Work

Liver lymphatic drainage patterns follow segmental anatomy

Year: 2022

Type: article

Abstract: Dear Editor The cellular functions of the liver are sustained by a hierarchical, segmental, organized network of arteries, portal veins, and hepatic veins. In addition to this threefold vascular network, the liver lymphatic system drains interstitial fluid from the parenchyma towards perihepatic lymph nodes1. The liver lymphatic system is estimated to produce 25–50 per cent of the lymph in the thoracic duct, and may play a crucial role in pathological processes such as cirrhosis and cancer dissemination1,2. Hepatic pedicle lymph node dissection is indicated, or at least frequently performed, in patients undergoing partial hepatectomy for hepatocellular carcinoma, cholangiocarcinoma, and colorectal metastases3,4. Surprisingly, the functional anatomy of the liver lymphatic system— whether the lymphatics follow the segmental organization of the vasculature and hence drain to specific lymph node chains—has not been mapped out. Recent work in mice showed that lymphatic tracer dye (blue dye) injected into the liver parenchyma is drained via the space of Disse and initial lymphatic vessels near the portal triads towards the perihepatic lymph nodes5. The liver lobes displayed preferential lymph node drainage patterns without interlobar lymphatic flow, providing direct evidence that liver lymphatic drainage adheres to the segmental anatomy5. Here, the authors show in humans that the primary lymphatic drainage route of blue dye injected into the liver parenchyma during surgery is different for the right versus the left hemiliver. In brief, 16 patients underwent partial hepatectomy with intraoperative liver lymphangiography by injecting Patent Blue dye deep into the liver parenchyma followed by inspection for blue discolouration of perihepatic lymph vessels and lymph nodes. The methods used are described in the Supplementary material. All eight patients who had dye injections into segments V–VIII exhibited blue staining of lymph node(s) on the right side of the portal vein (station 12r) and/or station 13 (pancreatic head) within 5 min. In seven patients, individual lymphatic vessels were also identified running in the fatty tissue along the right hepatic artery. None of these patients had evident blue staining of lymph nodes to the left of the portal vein, along the left hepatic artery, or in the gastrohepatic ligament. All eight patients who had dye injections into segments I–IV exhibited blue staining of lymph vessels and node(s) on the left side of the portal vein (station 12l), the gastrohepatic ligament (station 7), and/or the common hepatic artery (station 8A). In one patient who had blue dye injection into segment I, only a blue-stained lymph vessel along the middle hepatic vein/suprahepatic inferior vena cava was observed. None of these patients had evident blue staining of lymph nodes on the right side of the hepatoduodenal ligament. Results are shown in Fig. 1 and Table S1. Lymphatic drainage routes of blue dye injected into liver parenchyma a–d Injection of blue dye into the left hemiliver (images a–c are from the same patient). a Injection of blue dye during robot-assisted hepatectomy in segment (S) III; the asterisk indicates tumour. b The gastrohepatic ligament is partially opened. Lymphatic vessels draining blue-dyed fluid are seen emerging from the base of the round ligament towards both the lesser curvature and along the left hepatic artery towards lymph node station (LN) 8A. There is a complete absence of blue staining to the right of the common bile duct (CBD)/right side of the hepatoduodenal ligament. LN12l, LN station 12 on the left side of the hepatoduodenal ligament. c View of the lesser omentum (MO) with blue staining of lymphatic vessels. d Close-up of the exposed suprahepatic inferior vena cava (IVC) after injection of blue dye into segment I during open hepatectomy. No blue discolouration of lymph nodes or vessels in the hepatoduodenal ligament is observed, only a lymphatic vessel running along the middle hepatic vein (MHV). RHV, right hepatic vein. e–f Injection of blue dye into the right hemiliver (both images from the same patient). e Overview after lymphangiography in segment V (open hepatectomy); the asterisks indicate tumour. f Close-up of blue-stained lymph nodes (arrows) on the right side of the hepatoduodenal ligament. Lymphatic drainage routes of blue dye injected into liver parenchyma a–d Injection of blue dye into the left hemiliver (images a–c are from the same patient). a Injection of blue dye during robot-assisted hepatectomy in segment (S) III; the asterisk indicates tumour. b The gastrohepatic ligament is partially opened. Lymphatic vessels draining blue-dyed fluid are seen emerging from the base of the round ligament towards both the lesser curvature and along the left hepatic artery towards lymph node station (LN) 8A. There is a complete absence of blue staining to the right of the common bile duct (CBD)/right side of the hepatoduodenal ligament. LN12l, LN station 12 on the left side of the hepatoduodenal ligament. c View of the lesser omentum (MO) with blue staining of lymphatic vessels. d Close-up of the exposed suprahepatic inferior vena cava (IVC) after injection of blue dye into segment I during open hepatectomy. No blue discolouration of lymph nodes or vessels in the hepatoduodenal ligament is observed, only a lymphatic vessel running along the middle hepatic vein (MHV). RHV, right hepatic vein. e–f Injection of blue dye into the right hemiliver (both images from the same patient). e Overview after lymphangiography in segment V (open hepatectomy); the asterisks indicate tumour. f Close-up of blue-stained lymph nodes (arrows) on the right side of the hepatoduodenal ligament. These observations show a consistent division in lymphatic drainage patterns of the right- versus the left-sided liver segments. The authors speculate that segments V–VIII may preferentially drain to the right side of the hepatoduodenal ligament and then onwards to the peripancreatic and aortocaval nodes, whereas segments I–IV drain preferentially drain along the left and common hepatic artery and/or left gastric artery towards the coeliac trunk nodes. Remarkably, as in the median lobe of mice5, lymphatic drainage of segment I can occur directly to the mediastinum. Although this is a single observation, it is consistent with older anatomical studies and implies that part of the liver parenchyma can drain directly to mediastinal lymph nodes. Lymph node drainage patterns beyond perihepatic nodes need to be determined definitively in further studies, for example employing nuclear tracers. Ultimately, whether the lymphatic drainage of tracer dye injected in the liver parenchyma correlates with preferential localization of lymph node metastasis, thus influencing the use and extent of lymphadenectomy during partial hepatectomy for malignancy, is the subject of further clinical studies. This research was supported by the Dutch Cancer Society/KWF Kankerbestrijding (UU2014-6904). The authors thank J. Willem van Wijnbergen and C. Nota for their support. Disclosure. The authors declare no conflict of interest. Supplementary material is available at BJS online.

Source: British journal of surgery

DOI: 10.1093/bjs/znac076