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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 387-411 doi: 10.1007/s11684-018-0646-8

摘要：

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

关键词： TGF-β     EMT     lung cancer     pancreatic cancer     latent form     immune function     GARP    

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Laparoscopic surgery for pancreatic lesions: current status and future

Taiping Zhang, Xiao Du, Yupei Zhao

《医学前沿（英文）》 2011年 第5卷 第3期   页码 277-282 doi: 10.1007/s11684-011-0147-5

摘要： Laparoscopic pancreatic surgery has been gaining increasing recognition in recent years, and its practice has increased despite its highly complex procedure and longer learning curve compared with surgeries for other abdominal organs. Laparoscopic distal pancreatectomy and tumor enucleation are two of the fastest-growing techniques and are currently in wide use because of their comparable technical simplicity. Literature review showed that laparoscopic distal pancreatectomy and enucleation are safe and efficient approaches for benign and low-degree malignant tumors; however, the indication for malignant tumors remains controversial. Laparoscopic pancreaticoduodenectomy is practiced in a limited number of surgical centers and presented as case reports or in small series. Although its feasibility was demonstrated by many surgeons, whether the laparoscopic procedure can achieve benefits comparable to or even more prominent than those of an open procedure has not been clinically proven. Prospective, randomized, controlled trials of laparoscopic operation versus open pancreatic surgery are necessary to justify the wide application and routine practice of the laparoscopic procedure for pancreatic lesions.

关键词： minimally invasive surgery     pancreatic surgery     pancreatic neoplasm     distal pancreatic lesions     pancreatic fistula    

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Prevention and treatment of pancreatic fistula after pancreatic body and tail resection: current status

Li Jiang, Deng Ning, Xiaoping Chen

《医学前沿（英文）》 2020年 第14卷 第3期   页码 251-261 doi: 10.1007/s11684-019-0727-3

摘要： Postoperative pancreatic fistula (POPF) is the most common and critical complication after pancreatic body and tail resection. How to effectively reduce the occurrence of pancreatic fistula and conduct timely treatment thereafter is an urgent clinical issue to be solved. Recent research standardized the definition of pancreatic fistula and stressed the correlation between POPF classification and patient prognosis. According to the literature, identification of the risk factors for pancreatic fistula contributed to lowering the rate of the complication. Appropriate management of the pancreatic stump and perioperative treatment are of great significance to reduce the rate of POPF in clinical practice. After the occurrence of POPF, the treatment of choice should be determined according to the classification of the pancreatic fistula. However, despite the progress and promising treatment approaches, POPF remains to be a clinical issue that warrants further studies in the future.

关键词： pancreatic fistula     pancreatic body and tail resection     distal pancreatectomy    

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The role of prophylactic transpapillary pancreatic stenting in distal pancreatectomy: a meta-analysis

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 499-505 doi: 10.1007/s11684-013-0296-9

摘要：

Pancreatic fistula (PF) is the most frequent complication after distal pancreatectomy (DP). Prophylactic transpapillary pancreatic stenting (PTPS) has been proposed recently for the prevention of PF after DP. In this meta-analysis, a comprehensive search was performed in the PubMed, Embase, and Cochrane Library databases. Studies analyzing the results of PTPS in DP were considered eligible for this meta-analysis. The analyzed outcome variables included PF rate, postoperative morbidity, non-PF-related complications, mortality, operation duration, and hospital stay. Four studies with 200 patients were included in this review. Only one was a randomized controlled trial (RCT). The results showed that PTPS was associated with less PF formation (odds ratio, 0.45; 95% confidence interval [CI], 0.22–0.94; P = 0.03) and shorter hospital stay (mean difference, -6.31; 95% CI, -6.99 to -5.62; P<0.00001). There was no significant difference in terms of the other variables. In conclusion, current evidence indicates that PTPS could reduce PF incidence and hospital stay after DP, without increasing other complications or operative time. However, the evidence is not solid, because the single RCT conflicted with the other three retrospective reports. Thus, considering the limitation, more well-designed RCTs on this topic are needed in the future.

关键词： pancreatic fistula     distal pancreatectomy     pancreatic stent     meta-analysis    

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Influence of the adjuvant therapy on the survival of patients with stage II pancreatic carcinoma

Xi-Yan WANG, Hai-Jun LI, Dong YAN, Hao WEN, Shu-Yong PENG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 430-435 doi: 10.1007/s11684-010-0700-7

摘要： This study aimed to investigate the effect of adjuvant therapy on the treatment of stage II pancreatic carcinomas. The clinical data of 139 cases of stage II pancreatic carcinoma were analyzed retrospectively. The overall 1-, 3-, and 5-year cumulative survival rates of 139 patients were 40%, 6%, and 3%, respectively, and the median survival time (MST) was 279 days. The MST was 399 days for those with adjuvant therapy, 210 days for those without adjuvant therapy, 390 days for the radical resection group, 270 days for the bypass operation and laparotomy group, and 132 days for the nonsurgical group. The adjuvant therapy could not prolong the survival time and decrease the liver metastasis rate of the patients with stage II carcinoma significantly in radical resection group (>0.05). In the bypass operation and laparotomy group and nonsurgical group, the adjuvant therapy could improve the survival of the patients significantly (<0.05); however, the survival rate was not significantly different among systemic venous chemotherapy, radiation therapy, interventional therapy, and combination therapy (>0.05); or between gemcitabine (GEM) regimen and 5-fluorouracil regimen (>0.05); or between GEM monotherapy and GEM combined with platinum/capecitabine (>0.05). The proper adjuvant therapy can be suggested according to the general condition of the patients after radical resection for stage II pancreatic carcinoma. Chemotherapy combined with radiation should be applied actively for the patients whose cancerous tissues were not radically resected. The clinical efficacy of GEM combined with platinum/capecitabine is relatively better than GEM.

关键词： pancreatic neoplasms     neoadjuvant therapy     survival    

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Analysis of 100 consecutive cases of resectable pancreatic neuroendocrine neoplasms: clinicopathological

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 444-450 doi: 10.1007/s11684-016-0471-x

摘要：

The incidence rate of pancreatic neuroendocrine neoplasms (pNENs) has increased rapidly in recent years. However, the clinicopathological characteristics of pNENs are poorly understood. Medical records of patients who underwent surgery and were confirmed as pNENs by pathological examination from January 2003 to February 2015 in Qilu Hospital were reviewed retrospectively. A total of 100 patients, 36 males and 64 females, were included with a mean operation age of 46.26±13.41 years. Among the 100 cases, 76 had insulinomas and 24 had non-functional pNENs. Tumor size ranged from 0.5 cm to 9 cm, and the mean size was 2.20±1.40 cm. The percentages of TNM stages I, II, III, and IV tumors were 89.0%, 8.0%, 0.0%, and 3.0%, respectively. Based on the WHO classification, pNENs were classified into three grades: G1, G2, and G3. G1, G2, and G3 tumors were confirmed in 72.9%, 23.7%, and 3.4% patients, respectively. The positive rates of CgA and Syn immunohistochemical staining were 94.5% (69/73) and 100% (74/74), respectively. Compared with insulinoma, non-functional pNENs have larger tumor sizes, more advanced TNM staging, a higher Ki-67 index, and a higher rate of liver metastasis (P<0.05). In conclusion, pNENs are heterogeneous tumors with varying clinical manifestations, diverse tumor biological characteristics, and different prognoses. Non-functional pNENs present a more aggressive behavioral model and have poorer prognosis than functional pNENs.

关键词： pancreatic neuroendocrine neoplasms     clinicopathological characteristic     Ki-67     liver metastasis     outcomes    

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Laparoscopic hepato-biliary-pancreatic surgery: present practices and prospects

Yongjun Chen, Renyi Qin, Xiaoping Chen

《医学前沿（英文）》 2011年 第5卷 第3期   页码 235-238 doi: 10.1007/s11684-011-0156-4

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Immunotherapeutic effects on murine pancreatic carcinoma by β-elemene combined with dendritic cells modified

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

《医学前沿（英文）》 2007年 第1卷 第1期   页码 41-45 doi: 10.1007/s11684-007-0008-4

摘要： The dendritic cell vaccine is a treatment vaccine with potent clinical applications. Functional cytokines can enhance dendritic cell anti-tumor immune responses. This experiment was conducted to study the effects of bone marrow-deriv

关键词： Functional     experiment     anti-tumor     dendritic     clinical    

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Total pancreatic necrosis after organophosphate intoxication

Rui Hou, Hongmin Zhang, Huan Chen, Yuankai Zhou, Yun Long, Dawei Liu

《医学前沿（英文）》 2019年 第13卷 第2期   页码 285-288 doi: 10.1007/s11684-018-0626-z

摘要： Cases of acute pancreatitis induced by organophosphate intoxication are encountered occasionally in clinics, but very few of them develop into severe pancreas necrosis and irreversible pancreatic function impairment. Here, we report a 47-year-old female organophosphate poisoning case after ingestion of massive insecticides; she was considered to have total necrosis and function failure of the pancreas via serum amylase test, glucose level test, and CT imaging. The patient exhibited no relief under the regular medicine treatment, which included sandostatin, antibiotics, intravenous atropine, and pralidoxime methiodide. She received percutaneous catheterization and drainage of pancreatic zone to expel hazardous necrotic waste, also by which the pathogenic evidence was obtained and the antibiotics were adjusted subsequently. The patient recovered gradually, was discharged after 2 weeks, and was prescribed with oral pancreatin capsules before meals and hypodermic insulin at meals and bedtime to compensate the impaired pancreatic function.

关键词： organophosphate intoxication     severe acute pancreatitis     pancreas necrosis     percutaneous catheterization     sandostatin     insulin    

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Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal

Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang

《医学前沿（英文）》 2020年 第14卷 第1期   页码 91-100 doi: 10.1007/s11684-019-0696-6

摘要： Pancreatic ductal adenocarcinoma (PDAC) is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China. AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well. However, the role of AcK27-HOXB9 in PDAC is unclear. The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC. Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay, respectively. HOXB9 was upregulated ( <0.0001), and AcK27-HOXB9 ( =0.0023) was downregulated in patients with PDAC. HOXB9 promoted ( =0.0115), while AcK27-HOXB9 ( =0.0279) inhibited PDAC progression. AcK27-HOXB9 predicted favorable outcome in patients with PDAC ( =0.0412). AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay. The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression. The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.

关键词： HOXB9     AcK27-HOXB9     PDAC    

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Effect of end-to-end invagination pancreaticojejunostomy with circle discontinuous U suture in pancreatic

ZHANG Xuewen, XUAN Wei, JIANG Tao, JI Degang, YANG Yongsheng, ZHANG Dan, XIE Yingjun, MENG Zihui, ZHAO Jisheng

《医学前沿（英文）》 2007年 第1卷 第1期   页码 46-48 doi: 10.1007/s11684-007-0009-3

摘要： The aim of this paper is to summarize the methods of pancreaticojejunostomy in the pancreatic operation and to study the safety and feasibility of a new operative method called end-to-end invagination pancreaticojejunostomy with circle discontinuous U suture to prevent fistula of pancreaticojejunostomy. Eight-three patients with pancreaticoduodenectomy in the 3rd Hospital, Jilin University from 2001 January to 2006 April were reviewed. The incidences of pancreatic fistula with different types of pancreaticojejunostomy were compared. The overall incidence rate of pancreatic fistula was 26.5% (22/83). No pancreatic fistula occurred in end-to-end invagination pancreaticojejunostomy with circle discontinuous U suture. The incidence rate of the fistula following end-to-end invagination pancreaticojejunostomy with circle discontinuous U suture was significantly lower than that of traditional end-to-end pancreaticojejunostomy [40%, (10/25), <0.01] and end-to-side pancreaticojejunostomy [27.3%, (12/44), <0.05], but no significant difference (>0.05) between traditional end-to-end pancreaticojejunostomy and end-to-side pancreaticojejunostomy was discovered. End-to-end invagination pancreaticojejunostomy with circle discontinuous U suture has a definite effect on avoiding pancreatic fistula following pancreaticojejunostomy and is worth being recommended. But the cases were limited, so this method would still need to be observed and confirmed further in the future.
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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

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标题 作者 时间 类型 操作

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

期刊论文

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

期刊论文

Laparoscopic surgery for pancreatic lesions: current status and future

Taiping Zhang, Xiao Du, Yupei Zhao

期刊论文

Prevention and treatment of pancreatic fistula after pancreatic body and tail resection: current status

Li Jiang, Deng Ning, Xiaoping Chen

期刊论文

The role of prophylactic transpapillary pancreatic stenting in distal pancreatectomy: a meta-analysis

null

期刊论文

Influence of the adjuvant therapy on the survival of patients with stage II pancreatic carcinoma

Xi-Yan WANG, Hai-Jun LI, Dong YAN, Hao WEN, Shu-Yong PENG,

期刊论文

Analysis of 100 consecutive cases of resectable pancreatic neuroendocrine neoplasms: clinicopathological

null

期刊论文

Laparoscopic hepato-biliary-pancreatic surgery: present practices and prospects

Yongjun Chen, Renyi Qin, Xiaoping Chen

期刊论文

Immunotherapeutic effects on murine pancreatic carcinoma by β-elemene combined with dendritic cells modified

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

期刊论文

Total pancreatic necrosis after organophosphate intoxication

Rui Hou, Hongmin Zhang, Huan Chen, Yuankai Zhou, Yun Long, Dawei Liu

期刊论文

Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal

Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang

期刊论文

Effect of end-to-end invagination pancreaticojejunostomy with circle discontinuous U suture in pancreatic

ZHANG Xuewen, XUAN Wei, JIANG Tao, JI Degang, YANG Yongsheng, ZHANG Dan, XIE Yingjun, MENG Zihui, ZHAO Jisheng

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文