Indocyanine Green-Guided Intraoperative Imaging to Facilitate Video-Assisted Retroperitoneal Debridement for Treating Acute Necrotizing Pancreatitis

This protocol presents Indocyanine Green-guided video-assisted retroperitoneal debridement (ICG-guided VARD) for treating severe acute necrotizing pancreatitis.

Video-assisted retroperitoneal debridement (VARD) is a feasible, minimally invasive necrosectomy method for treating severe acute necrotizing pancreatitis, if it does not resolve or is accompanied with infected necrosis in the retroperitoneum. As there are rarely any visually clear separating surface in white light image between necrotic debris and adjacent inflammatory normal tissues due to extensive retroperitoneal adhesions, VARD is accompanied with the risk of vascular injury, external pancreatico-cutaneous or enterocutaneous fistulae. In view of the above disadvantages, we apply real-time intraoperative near-infrared fluorescence imaging with indocyanine green (ICG) during VARD, which enables visualization of the well-perfused adjacent normal tissues. This modified technique (ICG-guided VARD) can provide a clear separating surface during debridement and reduce the risk of vascular or enteric injury. ICG-guided VARD may facilitate surgeons to perform safer debridement in treating severe acute necrotizing pancreatitis.

Acute pancreatitis (AP) is one of the most common digestive diseases and brings enormous medical and economic burden to patients. About 20% of AP patients develop severe acute pancreatitis (SAP) that gets complicated with infected necrosis or persistent organ dysfunction¹. SAP is usually associated with higher morbidity rate and mortality rate (up to 30%)¹. In SAP patients with infected necrosis having persistent organ dysfunction or failure to recover after percutaneous drainage (PCD), or suffering from gastrointestinal or biliary obstruction, operative debridement should be considered^1,2.

In the minimally invasive era, there are multiple approaches to operative debridement beside open surgery, including endoscopic transluminal necrosectomy, laparoscopic or open transgastric debridement, and video-assisted retroperitoneal debridement (VARD), which is the part of the step-up approach^1,2. VARD is the preferred approach for patients with left-sided distribution of infected necrosis extended to paracolic gutter or deep to the retroperitoneum². As there are rarely any visually clear separating surface in white light image under laparoscopy between necrotic debris and adjacent inflammatory normal tissues due to extensive retroperitoneal adhesions, VARD is inevitably accompanied by the risk of vascular injury, external pancreatico-cutaneous, or enterocutaneous fistulae^3,4,5.

Real-time intraoperative near-infrared fluorescence imaging with indocyanine green (ICG) has been applied to facilitate perfusion assessment of bowel^6,7 and visualization of biliary and vascular anatomy^8,9. In view of the above disadvantages of VARD, we apply real-time near-infrared fluorescence imaging with ICG during VARD that enables the visualization of the well-perfused adjacent normal tissues and vascular structure. This modified technique (ICG-guided VARD) can provide a clear separating surface during operative debridement and reduced risk of vascular or enteric injury. ICG-guided VARD may facilitate surgeons to perform safer debridement in treating severe acute necrotizing pancreatitis.

Study protocol was approved by the ethics committee of the First Affiliated Hospital of Sun Yat-sen University and the study was conducted in accordance with the Helsinki Declaration. Written informed consents were obtained from patients.

1. Inclusion-exclusion criteria

1. Include adult acute pancreatitis patients with evidence of infected necrosis that required an indication for invasive intervention.
   NOTE: Acute pancreatitis is defined when at least two of the three following features are observed in patients 1) typical upper abdominal pain, 2) level of serum amylase or lipase above three times the upper level than normal, 3) typical findings of cross-sectional abdominal CT or MRI imaging^10,11,12. Infected necrosis is defined as a positive culture obtained by fine needle aspiration or PCD of necrotic collections, or the presence of gas configurations within necrotic collections on contrast enhanced CT image.
2. Exclude patients with previous invasive interventions for necrotizing pancreatitis, acute episode of chronic pancreatitis, recurrent acute pancreatitis and with indications for emergency laparotomy (i.e., abdominal compartment syndrome, perforation or bleeding of a visceral organ, and gastrointestinal or biliary obstruction).

2. VARD procedure

1. Firstly, in acute necrotizing pancreatitis patients with above criteria, place ultrasound-guided percutaneous pigtail catheters (14 Fr or 16 Fr) into the left or right retroperitoneum to drain peripancreatic or necrotic collections, that can be located on the contrast enhanced CT image. (If condition permitted, duration of PCD placement should be maintained within about 4 weeks after the onset of AP for necrotic collections to demarcate and wall-off.
2. If infected collections persisted and patients' clinical situation deteriorates (progressive elevation of body temperature, elevated white blood cell count, C-reactive protein and procalcitonin, new onset of progressive organ dysfunction), be sure to provide surgical intervention and apply VARD in these patients^1,2.
3. Place the patient in supine position or in supine position with the left side 30-40° elevated, and under general anesthesia.
4. Make a skin incision (12 mm) at the site of previous pigtail catheter and gently dilate the tract with forceps.
5. Insert a 12 mm laparoscopic trocar along the tract to the retroperitoneal necrotic collections followed by the removal of the pigtail catheter.
6. Apply carbon dioxide pneumoretroperitoneum (11 mmHg to 12 mmHg) if a wider debridement space is needed by insufflating carbon dioxide through this 12 mm trocar.
7. Place a near-infrared fluorescence laparoscopy via the observing trocar and make one additional incision (10 mm) subcostal in the left (or right) flank at the mid-axillary line, under laparoscopy monitoring (the incision can be close to the exit point of the percutaneous drain if another drainage pigtail catheter existed). The incision should be at least at a 8 cm distance from the observing trocar.
8. Insert a 10 mm laparoscopic trocar from above the incision and remove necrotic debris using laparoscopic graspers. Necrotic debris turn out to be a retroperitoneal mass with grayish yellow under white light image or low contrasted under fluorescence image. Aspirate the collections by laparoscopic aspirator via the operative trocar. Extend the above incision to 5 cm with electrotome under laparoscopy monitoring if removal of the larger pieces of necrosis is needed.

3. ICG-guided intraoperative fluorescence imaging

1. After insertion of a 10 mm operative trocar and before beginning to separate necrotic debris from adjacent normal tissue using laparoscopic forceps, switch the display mode of the laparoscopy to multi-display mode (white light image and fluorescence image are displayed separately in Picture-in-Picture mode).
2. Inject the first bolus of ICG (0.1 mg/kg body weight) intravenously in a peripheral vein. Then, follow with a flush of 10 mL of saline. After 10 to 20 s, visualize peak perfusion of adjacent normal tissues or vessels in the fluorescence field. A clearer separating surface can be distinguished from the debris.
3. Only remove poorly perfused and loosely adherent necrotic debris using laparoscopic graspers. Avoid tearing the underlying bowel or vessel.
4. Inject another bolus of ICG (0.1 mg/kg body weight) intravenously if ICG fluorescence decay.
5. After the removal of the bulk of necrotic debris, irrigate the cavity of the retroperitoneum with saline and aspirate with laparoscopic aspirator until the lavage fluid becomes clear.
6. Place at least one pair of drainage tubes at the deepest region of the cavity after debridement. Suture the fascia and skin and close.

4. Postoperative management

1. Perform continuous lavage with sterile saline and repeat CT scan 1 week after the VARD procedure.

ICG-guided VARD had been successfully performed in three severe acute necrotizing pancreatitis patients from June 2021. Characteristics of these patients at baseline and after VARD are included in Table 1. The first patient who received ICG-guided VARD was a male, 41-year-old patient who was admitted on 20th June 2021. He suffered from moderately acute necrotizing pancreatitis. Abdominal contrast enhanced CT scan revealed (as shown in Figure 1 and Table 1) that necrotic collections consist of the lesser arc, peri-pancreatic space, and extended to the bilateral retroperitoneum. Infected necrosis in the right retroperitoneum was persistent after initial PCD drainage and the first VARD was performed about 4 weeks after the onset of pancreatitis (Figure 1). After multidisciplinary team discussion, ICG-guided VARD was applied in this patient. Figure 1 shows representative intraoperative images of necrotic debris and adjacent normal tissue in the cavity of the right retroperitoneum after ICG injection, using near-infrared fluorescence laparoscopy. ICG perfusion of adjacent normal tissues or vessels can be visualized in the fluorescence field and a clearer separating surface can be distinguished from the debris. We removed necrotic debris using laparoscopic graspers while preserving the adjacent normal tissues or vessels. Infected necrosis was resolved and drainage tubes were removed on POD7 after ICG-guided VARD (Figure 2). The patient was discharged on POD14.

Table 1: Characteristics of the Patients at Baseline and after VARD. Please click here to download this Table.

Figure 1: ICG-guided VARD in the debridement of infected necrosis in the right retroperitoneum. (A) Coronary abdominal contrast enhanced CT image revealed that infected necrosis in the right retroperitoneum was persistent after PCD drainage; (B) intraoperative images of ICG perfused adjacent normal tissues or vessels and necrotic debris in the cavity of the right retroperitoneum by near-infrared fluorescence laparoscopy (simultaneous images of the white light field and the fluorescence field, which were displayed separately in Picture-in-Picture mode). Please click here to view a larger version of this figure.

Figure 2: Representative contrast enhanced CT images before and after ICG-guided VARD. Consecutive serial coronary abdominal contrast enhanced CT image revealed that infected necrosis (the presence of gas configurations within necrotic collections and indicated by the red arrows) were located in the right retroperitoneum (upper row of CT images revealed pancreatic necrosis before ICG-guided VARD) and were significantly resolved after ICG-guided VARD (lower row of CT images revealed pancreatic necrosis completely resolved after ICG-guided VARD). Please click here to view a larger version of this figure.

The present study reveals that ICG-guided real-time intraoperative near-infrared fluorescence imaging may provide benefit to perfusion assessment and visualization of adjacent normal tissues during debridement in VARD.

In the minimally invasive era, the step-up approach consisting of PCD or endoscopic transmural drainage followed by endoscopic necrosectomy or surgical debridement, such as VARD, has been regarded as standard treatment of severe acute necrotizing pancreatitis patients¹. As shown in several large randomized trials (PANTER trial, MISER trial, etc.)^10,11,12,13 and proven in clinical practice, in the past 10 years, these less invasive strategies compared to traditional open necrosectomy can reduce the risk of surgical stress, new-onset organ dysfunction, incisional hernia, external fistulas, pancreatic exocrine and endocrine insufficiency^1,2. Though debridement techniques have achieved great advancement in these years, retroperitoneal debridement is accompanied by a relatively high risk (up to 35%) of vascular injury, external pancreatico-cutaneous or enterocutaneous fistulae, partly since there is rarely a visually clear separating surface in white light image between necrotic debris and adjacent inflammatory normal tissues as a result of extensive retroperitoneal adhesions^3,4,5.

Real-time intraoperative near-infrared fluorescence imaging with (ICG) has been successfully applied to facilitate perfusion assessment of bowel for colectomy and visualization of biliary and vascular anatomy for pancreatic surgery or nephrectomy. In view of the above pitfalls of VARD, we apply real-time near-infrared fluorescence imaging with ICG during VARD, that enables visualization of the well-perfused adjacent normal tissues such as bile duct, posterior wall of small intestine and colon, and vascular structure of mesenteric vessels. etc., These are identified as ICG perfused (bright green in the fluorescence mode) while necrotic debris are not perfused (relatively dark in the fluorescence mode) and gray (in the white light mode). This modified technique (ICG-guided VARD) provides a clearer separating surface and reduced risk of iatrogenic vascular or enteric injury during operative debridement.

In conclusion, ICG-guided VARD is an easy and feasible approach to visualize the well-perfused adjacent normal tissues and vascular structure of mesenteric vessels, that may facilitate surgeons to perform safer debridement in treating severe acute necrotizing pancreatitis. It warrants further study to quantitate the time-intensity curve and time to peak perfusion of normal tissues and vessels, and randomized clinical trials to confirm the practicability of ICG-guided VARD in the future.

The authors declare that they have no competing interests.

The authors thank Prof. Yu Guo and Prof. Yunpeng Hua (Department of Liver Surgery, the First Affiliated Hospital, Sun Yat-sen University) for providing advice and careful review. This work was supported by the National Natural Science Foundation of China (81201919), the Natural Science Foundation of Guangdong Province (2017A030313495).