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生命之思与医学之悟
医学之美在于思维之花的绽放，从不思到寻思，从浅思到深思，从顺思到反思，从技术之思到哲学之思。一年又一年，为生命而战，为尊严而战。作为一名医者，今天，在资本追逐的热土中，仍然不忘当年的初心，“遵守誓约，矢忠不渝”。面对生命的博大，无论是医者，还是病患，都要接纳临床的复杂性，都要体验医学的不可先知、不可全知的不确定性。这，就构成了医学的永恒课题—不确定性的前提与对完美结局的希翼。这，就决定了医者的神圣使命—超越不确定性去追求完美。
相信很多医生都听过阿图·葛文德的医生三部曲《医生的修炼》、《医生的精进》、《最好的告别》。编者最近在读他的第二本书《医生的精进》，这本书非常适合具有一定基础技能开始通向进阶路上的医生阅读。全书围绕要创造医疗佳绩，医学知识和技能固然重要，但有勤奋、正直之“心”并勇于创新，才能更上一层楼。《柳叶新潮》愿意做医生进阶路上的同行人，为医生传播国际先进前沿的学术，为医生提供汲取知识的养料，为遇到各种不确定的情况下增加一丝自信和底气，助力其学术的发展，最终完成从仁心、仁术到追求卓越！
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欧洲胃肠道内镜学会临床指南
6ERCP 乳头插管和括约肌切开术技巧
The Lancet&BMJ
（第四、五章）
28 胰腺疾病的最新研究报告
在肺癌中的应用最新报告
68 呼吸科论文精读
74《柳叶新潮》带你去看展
ERCP 及其替代方法
94 治疗胆胰疾病的最新
研究病例分享
110 华盛顿印象
5欧洲胃肠道内镜学会ERCP 乳头插管和括约肌切开术技巧 （第四、五章） 导读： 本期《柳叶新潮》将继续对 ERCP 乳头插管和括约肌切 开术技巧的第 4、5 章内容进行编译，其中第 4 章主要 介绍胆管括约肌预切术的常用术式、临床疗效及选用时 机，并对不同术式进行对比，还单独阐释了胰腺支架置 入后预切术所能发挥的作用；第 5 章主要关乎经胰胆管 括约肌切开术的有效性及安全性，并提出一项尚无研究 能够予以解答的问题（接受经胰胆管括约肌切开术的患 者应置入胰腺支架以预防出现胰腺炎吗？）。希望上述 内容能对诸位读者有所裨益。
674 Precut biliary 胆管括约肌预切术
ESGE recommends needle-knife fistulotomy1 as the preferred technique for precutting (moderate
quality evidence strong recommendation).
[ 解读 ]：ESGE 建议，将针刀开窗术作为首选的预切术（证据质量中级，强烈推荐）。
ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary
cannulation in more than 80 % of cases using standard cannulation techniques. Endoscopists who do
not reach such a success rate should not be doing precuts independently (low quality evidence, weak
recommendation).
[ 解读 ]：ESGE 建议，预切术只能由那些使用标准插管术进行选择性胆管插管且成功率超过 80% 的内镜医师
操作。未达到上述成功率的内镜医师不能独立行预切术（证据质量中级，推荐强度弱）。
When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic
stent prior to precutting. It is suggested that endoscopists check for spontaneous2 pancreatic duct
stent migration at 1-week post insertion, using abdominal X-ray (moderate quality evidence, weak
recommendation).
[ 解读 ]：ESGE 建议，当胰管较易进入时，应于预切术前置入胰腺支架，内镜医师应于支架置入一周后利用腹
部 X 射线检查有无出现自发移位（证据质量中级，推荐强度弱）。
4.1 Definition of conventional precut and fistulotomy
常规预切术和开窗术的定义
Conventional precut technique. This is usually defined as the use of a needle-knife to perform a stepwise
incision of the mucosa starting at the upper margin of the papillary orifice in the direction of the bile duct until
the underlying biliary sphincter is visualized.
[ 解读 ]：常规预切术，即利用针刀自乳头上缘开始沿胆管方向逐步切开粘膜，直至下层的胆管括约肌可见。
Fistulotomy. The needle-knife fistulotomy technique is usually defined as the use of a needle-knife to perform a
stepwise incision of the mucosa starting directly over the roof of the papilla followed by upward or downward
cut until the underlying biliary sphincter is visualized. The goal of this technique is to avoid thermal injury to the
pancreatic orifice and therefore, heoretically, reduce the risk of PEP.
[ 解读 ]：针刀开窗术，即利用针刀直接自乳头顶部向上或向下切开粘膜，直至下层的胆管括约肌可见。此术式的
目的在于避免对胰管开口造成热损伤，从而在理论上降低 PEP 的发病风险。
4.2 Efficacy and timing of precutting during ERCP
ERCP 期间预切术的疗效及时机
The precut technique has been used to allow selective biliary cannulation in difficult cases. However, it has
been associated with a high risk of PEP and in many studies has been found to be an independent predictor
of PEP. Precutting is often performed after repeated cannulation attempts, which raises the question as to
whether it is difficult cannulation rather than the precut itself that is the true risk factor for PEP. This prompts
the question as to whether early precutting is preferable to prolonged3 attempts at cannulation using standard
techniques.8古巴云尼斯山谷[ 解读 ]：预切术可用于对插管困难患者行选择性胆管插管。然而，预切术与 PEP 的高发存在关联，并被多项研究证实为 PEP 的独立预测指标。预切术通常在反复插管尝试后进行，因此难以明确 PEP的真正风险因素究竟是插管困难还是切开术本身，这项问题进一步被延伸为：利用标准术式延长插管尝试与早期预切术相比，哪一项更为可取。[1] fistulotomy：开窗术[2] spontaneous：自发的[3] prolonged：延长4.2.1 Is precut biliary sphincterotomy better than repeated papillarycannulation attempts in terms of cannulation success?在插管成功率方面，胆管括约肌预切术优于反复的乳头插管尝试吗 ?Summary of the evidence 证据总结Successful biliary cannulation following an early precut has been assessed in three meta-analyses. Early precutting was comparable to multiple standard cannulation attempts followedby late precutting as a means to achieve deep cannulation. For example, a meta-analysis fromChina reported that primary cannulation success was 89.3% in the early precut group and 78.1% in the persistent attempts group (OR 2.05, 95%CI 0.64 – 6.63), with a similar overall finalcannulation success (OR 1.54; 95%CI 0.55 – 4.31).[ 解读 ]：三项荟萃分析评估了早期预切后胆管插管的成功病例。作为实现深度插管的手段，早期预切术与多次尝试后行预切术具有可比性。例如，一项中国的荟萃分析表明，早期预切组的初始成功率为 89.3%，持续插管组为 78.1%（OR 2.05，95%CI 0.64-6.63），但组间整体的最终成功率相似（OR 1.54；95%CI 0.55-4.31）。
本解读仅供各位同道学习交流，不作为临床实践的标准
9Medi-Trends
It should be noted that the studies included in meta-analyses differed in the timing of the precut (immediate,
or with 5,10, or 15 minutes allowed before randomization), in precut technique (at the orifice, fistulotomy,
or both), and duration of persistent attempts after randomization (from 10 to 20 minutes). Results are
summarized in Table 4.
[ 解读 ]：应当注意的是，荟萃分析纳入的研究在预切时机（即时，或随机分组前的 5、10 或 15 分钟）、预切术式（乳
头预切术、开窗术或兼而有之）以及随机分组后持续插管尝试时间（10-20 分钟）等方面有所不同。结果见表 4。
Table 4 Meta-analyses comparing precut and conventional multiple cannulation attempts in patients with difficult
biliary cannulation.
对比困难插管患者预切术及多次常规插管尝试的荟萃分析
RCT, randomized controlled trial 随机对照试验
PEP, post-ERCP pancreatitis ERCP 术后胰腺炎
NNT, number needed to treat 需治疗的人数
ERCP, endoscopic retrograde cholangiopancreatography 经内镜逆行性胰胆管造影术
4.2.2 Is early precut biliary sphincterotomy associated with a lower
incidence of PEP when compared with repeated papillary cannulation
较之反复尝试乳头插管，早期胆管括约肌预切是否与 PEP 发病率较低有关？
Summary of the evidence 证据总结
Four meta-analyses investigated the risk of PEP in patients undergoing early precut compared with a
prolonged standard cannulation technique. Two meta-analyses evaluated data from the same six RCTs,
all performed in high volume centers, whereas another more recent RCT was also included in the last two
analyses (Table 4). A total of 966 patients were included in the six RCTs with a significantly lower rate
of PEP in the early precut than in the persistent attempt group (OR 0.47, 95 %CI 0.24-0.91). The studies
included in the meta-analyses differed as described in section 4.2.1. None of the studies evaluated in the
meta-analyses were adequately powered to assess a significant PEP difference between the two methods.10ESGE 指南（第四章）
美国阿拉斯加风光[ 解读 ]：四项荟萃分析对接受早期预切术与延长的标准插管术的患者的 PEP 风险进行了调查。其中两项荟萃分析同时对来自六项 RCT 的数据进行了评估，六项研究均于高病例容量中心展开，而后两项荟萃分析还纳入了一项近期的 RCT（见表 4）。六项 RCT 共涉及患者 966 例，其中，预切组的 PEP 发病率显著低于持续尝试组（OR 0.47，95%CI 0.24-0.91）。上述荟萃分析纳入的研究与 4.2.1 章节不同。但这些荟萃分析中的任一一项研究均不足以界定两种术式间是否存在显著的 PEP 差异。The two later meta-analyses confirmed a decreased rate of PEP after early precut, but this was notstatistically significant (3.9 % in the precut sphincterotomy vs. 6.1 % in the persiOR 0.58, 95 %CI 0.32-1.05; P = 0.08). When analysis was restricted to the two RCTs that employedfistulotomy, this technique significantly reduced the odds of PEP (OR 0.27, 95 %CI 0.09-0.82; P = 0.02).This is discussed further in section 4.3.1.[ 解读 ]：后两项荟萃分析证实了预切后 PEP 的发病率有所下降，但这一差异无统计学意义（括约肌预切术组为 3.9%，持续尝试组为 6.1%；OR 0.58, 95%CI 0.32-1.05; P=0.08）。在仅对两项采用开窗术的 RCT 进行分析后发现，该术式显著降低了 PEP 发病率（OR 0.27, 95%CI 0.09-0.82; P=0.02）。详情可参见 4.3.1 章节。4.2.3 Does the expertise of the endoscopist influence the success andadverse event rate of precut-assisted biliary sphincterotomy?内镜医师的专业性是否会影响胆管括约肌预切术的成功率以及不良事件发生率？Summary of the evidence 证据总结Precut sphincterotomy has an associated learning curve. In almost all published studies the precuttechnique is performed by experienced endoscopists. However, most of them do not rely on precutmethods in more than 10 %-15 % of cases and it is not described as a substitute4 for standardcannulation techniques. The need for precutting is reported to decrease with an increase in theexperience of the endoscopist. There is no standard definition of what constitutes expertise in precuttechnique.[ 解读 ]：括约肌预切术具有相应的学习曲线。在几乎所有已发布的研究中，预切术操作者均为经验丰富的内镜医师。然而，在超过 10%-15% 的病例中，绝大多数术者并不依赖于预切术也未将其作为标准插管术的替代术式。报告显示，预切术的需求与内镜医师的经验成反比。目前还无法就预切术专业技术的构成给出标准定义。[4] substitute：替代品
本解读仅供各位同道学习交流，不作为临床实践的标准
11Medi-Trends
Four retrospective and two prospective studies have examined the relation
between precutting and the experience of the endoscopist. In these studies,
the endoscopist precut use ranged from 5 % to 31.5 % of overall ERCPs (mean
18.5 %), with variation in the timing and number of cannulation attempts at the
papilla before precut was performed. Five of the six published studies evaluated
a single endoscopist’s learning curve for precut sphincterotomy, starting at the
onset of their training and following progress over a period that varied from 17
months to 8 years. The most frequently used method was to retrospectively
divide the total number of precut procedures into chronologically5 ordered
groups of similar or identical size and compare outcomes between these
groups. Contradictory data were shown: in three studies, the likelihood of
successful cannulation of the bile duct correlated with endoscopist experience,
whereas in three studies it did not.
[ 解读 ]：四项回顾性研究以及两项前瞻性研究探索了预切术与内镜医师经验之间
的关系。在上述研究中，内镜医师选用预切术的比例占全部 ERCP 的 5%-31.5%（均
值为 18.5%），预切术前乳头处插管尝试的时间与次数存在差异。其中五项研究对
单个内镜医师的括约肌预切术学习曲线分别进行了评估——从训练开始到后续的
17 个月至 8 年不等。最常用的评估方法为按照时间顺序，回顾性地将某位医生所
行的全部预切术分为次数相同或相近的几组，并对组间的结果进行比较。评估得
到的数据相互矛盾：在其中三项研究中，胆管插管的成功率与内镜医师的经验相关，
而在另外三项研究中却并不存在此类关联。
In relation to adverse events, five of six studies were unable to demonstrate an
association between experience and overall rates or grade of severity. In one
study, the rates of immediate bleeding were significantly higher during the first
100 precuts compared with those done afterwards. On the basis of this result,
the authors suggested that experience of at least 100 procedures is required to
achieve competency in the technique.
[ 解读 ]：关于不良事件，六项研究中的五项无法证实内镜医师的经验与不良事件
的整体发生率或严重程度相关。在一项研究中，最初 100 次预切术的即时出血率
显著高于后续的预切术。在此基础上，作者表示，具有至少 100 例预切术经验的
内镜医师方可胜任此术式。
In the only study that compared the results of precutting between two
endoscopists, no differences were observed in success and adverse
events. One study assessed prospectively the success and safety of precut
performed by an “average” endoscopist skilled in ERCP (60–70 ERCPs per
year) compared with standard biliary sphincterotomy: the adverse events,
albeit with a doubled rate after precut (16.2%), were not significantly different
from those observed after standard biliary sphincterotomy (7.7%; P=0.14). Set
against the reported complication rate, precut in difficult cases increased the
overall success rate for selective biliary cannulation by 25 percentage points.
In a recent meta-analysis including five studies (523 participants), a subgroup
analysis of those three that involved only expert endoscopists (not fellows/
trainees) showed a significant reduction in risk of pancreatitis (risk ratio [RR]
0.29, 95%CI 0.10–0.86) among patients receiving early precut compared with
standard technique.
[ 解读 ]： 仅有一项研究对两位内镜医师的预切结果进行了比较，二者在手术成功
率和不良事件发生率方面不存在差异。一项研究前瞻性地比较了“平均”ERCP 技术
水平（每年 60-70 例 ERCP）的内镜医师所行预切术与标准胆管括约肌切开术的成
功率及安全性：尽管预切术后不良事件的发生率（16.2%）是标准胆管括约肌切开
术（7.7%）的 2 倍，但二者差异并不显著（P=0.14）。相比于已公布的并发症发生率，
预切术可使插管困难患者的选择性胆管插管的成功率上升 25%。在近期一项纳入 5
项研究（523 例患者）的荟萃分析中，研究人员针对其中的 3 项仅由专业内镜医师
（非助手或实习生）参与的研究进行亚组分析后发现，较之标准术式，接受早期
预切术的患者发生胰腺炎的概率显著降低。（风险比 [RR] 0.29, 95%CI 0.10–0.8）。
[5] chronologically：按年代地12ESGE 指南（第四章）4.3 Conventional precut biliary sphincterotomy vs. Fistulotomy常规的胆管括约肌预切术 vs 开窗术4.3.1 Does precut technique influence the likelihood of successful biliarycannulation or pancreatitis?预切术会影响胆管插管的成功率或胰腺炎的发病率吗？Both conventional precut biliary sphincterotomy and needle-knife fistulotomy are highly successful and safe whenperformed by experienced endoscopists from high volume centers, especially if implemented early in the procedure.However, most studies report on a single technique, and comparative data are scarce.[ 解读 ]： 高病例容量中心的内镜医师行常规胆管括约肌预切术和针刀开窗术时，都具有较高的成功率，尤其是在手术前期实施的情况时。但绝大部分研究的对象为单个术式且缺乏对比数据。A systematic review and meta-analysis was published investigating the role of early precut in the biliary cannulationstrategy. Four RCTs used conventional precut, whereas two used needle-knife fistulotomy. On pooled analysis,fistulotomy significantly decreased the odds of PEP (OR=0.27, 95%CI 0.09–0.82; P=0.02). Overall cannulation rateswere comparable between both precut techniques. In an RCT of 153 patients, comparing two precut techniques inthe management of choledocholithiasis6, the rate of PEP was significantly lower after fistulotomy (0%) compared withconventional precut (7.59%). In a retrospective study comparing three precut techniques, in which the selection ofthe precut technique was based on papillary morphology, the outcomes of 274 patients were assessed. The PEPrate was significantly lower in patients allocated to fistulotomy rather than to conventional precut (2.6% vs. 20.9%).In another retrospective study comparing two precut techniques, performed by three experienced endoscopists, anonsignificant trend to a lower rate of PEP was observed after fistulotomy (0%) compared with two variations of theconventional precut (12.8% and 6.3%). However, in this study there were differences between endoscopists in terms ofelectrosurgical7 current used and pancreatic stenting policy.[6] choledocholithiasis：胆总管结石[7] electrosurgical：电外科，电刀古巴巴拉德罗海滩
13Medi-Trends
[ 解读 ]：近期发布的一项系统性回顾与荟萃分析对胆管插管策略中早期预切术的作用进行了审查。其中 4 项
RCT 采用常规预切术，两项采用针刀开窗术。汇总分析显示，开窗术可显著降低 PEP 的发病率（OR=0.27,
95%CI 0.09–0.82; P=0.02）。两类预切术的整体插管成功率相似。一项纳入 153 例患者的 RCT 在对胆总管结石治
疗过程中的两类预切术进行比较后发现，开窗术后的 PEP 发病率（0%）显著低于常规预切术（7.59%）。一项
纳入 274 例患者的回顾性研究在对三类预切术进行比较（预切术的选择基于乳头形态）后发现，接受开窗术的
患者的 PEP 发病率显著低于常规预切术（2.6% vs 20.9%）。另一项回顾性研究在对两种预切术（由 3 位经验丰富
的内镜医师操作）进行比较后发现，开窗术（0%）的 PEP 发病率低于另外两种不同形式的预切术（12.8% 与 6.3%），
但不显著。然而，此次研究所纳入的内镜医师对于电刀电流及胰腺支架策略的选用有所差异。
4.3.2 Does papillary morphology influence the choice of precut
technique?
乳头形态会影响预切术的选择吗？14ESGE 指南（第四章）
Summary of the evidence 证据总结
The vast majority of endoscopists perform the same type of precut
over time, irrespective of the morphology of the papilla. There are no
randomized controlled trials or prospective cohort studies comparing the
success and safety of the two precut techniques in relation to papillary
morphology. Two retrospective cohort studies compared three precut
techniques, in which the selected precut was determined by the papillary
morphology, based on personal preferences of the endoscopists:
fistulotomy was reserved for papillas in which the intraduodenal8 segment
of the common bile duct bulged on the medial duodenal wall.
[ 解读 ]：绝大多数的内镜医师不会考虑乳头形态，而是采取统一的预切术式。
尚无 RCT 及前瞻性队列研究基于乳头形态对两类预切术的成功率及安全性
进行比较。两项回顾性队列研究对三种预切术进行了对比，研究中预切术
的选择基于内镜医师的个人偏好，以及乳头形态：开窗术适用于在胆总管
的十二指肠段内壁处突起的乳头。
During ERCP it would be useful if we could predict the diameter of the
bile duct based on endoscopic findings, as needle-knife fistulotomy
seems to be safer in patients with large distal bile ducts. However,
there are no studies addressing the value of papillary morphology as a
predictor of the diameter of the distal CBD.
[ 解读 ]： 鉴于针刀开窗术对于胆管远端较大的患者更具安全性，故而若能
在 ERCP 期间基于内镜检测结果预测胆管直径将大有裨益。但尚无研究对
乳头形态作为远端 CBD 直径预测因素的价值进行评估。
4.4 The role of precutting following pancreatic
stent placement
胰腺支架置入后预切术的作用
Summary of the evidence 证据总结
Prolonged attempts at cannulation have been linked with an increased
risk of PEP. This suggests that after a number of failed attempts to
achieve deep biliary cannulation (varying from 3 to 10 in studies),
alternative strategies must be pursued, including conventional “freehand”
needle-knife precut papillotomy (the technique used most often),
precut fistulotomy, the DGW cannulation technique, or transpancreatic9
sphincterotomy with or without placement of a pancreatic duct stent. The
rationale behind performance of precutting over a pancreatic duct stent
(PPDS) is the facilitation of biliary cannulation by using the stent as a guide
for precutting whilst reducing the incidence of PEP. As such, the ESGE
Guideline for PEP prophylaxis recommends that, when needle-knife precut
papillotomy is undertaken and pancreatic cannulation is easily obtained,
a small-diameter (usually 3-Fr or 5-Fr) pancreatic duct stent should be
placed to guide the cut, and that the stent should be left in place at the
end of the procedure.
[ 解读 ]：延长插管尝试与 PEP 风险的上升相关。这意味着在经过数次失败的
深度胆管插管后（3-10 次不等），必须选用替代插管策略，包括常规的“徒手”
针刀乳头预切术（最常用）、预切开窗术、DGW 插管术或在置入或不置入胰
管支架条件下的经胰管括约肌切开术。借助胰管支架行预切术（PPDS）的原
理为利用支架引导预切术，同时降低 PEP 发病率。因此，《ESGE 预防 PEP
指南》提出建议：行针刀乳头预切术后，如胰管插管较易实现，则应置入一
个小直径（常为 3Fr 或 5Fr）胰管支架以引导切开术，并在手术结束后将支
架留置于原位。
[8] intraduodenal：十二指肠内
[9] transpancreatic：经胰管法国 - 阿尔卑斯山脉
15Medi-Trends
4.4.1 Does precut over a pancreatic stent improve
the success rate and reduce the adverse event rate
compared with the conventional precut technique?
较之常规预切术，借助胰腺支架的预切术会改善插管成
功率并降低不良事件发生率吗？
Summary of the evidence 证据总结
A recent study tested the efficacy, feasibility and safety of PPDS compared
with freehand needle-knife precut papillotomy, by analyzing retrospective
data from an ERCP cohort where precutting was performed in cases
of difficult biliary cannulation. Out of 1619 patients with naive papillas,
precutting was undertaken in 8.3% (total 134: needle-knife papillotomy
36 patients, PPDS 98 patients). Biliary cannulation success rates were
significantly better for PPDS compared with the conventional needle-knife
technique (95/98 [96.9%] vs. 31/36 [86.1%]; P=0.0189). In terms of overall
adverse events, PPDS also performed better than conventional needle-
knife (7/98 [7.1%] vs. 12/36 [33%] including 1 P&0.001). Major
limitations of this study were its retrospective design and a chronological
bias in favor of PPDS.
[ 解读 ]：一项 ERCP 队列研究对胆管插管困难的患者行预切术，近期有研究
对该队列中的前瞻性数据进行了分析，测试了 PPDS 的功效、可行性及安全性，
并将其与徒手针刀括约肌预切术进行比较。在 1,619 例乳头未经处理的患者中，
8.3% 接受了预切术（共计 134 例：针刀乳头切开术 36 例，PPDS 98 例）。较
之常规的针刀术式，PPDS 具有更高的胆管插管成功率（31/36 [86.1%] vs 95/98
[96.9%]; P=0.0189）。就不良事件的整体发生率而言，PPDS 同样优于常规针刀
（7/98 [7.1%] vs 12/36 [33%] 包括一例致命出血，P&0.001）。该研究的主要局
限性在于其回顾性设计以及有利于 PPDS 的年代偏倚。
In another trial that included 151 consecutive patients, after successful
PPDS, patients were randomized to having the pancreatic duct stent in
situ10 for 7–10 days (n=46) or having the stent removed post-procedurally
(n=47). PEP rates were significantly lower in the group where the
pancreatic duct stent was left in situ (4.3% vs. 21.3%, P=0.027).
[ 解读 ]：另一项纳入 151 例连续患者的试验在 PPDS 成功后，将患者的胰管
支架随机留置 7-10 天（n=46），或在术后立即移除（n=47），其中前者的 PEP
发病率明显偏低（4.3% vs 21.3%, P=0.027）。
[10] insitu：原位
古巴－特立尼达16古巴哈瓦那街景Other studies did not answer the main key question, but did address some of its aspects. In a studyby Madácsy et al., 22 patients with sphincter of Oddi dysfunction11 (SOD) and difficult cannulation,who underwent early prophylactic pancreatic duct stenting followed by fistulotomy, were comparedwith a retrospective cohort of 35 SOD patients where repeated standard cannulation (with a pull-type sphincterotome) was attempted. Fistulotomy with the pancreatic duct stent in situ was safer thanconventional pull-type biliary sphincterotomy (PEP rates, respectively, 0% vs. 43%; P&0.001). Similarfindings have been reported elsewhere though the results for patients undergoing pancreatic or minorpapilla sphincterotomy are conflicting. In terms of choice of stent, most authors reported using short3– 6-Fr devices with external pigtails or flanges. Stents without the internal flange tend to migratespontaneously after the procedure. A recent meta-analysis on pancreatic duct stenting to preventPEP in a mixed population of high risk patients reported that 5-Fr stents were superior to 3-Fr stents,and, given that PPDS is most likely to be used after unintentional pancreatic duct cannulation with astandard 0.035-inch guidewire, this seems to be an appropriate option. The stent should be left in thepancreatic duct for at least 12–24 hours to reduce the risk for PEP.[ 解读 ]：其他研究虽未对关键问题予以回答，但也解决了其中的一些方面。在一项研究中，Madácsy 等人为 22 例 Oddi 扩约肌功能紊乱（SOD）且插管困难的患者置入早期预防性胰管支架后对其行开窗术，并将其与另一项由 35 例接受反复标准插管（利用牵引式括约肌切开器）尝试的 SOD 患者所组成的回顾性队列进行对比。借助于原位胰管支架的开窗术较之常规的牵引式胆管括约肌切开术更具安全性（PEP 发病率分别为：0% vs 43%, P ＜ 0.001）。类似的发现还可见于其他研究，但从接受胰管或小乳头括约肌切开术的患者处得到的结果与其相矛盾。绝大多数术者所选用的是 3-6Fr 的猪尾或蘑菇头短支架。无卷边法兰的支架更易在术后出现自发性移位。近期的一项荟萃分析显示，较之 3-Fr 支架，5-Fr 支架可更为有效地预防高危患者的混合群体感染 PEP，鉴于在插管无意进入胰管后多会采用标准 0.035 英寸导丝进行 PPDS，故 5-Fr 支架似乎是一项合理的选择。支架应在胰管内留置至少 12-24 小时以降低 PEP 风险。[11] ysfunction：紊乱
本解读仅供各位同道学习交流，不作为临床实践的标准
17Medi-Trends
Transpancreatic5. biliary sphincterotomy
经胰胆管括约肌切开术ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreaticbiliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreaticduct occurs. However this technique should only be performed by experts (moderate quality evidence,strong recommendation).[ 解读 ]：ESGE 建议，对于因乳头较小导致插管困难的患者而言，如导丝意外进入胰管，则应对其行经胰胆管括约肌切开术，此术式应由经验丰富的医师操作（中等质量证据，强烈推荐）。 In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreaticstenting (moderate quality evidence, strong recommendation).[ 解读 ]：对于曾接受经胰管括约肌切开术的患者而言，ESGE 建议置入预防性胰腺支架（中等质量证据，强烈推荐）。Transpancreatic biliary sphincterotomy (TPBS) is a technique for cannulating the bile duct when usual methodsfail. It involves the placement of a standard “traction-type” papillotome12 on a guidewire previously inserted intothe main pancreatic duct. A sphincterotomy is performed in the direction of the bile duct at an 11–12-o’clockposition. The aim is to make an incision through the septum between the pancreatic and biliary duct and toexpose the bile duct orifice. After this, the sphincterotomy is extended to expose the biliary lumen and the biliaryduct can be cannulated. The biliary orifice can be found either at the apex of the incision, immediately left ofthe pancreatic orifice (in patients with a ‘common channel’) or at the starting point of the incision along the leftedge (in patients with separate pancreatic and biliary orifices). TPBS is a technique usually performed only byendoscopists experienced in ERCP.[ 解读 ]：经胰胆管括约肌切开术（TPBS）是常规方法失败后的胆管插管术式。该术式先将导丝探入主胰管，随后沿导丝置入标准的“牵引式”乳头切开器。沿胆管的 11-12 点方向行括约肌切开术。其目的是经胰管及胆管间隔膜建立一个切口并使胆管开口露出。随后进一步建立切口以露出胆囊腔以便胆管插管。胆管开口可见于胰管开口左侧的切口端点处（针对具有“共同通道”的患者），或在切口左侧的起点处（针对胰管及胆管开口分离的患者）。5.1 Success and adverse events following transpancreatic biliarysphincterotomy经胰胆管括约肌切开术的成功率及不良事件Summary of the evidence 证据总结Four RCTs involving a total of 364 patients haveinvestigated the outcome of TPBS. Only one was amulticenter study and this was published in abstractform. Table5 summarizes the results of these trialsand of the two prospective nonrandomized studiesexamining TPBS. In combination with the threelargest retrospective series (each &200 patients),these studies suggest that the rate of successfulbiliary cannulation following TPBS ranges from 85%to 100% (median 92.9 %), and the rate of adverseevents ranges from 3.5% to 20.5% (median 13.1 %),
德国 - 天鹅堡18ESGE 指南（第五章）with PEP occurring in 3.5% to 22.4% of cases (median 10.4 %). One of the two prospective studies showed thatin expert hands, success correlated to the speed of biliary access after TPBS.[ 解读 ]：四项 RCT（共纳入 364 例患者）对 TPBS 的疗效进行了考察。其中仅一项为多中心研究并以摘要的形式发布。表 5 总结了这些试验以及两项针对 TPBS 的前瞻性非随机研究的结果。结合三大回顾性病例分析（均大于 200 例），上述研究表明，TPBS 后胆管插管的成功率介于 3.5%-20.5%（中值为 13.1%），PEP 发病率介于 3.5%-22.4%（中值为10.4%）。其中一项前瞻性研究证实，对于专业医师而言，插管成功率与 TPBS 后进入胆管的速度相关。[12] papillotome：乳头切开器
圣保罗州热带雨林
19Table 5 Randomized controlled trials (RCTs) and prospective studies comparing transpancreatic biliary
sphincterotomy (TPBS) and other techniques in patients with difficult biliary cannulation.
比较 TPBS 与其他术式的 RCT 与前瞻性研究
5.2 When should transpancreatic biliary sphincterotomy be performed?
何时行经胰胆管括约肌切开术？
TPBS is a technique that should be reserved for patients with difficult biliary cannulation (see definition above)
where attempts at standard and DGW cannulation have failed. There are no data to guide endoscopists when
selecting between TPBS and precutting. In the presence of a small papilla, TPBS has a theoretical advantage
in that the depth and location of incision in relation to the CBD is more controlled than with needle-knife
sphincterotomy. Conversely, in the presence of a protuberant13 papilla with a visible intraduodenal CBD segment,
needle-knife sphincterotomy may be easier to perform safely. When TPBS is selected first and is unsuccessful,
a crossover to needle-knife sphincterotomy would appear reasonable. Finally, it should be noted that no studies
have compared the strategy of a second ERCP with TPBS in terms of safety and efficacy.
[ 解读 ]：TPBS 适用于胆管插管困难且标准插管及 DGW 插管均告失败的患者。尚无数据可在内镜医生选择预切术及
TPBS 时给予指导。理论上讲，如患者乳头较小，那么与针刀括约肌切开术相比，TPBS 的优势在于 CBD 切口的深度
及位置更易于控制。与之相反，如患者乳头突起且十二指肠内的 CBD 段可见，则针刀括约肌切开术或许更为安全。
当首先选择 TPBS 但并未成功时，较为合理的做法是换用针刀括约肌切开术。最后，应当指出的是，尚无研究对二次
ERCP 与 TPBS 的安全性及疗效进行比较。
5.3 Should pancreatic stenting be performed to prevent pancreatitis in patients
undergoing transpancreatic biliary sphincterotomy?
是否应当置入胰腺支架以预防接受经胰胆管括约肌切开术患者出现胰腺炎？
With regard to patients undergoing needle-knife sphincterotomy, no studies have been published addressing
this question. An ESGE Clinical Guideline strongly recommends the placement of a pancreatic stent after TPBS.
Some experts suggest use of a flanged pancreatic stent to avoid early migration of the stent following pancreatic
sphincter ablation.
[ 解读 ]：尚无研究能够为接受针刀括约肌切开术的患者回答这一问题。ESGE 临床指南强烈建议于 TPBS 后置入胰腺
支架。某些专家建议使用蘑菇头胰腺支架以预防胰腺括约肌消融术后支架的早期移位。
[13] protuberant：突起20古巴萨尔萨舞An evidence-based algorithm for biliary cannulation during ERCP in difficult cases is described in Fig.1.[ 解读 ]：ERCP 期间适用于胆管插管困难患者的循证医学系统见图 1。Fig.1 Evidence-based algorithm for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP).CBD, common bile duct. 适用于 ERCP、CBD 及胆总管插管的的循证医学系统结语：本期因篇幅所限，为诸位解读 4、5 两章，下期开始，将刊登本指南中有关胆系括约肌切
21开术、内镜下十二指肠乳头球囊扩张术、胰管括约肌切开术等内容，敬请期待。
本解读仅供各位同道学习交流，不作为临床实践的标准22食管癌内镜治疗的最新研究进展 导读：目前，已有多种内镜技术应用于食管肿瘤的诊断和治疗，本期《柳叶新潮》从 Gastrointestinal Endoscopy 与 Endoscopy 中精选出三篇食管癌内镜诊治的文章，希望能为各位读者提供有益资讯。 第一篇：采用 I-SCAN 放大内镜与醋酸染色进行系统评估可提高 Barrett 食管患者的异型增生检出率 第二篇：内镜黏膜下剥离术治疗早期 Barrett 肿瘤：一项荟萃分析 第三篇：内镜下分段根治术治疗 Barrett 食管早期肿瘤的长期随访结果 食管癌内镜下诊治专题第一篇Systematic Assessment with I-Scan Magnification Endoscopy andAcetic Acid Improves Dysplasia Detection in Patients with Barrett’sEsophagus采用 I-SCAN 放大内镜与醋酸染色进行系统评估可提高Barrett 食管患者的异型增生检出率Gideon Lipman, Raf Bisschops, Vinay Sehgal, Jacobo Ortiz-Fernández-Sordo, Rami Sweis, Jose M. Esteban, Rifat Hamoudi, Matthew R. Banks, Krish Ragunath,Laurence B. Lovat, Rehan J. HaidryLeadAuthor's Affiliation: 1.University College,London, United Kingdom 2.University College Hospital NHS Foundation Trust, London,United KingdomEndoscopy ):
DOI: 10.1055/s-
Background and Aims 背景和目的
Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in
patients undergoing assessment of Barrett’s esophagus (BE). This may reduce the need for random
biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification
endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE
using a novel mucosal and vascular classification system.
色素内镜增强成像可在患者接受 Barrett 食管（BE）评估时提高异型增生的识别率，从而在一定程度上
避免了为测得更多异型增生而采取随机活检。本次研究采用新型的粘膜与血管分类系统，旨在评估放
大内镜联合 I-SCAN（日本，东京，宾得）与醋酸染色（ACA）检测 BE 异型增生的效果。
Methods 方法
BE segments and suspicious lesions were recorded with high definition white-light and magnification
endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and
vascular classification system based on similar previously validated classifications for narrow-band
imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation,
a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to
detect dysplasia in a routine clinical scenario.
结合所有的 I-SCAN 模式，采用高分别率白光与增强放大内镜记录 BE 食管段与可疑病变。基于此前经
过验证的窄带成像（NBI）分类，研究人员得出了新型粘膜与血管分类系统，ACA 前后总对 27 段影像
进行分级。随后予以验证，另对额外 20 例患者的完整镜检影像进行记录及分析，以模拟该系统在常规
临床情境下检测异型增生的情况。
23Medi-Trends
Results 结果
The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN
magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20
new patients, accuracy of dysplasia detection increased from 76 % using a “pull-through” alone
to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver
agreement between experts for dysplasia detection was substantial (0.69).
I-SCAN 放大将 I-SCAN 分类系统检测 BE 异型增生的准确率由 ACA 后 69% 提升至 79%（P=0.01）。在
对日常临床情境下的 20 例患者进行模拟时，异型增生检测精度由 76%（仅采用 “ 拖出” ） 上升至 83%
（AVA 联合放大内镜）（P=0.047）。在异型增生检测方面，观察者内一致性良好。
Conclusions 结论
A new I-SCAN classification system for BE was validated against similar systems for NBI with similar
outcomes. When used in combination with magnification and ACA, the classification detected BE
dysplasia in clinical practice with good accuracy.
参照类似的 NBI 分类系统对新型 I-SCAN BE 分类系统进行验证，二者结果相近。ISCN 联合放大内镜
与 AVA 进行临床实践时，精度良好。
基特曼斯胡普石漠化箭袋树，纳米比亚24食管癌内镜治疗的最新研究进展 食管癌内镜下诊治专题第二篇Endoscopic Submucosal Dissection for Early Barrett’s Neoplasia:A Meta-Analysis内镜黏膜下剥离术治疗早期 Barrett 肿瘤：一项荟萃分析Dennis Yang, Fei Zou, Sican Xiong, Justin J. Forde, Yu Wang, Peter V. DraganovLead Author's Affiliation: University of Florida, Gainesville, Florida, USAGastrointestinal Endoscopy, October 6, 2017
Background and Aims 背景和目的
The role of endoscopic submucosal dissection (ESD) in Barrett’s esophagus (BE) is not well
established. This meta-analysis aimed to evaluate the safety and efficacy of ESD for the
management of early BE neoplasia.
内镜黏膜下剥离术（ESD）治疗 Barrett 食管（BE）的作用尚未明确。本次荟萃分析旨在评估 ESD 治
疗早期 BE 肿瘤的安全性和有效性。
Methods 方法
Three online databases were searched. The Cochran Q test and I2 were used to test for heterogeneity.
Pooling was conducted using either fixed- or random-effects models depending on heterogeneity
across studies. For the main outcomes, potential sources of heterogeneity were evaluated via linear
regression analysis.
研究人员检索了 3 个线上数据库，并采用 Cochran Q 和 I2 检验对异质性进行检验。根据异质性采用固定
或随机效应模型对整个研究进行汇总。采用线性回归分析评估潜在的异质性来源作为主要预后。
Results 结果
Eleven studies (501 patients, 524 lesions) were included. Mean lesion size was 27 mm (95%
confidence interval [CI], 20.9-33.1). Pooled estimate for en bloc resection was 92.9% (95% CI,
90.3%-95.2%). The pooled R0 (complete) and curative resection rates were 74.5% (95% CI, 66.3%-
81.9%) and 64.9% (95% CI, 55.7%-73.6%), respectively. There was no association between R0
or curative resection rates and study setting (Asia vs West), length of BE, lesion characteristics,
procedural time, or length of follow-up. The pooled estimates for perforation and bleeding were 1.5%
(95% CI, 0.4%-3.0%) and 1.7% (95% CI,0.6%-3.4%), respectively. Esophageal stricture rate was
11.6% (95% CI, 0.9%-29.6%). Incidence of recurrence after curative resection was 0.17% (95% CI,
0%-0.3%) at a mean follow-up 22.9 months (95% CI, 17.5-28.3).
本次荟萃分析纳入了 11 项研究（501 例患者，524 处病灶）。平均病灶尺寸为 27mm（置信区间 [CI]
95%，20.9-33.1）。整块切除的估计值为 92.9%（95%CI，90.3%-95.2%）。总的 R0（完全）和根治性切
除率分别为 74.5%（95%CI，66.3%-81.9%）和 64.9%（95%CI，55.7%-73.6%）。R0 或根治性切除率与
研究的地点（亚洲 vs 西方）、BE 的长度、病灶特征、手术时间以及随访时间的长度无关。穿孔和出
血的估计值分别为 1.5% （95%CI，0.4%-3.0%）和 1.7%（95%CI，0.6%-3.4%）。食管狭窄率为 11.6%
（95%CI，0.9%-29.6%）。平均 22.9 个月的随访后，根治性切除后患者复发的发病率为 0.17%（95%CI，
0%-0.3%）。
25Medi-Trends
Conclusions 结论
ESD for early BE neoplasia is associated with a high en bloc resection rate, acceptable safety
profile, and low recurrence after curative resection. ESD should be considered as part of the
armamentarium for the management of BE neoplasia.
ESD 治疗早期 BE 肿瘤与整块切除率高、安全性在可接受范围内以及根治性切除后复发率低相关。应把
ESD 视为 BE 肿瘤的医疗设备管理的一部分。
食管癌内镜下诊治专题第三篇
Long-Term Follow-up Results of Stepwise Radical Endoscopic
Resection for Barrett’s Esophagus with Early Neoplasia
内镜下分段根治术治疗 Barrett 食管早期肿瘤的长期随访结果
Kamar Belghazi, Frederike G.I. van Vilsteren, Bas L.A.M. Weusten, Sybren L. Meijer, Jacques J.G.H.M. Bergman, Roos E. Pouw
Lead Author's Affiliation: Academic Medical Center, Amsterdam, the Netherlands
Gastrointestinal Endoscopy April 25, 2017
Introduction 引言
Stepwise radical endoscopic resection (SRER) allows for complete endoscopic resection of Barrett’s
esophagus (BE) with early neoplasia. This approach has been shown very effective in reaching
complete eradication of high-grade dysplasia (HGD) or early cancer (EC) (CE-neo) in 98% and all
intestinal metaplasia (CE-IM) in 85% of patients. Aim of this study was to report the long-term follow-
up (FU) results after successful SRER for BE with early neoplasia.
内镜下分段根治术（SRER）可在内镜下实现对于 Barrett 食管（BE）的完全切除。经证实，该术式可
有效根治 98% 的高级别异型增生（HGD）或早癌（EC）（CE 新生）以及 85% 的皮化生（CE-IM）。本
次研究的目的是评估 SRER 成功治疗 Barrett 食管早期肿瘤后的长期随访结果。
Methods 方法
We screened all patients treated with SRER in two centers between , for BE ≤5cm with
HGD/EC, without signs of invasion &T1sm1, G3/G4 differentiation, lymph-vascular invasion or
irradical deep resection margins in ER specimens. All patients who had reached endoscopic and
histologically confirmed CE-neo and CE-IM after SRER were included for evaluation of long-term
FU. All information from FU endoscopies and histological outcomes were collected and entered in
a dedicated database. Duration of FU was calculated from last treatment till last FU endoscopy.
Primary outcome: recurrence of HGD/EC and recurrence of IM combined with visible BE islands or
tongues. Secondary outcome: Buried Barrett’s (BB) in neosquamous biopsies, and IM in biopsies
obtained distal to the neo-z-line.
本次研究对 2001 至 2014 年间在两个医疗中心接受 SRER 治疗的患者进行了筛查：BE ≤ 5cm 并伴有
HGD/EC、无 T1sm1 以上侵犯迹象、G3/G4 分化、未在 ER 标本中发现淋巴管浸润或非根治术后深切缘。
所有经内镜或组织学检查证实为 CE 新生及 CE-IM 的患者在 SRER 后均接受长期 FU 评估。收集 FU 内
镜及组织学检查结果并将其记录于专用的数据库。最后一次治疗开始至最后一次 FU 内镜检查结束为
FU 持续时间。主要结局指标：HGD/EC 的复发，IM 复发并伴有可见的岛状及舌型 BE。次要结局指标：
新生鳞状上皮细胞活检中的 Buried Barrett，以及新生 z 线远端活检中的 IM。26食管癌内镜治疗的最新研究进展Results 结果Seventy-three patients were included (64 men, mean age 66 yrs, median BE C2M3). Worst baselinepathology: HGD, n=50; EC, n=23. Median FU was 76 mo (IQR 55-102) with a median of 6 (IQR 4-8)endoscopies. Recurrence of HGD/EC was observed in 1 patient (1.4%) after 129 mo FU (T1bN0M0treated with curative surgery). Recurrence of IM in endoscopically visible BE was observed in22% of patients (n=16, of which 2 had LGD) after a median FU of 31 mo. In all cases the extent ofrecurrence was limited to small (&1 cm) islands/tongues. Histological recurrence without visibleBE was found in 25 patients: 3 patients had BB in neosquamous biopsies (4% overall, 0.7% perpatient year); 24 patients (33%) showed IM in biopsies just distal to a normal appearing neo-z-line.A finding of IM of the neo-Z-line was reproduced in 50% of patients and BB in none of the patients.Additional treatment was performed in 8 patients: esophagectomy for T1b-cancer, ER of small islandwith LGD (n=1), APC for small islands (n=5), RFA for LGD in the neo-z-line (n=1). CE-neo and CE-IM (excluding IM in the neo-z-line) at the last FU endoscopy (after additional treatment) was seen in100% and 96% respectively.本次研究共纳入 73 例患者，（其中男性患者 64 例，平均年龄为 66 岁，BE 平均分型为 C2M3。）最差的基线病理为：HGD，n=50；EC，n=23。平均由 6 名（IQR 4-8）内镜医师进行随访，平均 FU 时长为 76个月（IQR 55-102）。一例患者在 129 个月的随访后出现 HGD/EC 复发（采用治愈性手术治疗 T1bN0M0期肿瘤）。在平均 31 个月的 FU 后，22% 的患者（n=16，其中两例出现 LGD）在内镜下可见 BE 处出现IM 复发，且复发范围均局限于小型（＜1cm）岛型或舌型 BE。25 例患者发生组织学复发但未出现可见BE：其中 3 例患者的新生鳞状上皮细胞活检中可见 BB（整体占比 4%，每年每例患者为 0.7%）；24 例（33%）患者仅在正常的新生 z 线远端的活检中可见 IM。新生 z 线的 IM 在 50% 的患者中复发，患者均未见 BB。8 例患者接受额外治疗：T1b 癌症患者接受食管切除术，伴有 LGD 的小型岛型 BE 患者接受 ER（n=1），小岛型 BE 患者接受 APC（n=5） , 新生 z 线处存在 LGD 的患者接受 RFA（n=1）。分别有 100% 及 96% 的患者在最后一次 FU 内镜检查时（额外治疗后）可见 CE-neo 生及 CE-IM（新生 z 线处的 IM 除外）。Conclusions 结论The 6-year follow-up results of this study show that after successful SRER of BE ≤5cm recurrenceof HGD/cancer is rare (1% overall, 0.2% per patient year). Recurrence of endoscopically visible BEwith IM or LGD was found in 22% of patients and was generally confined to small islands or tongues.Buried glands were rare (0.7% per patient year) and just as IM of the neo-z-line (33% of cases) ofinsignificant importance.本次研究的 6 年随访结果显示，在对≤ 5cm 的 BE 行 SRER 成功后，HGD/ 癌的复发较为罕见（整体占比 1%，每年每例患者为 0.2%）22% 的患者内镜下可见 BE 复发且伴有 IM 和 LGD，且大部分局限于小型岛型或舌型 BE。Buried 腺体较为罕见（每年每位患者 0.7%），与新生 z 线 IM（33% 的病例）同样无意义。安通吉尔湾—马达加斯加东部
27世界顶级期刊精选之胰腺疾病最新研究导读：众所周知，NEJM（新英格兰医学杂志）、The Lancet（柳叶刀）、JAMA（美国医学期刊）、The BMJ（英国医学期刊）这四本综合性医学周刊被誉为医学领域的“世界顶级四大期刊”。本期《柳叶新潮》从世界四大顶级医学期刊中的《英国医学期刊》（IF: 20.785）及《柳叶刀》（IF: 47.831）中精选了两篇胰腺疾病的相关研究，内容涉及胰腺囊肿发病率、患病率及 5 年胰腺相关死亡率的前瞻性人群研究，以及治疗慢性胰腺炎两种不同技术的对比。在此，小编对两篇研究的精彩之处进行了整理编译，希望为您的执业发展带去新思路。 28第一篇文章首先，第一篇来自《英国医学期刊》（BMJ）的文章，该研究基于人群，对胰腺囊肿发病率、患病率及 5 年胰腺相关死亡率进行了研究。胰腺囊性病变多被偶然发现，然而，相关的纵向研究很少。粘液型囊性病变有巨大的恶变风险。目前的共识指南从未基于人群对胰腺囊性病变的治疗方式进行评估。随着技术的发展，小型囊肿的检出率越来越高，但不同检查方法之间存在差异。为避免影像学随访检查及手术切除等不必要的流程，辨别良性、癌前或恶性胰腺囊肿对患者至关重要。本文旨在纵向分析偶然发现的胰腺囊肿患病率、发病率及临床意义。《柳叶新潮》编辑部对文章进行了详细的翻译，让我们先看一下文章的介绍。Cystic lesions of the pancreas are closed cavities containing liquid or semisolid material, which can eitherbe neoplastic or non-neoplastic. Among the neoplastic cysts accounting for 10%–15% of all pancreaticcystic lesions, the serous type is seen as benign, whereas the mucinous form tends to have malignantpotential. Reports indicate that common cystic tumours with a mucinous epithelial lining can harbourcarcinoma in situ or invasive cancer in up to 60% of resected specimen depending on the size of thelesion, clinical symptoms caused by the lesion as well as signs of malignancy on imaging. However, therate of malignancy is variable and precise risk assessment can only be given for an individual patientand should be based on current guideline recommendations. Most common are intraductal papillarymucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN) and serous cystic neoplasms, whilesolid pseudopapillary neoplasms are a rarity. Together these four types represent 90% of premalignantpancreatic primarily cystic tumours. In contrast, non-neoplastic cysts, which constitute the majority of cysts,are mostly of inflammatory or dysontogenetic origin.胰腺囊性病变是充满液体或半固体物质的封闭腔，既可为肿瘤性也可为非肿瘤性。肿瘤性囊肿占胰腺囊性病变的 10%-15%，其中浆液性看似为良性，但粘液形式具有恶性潜能。报告显示，根据病变大小、病变引起的临床症状及影像学显示的恶性迹象，高达 60% 的切除标本中，普通上皮膜为粘液型的囊性肿瘤中可含原位癌或侵袭癌。然而，恶性率不尽相同，并且仅能为个体患者进行精确的风险评估，且应基于现有指南中的建议做出。最常见的是胰腺导管内乳头状黏液肿瘤（IPMN），黏液性囊性肿瘤（MCN）以及浆液性囊腺瘤，而胰腺实性假乳突状瘤较为罕见。上述四种类型的病变占癌前原发性胰腺囊性肿瘤的 90%。相比之下，囊肿中的大多数为非肿瘤性，非肿瘤性囊肿大多数由炎症或发育不良引起的。Pancreatic cysts represent a small yet increasingly detected entity of pancreatic abnormalities.Approximately 70% of pancreatic cystic lesions are discovered incidentally.A variety of diagnostic methods to detect cystic lesions and to clarify their nature, such as MRI withsupplementary cholangiopancreaticography (MRCP), CT or endoscopic ultrasound (EUS) in combinationwith fine needle aspiration, exist. MRI is the preferred non-invasive imaging modality for assessingpancreatic pathologies because of its high soft tissue contrast. In addition, strong T2-weighted MRIlike MRCP allows an improved detection of cystic lesions including septa, mural nodules and ductalcommunication. Overall, discrimination between different cyst types tends to be difficult, with an accuracyof cross-sectional imaging of 39.5%–46%. Final diagnosis can often only be made on the basis of follow-upexaminations, histopathological processing after biopsy or postresection.胰腺囊肿是一种小型但检出率越来越高的胰腺病变。大约 70% 的胰腺囊性病变为偶然检出。为澄清囊性病变的性质，往往通过多种方法进行检查，例如磁共振胰胆管成像（MRCP）、CT 或内镜超声联合细针穿刺活检术。由于软组织对比度高，MRI 是评估胰腺病理首选的无创影像学方法。此外，T2 强加权 MRI，例如 MRCP，可提高隔膜、附壁结节及胰胆管合流等囊性病变的检出率。总体而言，区分不同的囊肿类型具有一定的困难，横断面成像检查的精确度为 39.5%-46%。最终诊断通常仅能基于随访检查、活检或切除后的组织病理学处理得出。The prevalence of pancreatic cysts varies extremely with the mode of imaging used and among differentstudies. In an ultrasound study pancreatic cysts were only detected in 0.21% of the subjects. On CT scan,pancreatic cysts were found in 2.6%, whereas their prevalence detected by thick-slice MRI ranges from13.5% to 19.6%. Autopsy studies, on the other hand, revealed a much higher number of pancreatic cystsup to 50% in an elderly population.使用不同的影像学检查方法检出的胰腺囊肿患病率大不相同，而且各个研究也存在巨大差异。在一项超声研究中，仅在 0.21% 的受试者中检出胰腺囊肿，使用 CT 扫描则检出 2.6%，而使用厚层 MRI 得到的患病率为13.5%-19.6%。另一方面，尸检研究发现老年人群的胰腺囊肿患病率更高，达 50%。
29Medi-Trends
Although in most cases pancreatic cysts are asymptomatic, their presence is a known independent
predictor of pancreatic cancer. The discrimination between benign and premalignant or malignant
pancreatic cysts proves to be of high importance for patients in order to avoid unnecessary procedures,
such as radiological follow-up examinations or surgical resection. In this context, longitudinal studies
are essential to improve diagnostic techniques for early diagnosis and to establish evidence-based
management algorithms and understanding the clinical relevance of incidentally detected cystic pancreatic
lesions. Therefore, the purpose of this study was to assess the prevalence of incidentally detected
pancreatic cysts in the healthy population in contrast to previous studies on patients, and to investigate
their incidence and clinical outcome by assessing pancreatic mortality risk in a prospective longitudinal
尽管大多数胰腺囊肿病例为无症状性，但胰腺囊肿仍是胰腺癌的一个独立预测因子。为避免影像学随访检查及
手术切除等不必要的流程，辨别良性、癌前或恶性胰腺囊肿对患者至关重要。本文中，纵向研究对改进早期诊
断技术、建立循证管理系统以及理解检出的偶然发现的囊性胰腺病变的临床相关性具有重要意义。因此，本次
研究的目的在于评估健康人群偶然发现的胰腺囊肿的患病率，并与先前的患者研究进行对比，同时，通过前瞻
性纵向评估胰腺死亡风险以调查胰腺囊肿的发病率和临床预后。
本 文 从 基 于 人 群 的 Pomerania 健 康 研 究（SHIP） 中 选 出 2,333 例 参 与 者， 共 有 1,077 例（521 名 男 性，
中 位 年 龄 55.8±12.8 岁） 在 基 线 状 态 下 接 受 了 磁 共 振 胰 胆 管 造 影（MRCP）（）。 对 MRCP
结果进行分析以找出直径≥ 2mm 的胰腺囊肿。676/1077 例受试者接受了为期 5 年的随访（）。
结合年龄、性别及疑似流行病学风险因素评估胰腺囊肿的患病率与发病率（研究参与加权），并于 2015 年对
全体 SHIP 参与者进行死亡率随访（中位随访期为 5.9 年，范围 3.2-7.5 年）。在此，我们对研究的材料和
方法进行了详细的翻译，参见下文。
Subjects were recruited from the Study of Health in Pomerania (SHIP). SHIP is a prospective, population-
based cohort study in Northeast Germany with the objective to rate the prevalence and incidence of
diseases, as well as to analyse associations between risk factors, subclinical disorders and manifest
affliction. The baseline cohort SHIP-0, conducted between 1997 and 2001, comprised a representative
sample of 4310 participants from a total population of 212 157 inhabitants. All participants from SHIP-
0 were invited to a 5-year follow-up (SHIP-1) between 2002 and 2006. The underlying data of this study
were derived from SHIP-2 (examination period ), when whole-body MRI including MRCP was
first offered as part of the investigational protocol. SHIP-2 is the 10-year follow-up of the SHIP cohort, in
which 2333 of the initial 4310 subjects agreed to participate. From the SHIP-2 cohort, MRI and MRCP were
accepted upon informed consent by 1275 subjects (response rate 54.7%). Analysis could be performed on
1077 subjects. In 165 cases MRI examination was prematurely terminated by the probands. Twenty-seven
subjects had to be excluded because of missing data sets or correlation factors. In six participants MR
images were of non-diagnostic quality. An overview of the study design is presented as flow chart in figure 1.
受试者均来自 Pomerania 健康研究（SHIP）。SHIP 是德国东北部一个前瞻性、基于人群的队列研究，其目的
是评估疾病的患病率和发病率，并分析风险因素、亚临床症状和明显痛苦之间的关系。基线队列为 SHIP-0，
于 1997 年至 2001 年间进行，由 212,157 名居民中 4,310 名参与者组成代表性样本。2002 年至 2006 年间，对
SHIP-0 中的所有参与者进行了为期 5 年的随访（SHIP-1），本次研究的源数据来自于 SHIP-2（检查时间 2008
年 -2012 年）, 并首次提出将包括 MRCP 在内的全身 MRI 作为研究方案的一部分。SHIP-2 队列中，对 1,275 名
知情同意的受试者行 MRI 和 MRCP（响应率 54.7%）。计划对 1，077 名受试者进行分析。但 165 名参与者提
前提出终止 MRI 检查。27 名受试者因缺少数据或相关因素被排除在外。6 名参与者的 MR 影像诊断质量不高。
研究设计的整体流程图见图 1.
The 5-year follow-up SHIP-3 started in 2014 and finished in March 2016. Out of 2333 possible participants
from SHIP-2, 1718 subjects consented on a follow-up examination. From the 1077 subjects with previous
MRI and MRCP, 686 agreed on follow-up examination (response rate 63.7%, mean follow-up period 4.8
years, range 2.7–7.5 years). From those, final analysis was performed on 676 10 participants
were excluded because of missing data sets.
5 年随访 SHIP-3 从 2014 年开始，2016 年 3 月结束。SHIP-2 中 2,333 名合适参与者中的 1,718 名受试者同意进行
随访检查。先前接受过 MRI 或 MRCP 的 1,077 名受试者中，688 名同意接受随访检查（响应率 63.7%，平均随
访时间为 4.8 年，范围 2.7-7.5 年）。这些人群中，最终有 676 名志愿者参与了最终研究；因 10 名参与者缺乏数据，
将其排除在外。30世界顶级期刊精读Figure 1 Study flow chart. MRCP, magnetic resonance cholan SHIP, Study of Health in P WB-MR, whole-body magnetic resonance imaging.SHIP was approved by the institutional review board and written informed consent was secured from eachparticipant. In addition, the associated project ‘Incidental Pancreatic Cysts in General Population’ wasapproved by the SHIP scientific advisory board (SHIP2012/69/D).SHIP 经机构审查委员会批准，而且每位参与者都签署了知情同意书。此外，相关项目“普通人群中的偶然发现的胰腺囊肿”获得了 SHIP 科学顾问委员会批准（SHIP2012/69/D）。Information on vital status of the whole SHIP cohort was collected at regular intervals from the time of studyenrolment until 31 December 2015, and participants were censored at death or loss to follow-up. The localhealth authority provided death certificates, which were then coded by a certified nosologist according tothe 10th revision of the International Classification of Disease. For the conducted substudy on pancreaticcysts, collected data were searched for the codes C25.0–9 (cancer of the pancreas) and K86.0–9 (otherdiseases of the pancreas). A mortality follow-up of all enclosed participants of SHIP was performed on 31December 2015, including all volunteers recruited for MRI and MRCP (mean mortality follow-up period 5.9years, range 3.2–7.5 years).自研究纳入至 2015 年 12 月期间，定期收集整个 SHIP 的生命体征信息，剔除死亡或失访的受试者。当地卫生管理当局提供死亡证明，并根据国际疾病分类（ICD-10）进行编码。胰腺囊肿的亚组研究对搜集的数据进行了编码为 C25.0–9（胰腺癌）和 K86.0–9（其他胰腺疾病）的检索。SHIP 参与者的死亡率随访于 2015 年 12 月开始，参与者包括被纳入 MRI 和 MRCP 检查的所有志愿者（平均死亡率随访时间 5.9 年，范围 3.2-7.5 年）。Whole-body MRI was performed using a 1.5 Tesla MagnetomAvanto (Siemens Healthcare, Erlangen,Germany) with a 280mT/m gradient. The protocol has previously been described by Hegenscheid et al andincluded a navigator-gated, strong T2-weighted, three-dimensional, turbo, spin-echo MRCP. The MRCPwas acquired in a thin-slice technique and the postprocessing included an automated maximum-intensityprojection reconstruction in coronal orientation. The following were the imaging parameters for MRCP: TR(resonance time) = ~900 ms (adapted to navigator-triggered data), TE (echo time)=742 ms, bandwidth:260 Hz/pixel, matrix: 384×384×44, slicethickness = 1.5 mm.全身 MRI 使用 1.5 特斯拉磁共振系统（Siemens Healthcare, Erlangen, Germany），梯度磁场强度为 280mT/m。参与者此前接受了 Hegenscheid 等人的检查，检查内容为导航门控、T2 强加权、三维、快速自旋回波 MRCP。MRCP 需使用薄层技术，后续包括冠状缝定位中的自动最大信号强度投影重建技术。以下是 MRCP 影像参数：TR（重复时间）= ~900ms，TE（回波时间）=742ms，带宽：260Hz/pixel，矩阵：384×384×44，层厚=1.5mm。
31Medi-Trends
Image analysis was performed using OsiriX V.4.6 (Bernex, Switzerland). One certified observer with
1 year of experience in abdominal radiology scrutinised the images of each participant for pancreatic
cysts. For this purpose, the pancreatic duct was localised and strong T2-weighted hyperintense lesions
with a diameter of 2 mm or more within the pancreas were assessed. In addition, observer 1 and a
second observer with more than12 years of experience in abdominal radiology re-evaluated a convenient
sample of 72 MRI examinations to determine the interobserver and intraobserver reliability, accordingly.
Remeasurements by observer 1 were undertaken after a period of 6 months.
使用 OsiriX V.4.6（Bernex, Switzerland）进行影像分析。一位具有一年腹部影像学影像阅片经验的认证观察
员对每位参与者的影像进行检查，以发现胰腺囊肿。为此，对胰管进行定位，并对呈 T2 强加权像高信号的
≥ 2mm 的胰腺病变进行评估。此外，该观察员与另一名有超过 12 年腹部影像研究经验的观察员对 72 例 MRI
检查结果进行再次评估，以确定观察者内及观察者间的可靠性。第一名观察员在六个月后进行再次评估。
For data analysis, cysts were categorised according to their number and diameter of the largest cyst during
baseline and 5-year follow-up examination.
数据分析方面，根据基线和 5 年随访检查期间的囊肿数量及最大直径，对囊肿进行分类。
All participants of the SHIP cohort answered standardised questions about their health status and lifestyle
factors. Furthermore, blood samples were taken and analysed according to a preset protocol. From these
data, information on body mass index (BMI), smoking status, serum lipase level, haemoglobin A1c (HbA1c),
diabetes and alcohol consumption during the last 30 days of all participants were retrieved and used for
correlation analysis.
SHIP 队列中的所有参与者均对其健康状况和生活方式等标准化问题进行了回答。此外，依据预设方案进行血
样采集和分析。从这些数据中得出所有参与者身高体重指数（BMI）、吸烟状况、血清酶水平、血红蛋白 A1c
（HbA1c）、糖尿病及过去三十天的酒精摄入，并用于相关性分析。
These variables were selected, as they in our opinion constitute an influence on pancreatic diseases.
Dependency of pancreatic cyst prevalence on gender was analysed, as the prevalence for specific cystic
lesions of the pancreas, such as MCN, serous cyst adenomas or solid papillary neoplasia, is more prone in
women, while IPMNs are equally distributed between gender. BMI, HbA1c and diabetes were investigated
as metabolic syndrome might predispose to an attack of acute pancreatitis with residual cysts. Subclinical
increase of lipase level is associated with blood group B, which also predisposes to chronic pancreatitis.
Furthermore, smoking and alcohol are risk factors of chronic pancreatitis frequently associated with cyst
occurrence.
选择上述变量的原因是，研究人员认为其可能对胰腺疾病产生影响。分析胰腺囊肿患病率对性别的依赖性，发
现浆液性囊性腺瘤或实性乳头状瘤多发于女性患者，而 IPMN 的患病情况无性别差异。鉴于代谢症候群可能诱
发残余囊肿引起急性胰腺炎，于是对参与者的 BMI、HbA1c 及糖尿病进行了调查。亚临床脂肪酶上升与 B 型
血有关，同时也可能诱发慢性胰腺炎。此外，吸烟和饮酒是囊肿相关慢性胰腺炎的风险因素。
To evaluate the quality of our data, interobserver and intraobserver reliability was calculated by using
kappa statistics. Hereby, a value below 0.20 defines disagreement, 0.20–0.40 poor agreement, 0.41–0.60
moderate agreement, 0.61–0.80 good agreement and over 0.80 excellent agreement.
为评估数据质量，使用 kappa 统计来计算观察者内及观察者间的可靠性。在此，数值低于 0.20 为不一致，0.20-0.40
一致性较差，0.41-0.60 一致性中等，0.61-0.80 与 &0.80 为一致性优秀。32世界顶级期刊精读
芬兰 - 北博滕区All analyses were weighted for the whole study population in SHIP at baseline. For this we used two inverseprobability weights multiplicatively. The first weight describes the dropout from baseline SHIP to SHIP-2,and the second weight describes the dropout from the core examinations to the MRI examinations in SHIP-2. To calculate these weights we used the predictions from logistic regression models with participation (yes/no) as outcome, and age, sex, BMI, HbA1c levels, diabetes, lipid levels, smoking status and income asexplanatory variables.对 SHIP 中整个基线研究人群的所有分析加以权衡。为此，研究人员将两种逆概率权重相乘。第一个权重是从基线 SHIP 到 SHIP-2 时的退出者，第二个权重为核心检查到 SHIP-2 中 MRI 检查时的退出者。研究人员使用概率模型中预测量来计算这些权重，其中，参与（是 / 否）为结果，年龄、性别、BMI、HbA1c 水平、糖尿病、血脂水平、吸烟状况及收入为解释变量。First we present descriptive statistics of the sample by the presence of cystic lesions. Data are describedas absolute numbers and percentages or as means and SD. The total number of pancreatic cysts in oneperson was counted and assigned into the following groups: 1–5, 6–10, 11–20 and &20. Furthermore, thediameter of the largest cyst in one subject, ranging from 2.00 to 5.00 mm, 5.01–10.00 mm, 10.01–20.00 mmand &20 mm, was assessed.首先，研究人员按照存在的囊性病变来进行样本的描述性统计。数据形式为绝对数量、百分比或平均数及SD。计算个体携带胰腺囊肿总数量并分为以下几组：1-5、6-10、11-20 以及 &20。此外，还对单个受试者携带最大囊肿的直径进行了评估，范围为 2.00-5.00mm、5.01-10.00mm、10.01-20.00mm 以及 &20mm。Prevalence of cyst occurrence, cyst number and cyst size were reported stratified by sex and the agegroups &30, 30–39, 40–49, 50–59, 60–69, 70–79 and ≥80 years. Comparisons between the groupswere calculated using Χ2 test and Wilcoxon test. The associations between putative risk factors and cystoccurrence, number and size were assessed using age-adjusted and BMI-adjusted multivariable Poissonand linear regression models. Furthermore, we examined changes in the size and number of cyst size. Anincrease was defined as a rise in cyst size of at least 1 mm or in number of one additional cyst. Decreasewas set as decline in cyst size of more than 1 mm or of one cyst less in number. Age and sex wereassociated with incident cyst occurrence by Poisson regression. In all analyses a p&0.05 was consideredas statistically significant. All analyses were carried out by Stata V.14.2.按照性别和年龄 &30 岁、30-39 岁、40-49 岁、50-59 岁、60-69 岁、70-79 岁、及≥ 80 岁分层，对胰腺囊肿患病率、囊肿数量及囊肿大小进行报告。使用 Χ2 和 Wilcoxon 检验，进行组间对比。使用年龄调整和 BMI 调整多变量的泊松及线性回归模型，评估既定风险因素和囊肿的出现、囊肿数量和大小之间的关联。此外，研究人员对囊肿大小及相应尺寸下囊肿的数量变化进行了检查。囊肿增大≥ 1mm 或新增一个囊肿视为增加；囊肿缩小&1mm 或减少一个则视为减少。泊松回归显示，年龄和性别与囊肿易发有关。所有 p&0.05 的研究均有统计学意义。所有分析均使用 Stata V.14.2 进行。
33Medi-Trends
研究人员从研究人群、死亡率随访、MRI、影像分析、临床相关性及统计学六个方面对方法进行了详细地介绍，
下面让我们一同领略本文的研究结果。
MR images of 1077 subjects who received an MRCP examination were examined at baseline. Six
hundred and seventy-six subjects received a 5-year follow-up. Gender distribution of included subjects
in SHIP-2 was as follows: 521 men (48.4%) and 556 women (51.6%) with a mean age ± SD of 55.8 ±
12.8 years. Participants of the pancreatic substudy included in SHIP-3 encompassed 325 men and 351
women (figure 1).
对接受过 MRCP 检查的 1,077 名受试者的基线 MR 影像进行了审查。676 名受试者接受 5 年随访。SHIP-2 纳入
的受试者的性别分布如下：521 名男性（48.4%），556 名女性（51.6%），平均年龄 ±SD 为 55.8±12.8 岁。
SHIP-3 纳入的胰腺亚组研究参与者中有 325 名男性及 351 名女性（图 1）。
The interobserver agreement with regard to the presence of pancreatic cysts was excellent with kappa =
0.9305 (SE 0.0832). Concerning the quantity and size of pancreatic cysts (&2 mm), the mean difference ±
SD between both observers was found to be 0.04 (-1.66; 1.73) and -0.18 (-2.16; 1.81), respectively.
当 kappa=0.9305（SE 0.0832）时，在胰腺囊肿发病方面，观察者间一致性好。就胰腺囊肿的数量和大小（&2mm）
而言，两位观察者间的平均差 ±SD 分别为 0.04（-1.66；1.73）和- 0.18（-2.16；1.81）。
The intraobserver variability exhibited an excellent agreement of kappa = 0.9442 (SE 0.0833) for the
presence of cysts and a mean difference in cyst number of -0.01 (-1.24; 1.23) or size of -0.27 (-2.06; 1.55).
观察者间变异性显示，在囊肿检出方面，一致性好，kappa=0.9442 (SE 0.0833)，囊肿数量和囊肿大小平均差分
别为 0.01（-1.24；1.23）和 -0.27（-2.06；1.55）。
Among the 1077 probands screened at baseline examination, a total of 1681 cysts &2 mm were detected in
494 subjects. Characteristics of the study population overall and of the subgroups with/without pancreatic
cysts at baseline are presented in table 1.Subjects with cystic lesions appeared to be older and presented
with higher BMI and diagnosis of diabetes than those without.
1,077 名接受基线检查筛查的受试者中，于 494 名受试者体内检出 1,681 个 &2mm 的囊肿。表 1 描述了研究人群
的总体特征及有（无）胰腺囊肿亚组的基线特征。携带囊性病变的受试者与未携带的受试者相比，年龄偏大，
BMI 高并被检出糖尿病。
Figure 1 Study flow chart. MRCP, magnetic re}