The Application of Laparoscopy Combined With Indocyanine Green Fluorescence Imaging Technique for Hepatic Cystic Echinococcosis

doi:10.21203/rs.3.rs-48387/v1

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The Application of Laparoscopy Combined With Indocyanine Green Fluorescence Imaging Technique for Hepatic Cystic Echinococcosis

https://doi.org/10.21203/rs.3.rs-48387/v1

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published 22 Oct, 2020

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BACKGROUND: With the mature application of laparoscopy in hepatobiliary surgery, laparoscopic treatment of hepatic cystic echinococcosis(CE) has made certain progress. But, due to the inherent limitations of laparoscopy and the growth characteristics of cystic echinococcosis, distinguishing the boundary between cystic lesion and normal hepatic parenchyma is pivotal importance for successful sugery. Indocyanine green(ICG) fluorescence imaging technology can view the boundary of lesion and normal tissue during the treatment of hepatic cystic echinococcosis. Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis may be an effective surgical strategy.

AIM: To report and discuss single center experience of indocyanine green fluorescence imaging during laparoscopic management of hepatic cystic echinococcosis patients.

METHODS: The clinical data contained nine patients with hepatic cystic echinococcosis who underwent laparoscopic surgery with indocyanine green fluorescence imaging technique in authors’ institution from December 2018 to December 2019 were retrospectively analyzed. Indocyanine green was administered intravenously three days prior to surgery. The fluorescence acquisition system for real-time imaging was used during the surgery and the patients were followed up after surgery.

RESULTS: Of reported nine patients, six are male and the remaining three are female. The average age is (36.5 ± 7.6) years with their body weight (70.6 ± 7.2) kg. For all subjects, surgical procedures were performed under laparoscopy with indocyanine green fluorescence system. This technique showed the clear boundary of the hepatic cyst with normal liver paranchyma. Total cystectomy in six patients, subtotal cystectomy in two patients and partial hepatectomy in one patient were performed repectively. The average operation time was 228 ± 54 minutes, blood loss 206.3 ± 120.8 ml. Neither blood transfusion nor post-operative complication was experienced. The average abdominal drainage time was 3.4 ± 0.9 days with hospital stay 5.7 ± 2.1 days. During the 6-12 months follow-up period, neither recurrence nor intraperitoneal implantation was found.

CONCLUSION: Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis is safe and feasible. Enhanced boundary image can assist surgeons to complete radical resection and reduce complications.

Surgery

General Surgery

Hepatic cystic echinococcosis

Laparoscopy

Pericystectomy

Indocyanine Green (ICG)

Fluorescence imaging

Boundary

This study aimed to elucidate the safety and effectiveness of laparoscopy combined with indocyanine green fluorescence imaging technique for hepatic cystic echinococcosis. Our results demonstrated that laparoscopic management of hepatic cystic echinococcosis under the guidance of intraoperative indocyanine green imaging can improve the resection rate of pericystectomy, achieve the purpose of radical surgery, reduce perioperative complications, and make patients benefit.

Hepatic cystic echinococcosis is a zoonosis caused by the larval stage of Echinococcus granulosus and continues to be a public health threat in northwest China. Despite the sustained efforts to control and manage, the number of cystic echinococcosis patients are increasing^[1]. After entering the alimentary tract, the parasite resides itself mainly in the liver. As the mostly targeted organ, hepatic cystic echinococcosis accounts for 75% of all human cases. The treatment approach is diversiform and stage dependent according to WHO-IWGE (World Health Organization-Informal Working Group on Echinococcosis) classification^[2]. Radical resection is advocated whenever surgery is indicated. Up to now, pericystectomy and hepatectomy are the radical procedure with lower recurrence rate. However, these techniques require sophisticated hands and selective patients. Therefore, there are still space room for conservative surgery including subtotal cystectomy and endo-cystectomy^[3]. With the introduction of laparoscopic technique, the safety, feasibility and efficacy of minimal invasive technique has been approved with acceptable mortality and morbidity.

The choice for laparoscopy is usually limited by the size, site, skills and intraoperative anatomy, especially the real boundary of lesion with the normal parenchyma^[4]. Mostly, laparoscopic pericystectomy is converted to subtotal cystectomy or endo-cystectomy due to inaccurate identification of the boundary. Although, preoperative three-dimensional imaging would help surgeons to gain more detailed anatomical information, it would be more helpful if the boundary be identified intraoperatively. Previously, indocyanine green administration was reported to show the hepatocellular margins during laparoscopic resection^[5]. However, no experience is reported the feasibility of indocyanine green administration in cystic echinococcosis patients undergoing laparoscopic resection. Herein, we report our single center experience laparoscopic resection of cystic echinococcosis with indocyanine green imaging and discuss its safety, feasibility as well as effectiveness along with surgical outcomes.

Clinical information

In current study, we have retrospectively analyzed the clinical data of nine patients who were diagnosed with hepatic cystic echinococcosis and received laparoscopic resection at Hepatobiliary Surgery Department of People's Hospital of Xinjiang Uygur Autonomous Region from December 2018 to December 2019. Routine cardio-pulmonary evaluation was carried out for all subjects. Serum analysis, abdominal ultrasound and computed tomography (CT) were also routinely carried out for the diagnosis and evaluation for lesion size, site and its correlation with major vessels. The diagnosis for cystic echinococcosis was confirmed by postoperative pathology in all subjects. No patients were preoperatively administered with albendazole.

Configuration and injection of ICG

ICG (Brand name: Ruidu, SFDA approval number H20055881), specification 25 mg / piece, solvent is sterilized water for injection. Generally, it is injected intravenously in the periphery. Slowly and uniformly during the injection, closely observe the changes of the patient's heart rate, blood pressure, breathing, and oxygen saturation, and beware of allergic reactions. The injection timing is divided into preoperative injection and intraoperative injection.

Preoperative injection: 3 days before surgery, the dose is 0.5 mg/kg and the concentration is 5 mg/ml; Intraoperative injection: When the laparoscopic lens is inserted into the operation, the dose is 2.5 mg and the concentration is 2.5 mg/ml. When configured, the ICG powder is thoroughly mixed with the sterilized water for injection, and can be used for injection after it is completely dissolved. Note: The ICG solution should be freshly prepared. Do not use normal saline to dissolve the powder.

ICG fluorescence imaging: The fluorescence imaging system is an endoscopic fluorescence imaging system (PINPIONT), which consists of a video processor/light source (VPI), a camera, and a display. The camera irradiates the liver with excitation light at about 780 nm, and collects near-infrared light at about 840 nm. After processing by the host, the image is displayed.

Surgical methods

The patients were positioned in supine position and intubated, then 100 mg of hydrocortisone was administered intravenously to prevent possible allergic reactions. During the surgery, the central venous pressure was reduced to less than 5 cm of water column. The pneumopertonean was established and pressure maintained at 10-12 mmHg. The trocars were positioned corresponding to the size and site of the lesion. After thorough exploration, the small omental sac was dissected by using harmonic. First hilum was suspended ventricle drainage tube for hilar control whenever needed. Hepatic tissue was isolated from the gastrointestinal with hypertonic saline (100 g/kg) gauze. When the cystic wall is thin with high tension, the puncture device combined with echinococcosis rotary cutter was introduced decompress the cyst. Puncture site was carefully clipped or suture closed.

Pericystectomy is indicated for patients with single superficial lesion whose outer capsule wall thickness more than 3mm and no major vascular involvement. Hepatic parenchyma was dissected by using ultrasonic scalpel and CUSA under direct vision of PINPOINT system. Any vessels entering the lesion was clipped or sutured closed, and Endo-GIA was used whenever needed.

Subtotal cystectomy: Subtotal cystectomy was performed when the cyst was critically adjunct with major vasculatures. The space between cyst and hepatic parenchyma was identified following the PINPOINT system. The partial wall of the cyst was reserved aiming to avoid possible bleeding and / or leakage. Any larger biliary tracts or blood vessels entering the lesions was clipped whenever needed.

Partial hepatectomy：Due to the obvious fibrosis or atrophy of the liver tissue at the lesion site, it is located in the liver parenchyma, cause difficulties for hydatid cyst external cystectomy. Partial hepatectomy should be performed for cases involving invasion of liver important ducts. Use ultrasound knife combined with CUSA to cut off liver tissue, for larger bile ducts or blood vessels, titanium clips or bioclamps should be used for clamping, and Endo-GIA should be used for the second hepatic hilum.

ICG fluorescence imaging: The lesion boundary was clearly marked via PINPOINT system by using green fluorescence. The accurate site of the lesion and boundary with normal parenchyma was determined.

Routine abdominal drainage was practiced in all subjects and removed after surgery After the patients' liver function was normal, they were routinely given. Oral albendazole with dose of 20 mg/kg per day was administered for at least one month each course, for 6 consecutive courses of treatment with intervals of 7 to 10 days between each course of treatment.

Follow-up

Patients were followed up by telephone or outpatient after discharge. Ultrasound, routine blood test, liver function, medication status and any possible symptoms were carefully followed-up to June 30, 2020.

Statistics

IBM SPSS22.0 statistical software was used for data analysis. Quantitative data were expressed as mean ± standard deviation, qualitative data were used with rate description.

Baseline information

A total of 9 patients were included in this study, 6 males and 3 females, with average age of (36.5 ± 7.6) years and body weight of (70.6 ± 7.2) kg. Five Uyghur, two Kazakh, one Han and one Tibet patients were enrolled current study. All subjects have lived or ever travelled to affected area for cystic echinococcosis. The most frequent symptoms are intermittent upper abdominal pain in five patients, while, remaining four patients were identified during the routine physical examination. Of reported nine patients, five were positive and the rest four were negative. The preoperative abdominal ultrasonographical image and CT (Fig. 1A) indicated the diagnosis for cystic echinococcosis. All subjects were graded as Child-Pugh grade A ans no patients have previous surgical history. The cysts were categorized according to the WHO/IWGE classification. There were 4 cases of multiple daughter cyst (CE2) and 5 cases of Ruptured cyst (CE3). The lesion is mainly located in the right lobe of the liver, with a maximum diameter of 9.4 ± 2.3 cm. There is no biliary obstruction and jaundice before surgery. The bile component can be seen in the cyst contents in some lesions, suggesting that it may occurs slightly bile leaks. (Table 1).

Table 1

General clinical information
Cases	Pathology (WHO-IWGE)	Lesion location	Maximum diameter (cm)	Preoperative infection/bile leakage	Operation method
1	CE2	S3	6	No	Pericystectomy
2	CE2	S5-6	9	No	Pericystectomy
3	CE2	S3-4	10	Bile leakage	Subtotal cystectomy
4	CE2	S7-8	10	Infection, bile leakage	Pericystectomy
5	CE3a	S5-8	8	Bile leakage	Pericystectomy
6	CE3a	S6-7	11	Bile leakage	Subtotal cystectomy
7	CE3b	S5-6-7-8	14	Infection, bile leakage	Right hemihepatectomy
8	CE3b	S5-6	10	Bile leakage	Pericystectomy
9	CE3a	S6	7	No	Pericystectomy
Two cases underwent subtotal cystectomy due to major vascular invasion in the liver. One case underwent right hemihepatectomy due to the first hepatic portal vascular invasion of the right liver.

Surgical parameters of patients

All patients successfully underwent laparoscopic surgery. Neither conversion to open laparotomy occurred nor allergic reaction caused by the overflow of hydatid cyst fluid during the operation was occurred; Among them, 6 patients underwent laparoscopic pericystectomy, 2 patients underwent subtotal cystectomy and 1 patient underwent partial hepatectomy. The average operation time was 3.8 ± 0.9 hours, taverage intraoperative bleeding was 206.3 ± 120.8 ml, and no blood transfusion occurred. Exploration of cutting edges resulted with small biliary leakage in four patients and laparoscopically sutured. No bile leakage was observed, no T-tube was placed in the patients, and no complications such as bile leakage or bleeding occurred after surgery. The patients carried drainage tube after operation for average 3.4 ± 0.9 days, and the average postoperative hospital stay was 5.7 ± 2.1 days. The patients were followed-up averagely for 9.7 ± 1.9 months. All of them completed the follow-up. None of the patients had recurrence of hepatic cystic echinococcosis or abdominal implantation.

Results of fluorescence imaging of hepatic cystic echinococcosis

ICG was intravenously administered three days prior to surgery with no allergy. A weak circular fluorescent shadow was imaged in one CE3b patient, which was thought to as the patient's lesion is huge and compress the surrounding bile ducts, which caused the obstruction of ICG excretion. In the remaining cases, their ICG metabolism was complete, and their normal liver and hydatid lesions showed no fluorescence.

All patients received intraperitoneal injection of ICG. From Fig. 1B, it can be seen that sometimes the boundary between cystic hydatid lesions and normal liver tissue is not very clear. From Fig. 1C, it can be seen that the hepatic cystic echinococcosis lesion has no fluorescence display, the image is black, and it will not change significantly with the extension of the ICG injection time. The surrounding liver tissue is green fluorescent. A clear dividing line can be seen between the two parts. If the lesion is located in the liver parenchyma, the fluorescence imaging cannot show the echinococcal lesion. After the liver parenchyma is disconnected, the light green fluorescence of the liver cut surface can be seen, and the liver hydatid lesion is still black. Observing the liver section and imaging after hepatic cystic echinococcosis lesion resection, no residual lesion was found (Fig. 2).

To the best of out knowledge, this is one of the few reports about laparoscopic management of hepatic cystic echinococcosis under the guidance of intraoperative ICG imaging. Our results showed that ICG imaging could help surgeon to find the space between the lesion and normal parenchymal lesion and facilitate surgical process.

With the mature application of laparoscopy in hepatobiliary surgery, laparoscopic treatment of hepatic cystic echinococcosis has made great progress and achieved good results^[6]. Endo-cystectomy is related withhigher incidence of residual cavity complications (8.28% ~ 65.8%), recurrence rate (1.5% ~ 36.6%), and reoperation rate (2.2% ~ 3.2%) as well as biliary fistula (19.4%) compared to pericystectomy^[7]. As radical modality option, pericystectomy and hepatectomy hydatid significantly reduce the risk of postoperative complication^[8]. However, due to the inherent limitations of laparoscopy and the growth characteristics of cystic echinococcosis, distinguishing the boundary between cystic lesion and normal hepatic parenchyma is pivotal importance for successful sugery. Although laparoscopic ultrasound can determine the location of the tumor during the operation, it may fail to monitor the resection margin in real time. In recent years, with the application of ICG fluorescence imaging in laparoscopic surgery, laparoscopic liver tumor resection has realized visualization of tumor resection margins^[9]. Laparoscopic pericystectomy and / or partial hepatectomy as the radical option for cystic echinococcosis still limited due to accessibility to lesion, visibility of boundary between lesion and normal tissue. Besides, failing to identify boundary may result in devastating rupture of the cyst and concurrent possible septic shock and implantation of the cystic lesion^[10]. In current study, we have applied ICG fluorescence imaging technology to view the boundary of lesion and normal tissue during laparoscopic treatment of hepatic cystic echinococcosis. We observed that at the beginning of the surgery, after ICG was administered peripherally, a certain intensity of fluorescence could be observed in normal liver tissues after 3 to 5 minutes, but no fluorescence appeared in the cystic hydatid lesion tissue, and this part was shown as in black. With the extension of observation time, the fluorescence intensity of normal liver tissues of patients will become greener, but the lesion tissues have no obvious changes. Laparoscopic ICG fluorescence imaging can visualize the lesion boundary in real time, define the surgical margin, improve the rate of complete excision of the outer capsule, and reduce complications such as postoperative bile leakage and recurrence. When the surgeon dissects the liver along the vixulization ischemic line, even in the absence of clear markers in the liver parenchyma, the boundaries between the liver segments can be clearly shown inside the liver parenchyma, thereby reducing the need the stripping operation. When the location of the lesion is so deep that the location of the lesion cannot be determined by fluorescence imaging of the liver surface, intraoperative ultrasound detection can be used in combination, or the liver parenchyma can be cut at a pre-determined location to find the lesion.

Bile leakage is one of the common complications after surgery and severly affects the postoperative recovery of patients, and even requires indwelling bile duct T-tube drainage during operation, sometime, causing the patients need long-term T-ub^[11]. Since ICG is excreted from the body through bile metabolism, that can help determine bile leakage during surgery. At the same time, the ICG fluorescence fusion image can show the biliary tract movement and the existence of mutations, which has a certain effect on reducing biliary tract injury during the operation. In addition, the application of ICG fluorescence imaging can find other imaging techniques or lesions that cannot be found by inspection and palpation, which can effectively reduce the postoperative recurrence of the lesions^[12]. In laparoscopic metastatic liver cancer resection, ICG fluorescence imaging combined with intraoperative ultrasound detection is significantly better than preoperative CT or intraoperative ultrasound in detecting lesions smaller than 3mm^[13]. In this group of cases, we performed intraoperative ICG fluorescence examination of the liver section without residual lesions. In the imaging review performed after operation, and no lesion remained. This method achieves the goal of radical resection, avoids residual lesions, and benefits for the patients.

However, we also recognize that ICG fluorescence development also has certain limitations: (1) The penetration depth of the fluorescent tissue emitted by ICG is only 5–10 mm, so for deeper hydatid lesions, intraoperative ultrasound should be used in combination. (2) The uptake and distribution of ICG in the liver are affected by many factors. The diffusion imaging of the fluorescence boundary is common, and the recirculation can also reduce the fluorescence difference in the liver area. (3) The imaging effect of ICG is affected by many factors such as liver function status, so, it is difficult to choose the precise time and dose of administration according to the specific condition of the patient.

This study retrospectively analyzed the data of 9 patients with hepatic cystic echinococcosis who underwent laparoscopic combined ICG. This method may improve the opportunity of radical resection of the disease and reduce the incidence of common intraoperative and postoperative complications.

ICG: Indocyanine green; CE: Cystic echinococcosis; WHO-IWGE: World Health Organization-Informal Working Group on Echinococcosis; CT: Computed tomography; S: Liver segmentation, according to Couinaud.

Acknowledgements

Not applicable.

Author contributions

Li YP and Ma ZG contribute equally to this work; Li YP and Ma ZG analyzed and interpreted data and wrote the article; Tuxun T and Li ZD collected the data; Meng Y provided clinical advice; Chen X designed the study.

Source of Funding

No funding.

Availability of data and materials

All data generated or analysed during this study are included in this published article. No additional data are available.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in

accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was reviewed and approved by Ethics Committee of People's Hospital of Xinjiang Uygur Autonomous Region.

Informed written consent (not separate, but included in the preoperative consent) was obtained from all individual participants included in the study. The analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Writing assistance: No writing assistance was needed for the preparation of this manuscript.

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The Application of Laparoscopy Combined With Indocyanine Green Fluorescence Imaging Technique for Hepatic Cystic Echinococcosis

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