胰腺切除术后乳糜瘘

cqk360 2020-07-12

展开全文

乳糜漏和乳糜性腹水是一种腹部手术后并发症，由于发生率不高大家常有认识误区。最近我们在一本专著上发现相关章节，专门讨论了这一问题，现编译出来和大家共享。因为涉及知识产权的原因。不便通篇翻译发布。如果大家需要可以关注公众号留言个别交流（公众号：wcwk2016）。此间得到好友我国著名普外科专家东南大学李俊生教授指导，在此表示感谢！

Management of Chyle Leaks Following Pancreatic Resection

胰腺切除后乳糜漏的治疗

编译：清远市第二人民医院普外科刘为民

审校：东南大学附属大中医院李俊生教授

Introduction

Significant morbidity following pancreatic resection is common with reported rates of overall complications ranging between 40 and 60 %. The most common complications following pancreatectomy include postoperative pancreatic fistula and wound infection. In addition, delayed gastric emptying occurs in up to 25 % of patients undergoing pancreaticoduodenectomy. These complications impede recovery,prolong hospitalization, and increase the risk of readmission [1]—but are seldom life-threatening. In contrast, some of the less frequent complications are associated with a greater risk of mortality. This is the case for certain forms of postoperative chyle leak in which the accompanying malnutrition and immunosuppression significantly reduce the rate of long-term survival. This chapter focuses on the management of a chyle leak following pancreatic resection and includes a discussion of the general physiology and anatomy of the abdominal lymphatic system as it relates to pancreatic surgery, the composition of chyle, a review of the literature that specifically studies chyle leak following pancreatic resection, and an algorithm for the management of chyle leak following pancreatectomy.

引言

胰腺切除术后常常发生严重并发症，据报道整体并发症发生率为40%-60%。最常见并发症包括：术后胰瘘和伤口感染。另外，胃排空延迟在胰十二指肠切除术后高达25%。这些并发症阻碍了恢复、延长了住院时间并增加了再住院率^[1]-但是这些并发症很少危及生命。相对而言，一些少见并发症具有较高的死亡风险性。一些特定形式手术后胰瘘就是如此，这种伴发营养不良和免疫低下的并发症可以明显降低患者长期生存率^[2]。本章主要关注胰腺切除手术后乳糜漏的治疗，包括讨论与胰腺手术相关的基本生理和解剖内容、乳糜的成分、胰腺切除后乳糜漏相关文献的回顾和胰腺手术后乳糜漏治疗程序。

Background

Chyle leak is not unique to pancreatic resection and is also observed in other operations in which an extensive retroperitoneal dissection is performed. The operations in which chyle leak is commonly reported include abdominal aortic aneurysm repair, resection of large retroperitoneal tumors, extensive retroperitoneal lymph node dissection, and liver transplantation [3–6].The rate of chyle leak following pancreatectomy varies greatly.For example, the largest series on this topic reported a rate of 1.3 % in a cohort of 3532 patients undergoing pancreatic resection. At the other end of the reported range, Hilal et al. [7] published a 16.3 % rate of chyle leak in 245 patients undergoing pancreatectomy. The variation in published rates may result from differences in surgical technique, such as the extent of retroperitoneal dissection, and with differences in management, such as early postoperative initiation of enteral feeding. Several factors appear to be related to postoperative chyle leakage following pancreatectomy. These include factors resulting in a more extensive or difficult dissection such as peripancreatic fibrosis from pancreatitis or neoadjuvant radiation, major vascular resection and reconstruction [2], and early enteral feeding.

背景

乳糜漏不仅发生在胰腺手术后，同时也可以发生在腹膜后接受广泛游离其它手术后。经常并发乳糜漏的手术包括：腹主动脉瘤修补手术、腹膜后肿瘤切除、广泛的腹膜后淋巴结清扫术和肝脏移植手术^[3–6]。胰腺切除手术后胰漏的发生率存在很大差异^{[2, 6–13]}。比如，最大的一宗报道为包括3532例胰腺切除病人的一篇大型队列研究，其发生率为1.3%。在报告发病率范围的另一端，Hilal等人发表了245例胰腺切除术后病人乳糜漏发生率为16.3%^[7]。已经发表文章中乳糜漏的发生率变化范围可能是因为手术技术不同，像腹膜后解剖的范围；处理方法差异，比如：手术后早期肠内营养。部分因素似乎与胰腺切除手术后乳糜漏相关。这些因素包括：较大范围解剖、由于胰腺炎^[6]引起的胰周纤维化造成解剖困难或者新辅助放疗、大血管切除重建^[2]以及早期进食^{[7, 8, 12]}。

Specifically,in the series from Johns Hopkins when matching for tumor size, tumor type, and resection type, the number of harvested lymph nodes and concomitant vascular resection were both significant predictors of increased risk of chyle leak [2].Similarly, Hilal et al. reported that both extensive lymphadenectomy and postoperative portal/ mesenteric vein thrombosis were risk factors. It is interesting that this series reported the highest rate of postoperative chyleleaks in the literature and the general practice of this group is to initiate early enteral feeding using a semi-elemental tube feed on postoperative day 1.The possibility that early enteral feeding may promote chyle leak following pancreatectomy is supported by work from Kuboki et al. [8], who reported that the early initiation of enteral nutrition is an independent risk factor for chyle leak. In addition, this group also reported manipulation of the para-aortic area as a risk factor.

特别需要注意的是，在来自约翰霍普金斯医院的研究中，当与肿瘤大小、肿瘤类型和切除类型相配对时，切除淋巴结的数量和同时血管重建是乳糜漏发生率增加的重要预测因素^[2]。与此相似的是，Hilal等人^[7]报道广泛淋巴结切除和手术后门静脉或肠系膜静脉血栓形成为危险因素。有趣的是文献中这些研究报道了手术后较高的发生率，报道组病例临床过程中应用半营养素营养管术后第一天给予早期肠内营养。早期肠内营养可能增加了胰腺切除术后乳糜漏，这一观点得到了Kuboki等人研究的支持^[8]，他们报道早期肠内营养是发生乳糜漏的独立预后因素。另外，此组研究也报道了腹主动脉周围手术操作是发生乳糜漏的一个危险因素。

It is difficult to know if early enteral feeding actually promotes chyle leaks or simply uncovers low-level chyle leaks that otherwise would have gone undetected had a diet been started later in the postoperative course. The term “chyle leak” is a general term that includes two distinct entities each with a unique natural history. These include a contained chyle leak and chylous ascites.These two types of chyle leaks are very different in regard to management and outcome.

我们很难得知是否早期肠内营养确实增加了乳糜漏的发生率还是仅仅发现了低流量乳糜漏，而这种乳糜漏如果延迟进食或许会不被发现而自行愈合。乳糜漏一词仅为一般概念，它包括两个具有独特自然史且完全不同的内容。那就是包裹性乳糜漏和乳糜性腹水。两者在治疗方法和预后方面截然不同。

A contained chyle leak is a that communicates with disrupted visceral lymphatics,whereas chylous ascites is a diffuse free-flowing chyle leak. The latter has a much higher impact on survival since it results in more significant immunosuppression, malnutrition, and fluid/electrolyte imbalances. Moreover, the risk for abdominal infection and fascial dehiscence is higher with chylous ascites. The increased mortality with chylous ascites following pancreatectomy has been reported [2]. In a large series of pancreatectomies, the overall survival for patients developing chylous ascites was 19 % at 3 years compared to 53.4 %for those with a contained chyle leak.

局限性乳糜漏是指与破裂的淋巴管相通的局限性积液，而乳糜性腹水是指腹腔内弥漫性游离性乳糜积液。由于后者会导致更严重的免疫抑制、营养不良、和水电解质失衡，因此对患者生存有更严重的影响。而且，游离性乳糜性腹水存在更高的腹腔感染和切口裂开的危险性。据报道胰腺切除术后乳糜性腹水有更较高的死亡率^[2]。在一项大型胰腺切除手术研究中，形成乳糜性腹水的病人3年生存率为19%，而局限性乳糜漏者可达53.4%。

Anatomy and Physiologyof Visceral Lymphatics

In order to better understand the etiology and the management of chyle leaks following pancreatectomy, it is important to understand the function and anatomy of the abdominal lymphatic system. The following section reviews information that is pertinent to this topic.The lymphatic system functions as a tissue drainage network and also plays a role in immune function. Essentially every tissue in the body has lymphatic drainage. Lymph fluid is produced at the level of the capillaries where the intravascular hydrostatic pressure is higher than that of the surrounding interstitial compartment resulting in the out flow of fluid into this space. The electrolyte composition of lymph fluid is similar to that of plasma [14] (Table29.1).

内脏淋巴管的解剖与生理

为了更好地理解胰腺切除术后乳糜漏的发病原因及其治疗，理解腹部淋巴系统的解剖和功能十分重要。下面部分将复习与此相关的话题。淋巴系统发挥着组织引流网络的功能，同时也具有免疫功能。体内任何组织都基本上存在淋巴系统。淋巴液产生于毛细血管水平，血管内的静水压高于间质内的压力使液体流入这个低压间隙。淋巴液中电解质成分与血浆相似(Table 29.1)^[14]。

In addition, there is a colloid component of lymphatic fluid which consists of protein at a relatively low concentration and a cellular component consisting of immune cells. A breach of the interstitial space by trauma, infection, or malignancy can result in further interstitial fluid components within the lymph fluid such as cellular debris, cancer cells, and bacteria.This fluid is taken up by passive diffusion into the thin-walled porous lymphatic capillaries that lack a continuous basement membrane. Small lymphatic capillaries coalesce into larger vessels that contain one-way valves. The action of muscular contraction, respiratory pressure variation, and gravity result in the flow of lymphatic fluid into successively larger and more centrally located vessels. Anatomic regions of lymphatic drainage are channeled through lymphnode basins that “filter” the lymphatic fluid by means of immune cell function.The importance of lymph drainage is more evident in conditions leading to lymph flow obstruction such as axillary or groin lymph node dissection or parasitic infestation that may result in lymph edema or even “elephantitis”. In addition to the general role of lymphatics for immune function and interstitial fluid balance, the abdominal lymphatic system is necessary for normal fat absorption.

另外，淋巴液中存在胶体成分，包括相对较低浓度的蛋白质、和构成免疫系统的细胞成分。创伤、感染和恶性肿瘤引起的组织间隙裂口能够增加淋巴液中的间质液体成分，比如：细胞碎片、癌细胞和细菌。这种液体通过被动扩散吸收进入带有空隙的薄壁缺乏基地膜的毛细淋巴管。小的毛细淋巴管汇入粗的带有单向瓣膜的管道中。肌肉收缩运动、呼吸压力变化和重力导致淋巴液连续流入较大和中央区的淋巴管。淋巴引流的解剖部位流过淋巴结盆，通过淋巴细胞的功能过滤淋巴液。淋巴引流的重要性在引起淋巴流动梗阻状态是更加明显，例如：腋窝和腹股沟淋巴结清除术后或者寄生虫感染时，可以导致淋巴水肿和橡皮腿。除了淋巴管在免疫和间质液体平衡方面的一般作用外，腹部淋巴系统在正常脂肪吸收方面也是必不可少的。

The process of fat absorption begins with the breakdown of triglycerides into monoglycerides and fatty acids within the gut. This is mainly through the action of pancreatic lipase and is facilitated by the formation of micelles consisting of bile salts, monoglycerides, and fatty acids.Micelles are absorbed within the intestinal villi where triglycerides are enzymatically reformed. Triglycerides consisting of long-chain fatty acids (> 12 carbons)combine with cholesterol and specific proteins to form chylomicrons. The small intestine has a rich lymphatic network with specialized terminal branches known as lacteals that are necessary for the uptake of chylomicrons. Once within the lymphatic system, this fluid is known as chyle and ultimately enters the systemic circulation through the thoracic duct.

脂肪吸收的过程始于肠道内的甘油三酯分解成甘油一酯和脂肪酸。此反应主要通过胰腺脂肪酶完成，通过包含胆盐、甘油一酯和脂肪酸的微胶粒形成更利于吸收。微胶粒在小肠绒毛内吸收，并且甘油三酯在此重新合成。甘油三酯包括长链脂肪酸(> 12 碳原子)、胆固醇和形成乳糜微粒的特殊蛋白质。小肠富含专门终末分支淋巴网络-乳糜管，这一结构对于乳糜微粒的吸收是必要的。一旦进入淋巴系统中，这种液体就成为乳糜，最终通过胸导管进入体循环。

Lymph drainage from all structures below the diaphragm, as well as the left upper extremity and left chest enters the thoracic duct viathe cysterna chyli and returns to the circulatory system at the level of the left subclavian vein. This includes the lymphatic system of the gut. Lymphatic drainage of the right chest and upper extremity drains into the right subclavian vein. Lymphatic drainage of the abdominal visceral connects to systemic lymphatic drainage at the level of the cysterna chyli. The cysterna chyli is a roughly 5-cm sack-like dilatation of the lymphatic system located deep within the retroperitoneum at the level of the first and second lumbar vertebrae.The structure is located to the right of the aorta, deep within the interval between the aorta and the inferior vena cava. The function of the cysterna chyli is unclear, but it has been suggested that it functions as a bellows that drives lymph flow via the abdominal pressure changes that occur with normal respiration. The cysterna chyli receives systemic lymphatic drainage from the lower body, lumbar drainage beds, and the visceral drainage beds including the liver.Lymphatic drainage from the intestine and portions of the head of the pancreas course along the superior mesenteric artery through the base of the mesentery and join the cysterna chyli near the junction of the superior mesenteric artery (SMA)with the aorta.

膈肌下所有结构的淋巴引流，包括左上肢和左侧胸部结构的淋巴管均经中央乳糜池汇入胸导管，在左侧锁骨下静脉水平进入循环系统。包括肠道的淋巴系统。右侧胸腔和上肢的淋巴引流进入右锁骨下静脉。腹部脏器淋巴引流在中央乳糜池水平汇入淋巴系统。中央乳糜池大约为5cm的囊状扩张淋巴系统结构，位于第一、二腰椎水平腹膜后较深位置。这一结构位于腹主动脉的右侧，在腹主动脉和下腔静脉之间较深的部位。。中央乳糜池的功能尚不清楚，但是据认为它有风箱样作用，和呼吸运动和腹压下驱动着淋巴流动。中央乳糜池接受来自下肢、腰床和包括肝脏在内的内脏引流床生成的淋巴液。来自肠道和部分胰头的淋巴液沿着肠系膜上动脉在肠系膜根部汇入中央乳糜池，具体位置接近肠系膜上动脉和腹主动脉交汇处。

The liver, portal, and remainder of the pancreatic lymphatic flow follow the course of the celiac axis distribution retrograde to its junction with the aorta. The exact location of the disruption of the lymphatic system resulting in chyle leak following pancreatic resection is unknown. However, based on this understanding of lymphatic anatomy and chyle flow, one can speculate on the potential areas of disruption of these vessels and the resulting chyle leak.These areas include dissection of the hepatoduodenal ligament, the base of the mesentery at the mid portion of the SMA, the soft tissue surrounding the celiac trunk, and retroperitoneal space in the interval between the inferior vena cava and the right side of the aorta. The volume of chyle flow ranges from 2 to 4 L/day and varies depending on numerous factors including the composition of the diet [14]. The majority of lymph flow through the thoracic duct is from visceral sources.

肝脏、门静脉和胰腺的其他部分的淋巴液沿着腹腔干分布区域逆行至腹主动脉交汇处。胰腺切除后引起乳糜漏的淋巴系统破损确切部位尚不清楚。然而，基于对淋巴系统解剖和乳糜流向的理解，我们可以推测这些管道破裂导致乳糜漏的潜在区域。这些区域包括肝十二指肠游离区域、位于肠系膜上动脉中部的系膜基底部、腹腔干周围软组织和下腔静脉与腹主动脉右侧之间的腹膜后区域。每天乳糜流量约2-4升，根据包括饮食成分在内的诸多因素不同而有所变化^[14]。流经胸导管的多数淋巴液起源于内脏。

It is estimated that 25–50 % of all flow from through the thoracic duct originates from the liver. The majority of the remainder comes from the other viscera(chyle) while the minority of lymph through the thoracic duct is from the lower extremities.Approximately 70 % of chyle consists of dietary fat mainly in the form of triglycerides. The concentration of fat varies and ranges from 5 to 30 g/L and has an energy value of approximately 200kcal/L (Table 29.1). The volume of lymphatic drainage from the abdominal viscera is evident in pathological conditions such as chylous ascites resulting from cirrhosis, pancreatitis, or malignancy in which liters of chyle can be produced each day.

据估计流经胸导管25–50 %的淋巴液来源自肝脏。其余的多数来自其他内脏（乳糜），少数来自下肢。大约70%乳糜由饮食中甘油三酯形式的脂肪组成。脂肪的浓度不稳定，在5 到30 g/L，能量效价约为200 kcal/L(Table 29.1)。在一些病理状态下来自腹部脏器淋巴液的体积会明显增加，比如源自肝硬化的乳糜性腹水、胰腺炎、恶性肿瘤，此时每天可以有数升乳糜生成。

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