2020年《欧洲临床营养和代谢学会急慢性胰腺炎临床营养指南》解读

急性胰腺炎和慢性胰腺炎是炎性胰腺疾病的两种主要形式,需要不同的营养治疗策略。近年来,对代谢、饮食、临床营养和胰腺关系的研究逐渐深入,急慢性胰腺炎的营养治疗也越来越受到重视。2020年1月欧洲临床营养和代谢学会（ESPEN）发布了最新的急慢性胰腺炎临床营养指南。这是在2002年急性胰腺炎的临床营养指南、2006年慢性胰腺炎的肠内营养指南、2009年胰腺胃肠外营养指南的基础上,进行高度总结发布的最新的急慢性胰腺炎临床营养指南。改版指南针对急慢性胰腺炎的31个关键问题提出了42条共识性建议和7个声明,主要涉及急慢性胰腺炎的临床营养风险评估、营养干预时机、干预途径、干预类型等治疗过程中的关键问题。较全面地总结和概括了最新的急慢性胰腺炎的临床营养诊治原则和诊疗措施,为急慢性胰腺炎的临床营养诊疗提供了更全面的指导。     

实验性急性胰腺炎胰腺缺血的机制、重要性及治疗

大量的临床和实验证据表明,急性胰腺炎初期胰腺缺血在胰腺坏死的形成中具有重要意义。实验证实,血管内血容量丢失引起全身循环衰竭时,多合并胰腺循环紊乱,可能的机制包括:化学物质引起血管收缩、直接损伤血管壁、血管内凝血和血管内膜通透性增加,结果导致胰腺水肿、血液浓缩及静脉回流障碍。以上局部病变所引起的胰腺缺血,可使轻度的胰腺炎演变为实质坏死。本文作者研究了急性胰腺炎时血流变化的重要性,以及改善微循环的最新措施。缺血是急性胰腺炎起病及恶化的因素:经动脉注射8～20μm的微球能不可逆地阻塞终未小动脉,可复     

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慢性胰腺炎(chronic pancreatitis,CP)发病率逐年增加,为了规范慢性胰腺炎的诊断和治疗,提高多学科综合诊治水平,中华医学会外科学分会胰腺外科学组对2008年制定的《慢性胰腺炎诊治指南(讨论稿)》予以修订。本次修订在原版本基础上,参照国际相关指南和最新研究成果,依据流行病学资料、循证医学证据和临床基础研究结果,结合近年来国内外在慢性胰腺炎诊治领域的进展,经中华医学会外科学分会胰腺外科学组全体成员大会共同讨论审阅,     

慢性胰腺炎的诊治策略

慢性胰腺炎临床并不少见,为各种病因引起的胰腺组织和功能不可逆的慢性炎症性疾病,其病理特征为胰腺腺泡萎缩、破坏和间质纤维化.其早期临床症状为反复发作的上腹部疼痛或胰腺炎,进展期可合并胰腺外、内分泌功能不全的症状.影像学上表现为胰腺实质钙化、胰管扩张、胰管结石和胰腺假性囊肿形成等.而大量流行病学研究表明,慢性胰腺炎是胰腺癌的高危因素.     

急性坏死性胰腺炎 外科医生的困惑何在？

外科医生对急性坏死性胰腺炎的困惑多反映在对其分类和治疗措施上的频繁改变。Ｆｉｔｚ (1889)在其关于急性胰腺炎的经典著作中 ,从病理学上将急性胰腺炎分为水肿性、出血坏死性和化脓性。急性胰腺炎的临床表现与胰腺的病理改变常不相符 ,这似乎是“注定”要发生的。因为急性胰腺炎本身只不过是一个以胰腺的炎症、坏死为特点的临床征候 (ｃｌｉｎｉｃａｌｅｎｔｉｔｙ) ;而胰腺对不同致伤因子的反应是类似的、是由其功能状态决定的 ,因而造成急性胰腺炎在临床和病理上的多态性。临床上表现为重症胰腺炎者 ,胰腺不一定有广泛的出血、坏死 ;不…     

急性胰腺炎的诊治共识解读

1992年亚特兰大研讨会提出了一个全球性共识和普遍适用的急性胰腺炎分类系统,虽然其分类一直是有用的,但临床应用混乱。本文结合最新进展,对国际上最新修订亚特兰大成人急性胰腺炎(>18岁)的共识作一解读,主要论述急性胰腺炎的诊断标准、严重程度分类及急性胰腺炎出现并发症时胰腺及胰周影像学上的形态变化,并对中国中西医结合学会普通外科专业委员会最新制定的重症急性胰腺炎中西医结合诊治指南中的中医治疗做一研读。     

慢性胰腺炎的病因和发病机制

慢性胰腺炎可由多种因素所致,以胰腺组织结构的进行性、不可逆性损害和内外分泌功能不全为主要表现。胰腺纤维化为其典型的病理学改变,临床表现有反复发作的腹痛及胰腺内、外分泌功能不全等。与慢性胰腺炎相关的病因及危险因素主要包括胆石病、酗酒、遗传因素、自身免疫因素等,其发病机制仍不甚明确,临床中慢性胰腺炎的发生更是多种病因、多种发病机制共同作用的结果。进一步研究慢性胰腺炎的具体病因及发病机制,对预防和治疗慢性胰腺炎具有重要意义。     

胰腺外科主要疾病的研究热点

胰腺疾病特别是重症急性胰腺炎（SAP）、慢性胰腺炎（CP）和胰腺癌（PC），近年来在我国发病率均呈上升趋势，已严重危及人民的生命健康。因此，了解当前胰腺疾病研究的热点问题、掌握胰腺疾病诊治的最新动态，进一步加强此领域的交流与协作，对提高我国胰腺疾病的研究水平意义重大。     

慢性胰腺炎时胰腺内、外分泌功能不全的发生机制及处理

目的总结慢性胰腺炎时胰腺内、外分泌功能不全的发生机制及处理方法的研究进展。方法检索近年来国内外有关慢性胰腺炎时胰腺内、外分泌功能不全研究的相关文献并对其研究进展作一综述。结果近几年对慢性胰腺炎时出现胰腺内、外分泌功能不全有了很多新的研究和发现。慢性胰腺炎时胰腺外分泌功能不全的发生机制主要是因为患者胰酶分泌减少;胰腺内分泌功能不全的发生机制主要是由于慢性胰腺炎时胰腺外分泌腺体及胰岛组织的损伤导致胰腺内分泌细胞、其他内分泌细胞的破坏以及肠-胰岛轴紊乱,继而出现各种激素(胰岛素、胰高血糖素、胰多肽等)的紊乱,最终表现出糖耐量异常或显性糖尿病。当前的治疗方法胰腺外分泌功能不全包括针对病因治疗、饮食调节及胰酶替代治疗;胰腺内分泌功能不全应提倡使用动态血糖监测系统,2型糖尿病的管理治疗方案可以用于慢性胰腺炎糖尿病,强化胰岛素治疗方案仍是慢性胰腺炎糖尿病的首选。结论目前虽然对慢性胰腺炎时胰腺内、外分泌功能不全已经有了一定程度的了解,但其有关发病机制、诊疗方案尚无突破性的进展,缺乏大样本、多中心的临床对照研究的疗效,探索更加优化的检测手段,建立完善的治疗体系,是未来的发展趋势及研究的重点。     

主胰管减压可延迟慢性胰腺炎中胰腺功能的进行性丧失

慢性胰腺炎常伴发胰腺功能进行性损害,1988年作者曾对68例慢性胰腺炎平均随访14个月,证实手术病人的胰腺功能损害得以延缓。这次作者报告143例慢性胰腺炎的前瞻性研究结果。均作ERCP检查、脂餐胰多肽释放和口服葡萄糖耐量试验、胰岛素测定、     

Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.

The recent clinical trials of lexipafant in the treatment of acute pancreatitis were undertaken with considerable optimism. It was expected that this single agent anticytokine would reduce the morbidity and mortality of this disease. Published clinical trials of lexipafant (BB-882) in acute pancreatitis were retrieved by MEDLINE, EM Base, and Science Citation Index. The critical appraisal included the question asked, design of the study, group and selection of patients, results, and statistical analysis. The historical sequence of the trials and the impact of commerce on their performance were highlighted. Lexipafant did not reduce mortality in severe acute pancreatitis. Comparison between the trials is difficult because of changes in study groups and dose. The clinical trials were designed without the benefit of open discussion of the preliminary pharmacological studies. The results of the trials have not been communicated in an open, timely, and systematic manner, probably because of commercial constraints.     

重症急性胰腺炎早期肠内营养和肠外营养疗效的荟萃分析

目的为明确早期肠内营养(EN)和全胃肠外营养(TPN)对重症急性胰腺炎(SAP)患者的疗效,对相关文献进行荟萃分析。方法检索1970年1月—2009年6月发表的有关早期EN和TPN治疗SAP的临床随机对照试验的文献。按入选标准,有7项临床试验纳入研究范围,由2名评价者对入选研究中有关试验设计、研究对象的特征、研究结果等内容独立进行摘录,并用RevMan5.0.18软件进行分析。结果早期EN与TPN比较,前者能显著降低胰腺感染发生率(OR=0.38,95%CI:0.18~0.82,P=0.01)及器官衰竭发生率(OR=0.43,95%CI:0.23~0.79,P=0.007),减少手术干预(OR=0.34,95%CI:0.18~0.63,P=0.0006)及病死率(OR=0.41,95%CI:0.19~0.88,P=0.02)。但总的感染率两者差异无统计学意义[OR=0.43,95%CI(0.17,1.10),P=0.08]。结论SAP患者早期EN比TPN更为安全有利。     

Methodologic issues in randomized controlled trials of surgical interventions

A physician's ability to make conclusions about the relative efficacy of interventions based on their clinical experience is limited frequently. Therefore, surgeons commonly use research evidence to guide their clinical practice. The randomized controlled trial is the strongest study design. However, randomization in itself does not guarantee the trial results are valid (free from bias). Understanding the potential impact of various methodologic features of a randomized controlled trial allows a clinician to determine the validity of a trial. We present a guide for evaluating the validity of randomized controlled trials giving special consideration to issues confronted in surgical trials.     

Early ERCP for Gallstone Pancreatitis: For Whom and When?

The indications for early endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis are unclear, and the examination is often requested or performed without substantial supporting evidence. Several trials have been performed to determine the benefit of early ERCP in pancreatitis, yet the results of these studies are inconsistent. To more closely analyze these studies, we performed an evidence-based review of the outcomes of early ERCP in gallstone pancreatitis. To obtain the best available evidence, a PubMed search using the MeSH terms “gallstones” and “pancreatitis” was performed and further refined to identify appropriate studies. We included five randomized trials, a meta-analysis, and a Cochrane Database Systematic Review in our detailed examination of the pertinent literature. Collectively, these studies suggest that early ERCP does not alter mortality in gallstone pancreatitis. In addition, few patients with mild pancreatitis benefit from the procedure, whereas some studies indicate that patients with severe pancreatitis or documented biliary obstruction may experience fewer complications if ERCP is performed. The data in the studies are confounding because of heterogeneity of the patient population and the inability to confirm gallstones in up to one third of patients. In conclusion, ERCP is not indicated for patients with mild pancreatitis. In select patients with severe disease or biliary obstruction, ERCP may be indicated. A multicenter trial designed to study the effect of early ERCP in severe pancreatitis only may provide additional useful information in patients with documented gallstones. Presented at the Postgraduate Course of the 48th Annual Meeting of The Society for Surgery of the Alimentary Tract (Digestive Disease Week 2007), Washington DC, USA, May 20, 2007.     

The State of the Highest Level of Evidence: An Overview of Systematic Reviews of Pancreaticobiliary Disease Customized for the Gastroenterologist and GI Surgeon

Trends emerged as randomized controlled trials (RCTs) on pancreaticobiliary disease were reviewed by each panel of experts. There were few RCTs. Although studies observed statistical differences between their treatment groups, many of them were underpowered. The studies with the most patients were sponsored by industry—on adjuvant therapy and biliary stents. Two subjects did not have an RCT [necrotizing pancreatitis and intraductal papillary mucinous tumors (IPMN) of the pancreas]. Constant heterogeneity between RCTs was observed. A good example was the 22 variations in study designs noted between the 5 RCTs of the adjuvant chemotherapy panel. Some of these RCTs had no inclusion criteria while a more recent trial utilized very specific measures. Many trials had insufficient follow-up (6 months in one study of chronic pancreatitis surgery). Each randomized controlled trial may have reached a different conclusion than another one on the same topic although they had similar results (adjuvant treatment for resected pancreatic cancer). From this review of the highest level of evidence in the literature for pancreaticobiliary disease, it is apparent that the lack of quantity and quality of the highest level of evidence provides us with a challenge to improve the quality of our literature. Cooperation is required, which might begin by an international consensus on definitions, inclusion criteria, and the minimum length of follow-up. Presented at the Postgraduate Course of the 48th Annual Meeting of Society of Surgery of the Alimentary Tract, May 20, 2007, Washington, DC.     

Role of antibiotics in acute pancreatitis: A meta-analysis

In an attempt to decrease the infectious complications of acute pancreatitis and its high mortality, many investigators have conducted randomized prospective trials on the efficacy of prophylactic antibiotics. The results of these studies are conflicting, and many have called for a large multicenter study. Because multicenter trials are costly and difficult to organize, we believe that meta-analysis is a reasonable alternative. A meta-analysis of all eight previously published trials of prophylactic antibiotics in acute pancreatitis was performed. The end point was death. The Mantel-Haenszel statistic was used to summarize odds ratios across studies in a fixed effects model, after homogeneity was assessed. Sensitivity analysis was performed as appropriate. The meta-analysis of all eight trials showed a positive benefit for antibiotics in reducing mortality. Sensitivity analysis showed that the advantage was limited to patients with severe pancreatitis who received broad-spectrum antibiotics that achieve therapeutic pancreatic tissue levels. It is recommended that all patients with severe pancreatitis be treated with broad-spectrum antibiotics that achieve therapeutic levels in pancreatic tissue.     

Influence and critique of the PIVOTAL and the EVAR 2 Trials

Management of a condition that has potentially life-threatening consequences may not lend itself effectively to the scrutiny of a randomized clinical trial when an observation or no treatment option is offered as part of the trial. This type of trial often experiences a significant rate of crossover of subjects from no treatment to treatment, and when results are analyzed on an intent-to-treat basis, they may fail to resolve the issue under study. These trials are frequently used as Level 1 medical evidence and the potential impact on clinical decision-making and reimbursement can be quite significant and long-lasting. The authors observed this phenomenon during participation in the Positive Impact of Endovascular Options for Treating Aneurysms Early (PIVOTAL) trial and have observed it in an analysis of the Endovascular Aneurysm Repair 2 (EVAR 2) trial. Possible solutions to mitigate the high crossover effect are offered for consideration. Some clinical conditions dealing with potentially life-threatening problems probably do not lend themselves to be studied in randomized prospective clinical trials containing an observation or no treatment arm.     

Questions about the use of antibiotics in acute pancreatitis

Background and objective  

The use of antibiotics in acute pancreatitis despite recent clinical trials remains controversial. The aim of this study is to review the latest clinical trials and guidelines about antibiotics in acute pancreatitis and determine its proper use.     

Methods and design considerations for randomized clinical trials evaluating surgical or endovascular treatments for cerebrovascular diseases

OBJECTIVE: The results of clinical trials affect the practice of surgery and endovascular therapy for cerebrovascular diseases. The purpose of this report is to review the basic components of the designs and methods for randomized clinical trials and to describe the influence of those components on the interpretation of trial results. METHODS: The goal of an optimal clinical trial of a new procedure is to provide the most objective and rigorous evaluation of the safety and effectiveness of that procedure. Anything in the design, performance, or analysis that impairs such an assessment decreases the ability of the trial to achieve its goal and answer the research question. To highlight the components of a clinical trial, this report uses examples of Phase III clinical trials that have influenced the practice of cerebrovascular surgery and endovascular therapy in the past three decades, including the International Cooperative Study of Extracranial/Intracranial Arterial Anastomosis, the North American Symptomatic Carotid Endarterectomy Trial, the Asymptomatic Carotid Atherosclerosis Study, the Prolyse in Acute Cerebral Thromboembolism II study, and the International Subarachnoid Aneurysm Trial. RESULTS: The research question (objective) of the trial must be clearly defined, with an objective measure of efficacy and a specified quantitative difference to define the superiority of one intervention over another, in a relatively homogeneous patient population. Allocation concealment, randomization with or without stratification, and blinding (or masking) are important strategies to prevent differences in the study populations that could adversely affect the conclusions of the study. The primary end point must correspond to the specific aims of the trial. It should be objectively defined, quantifiable, reliable, and reproducible. Commonly defined end points in surgical trials include changes from baseline illness or disease severity scores, morbidity and mortality rates, and relative risks of reaching an end point with time. The statistical methods used for interim and final analyses are important. The effects of dropouts, crossovers, and missing data should be understood in the context of the final analysis. Additional concepts, such as intention-to-treat analysis and use of actual versus predicted outcomes, are important with respect to interpretation of the final results of the study. CONCLUSION: The neurosurgical and neuroendovascular communities are currently planning or conducting several clinical trials to evaluate new procedures for the treatment of cerebrovascular diseases. It is hoped that a better understanding of the components of clinical trials will facilitate the design and implementation of effective studies.     

What's new in the management of acute pancreatitis?

Acute severe pancreatitis remains a disease with multiple complications and high mortality rates. The body of knowledge about clinical pancreatitis is being subjected to rigorous evidence-based analysis, and relevant, practical guidelines have been issued. Great efforts are being made to identify and profile the mediators involved in the systemic hyperinflammatory response to acute pancreatic injury. Lexipafant, a platelet-activating factor antagonist that showed promising results in initial trials, failed to reduce the incidence of new organ failures or mortality in a large double-blind study. The search for an early and accurate prognostic marker for severity persists, with urinary trypsinogen activation peptide as a potentially suitable candidate. Patients with acute pancreatitis do not benefit from anti-secretory therapy with octreotide. Percutaneous, radiological, drainage techniques may eventually play an important role in the management of infected necrosis.