Arterial Base Fluorescence Segmental Positive Staining

Hepatic Carcinoma Clinical Trial

Official title:

Superselective Intra-arterial Hepatic Injection of Indocyanine Green (ICG) for Fluorescence Image-guided Segmental Positive Staining

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04266548
• Other study ID #: CGMH-20170147A3
• Status: Completed
• Phase: N/A
• Start date: July 9, 2018
• Est. completion date: January 6, 2020

Study information

• Verified date: February 2020
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

More and more laparoscopic hepatectomy were performed due to increasing experience, well designed instruments and energy device. But the localization of tumor and resection line design are still relative difficult comparing open approach due to limit space. Intraoperative liver segmentation can be obtained by ultrasound-guide intraportal injection of a fluorophore and illuminating with a Near-Infrared light source for positive staining and by intravenous injection after ligation of segmental vessels for negative staining .The ultrasound guide intraportal injection approach is challenging in the minimally-invasive setting. However hepatocelluar carcinoma(HCC) was supplied by hepatic artery mainly. The investigators aimed to evaluate the feasibility of arterial base positive staining for fluorescence liver segmentation in human by superselective intra-hepatic artery injection of Indocyanine Green (ICG) .

Description:

Materials and Methods

1. Participants The present prospective, single-center, feasibility study of fluorescence demarcation of hepatic segment including HCC by means of direct super-selective intrahepatic artery ICG injection. Patients were enrolled according to the following criteria: single HCC, scheduled for laparoscopic hepatectomy for curative resection, age ranging from 20 to 85 years old, absence of proven or suspected allergies to iodine or ICG, absence of coagulopathy, absence of diseases contraindicating general anesthesia, and absence of pregnancy.

All the bio-chemical test, cardiac echo , cardiac thalium test, ICG clearance test, Liver CT or MRI were obtained before operation

2. Equipment Endovascular procedure was performed in the conventional angiography room and laparoscopic hepatecotmy was done in operating room at the Kaohsiung Chang Gung memorial hospital. Near infra-red fluorescence laparoscopy was used to acquire the fluorescence signal arising from the liver parenchyma after Indocyanine Green (ICG) injection.

3. Procedures

1. Celiac trunk angiography and super-selective hepatic angiography:

A 4 Fr angiography sheath (Terumo Europe NV, Belgium) was placed under aseptic conditions in the right femoral artery, using the Seldinger technique. A 4 Fr Cobra-2 catheter (Terumo Europe NV, Belgium) was positioned at the origin of the celiac trunk. A selective celiac trunk digital subtraction angiographic (DSA) run was performed, after injection of a contrast medium (Visipaque 270, GE Healthcare; Buckinghamshire, United Kingdom), 28mL at a rate of 4mL/sec. A 2.7 French micro-catheter (Progreat™, Terumo Europe NV; Belgium) was used to super-selectively catheterize different hepatic segmental arteries supplying the target hepatic segment including HCC. In all cases, the position was controlled by performing DSA and angio computer tomography runs with selective micro-catheter injections. The micro-catheter was then perfused with saline and left in place until surgery. Then the patients were transferred to operative room while operative room available.

2. Evaluation of hepatic segmental demarcation using NIR real-time imaging during laparoscopic hepatectomy:

The patients underwent a standard 5-port laparoscopic hepatectomy, which was performed by 2 experienced laparoscopic surgeons .

Stage I : the liver mobilization was performed for preparing the hepatectomy. The intraoperative ultrasound was used for localization of HCC. The resection line was defined as principle of laparoscopic hepatectomy such as surgical margin, surgical volume and etc. The pringle control device was prepared.

Stage II : Rea-time enhanced visualization of the hepatic segment which were supplied feeding artery was achieved by means of fluorescence imaging using a direct selective intrahepatic artery injection of a 5 mL bolus of ICG (DiagnoGreen®, Taiwan, ROC) at a concentration of 0.125mg/mL. The demarcation of enhanced hepatic segment were defined. The correspondence between the fluorescence margin and ultrasound(US) guide resection line were analized.

Stage III: The surgical resection line was chose by real time clinical judgement including analysis of information of US, artery-base CT, fluorescence image, liver anatomy and patient condition. The laparoscopic hepatectomy was performed with pringle vascular control.

Stage IV: the specimen information including tumor size and margin in vitro was recoded. The distance between surgical margin and enhanced liver were measured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 6, 2020
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 85 Years

Eligibility

Inclusion Criteria:

• Single Hepatocellular carcinoma.

• plan of Laparoscopic hepatectomy.

• Age between 20 to 85 y/o.

Exclusion Criteria:

• allergies to iodine or ICG

• Liver cirrhosis

• coagulopathy

• chronic kidney disease

• pregnancy

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatic Carcinoma

Intervention

Procedure:
• Superselective Intra-arterial Hepatic Injection of Indocyanine Green (ICG) for Fluorescence Image-guided Segmental Positive Staining
The patients with single HCC which is planned to received laparoscopic hepatectomy were involved. Procedures were performed in conventional angiography room. The celiac trunk was catheterized and a microcatheter was advanced into segmental hepatic artery branches which supplied the HCC. The 5cc 0.125 mg/cc ICG was injected from super-selective hepatic artery in operative room. A Near-Infrared laparoscope was used to detect the fluorescent signal to assess the correspondence between arterial-based fluorescence demarcation and ultrasound-based surgical demarcation.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Niaosong	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (11)

Aoki T, Yasuda D, Shimizu Y, Odaira M, Niiya T, Kusano T, Mitamura K, Hayashi K, Murai N, Koizumi T, Kato H, Enami Y, Miwa M, Kusano M. Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection — View Citation

Diana M, Liu YY, Pop R, Kong SH, Legnèr A, Beaujeux R, Pessaux P, Soler L, Mutter D, Dallemagne B, Marescaux J. Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept. Surg Endosc. 2017 Mar;31(3):1451-1460. doi: 10.1007/s00464-016-5136-y. Epub 2016 Aug 5. — View Citation

Ferrero A, Lo Tesoriere R, Russolillo N, Viganò L, Forchino F, Capussotti L. Ultrasound-guided laparoscopic liver resections. Surg Endosc. 2015 Apr;29(4):1002-5. doi: 10.1007/s00464-014-3762-9. Epub 2014 Aug 19. — View Citation

Gotoh K, Yamada T, Ishikawa O, Takahashi H, Eguchi H, Yano M, Ohigashi H, Tomita Y, Miyamoto Y, Imaoka S. A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol. 2009 Jul 1;100(1):75-9. — View Citation

Ishizawa T, Gumbs AA, Kokudo N, Gayet B. Laparoscopic segmentectomy of the liver: from segment I to VIII. Ann Surg. 2012 Dec;256(6):959-64. doi: 10.1097/SLA.0b013e31825ffed3. — View Citation

Ishizawa T, Zuker NB, Kokudo N, Gayet B. Positive and negative staining of hepatic segments by use of fluorescent imaging techniques during laparoscopic hepatectomy. Arch Surg. 2012 Apr;147(4):393-4. doi: 10.1001/archsurg.2012.59. — View Citation

Makuuchi M, Hasegawa H, Yamazaki S. Ultrasonically guided subsegmentectomy. Surg Gynecol Obstet. 1985 Oct;161(4):346-50. — View Citation

Rethy A, Langø T, Mårvik R. Laparoscopic ultrasound for hepatocellular carcinoma and colorectal liver metastasis: an overview. Surg Laparosc Endosc Percutan Tech. 2013 Apr;23(2):135-44. doi: 10.1097/SLE.0b013e31828a0b9a. Review. — View Citation

Sakoda M, Ueno S, Iino S, Hiwatashi K, Minami K, Kawasaki Y, Kurahara H, Mataki Y, Maemura K, Uenosono Y, Shinchi H, Natsugoe S. Anatomical laparoscopic hepatectomy for hepatocellular carcinoma using indocyanine green fluorescence imaging. J Laparoendosc — View Citation

Shindoh J, Seyama Y, Matsuda M, Miyata Y, Shida D, Maeshiro T, Miyamoto S, Inoue S, Umekita N. Continuous ultrasound navigation for safe and precise anatomic resection of the liver. Hepatogastroenterology. 2013 May;60(123):590-4. — View Citation

Tanaka T, Takatsuki M, Hidaka M, Hara T, Muraoka I, Soyama A, Adachi T, Kuroki T, Eguchi S. Is a fluorescence navigation system with indocyanine green effective enough to detect liver malignancies? J Hepatobiliary Pancreat Sci. 2014 Mar;21(3):199-204. doi — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fluorescent hepatic segment demarcation area	The surface size of fluorescent enhanced hepatic segment were measured as cm x cm .	intra-operative period
Primary	the rate of fluorescent demarcation corresponding to US guide resection area	The evaluation of the fluorescent hepatic surface which is included in the resected area or not	intra-operative period
Primary	The minimal distance between tumor and fluorescent margin	The distance between tumor edge and fluorescent parenchyma edge was measured as cm. This purpose was to evaluation the oncologic safety if the resection line is following the fluorescent margin	intra-operative period
Primary	The minimal surgical margin	The distance between tumor edge and resected parenchyma edge was measured as cm.	intra-operative period
Primary	surgical benefit rate of fluorescent image	If the fluorescent enhanced area is similar to resected parenchyma or the information of fluorescent image change the primary surgical plan, it was indicated benefit for surgery.	intra-operative period
Secondary	Post operative complication	any complication related to surgery	one months after operation
Secondary	Post operative angiography procedure complication	any complication related to angiography procedure	one months after operation
Secondary	Post operative hospital stay	The day in hospital after operation	one months after operation
Secondary	Post operative Mortality	any mortality related to surgery	any complication related to surgery