The biochemical profile of the milky drained material was as follows: total bilirubin 0 mg/dl, amylase 0 mg/dl, triglycerides 262 mg/dl, total proteins 4.2 g/dl, glucose 71 mg/dl, while the serum triglycerides level was 126 mg/dl. Moreover, the milky drained material was positive in Sudan III stain, while culture and sensitivity was reported as sterile.
From the 28th to the 50th postoperative day, 15 ml of chyle was steadily drained every day. On the 35th postoperative day the drain tube was withdrawn, establishing a chylous-cutaneous fistula, but as this fistula was classified as extremely low-output (15 ml/day), the use of total parenteral nutrition or enteral nutrition with medium chain trigycerides or fat-free diet or Sandostatin/Ocreotide administration was not advocated as a therapeutic option.
On the 50th postoperative day, a radionuclide lymphangiography was performed. Human albumin nanocolloid with a diameter <80 nm from a commercially available kit (Nanocoll, GE Healthcare, Italy) was used for the delineation of the lymphatic vessels. Tc-99m nanocolloid was prepared by addition of 20 mCi sodium99mTc-pertechnetate in 2 ml saline to lyophilized kit. The pertechnetate was used within 4 hours of elution from a generator which had been eluted within the previous 24 hours. Slowly subcutaneous injections through a 25G needle of 1 mCi 99mTc-nanocolloid in a volume of 0.1 ml into the 2nd and 4th interdigital space of the patient's lower extremities bilaterally, were performed. Scintigraphy was carried out on a single-head γ-camera (Simens Orbiter, Germany) equipped with a low energy general purpose (LEGP) parallel hole collimator. The matrix was 128 × 128 pixels and the photo-peak was focused at 140 keV with a symmetric 20% window. Anterior views were obtained at 0, 15, 30, 45 and 60 minutes, as well as at 4 and 24 hours post injection. Images were recorded with an acquisition time of 5 minutes, covering lower extremities, tibias, thighs, pelvis, abdomen and thorax, according to radiopharmaceutical flow. At 24 hours post injection, a mild diffused activity was observed at the upper abdomen just inferiorly to the liver (Figure 3).
Within 24 hours from the radionuclide lymphangiography, the chylous-cutaneous fistula was spontaneously subsided. Twelve months since the subsidence, the patient remains in an excellent general condition.
A MEDLINE, EMBASE and google.scholar databases search was conducted using these terms as key words: chyle leakage, chylous fistulae, chylorrhea, chylous ascites, chyloperitoneum, lymphorrhea, gastric cancer, D2 gastrectomy, extended lymphadenectomy, superextended lymphadenectomy, radical gastrectomy and postoperative complications, in various combinations. References were limited to articles of which at least the abstract was in the English language.
Because of the confusion in the classification and terminology, we proposed as diagnosis for “chylorrhea” the following criteria: presence in the drainage tubes or on aspiration of a non-bloody, amylase and bilirubin free, milky or creamy peritoneal fluid, rich in triglycerides, from the 3rd postoperative day onwards, independently to the amount of fluid drained daily. According to these criteria 133 previous cases of chylorrhea development following lymphadenectomy for gastric cancer have been published (Table).3–19
Anatomically, the lymphatic system is described as an extensive one-way transport network spreading throughout all areas of the body, providing the return of fluid and proteins, which have leaked into the interstitial space, back to the blood circulation. The intestinal lymphatics also play an essential role in absorption of lipid digestion products such as long chain fatty acids and lipid soluble vitamins.20
Physiologically, after their absorption, molecules must travel at least some distance through the interstitium before entering the lymphatic capillaries (initial lymphatics), which rely on sensitive connections to the interstitium called anchoring filaments.21 The interstitial resistance to molecular transport greatly affects the apparent lymphatic uptake rate. In general, lymph has nearly the same concentration as interstitial fluid and their osmotic pressures are essentially equal.22 Molecules enter lymphatic capillaries by way of the hydrostatic and oncotic forces and the vesicular transport.23 Then, the fluid is propelled further following the route: initial lymphatics → prenodal collecting lymphatics → lymphnodes → postnodal collecting lymphatics → lymphatic trunks → cisterna chyli → thoracic duct. From the level of collecting lymphatics, lymph propulsion through the lymphnodes into the ducts, is favored by the presence of contractive smooth muscle and valves.21 Significant changes in lymph concentration occur as the fluid passes through the various components of the lymphatic system. It becomes concentrated along the contracting lymphangion (the segment of a collecting lymphatic between valves) segments, possibly due to water filtration across the vessel wall,24 while protein concentration decreases during its residence in the lymph nodes from osmotically driven fluid exchange with nodal blood vessels and phagocytosis by white cells.25 Thus, the sampling point of lymph fluid (eg. prenodal versus postnodal lymphatics, lymph node versus duct, etc) strongly affect molecule uptake data reported in the literature.21
Based on the above, any disruption of the lymphatic system at the level of initial lymphatics causes accumulation of a fluid iso-osmotic to interstitial one; thus fluid triglycerides levels are nearly equal to serum ones. As more distal to the collecting lymphatics the disruption occurs, the more concentrated the absorbed molecules are; thus fluid triglycerides levels are higher to serum ones. At which level of the lymphatic system, the fluid triglycerides levels becomes doubled to the interstitial one, is not clear.
The results of published reports from Eastern Asia, where extended and superextended lymphadenectomies including the No. 13 and/or No. 16 perigastric lymphnode stations in the dissection constitute a common practice for the treatment of gastric cancer, indicate that disruption at the level of cisterna chyli, which is classically described as a fusiform stricture between inferior vena cava and aorta anterior to the bodies of L1-L2 vertebrae,23 represents the most possible causative mechanism for postoperative chylorrhea development. On the other hand, the statement of Tanaka et al,26 that lymphorrhea, not containing chyle, involves an internal lymph fistula between the lymphatic channels toward the cisterna chyli (collecting lymphatics) and the peritoneal cavity, indicates that any lymphatic injury proximal to cisterna chyli should not lead to chylorrhea development.
Meanwhile, development of chylorrhea has been reported following lymphadenectomy for gastric cancer not including the No. 13 and/or No. 16 perigastric lymphnode stations,6,8,11 or even after D1 gastrectomy.19 As possible explanations could be proposed: (1) a disruption at the level of a confluence of the abdominal lymph trunks (forming the abdominal origin of the thoracic duct) instead of the commonly described cisterna chyli,6 (2) the possibility that in some instances the lymphatic fluid has already been concentrated at the level of collecting lymphatics, prior to cisterna chyli formation or (3) the presence of anatomic variation at the origin of the confluence of the abdominal lymph trunks or the cisterna chyli itself.
We propose that chylorrhea and its synonyms (chyle leakage, chylous fistula, chylous ascites or chyloperitoneum) should be defined as a non-bloody, bile and amylase-free, milky, sterile, odorless and rich in triglycerides peritoneal fluid, drained from the 3rd postoperative day onwards, independently to the amount of fluid drained daily.
The creamy appearance of the fluid cannot be used as criterion since this can be a result of a secondary infection of any abdominal collection; pus collections or infected hematomas are creamy but not milky. The sterile and the odorless nature of the fluid are mandatory, since the presence of both of them exclude the possibility of bacterial overgrowth. Ideally, the ratio of fluid triglycerides/serum triglycerides should be above 2 or alternatively,23 fluid triglycerides levels should always be above 200 mg/dl.27 Fluid triglycerides levels between 100 and 200 mg/dl should be considered as “highly suggestive”, not yet diagnostic for chylorrhea and lipoprotein analysis which in chyle shows predominantly chylomicrons, should be obtained.28 However, we propose that fluid triglycerides levels <100 mg/dl should be considered as interstitial fluid rather than true chylorrhea. We propose that injury at any point distal to the postnodal collecting lymphatics and not only to the cisterna chyli, can cause this complication.
Ideally, all the previously mentioned criteria should be met in order to be established the diagnosis of chylorrhea. However, the review of the literature disclosed that all criteria were present in only 57 out of the 133 reported cases, at least one criterion (mainly the milky appearance of the fluid) were present in 37 out of the 133 reported cases, while in 39 cases no diagnostic criteria were reported. The confusion in terminology becomes even more obvious in the article published by Zhang et al19 who although describe the above criteria, however nominate the complication as “lymphorrhea”.
“Chyliform” and “pseudochylous” abdominal fluid, should be defined as any abdominal fluid with turbid appearance due to cellular and tissue degeneration secondary to bacteria overgrowth or malignancy, which is marked by low triglyceride levels.23
Lymphorrhea should be defined as a serous or yellow-colored abdominal fluid iso-osmotic to interstitial one, not containing chyle; thus fluid and serum triglycerides levels are nearly equal. Injury up to the level of prenodal collecting lymphatics causes this complication.
Despite the limited number of studies addressing the best treatment options, all authors agree that the treatment should be mainly nonsurgical and the goals include: maintaining or improving nutrition, decreasing the rate of chyle formation and correcting the underlying disorder. As an algorithm, Kaas et al8 proposed that once the diagnosis is established, dietary restrictions should start in the form of medium chain triglycerides (MCT) drip feed/diet or total parenteral nutrition (TPN) to reduce chyle flow and maintain proper nutrition. Paracenteses may be performed one or two times for debilitating chylous ascites, while the insertion of a peritoneovenous shunt should be reserved for patients with persisting chylous ascites.
Controversies still exist regarding the effectiveness of a high-protein, low-fat diet with MCT versus TPN alone, as a measurement to reduce chyle formation. Theoretically, TPN is superior to any enteral feedings since it bypasses the bowel and because the simple presence of intraluminal water has been shown to increase thoracic duct lymph flow.23 However, dietary restriction of long-chain triglycerides avoids the conversion of them into monoglycerides and free fatty acids, which are transported as chylomicrons to the intestinal lymph ducts, while medium-chain triglycerides are absorbed directly into intestinal cells and transported as free fatty acids and glycerol directly to the liver via the portal vein. Therefore, the use of a low-fat diet with medium-chain triglyceride supplementation reduces the production and flow of chyle and is recommended as first-line therapeutic option.29
By which mechanism somatostatin and octreotide affect lymphorrhea, is unknown. It has been proposed, that somatostatin inhibits lymph fluid excretion through specific receptors found in the normal lymphatic vessels of the intestinal wall.30,31
Paracentesis is indicated for patients with gross abdominal distention,32 while the peritoneovenous shunt should be reserved for chylous ascites refractory to medical therapy in poor surgical candidates, because it is associated with considerable morbidity.33
Re-laparotomy is seldom necessary. It should be reserved for good surgical candidates and definitive ligation of the lymphatic leak or small bowel resection of the leaking mesentery, may be required.23
In recent years, either introperative spray of fibrin glue over the area of the cisterna chyli or percutaneous injection of it throughout the fistulous tract, have been reported as successful in cases of persistent chylous leakage.34 Even more recently, pedal lymphangiography has been reported not only as diagnostic, but also as therapeutic in cases of high-output or refractory to the conservative management chyle leakages35 and Lipiodol's ability to act as an embolus inside the lymphatic vessels, has been proposed as a possible explanation.36
Since the patient we describe herein was classified as suffering from low output (<200 ml/day) chylous-cutaneous fistula, none of the above measurements were required, therefore only free-fat diet was advocated.
Radionuclide lymphangiography has no specific contraindications, lacks complications and adverse effects, is well tolerated by the patient and its radiation burden is low.37 Since spontaneous subsidence of the fistula was noticed following the lymphoscintigraphy in the present case, we propose that nanocolloids with diameter of 80 nm may also act as embolus inside the lymphatic vessels in cases of low output chyle leakages.
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Keywords:© 2010 Chinese Medical Association
chylous leakage; D2 gastrectomy; extended lymphadenectomy; gastric cancer; lymphoscintigraphy