This work was supported by grants from the National Natural Science Foundation of China (No. 81702406) and the Natural Science Foundation of Guangdong Province of China (2016A030310207).

This protocol follows the guidelines of the human research ethics committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Written informed consent was obtained from the patients for performing this study.
1. Patient selection
<ol>
	<li>Select patients with a malignant tumor in the middle section of the liver, including patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).</li>
	<li>Ensure that these patients show no invasion of t...

<ol>
	<li>Hu, R. H., Lee, P. H., Chang, Y. C., Ho, M. C., Yu, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+centrally+located+hepatocellular+carcinoma+with+central+hepatectomy.">Treatment of centrally located hepatocellular carcinoma with central hepatectomy.</a> Surgery. 133 (3), 251-256 (2003).</li><li>Stratopoulos, C., Soonawalla, Z., Brockmann, J., Hoffmann, K., Friend, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+hepatectomy:+The+golden+mean+for+treating+central+liver+tumors.">Central hepatectomy: The golden mean for treating central liver tumors.</a> Surgical Oncology. 16 (2), 99-106 (2007).</li><li>Lee, S. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+hepatectomy+for+centrally+located+malignant+liver+tumors:+A+systematic+review.">Central hepatectomy for centrally located malignant liver tumors: A systematic review.</a> World Journal of Hepatology. 6 (5), 347-357 (2014).</li><li>Takasaki, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glissonean+pedicle+transection+method+for+hepatic+resection:+a+new+concept+of+liver+segmentation.">Glissonean pedicle transection method for hepatic resection: a new concept of liver segmentation.</a> Journal of Hepato-Biliary-Pancreatic Surgery. 5 (3), 286-291 (1998).</li><li>Torzilli, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+liver+resections+for+hepatocellular+carcinoma.">Ultrasound-guided liver resections for hepatocellular carcinoma.</a> Hepato-Gastroenterology. 49 (43), 21-27 (2002).</li><li>Takamoto, T., Makuuchi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Precision+surgery+for+primary+liver+cancer.">Precision surgery for primary liver cancer.</a> Cancer Biology &amp; Medicine. 16 (3), 475-485 (2019).</li><li>Makuuchi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+treatment+for+HCC--special+reference+to+anatomical+resection.">Surgical treatment for HCC--special reference to anatomical resection.</a> International Journal of Surgery. 11, 47-49 (2013).</li><li>Aoki, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+liver+mapping+using+fluorescence+navigation+system+with+indocyanine+green+for+anatomical+hepatic+resection.">Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection.</a> World Journal of Surgery. 32 (8), 1763-1767 (2008).</li><li>Felli, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laparoscopic+anatomical+liver+resection+for+malignancies+using+positive+or+negative+staining+technique+with+intraoperative+indocyanine+green-fluorescence+imaging.">Laparoscopic anatomical liver resection for malignancies using positive or negative staining technique with intraoperative indocyanine green-fluorescence imaging.</a> HPB. 23 (11), 1647-1655 (2021).</li><li>Ishizawa, T., Zuker, N. B., Kokudo, N., Gayet, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positive+and+negative+staining+of+hepatic+segments+by+use+of+fluorescent+imaging+techniques+during+laparoscopic+hepatectomy.">Positive and negative staining of hepatic segments by use of fluorescent imaging techniques during laparoscopic hepatectomy.</a> Archives of Surgery. 147 (4), 393-394 (2012).</li><li>Procopio, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+anatomical+liver+resection+using+a+compression+technique+combined+with+indocyanine+green+fluorescence+imaging.">Ultrasound-guided anatomical liver resection using a compression technique combined with indocyanine green fluorescence imaging.</a> HPB. 23 (2), 206-211 (2021).</li><li>Takemura, N., Ito, K., Inagaki, F., Mihara, F., Kokudo, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Added+value+of+indocyanine+green+fluorescence+imaging+in+liver+surgery.">Added value of indocyanine green fluorescence imaging in liver surgery.</a> Hepatobiliary &amp; Pancreatic Diseases International. 21 (4), 310-317 (2022).</li><li>Maluccio, M., Covey, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+progress+in+understanding,+diagnosing,+and+treating+hepatocellular+carcinoma.">Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma.</a> CA: A Cancer Journal for Clinicians. 62 (6), 394-399 (2012).</li><li>Lamade, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+3-dimensional+reconstructions+on+operation+planning+in+liver+surgery.">The impact of 3-dimensional reconstructions on operation planning in liver surgery.</a> Archives of Surgery. 135 (11), 1256-1261 (2000).</li><li>Pringle, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Notes+on+the+arrest+of+hepatic+hemorrhage+due+to+trauma.">Notes on the arrest of hepatic hemorrhage due to trauma.</a> Annals of Surgery. 48 (4), 541-549 (1908).</li><li>Yamamoto, M., Ariizumi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glissonean+pedicle+approach+in+liver+surgery.">Glissonean pedicle approach in liver surgery.</a> Annals of Gastroenterological Surgery. 2 (2), 124-128 (2018).</li><li>Cho, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relation+between+hepatic+and+portal+veins+in+the+right+paramedian+sector:+proposal+for+anatomical+reclassification+of+the+liver.">Relation between hepatic and portal veins in the right paramedian sector: proposal for anatomical reclassification of the liver.</a> World Journal of Surgery. 28 (1), 8-12 (2004).</li><li>Shindoh, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complete+removal+of+the+tumor-bearing+portal+territory+decreases+local+tumor+recurrence+and+improves+disease-specific+survival+of+patients+with+hepatocellular+carcinoma.">Complete removal of the tumor-bearing portal territory decreases local tumor recurrence and improves disease-specific survival of patients with hepatocellular carcinoma.</a> Journal of Hepatology. 64 (3), 594-600 (2016).</li><li>Ishizawa, T., Saiura, A., Kokudo, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+application+of+indocyanine+green-fluorescence+imaging+during+hepatectomy.">Clinical application of indocyanine green-fluorescence imaging during hepatectomy.</a> Hepatobiliary Surgery and Nutrition. 5 (4), 322-328 (2016).</li><li>Nishino, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+is+a+precise+anatomic+resection+of+the+liver?+Proposal+of+a+new+evaluation+method+in+the+era+of+fluorescence+navigation+surgery.">What is a precise anatomic resection of the liver? Proposal of a new evaluation method in the era of fluorescence navigation surgery.</a> Journal of Hepato-Biliary-Pancreatic Sciences. 28 (6), 479-488 (2021).</li><li>Le Treut, Y. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+technique+and+outcomes+of+central+hepatectomy+by+the+Glissonian+suprahilar+approach.">The technique and outcomes of central hepatectomy by the Glissonian suprahilar approach.</a> European Journal of Surgical Oncology. 45 (12), 2369-2374 (2019).</li><li>Rotellar, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardized+laparoscopic+central+hepatectomy+based+on+hilar+caudal+view+and+root+approach+of+the+right+hepatic+vein.">Standardized laparoscopic central hepatectomy based on hilar caudal view and root approach of the right hepatic vein.</a> Journal of Hepato-Biliary-Pancreatic Sciences. 27 (1), 7-8 (2019).</li><li>Muttillo, E. M., Felli, E., Cinelli, L., Giannone, F., Felli, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+counterclock-clockwise+approach+for+central+hepatectomy:+A+useful+strategy+for+a+safe+vascular+control.">The counterclock-clockwise approach for central hepatectomy: A useful strategy for a safe vascular control.</a> Journal of Surgical Oncology. 125 (2), 175-178 (2022).</li></ol>

Anatomical hepatectomy is based on portal territory, and its therapeutic effect on liver cancer is still being explored. The theoretical basis for this is that the spread of liver cancer along the portal vein is the main reason for its recurrence and metastasis18. In the 20th century, Makuuchi first proposed anatomical hepatectomy from the initial open portal vein puncture with methylene blue staining, revealing the landmark hepatic veins, which has advanced to the current preoperative analysis of...

Central hepatectomy is the main surgical method used to treat liver malignancies located in segments 4, 5, and 81,2. Standard central hepatectomy requires the complete resection of these segments, which necessitates exposing the sagittal portion, middle hepatic vein (MHV), and right hepatic vein (RHV)3. Segments 4, 5, and 8 belong to the category of central hepatectomy2.
With the advancement of precision liver surgery, anatomical hepatectomy has developed rapidly. However, the method to accurately determine the resection plane of hepatectomy is a key point and area of uncertainty. Generally, the Glisson pedicle is ligated to delimit the surface boundary according to the ischemic area4. For control of the deep plane, anatomical landmarks, including hepatic veins and portal branches, are often used under intraoperative ultrasound guidance during the transection5. Makuuchi&#39;s method shows the resection margin by injecting methylene blue into the portal vein under ultrasound guidance, exposing important hepatic veins at the liver resection plane after removing the specimen5,6,7.
Because hepatocytes specifically absorb indocyanine green (ICG), its fluorescence clearly shows the resection boundary. Anatomical hepatectomy guided by ICG fluorescence was first reported by Aoki in 20088. ICG fluorescent staining methods can be divided into positive and negative staining9. The negative staining technique is performed by intravenous ICG injection after clamping the segmental portal pedicle10. Then, the remnant liver displays fluorescence, but the portal territory does not. Compared with traditional methods, anatomical hepatectomy under fluorescence navigation can not only display the resection boundary on the surface of the liver, but also guide the deep resection plane. For hemihepatectomy and segmental hepatectomy, negative staining technology is recommended. To date, anatomical hepatectomy using fluorescence navigation has become a popular method for liver surgery11,12. This article describes a negative staining technique for fluorescent laparoscopic central hepatectomy. The patients were classified preoperatively by the Child-Pugh scoring system, and accordingly, patients with class A scores were selected13.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>BK Flex Focus 800</td>
			<td>BK Medical</td>
			<td>8666-RF</td>
			<td>Intraoperative ultrasound</td>
		</tr>
		<tr>
			<td>Entecavir</td>
			<td>Bristol Myers Squibb</td>
			<td>H20052237</td>
			<td>Antiviral drugs</td>
		</tr>
		<tr>
			<td>Hakko Sonoguide PTC Needle</td>
			<td>Hakko-medical</td>
			<td>&#160;PTC-B 18G/20G</td>
			<td>Portal vein puncture</td>
		</tr>
		<tr>
			<td>Indocyanine green</td>
			<td>Dandong Yichuang Pharmaceutical</td>
			<td>0902007 GH102</td>
			<td>Fluorescent dye</td>
		</tr>
		<tr>
			<td>PINPOINT Endoscopic Fluorescence Imaging System</td>
			<td>Stryker</td>
			<td>PC9000</td>
			<td>Fluorescent laparoscope</td>
		</tr>
		<tr>
			<td>Tenofovir</td>
			<td>GILEAD</td>
			<td>H20180060</td>
			<td>Antiviral drugs</td>
		</tr>
		<tr>
			<td>Trocar</td>
			<td>Ethicon Endo-Surgery</td>
			<td>B5LT/B12LT</td>
			<td>Trocar</td>
		</tr>
	</tbody>
</table>

fluorescent laparoscopic central hepatectomy for liver cancer using indocyanine green negative staining

Laparoscopic hepatectomy is an important treatment method for liver cancer. In the past, the resection boundary was usually determined by intraoperative ultrasound, important vascular structures, and surgeon experience. With the development of anatomical hepatectomy, visual surgery technology has gradually been applied to this type of surgery, particularly indocyanine green (ICG)-guided anatomical hepatectomy. As ICG can be specifically ingested by hepatocytes and used for fluorescence tracing, negative staining techniques have been applied according to different tumor positions. Under ICG fluorescent guidance, the surface boundary and deep resection plane can be more accurately displayed during liver resection. Thus, the tumor-bearing liver segment can be anatomically removed, which helps to avoid damage to important vessels and reduce ischemia or congestion of the remaining liver tissue. Finally, the incidence of postoperative biliary fistula and liver dysfunction is reduced; therefore, a better prognosis is obtained after the resection of liver cancer. Centrally located liver cancer is usually defined as a tumor located at segments 4, 5, or 8 that requires resection of the middle section of the liver. These are among the most difficult hepatectomies to perform because of the large surgical wounds and multiple vessel transections. Based on the specific tumor location, we formulated the required resection ranges by designing personalized fluorescent staining strategies. By completing anatomical resection based on the portal territory, this work aims to achieve the best therapeutic effect.

From 2020 to 2022, six patients with HCC underwent fluorescent laparoscopic central hepatectomy. Among these, four patients underwent resection of segments 4, 5, and 8, and two patients underwent resection only of segments 5 and 8 (Table 1). None of the patients were converted to open surgery. Their ages ranged from 46 to 74 years. The tumor sizes ranged from 5 to 9 cm. The median operative time was 240 min, and the median intraoperative blood loss was 450 mL. The median postoperative hospital stay was 7...

Watch this Scientific Journal Video about Fluorescent Laparoscopic Central Hepatectomy for Liver Cancer Using Indocyanine Green Negative Staining at JoVE.com

Fluorescent Laparoscopic Central Hepatectomy for Liver Cancer Using Indocyanine Green Negative Staining

The present protocol describes fluorescent negative staining in laparoscopic central hepatectomy. This technique can make hepatectomy more accurate and precise.

Laparoscopic hepatectomy is an important treatment method for liver cancer. In the past, the resection boundary was usually determined by intraoperative ...

This protocol can accurately determine the resection plane of anatomical hepatectomy. Surgeons can conduct right plane resection leisurely using the fluorescence technique under fluorescent guidance in central hepatectomy. After the preoperative preparations, separate the liver parenchyma at one centimeter on the falciform ligament's right side.Using clips, ligate and transect several segments for Glisson pedicle branches. Next, separate the right anterior hepatic pedicle along the Laennec's capsule and ligate or occlude the right anterior hepatic pedicle. To define the boundary between the right anterior and right posterior sections, inject two milliliters of 1 to 100 diluted ICG peripherally for negative staining.Then, dissect the liver parenchyma along the right fluorescent border and transect the right anterior hepatic pedicle using a linear stapler after obtaining sufficient space. Separate the middle hepatic vein at the root and transect it using a linear stapler. Under fluorescence tracing, reserve the trunk of the right hepatic vein, transect the V5d and V8d branches of the right hepatic vein and finish resecting the specimens.To resect segments five and eight, separate the right anterior hepatic pedicle along the Laennec's capsule. Perform a peripheral injection of two milliliters of 1 to 100 diluted ICG for negative staining to define the boundaries between the left, right anterior, and right posterior sections. Then, process the left resection plane, dissect the liver parenchyma along the left fluorescent border, preserve the trunk of the main hepatic vein, and transect the V5v and V8v branches of the main hepatic vein.After obtaining sufficient space, transect the right anterior hepatic pedicle using a linear stapler. Next, dissect the liver parenchyma along the right fluorescent border, preserve the trunk of the right hepatic vein, transect the V5d and V8d branches of the right hepatic vein, and finish resecting the specimen. Six patients with hepatocellular carcinoma underwent fluorescent laparoscopic central hepatectomy.Among these, four patients underwent resections of segments four, five, and eight, and two underwent resections of only segments five and eight. The clinical parameters for the six patients are shown. It is important to separate the right anterior hepatic pedicle along the Laennec's capsule, ligate or occlude the right anterior hepatic pedicle.When there is an inaccurate fluorescent boundary, complete the operation with the help of intraoperative ultrasound and the guidance of important anatomical landmarks, like the MHV or RHV.

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573 visualizações.  Sun Yat-sen University. Este protocolo pode determinar com precisão o plano de ressecção da hepatectomia anatômica. Os cirurgiões podem realizar a ressecção no plano direito de forma tranquila usando a técnica de fluorescência sob orientação fluorescente na hepatectomia central. Após as preparações pré-operatórias, separar o parênquima hepático em um centímetro do lado direito do ligamento falciforme.Utilizando clipes, ligamos e transeccionamos vários segmentos para ramos pediculares de Gl...