What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

胰腺切除患者围术期血糖管理的最佳证据总结

背景血糖紊乱是胰腺切除患者围术期常见问题。然而，目前国内开展的胰腺切除患者围术期血糖管理实践多以经验为指导，缺乏循证依据。目的总结胰腺切除患者围术期血糖管理的最佳证据。方法系统检索BMJ最佳临床实践、Up to Date、国际指南协作组、国际糖尿病联盟（IDF）、世界卫生组织（WHO）、美国国立指南数据库（NGC）、美国糖尿病协会、英国国家临床优化研究所（NICE）、新西兰指南研究组、加拿大糖尿病协会、澳大利亚糖尿病协会、苏格兰校际指南网络（SIGN）、PubMed、Web of Science、EMBase、CINHAL数据库、Cochrane图书馆、乔安娜布里格斯研究所（JBI）循证卫生保健中心、医脉通、万方数据知识服务平台、中国知网（CNKI）、生物医学数据库（CBM），筛选关于胰腺切除患者围术期血糖管理的文献。检索时间为建库至2020年12月。指南的质量评价采用国际AGREE协作组织2009年更新的AGREE Ⅱ量表。专家共识的质量评价采用澳大利亚JBI循证卫生保健中心专家共识评价标准2017版。随机对照试验的评价采用Jadad评分量表。结果通过初步检索筛选出文献6 637篇，最终纳入文献13篇，其中7篇为临床实践指南，4篇为专家共识，2篇为随机对照试验。评价结果显示，7篇临床实践指南中3篇总体质量评价为A级，剩下4篇为B级；4篇专家共识的质量评价在"观点与其他文献不一致的地方是否有合理解释？"条目的评价结果为"不清楚"，其余条目的评价结果均为"是"。2篇随机对照试验均为高质量文献。共汇总了62条最佳证据，主要涉及围术期组织管理、入院评估及处理、血糖控制目标、血糖监测、术前血糖管理策略、术中血糖管理策略、术后血糖管理策略、危急状况处理以及出院指导9个方面。结论临床医务人员应根据总结的9个方面最佳证据（包括围术期组织管理、入院评估及处理、血糖控制目标、血糖监测、术前血糖管理策略、术中血糖管理策略、术后血糖管理策略、危急状况处理以及出院指导）为胰腺切除患者制定个体化、全程化的围术期血糖管理方案。     

MR引导放疗在胰腺癌中的应用

放疗是治疗胰腺癌的重要手段。但受胰腺运动等因素影响,放疗疗效难以充分发挥。更高效的胰腺癌放疗有赖于运动管理方式的改进与高质量的图像引导。新兴的MR引导放疗技术软组织分辨率高、无额外辐射、能进行功能成像,经过大量研究评估与验证,其在靶区与危及器官的精准勾画、辅助运动管理和自适应放疗等方面有着巨大优势,有望更好地发挥放疗在胰腺癌治疗中的作用。本文就MR引导放疗在胰腺癌治疗中的应用作一综述和展望。     

Prognostic impact of conservative surgery for pancreatic IPMNs

BackgroundThe extent of pancreatic resection for intraductal papillary mucinous neoplasms (IPMNs) remains an unresolved issue. The study aims at analyzing the prognostic impact of conservative surgery (CS) i.e. of pancreatoduodenectomy or distal pancreatectomy, versus total pancreatectomy (TP), for pancreatic IPMNs.MethodsWe retrospectively analyzed and compared data of patients who had undergone pancreatic resection for IPMNs at our center between November 2007 and April 2019. Patients were divided into two main groups based on the extent of surgery: TP-group and CS-group. Subsequently, the perioperative and the long-term outcomes were compared. Moreover, a sub-group analysis of patients with IPMN alone and patients with malignant IPMN, based on preoperative indications to surgery and post-operative histopathological findings, was also performed.ResultsFifty-three patients were included in the TP-group and 73 in the CS-group. In 50 (39.7%) cases the frozen section changed the pre-operative surgical planning, with an extension of the pancreatic resection, in 43 (34.1%) cases up to a total pancreatectomy. Twenty-six patients (20.6%) with low-grade dysplasia at the frozen section underwent CS, while twenty (15.8%) underwent TP. Comparing these two sub-groups no differences were found in surgical IPMN recurrence, nor progression. The rate of overall postoperative complications was 56.6% in the TP-group and 57.5% in the CS-group (p = 0.940). Fifteen patients (20.5%) developed diabetes in the CS-group.None of the patients treated with CS developed a surgical IPMN recurrence or progression during the follow-up period. Comparing OS and DFS of the two groups, we did not find any statistically significant difference (p = 0.619 and 0.315).ConclusionA timely CS can be considered an appropriate and valid strategy in the surgical treatment of the majority of pancreatic IPMNs, as it can avoid the serious long-term metabolic consequences of TP in patients with a long-life expectancy. On the contrary, TP remains mandatory in case of PDAC or high-risk features involving the entire gland.     

Phase I Study of Afatinib and Selumetinib in Patients with KRAS-Mutated Colorectal,Non-Small Cell Lung,and Pancreatic Cancer

Lessons Learned

• Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy.
• Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg once daily and selumetinib 25 mg b.i.d.
• Because the anticancer activity was limited, further development of this combination is not recommended until better biomarkers for response and resistance are defined.

BackgroundAntitumor effects of MEK inhibitors are limited in KRAS‐mutated tumors because of feedback activation of upstream epidermal growth factor receptors, which reactivates the MAPK and the phosphoinositide 3‐kinase–AKT pathway. Therefore, this phase I trial was initiated with the pan‐HER inhibitor afatinib plus the MEK inhibitor selumetinib in patients with KRAS mutant, PIK3CA wild‐type tumors.MethodsAfatinib and selumetinib were administered according to a 3+3 design in continuous and intermittent schedules. The primary objective was safety, and the secondary objective was clinical efficacy.ResultsTwenty‐six patients were enrolled with colorectal cancer (n = 19), non‐small cell lung cancer (NSCLC) (n = 6), and pancreatic cancer (n = 1). Dose‐limiting toxicities occurred in six patients, including grade 3 diarrhea, dehydration, decreased appetite, nausea, vomiting, and mucositis. The recommended phase II dose (RP2D) was 20 mg afatinib once daily (QD) and 25 mg selumetinib b.i.d. (21 days on/7 days off) for continuous afatinib dosing and for intermittent dosing with both drugs 5 days on/2 days off. Efficacy was limited with disease stabilization for 221 days in a patient with NSCLC as best response.ConclusionAfatinib and selumetinib can be combined in continuous and intermittent schedules in patients with KRAS mutant tumors. Although target engagement was observed, the clinical efficacy was limited.