December 31, 2020, there was 1 case suffered grade B pancreatic leakage and abdominal infection. The numbers of resected lymph nodes were 9 to 31. All patients received R0 resection. The follow-up times were 4.5 to 9.5 months. One patient underwent RAMPS was diagnosed as liver metastasis after 2 months of the operation,and the other 7 patients still survived without tumor recurrence. Conclusion: Minimally invasive surgery of pancreatic cancer after neoadjuvant chemotherapy is safe and feasible in experienced pancreatic minimally invasive centers.

[Advances in basic and translational research in neuroendocrine neoplasms].

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

[Surgical treatment for pancreatic cancer with liver metastasis:exploration and innovation].

The prognosis of pancreatic cancer patients with liver metastasis (PCLM) is very poor and the median overall survival(OS) is less than 6 months.The current standard treatment for PCLM is systematic chemotherapy.Though the chemotherapeutic regimens are better than gemcitabine only,the OS remains dissatisfied.A lot of retrospective studies identified that surgical treatment can only offer survival benefits for highly selected rather than entire PCLM patients.The Chinese Study Group for Pancreatic Cancer (CSPAC) has initiated a multiple-center,prospective,randomized comparison clinical trial,named CSPAC-1 to identify the standard and value of surgical treatment of PCLM patients.This manuscript reviewed the current progress of surgical treatment for pancreatic cancer with liver metastasis and looked forward to opportunities and challenges in the future.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

[Impact of neoadjuvant therapy on the perioperative complications of pancreatic cancer].

Pancreatic cancer is one of the most malignant digestive tract tumors with a 5-year survival rate of less than 10%. Surgery remains the basis of long-term survival of pancreatic cancer patients. With the progress of chemotherapy, neoadjuvant therapy has been gradually carried out in pancreatic cancer. There are more and more studies on the effects of neoadjuvant therapy on perioperative complications of pancreatic cancer, but the results are not consistent. This article reviews the recent studies on neoadjuvant therapy for pancreatic cancer and analyzes the impact of some key factors on perioperative complications.

MicroRNA-429 inhibits the proliferation and migration of esophageal squamous cell carcinoma cells by targeting RAB23 through the NF-κB pathway.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer and is a devastating malignancy. Recent research shows that microRNA-429 (miR-429) has a role in suppressing cell proliferation, cell cycle and promoting apoptosis in many cancers. This study aims to explore the great role of miR-429 in esophageal squamous cell carcinoma. MATERIAL AND METHODS: The mRNA and protein levels of miR-429 and genes were calculated by using Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot. We applied Cell Counting Kit-8 (CCK-8) and transwell assays to measure the proliferative and migratory abilities. Meanwhile, the Kaplan-Meier method was used to calculate the overall survival of esophageal squamous cell carcinoma patients. RESULTS: MiR-429 was downregulated while RAB23 was upregulated in ESCC tissues and cell lines, and downregulation of miR-429 predicted poor prognosis in ESCC. RAB23 was found to be a direct target gene of miR-429 and its expression was regulated by miR-429 in ESCC. Moreover, miR-429 inhibited the proliferation through nuclear factor-kappa B (NF-κB) pathway and inhibited cell migration-mediated epithelial-mesenchymal transition (EMT) in TE-2 cells. In addition, overexpression of miR-429 suppressed tumor growth of ESCC in vivo. CONCLUSIONS: MiR-429 inhibited the proliferation through the RAB23/NF-κB pathway and the migration-mediated EMT in ESCC. The newly identified miR-429/RAB23 axis provides novel insight into the pathogenesis of ESCC.

Upregulation of long noncoding RNA LEF1-AS1 predicts a poor prognosis in patients with esophageal squamous cell carcinoma.

OBJECTIVE: Recent studies have suggested that long noncoding RNAs (lncRNAs) are involved in various tumors. The present research was designed to examine the prognostic values of a newly identified lncRNA, lncRNA LEF1-AS1 (LEF1-AS1), in esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: The relative levels of LEF1-AS1 in ESCC tissues and normal esophageal tissues were examined by applying quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relations between LEF1-AS1 expressions and clinical factors were analyzed by conducting the Chi-square test. The Kaplan-Meier assay was used for assays of the overall survival (OS) and disease-free survival (DFS) dates. Univariate and multivariate analyses were applied for the identification of the independent prognostic factors for ESCC. RESULTS: We showed that LEF1-AS1 was distinctly upregulated in ESCC tissues compared with the matched normal tissues (p < 0.01). Higher levels of LEF1-AS1 were associated with lymph nodes metastasis (p = 0.009) and clinical stage (p = 0.008). Clinical investigation revealed that ESCC patients with high LEF1-AS1 level showed a significant shorter 5-year OS (p = 0.0028) and DFS (p = 0.0025). Multivariate analyses confirmed LEF1-AS1 as an independent prognostic parameter indicating unfavorable clinical prognosis for ESCC patients. CONCLUSIONS: The present study suggested that LEF1-AS1 could be a novel ESCC-related lncRNA involved in the clinical progression of ESCC, which may be used as a potential predictor.

Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by CHRNA5-A3 and CHRNB3-A6 Variation in a Chinese Male Population.

Most studies in the field of CHRNA5-A3 and CHRNB3-A6 have only focused on lung cancer risk; however, the associations with chronic obstructive pulmonary disease (COPD) risk and smoking cessation is less understood, particularly in the Chinese male population. In this study, samples from 823 male patients with COPD (non smokers: 416; still smoking: 407) and 435 smoking male healthy control subjects were performed with DNA extraction and single nucleotide polymorphism (SNP) genotyping. We studied three SNPS in two genes, namely rs667282 and rs3743073 in CHRNA5-A3 and rs4950 in CHRNB3-A6, and their distributions in the three groups are not statistically different (p >0.05). We grouped COPD patients according to whether they had successfully quit smoking, the CT genotype of rs667282 demonstrated association with an increased rate of successful smoking cessation compared with the TT genotype [adjusted odds ratio (OR) = 0.54, 95% confidence interval (95% CI) = 0.37-0.7, p <0.001); rs4950 AG genotypes were distinctly associated with increased rates of successful smoking cessation (adjusted OR = 0.55, 95% CI = 0.40-0.76, p <0.001). The effect is significant under the assumption of an over dominant mode of inheritance (adjusted OR = 0.58, 95% CI = 0.43 to 0.79, p <0.001). No significant difference in rs3743073 was found (p >0.05). Our findings confirmed the hypothesis that CHRNA5-A3 and CHRNB3-A6 variation are not associated with the risk of COPD. We found CHRNA5-A3 and CHRNB3-A6 were significantly associated with successful smoking cessation in smoking COPD patients.

Microbial community reshaped in gastric cancer.

Patients with gastric cancer harbor distinct microbiota in the stomach. It features with lowered biodiversity, discrete structure, and varied composition. Some bacteria from gastric microbiota are potentially carcinogenic as they are enriched or depleted in gastric cancer. Distinct profile of microbial community in gastric cancer is possibly resulted from altered caused by pathophysiological and environmental factors. H. pylori is a carcinogen colonizing the human stomach. Although persisting for decades, it rarely causes compositional alteration of microbiota. Secretion of acid decreases gradually during the carcinogenic process. Increased pH results in overgrowth of bacteria in gastric fluid. The abundance of a particular taxon, but not the profile of microbiota, is altered in proton pump inhibitor users. Compositions of microbiota vary substantially between individuals, which may account for differential cancer risk. It has been demonstrated that genetic variations contribute to inter-individual variations in gut microbiota. However, their influence on the composition of gastric microbiota requires further exploration. Currently, it appears disrupted homeostasis and inter-individual variations of gastric microbiota are involved in cancer development. Clarifying factors responsible for these changes would reveal how microbiota induces carcinogenesis, benefiting the prevention of gastric cancer.

[2017 ENETS consensus guidelines: update for the standard of care of pancreatic neuroendocrine tumors].

Neuroendocrine tumors(NET) is a rare tumor with high heterogeneity.Pancreatic NET is the most common type in China. European Neuroendocrine Tumor Society(ENETS) has launched the ENETS guidelines since 2006 and published the ENETS standard of care in 2009. With the newly targeted therapies and further research on NET, 2017 new edition of the ENETS standard of care has changed a lot in the diagnosis and treatment of NET. This article explains the update of pancreatic NET in the 2017 edition of the ENETS standard of care, and introduces pancreatic NET from pathology, imaging examination, surgery, systemic therapy, etc., and deepens the understanding of the diagnosis and treatment of pancreatic NET.

[Development and Optimization of Therapeutic Analogues of Anti-TNFα Antibody Infliximab].

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.