Living-donor small bowel transplant has emerged as a modality to transplant patients with short bowel syndrome without prolonged wait time, albeit at the cost of technical challenges associated with vascular anastomosis due to the small size of vessels. Suboptimal perfusion in a transplanted bowel can lead to a devastating outcome, and clinical judgment alone is not completely reliable for assessment of bowel microcirculation. Here, we report a 55-year-old female patient who underwent flow cytometric cross-match-positive living-donor bowel transplant from her daughter. Initial suboptimal perfusion prompted a revision of the arterial anastomoses. Despite normal Doppler signals over the mesenteric vessels, the bowel had a variegated appearance. The microcirculation of the bowel wall was subsequently assessed in a real-time fashion by indocyanine green fluorescence angiography, which showed improved perfusion indices with time. Hence, this simple test helped us to avoid another unnecessary exploration and revision of the anastomoses. At present, the patient is thriving on an enteral diet. This case underpins the importance of real-time intraoperative assessment of bowel per-fusion and microcirculation in difficult cases.
These assessments are needed to help surgeons identify tissues at risk for ischemia and necrosis, thereby allowing for maneuvers to improve intestinal viability.
Key words : Bowel perfusion, Fluorescence, Indocyanine green, Near-infrared fluorescence
Central to the success of bowel transplant is adequate revascularization and perfusion during the process of implantation. Compared with deceased-donor small bowel transplant, vascular anastomosis is more challenging in living-donor small bowel transplant procedures due to the small size of donor vessels. Despite improvements in vascular implantation techniques, vascular complications in organ transplant still pose a significant problem and may jeopardize outcomes.1 Most early vascular problems are due to technical inaccuracies. Clinical assessment of intestinal perfusion and viability based on the color of the serosal surface, the presence of bowel peristalsis, pulsation, and bleeding from the marginal arteries may be subjective and deceptive.2 Moreover, it does not provide objective information about microcirculation. Numerous techniques for assessing various parameters of intestinal viability have been described in gastrointestinal surgery.3 However, surgeons have been unable to incorporate these technologies into clinical practice as they are highly user dependent and involve a steep learning curve. Therefore, simple, quantitative, real-time, intra-operative methods of assessment of bowel micro-circulation are of paramount importance. The ability to recognize suboptimal bowel perfusion intraop-eratively could help avoid disastrous posttransplant consequences.
Recently, near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) has emerged as a valuable method, offering real-time intra-operative imaging, perfusion, and microcirculation assessment capabilities in a number of clinical scenarios.4 Indocyanine green is an inert, safe, water-soluble, nonradioactive, and nontoxic contrast agent, which was approved by the US Food and Drug Administration in 1959. After intravenous admin-istration, it is rapidly bound to plasma proteins and exclusively excreted through the biliary system, with a half-life in blood of 2.5 to 3 minutes. With the use of a laser light source at 40 mW/cm at 806 nm, a molecule will fluoresce in a predictable fashion at 830 nm, which can be detected by a charged-couple device camera system (Spy Elite, Novadaq Technologies, San Jose, CA, USA) with florescence intensity proportional to the perfusion of a given area. The area of florescence can be viewed in gray scale or heat map mode, as relative quantification in percentages from 0% to 100% in relation to an internal anatomic reference that is positioned based on clinical judgment. In addition, various perfusion indices can be calculated by Spy software derived from the relation between pixel strength over time.
This case describes the use of a NIRF imaging system using ICG to evaluate the adequacy of bowel microcirculation after living-donor small bowel transplant. We believe this is the first report of such a kind in the field of living-donor small bowel transplant.
A 55-year-old white woman with short bowel syndrome and severe malnourishment was offered bowel transplant because of near loss of central venous access, severe growth retardation, and total parenteral nutrition (TPN) dependence. Her 36-year-old daughter volunteered to donate. The blood type was ABO compatible, and HLA haplotypes revealed 3/6 antigen mismatch. The recipient had class I and class II panel reactive antibodies of 80% and 26%, respectively. She received desensitization therapy with plasmapheresis along with intravenous immunoglobulins and pre- and postoperative immunosuppression as per our hospital’s protocol.
The intestine was procured from the donor by following a technique previously described by our group.5 Abdominal exploration of the recipient revealed remnant distal colon with a distal third of transverse colon in situ and the fourth part of the duodenum at the ligament of Treitz. The recipient’s aorta and inferior vena cava (IVC) were prepared. The graft artery was anastomosed to the infrarenal aorta using 6-0 Prolene, and venous anastomosis was done with the IVC. After reperfusion, the bowel remained cyanotic. Our evaluation of the bowel revealed diminished pulsations on the mesentery. Doppler evaluation showed the absence of diastolic flow over the mesenteric arcade, and signals from the intestinal wall could not be appreciated. Based on these signs, we decided to revise the arterial anastomosis. During reexploration, it was found that the arterial anastomosis had positional flow. The arterial anastomosis was then taken down and redone after altering the orientation of the artery to ensure that the flow was not position dependent. After the second reperfusion, there was a strong, palpable pulse and normal arterial Doppler signals over the mesenteric arcade, but there was still discoloration of the intestinal wall. Therefore, we decided to test the microcirculation of the bowel wall.
We elected to use for the first time NIRF using ICG for assessment of microcirculation. We have been using ICG in robotic kidney transplants as a matter of routine with good outcomes. The Spy Elite System was positioned over the bowel, and 0.16 mg/kg ICG (2.5 mg/mL, total dose of 10 mg) was administered intravenously. At the same time, the machine was buffered and the sequence was captured for 136 seconds as soon as a blush appeared on the screen without moving the area of interest. The fluorescence signals of the blood perfusion were visualized in the regions of interest by the Spy Elite software. The reference region of the measurement was the stomach, which was set at 100%. For comparative measurements, different areas of the mesentery and the small bowel wall were defined as other regions of interest. The software calculated the perfusion index in these regions as the steepness of the curve of fluorescence intensity over time (pixel intensity per second). Results were computed and given as a percentage of the perfusion index compared with the reference area.
After the second reperfusion, we observed subop-timal bowel microcirculation as indicated by fluorescent and heat map images (Figure 1, A and B). The bowel was rewarmed for about 15 minutes, and the test was repeated, which revealed good microcirculation (Figure 2, A and B). Furthermore, more different perfusion indices at these 2 time intervals were compared by focusing on a region of interest point with the stomach as a reference, lending credence to the adequacy of arterial anastomosis with good blood flow.
Bowel continuity was restored proximally to the duodenum and distally to the remnant colon. We always make a loop ileostomy to facilitate the post-operative monitoring of blood flow and surveillance endoscopies for rejection. The pos-toperative course was uneventful. By the third postoperative week, a full diet was introduced, and TPN was gradually weaned. Graft surveillance for acute cellular rejection was accomplished by weekly zoom enteroscopy and biopsies, which did not reveal any rejection. She was discharged on postoperative day 41. Since discharge, she has recuperated well, has been weaned off TPN, and remains on an enteral diet.
Adequacy of bowel perfusion cannot reliably be predicted for a number of reasons. These include patient factors, such as atherosclerotic disease, varied pathology location, and vascular variability.6 In addition, several surgical factors such as overag-gressive dissection, bowel manipulation, and anastomotic tension may further compound the problem. Visual inspection is a poor predictor of adequate blood flow.7 There is, therefore, a pressing need for a technique that can accurately and consistently assess tissue perfusion in real time. Near-infrared fluorescence has proved useful in evaluating tissue perfusion in peripheral vascular procedures,8 colorectal surgery,9 kidney transplant,10 plastic surgery,11 and recently pancreatic transplant.4
In our center as a matter of routine, we had been using clinical assessment along with Doppler assessment of intestinal viability and circulation after implantation to assess the adequacy of bowel perfusion. In our present case, after successful implantation of a bowel from a living donor on the recipient’s aorta and IVC, clinical assessment was satisfactory, and the Doppler signals were normal over the vessels by the mesenteric border. Although Doppler examination of mesenteric vessels has been historically shown to be a reliable predictor of intraoperative bowel perfusion and viability compared with clinical assessment alone,12 some authors contend that it adds little to the clinical judgment.13 A study by Dyess and associates revealed that Doppler ultrasonography resulted in a high rate of false-negative and false-positive results.14 The limitations of this technique have been widely discussed. The technique is considered to be vulnerable to signals from neighboring large vessels and requires an arterial exposure and a pulsatile blood flow; in addition, tissue contact is required, which can impair local blood flow.15
In the present case, clinical assessment and Doppler assessment of the mesenteric blood vessels were normal despite the bowel having a variegated appearance. Although the anatomic orientation of the artery was corrected on the revision of the anastomoses, the chances of vascular thrombosis were still high due to the case being T- and B-cell flow cytometric cross-match positive. Therefore, a robust method of establishment of microcirculation was required. Hence, NIRF using ICG was used for assessment of microcirculation. The initial films revealed different perfusion intensities in different segments of the transplanted small bowel with the absence of microcirculation in such segments as shown in Figure 1. However, repeat examination revealed the increased intensity of uptake to 100% matching the intensity of the control, which was the native stomach. Thus, it helped us to assess the bowel wall microcirculation, attesting to the overall good perfusion of the bowel. Based on this expe-rience, we suggest that utilization of this technology is another step up in difficult transplant cases with questionable initial perfusion of the graft, which can provide real-time intraoperative assessment of bowel perfusion. In particular, surgeons and patients will benefit from the application of this technique as it can identify ischemia in tissues, allowing surgeons the opportunity to perform operative revisions and prevent ischemia-related complications.
Indocyanine green fluorescence measurement, which is now widely available, is a simple and reliable method to evaluate bowel wall microcirculation in vivo during bowel transplant. It can assist surgeons with critical decisions in the operating room, thus contributing to the overall procedural success and good patient outcomes.
DOI : 10.6002/ect.2019.0039
From the 1Division of Transplantation and Division of Surgery,
College of Medicine, The University of Illinois at Chicago, Chicago, Illinois;
the 2Department of Surgery, Altru Health System, Grand Forks, North
Dakota; and the 3Division of Transplantation, Tulane University, New
Orleans, Louisiana, USA
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Arshad Khan, 711 Delmore Drive, Roseau MN 56751, USA
Phone: +1 218 463 1365
Figure 1. Indocyanine Green Gray Scale and Heat Map Images of Poor Microcirculation
Figure 2. Indocyanine Green Gray Scale and Heat Map Images of Optimal Microcirculation