Perfusion assessment by fluorescence time curves in esophagectomy with gastric conduit reconstruction: a prospective clinical study.

BACKGROUND: Intraoperative perfusion assessment with indocyanine green fluorescence angiography (ICG-FA) may reduce postoperative anastomotic leakage rates after esophagectomy with gastric conduit reconstruction. This study evaluated quantitative parameters derived from fluorescence time curves to determine a threshold for adequate perfusion and predict postoperative anastomotic complications. METHODS: This prospective cohort study included consecutive patients who underwent FA-guided esophagectomy with gastric conduit reconstruction between August 2020 and February 2022. After intravenous bolus injection of 0.05-mg/kg ICG, fluorescence intensity was registered over time by PINPOINT camera (Stryker, USA). Fluorescent angiograms were quantitatively analyzed at a region of interest of 1 cm diameter at the anastomotic site on the conduit using tailor-made software. Extracted fluorescence parameters were both inflow (T0, Tmax, Fmax, slope, Time-to-peak) as outflow parameters (T90% and T80%). Anastomotic complications including anastomotic leakage (AL) and strictures were documented. Fluorescence parameters in patients with AL were compared to those without AL. RESULTS: One hundred and three patients (81 male, 65.7 ± 9.9 years) were included, the majority of whom (88%) underwent an Ivor Lewis procedure. AL occurred in 19% of patients (n = 20/103). Both time to peak as Tmax were significantly longer for the AL group in comparison to the non-AL group (39 s vs. 26 s, p = 0.04 and 65 vs. 51 s, p = 0.03, respectively). Slope was 1.0 (IQR 0.3-2.5) and 1.7 (IQR 1.0-3.0) for the AL and non-AL group (p = 0.11). Outflow was longer in the AL group, although not significantly, T90% 30 versus 15 s, respectively, p = 0.20). Univariate analysis indicated that Tmax might be predictive for AL, although not reaching significance (p = 0.10, area under the curve 0.71) and a cut-off value of 97 s was derived, with a specificity of 92%. CONCLUSION: This study demonstrated quantitative parameters and identified a fluorescent threshold which could be used for intraoperative decision-making and to identify high-risk patients for anastomotic leakage during esophagectomy with gastric conduit reconstruction. A significant predictive value remains to be determined in future studies.

Understanding fluorescence time curves during ileal pouch-anal anastomosis with or without vascular ligation.

BACKGROUND: Intraoperative indocyanine green fluorescence angiography (ICG-FA) may be of added value during pouch surgery, in particular after vascular ligations as lengthening maneuver. The aim was to determine quantitative perfusion parameters within the efferent/afferent loop and explore the impact of vascular ligation. Perfusion parameters were also compared in patients with and without anastomotic leakage (AL). METHODS: All consenting patients that underwent FA-guided ileal pouch-anal anastomosis (IPAA) between July 2020 and December 2021 were included. After intravenous bolus injection of 0.1 mg/kg ICG, the near-infrared camera (Stryker Aim 1688) registered the fluorescence intensity over time. Quantitative analysis of ICG-FA from standardized regions of interests on the pouch was performed using software. Fluorescence parameters were extracted for inflow (T0, Tmax, Fmax, slope, Time-to-peak) and outflow (T90% and T80%). Change of management related to FA findings and AL rates were recorded. RESULTS: Twenty-one patients were included, three patients (14%) required vascular ligation to obtain additional length, by ligating terminal ileal branches in two and the ileocolic artery (ICA) in one patient. In nine patients the ICA was already ligated during subtotal colectomy. ICG-FA triggered a change of management in 19% of patients (n = 4/21), all of them had impaired vascular supply (ligated ileocolic/ terminal ileal branches). Overall, patients with intact vascular supply had similar perfusion patterns for the afferent and efferent loop. Pouches with ICA ligation had longer Tmax in both afferent as efferent loop than pouches with intact ICA (afferent 51 and efferent 53 versus 41 and 43 s respectively). Mean slope of the efferent loop diminished in ICA ligated patients 1.5(IQR 0.8-4.4) versus 2.2 (1.3-3.6) in ICA intact patients. CONCLUSION: Quantitative analysis of ICG-FA perfusion during IPAA is feasible and reflects the ligation of the supplying vessels.

Fluorescence perfusion assessment of vascular ligation during ileal pouch-anal anastomosis.

BACKGROUND: Intraoperative fluorescence angiography (FA) is of potential added value during ileal pouch-anal anastomosis (IPAA), especially after vascular ligation as part of lengthening measures. In this study, time to fluorescent enhancement during FA was evaluated in patients with or without vascular ligation during IPAA. METHODS: This is a retrospective cohort study of all consecutive patients that underwent FA-guided IPAA between August 2018 and December 2019 in our tertiary referral centre. Vascular ligation was defined as disruption of the ileocolic arcade or ligation of interconnecting terminal ileal branches. FA was performed before and after ileoanal anastomotic reconstruction. During FA, time to fluorescent enhancement was recorded at different sites of the pouch. RESULTS: Thirty-eight patients [55.3% male, median age 45 years (IQR 24-51 years)] were included, of whom the majority (89.5%) underwent a modified-2-stage restorative proctocolectomy. Vascular ligation was performed in 15 patients (39.5%), and concerned central ligation of the ileocolic arcade in 3 cases, interconnecting branches in 10, and a combination in 2. For the entire cohort, time between indocyanine green (ICG) injection and first fluorescent signal in the pouch was 20 s (IQR 15-31 s) before and 25 s (IQR 20-36 s) after anal anastomotic reconstruction. Time from ICG injection to the first fluorescent signal at the inlet, anvil and blind loop of the pouch were non-significantly prolonged in patients that received vascular ligation. CONCLUSIONS: Results from this study indicate that time to fluorescence enhancement during FA might be prolonged due to arterial rerouting through the arcade or venous outflow obstruction in case of vascular ligation.

Fluorescence angiography after vascular ligation to make the ileo-anal pouch reach.

The two most essential technical aspects of any gastrointestinal anastomosis are adequate perfusion and sufficient reach. For ileal pouch-anal anastomosis (IPAA), a trade-off exists between these two factors, as lengthening manoeuvers to avoid tension may require vascular ligation. In this technical note, we describe two cases in which we used indocyanine green (ICG) fluorescence angiography (FA) to assess perfusion of the pouch after vascular ligation to acquire sufficient reach. In both cases, FA allowed us to distinguish better between an arterial inflow problem and venous congestion than white light assessment. Both pouches remained viable and no anastomotic leakage occurred. Our results indicate that ICG FA is of great value after vascular ligation to obtain reach during IPAA.

Defining indocyanine green fluorescence to assess anastomotic perfusion during gastrointestinal surgery: systematic review.

BACKGROUND: The aim of this systematic review was to identify all methods to quantify intraoperative fluorescence angiography (FA) of the gastrointestinal anastomosis, and to find potential thresholds to predict patient outcomes, including anastomotic leakage and necrosis. METHODS: This systematic review adhered to the PRISMA guidelines. A PubMed and Embase literature search was performed. Articles were included when FA with indocyanine green was performed to assess gastrointestinal perfusion in human or animals, and the fluorescence signal was analysed using quantitative parameters. A parameter was defined as quantitative when a diagnostic numeral threshold for patient outcomes could potentially be produced. RESULTS: Some 1317 articles were identified, of which 23 were included. Fourteen studies were done in patients and nine in animals. Eight studies applied FA during upper and 15 during lower gastrointestinal surgery. The quantitative parameters were divided into four categories: time to fluorescence (20 studies); contrast-to-background ratio (3); pixel intensity (2); and numeric classification score (2). The first category was subdivided into manually assessed time (7 studies) and software-derived fluorescence-time curves (13). Cut-off values were derived for manually assessed time (speed in gastric conduit wall) and derivatives of the fluorescence-time curves (Fmax, T1/2, TR and slope) to predict patient outcomes. CONCLUSION: Time to fluorescence seems the most promising category for quantitation of FA. Future research might focus on fluorescence-time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set-up, calibration of fluorescence imaging systems, and validation of software programs is mandatory to allow future data comparison.

Quantitative fluorescence-guided perfusion assessment of the gastric conduit to predict anastomotic complications after esophagectomy.

BACKGROUND: Fluorescence angiography (FA) assesses anastomotic perfusion during esophagectomy with gastric conduit reconstruction, but its interpretation is subjective. This study evaluated time to fluorescent enhancement in the gastric conduit, with the aim to determine a threshold to predict postoperative anastomotic complications. METHODS: In a prospective cohort study, all consecutive patients undergoing esophagectomy with gastric conduit reconstruction from July 2018 to October 2019 were included. FA was performed before anastomotic reconstruction following injection of indocyanine green (ICG). During FA, the following time points were recorded: ICG injection, first fluorescent enhancement in the lung, at the base of the gastric conduit, at the planned anastomotic site, and at ICG watershed or in the tip of the gastric conduit. Anastomotic complications including anastomotic leakage and clinically relevant strictures were documented. RESULTS: Eighty-four patients were included, the majority (67 out of 84, 80%) of which underwent an Ivor Lewis procedure. After a median follow-up of 297 days, anastomotic leakage was observed in 12 out of 84 (14.3%) and anastomotic stricture in 12 out of 82 (14.6%). Time between ICG injection and enhancement in the tip was predictive for anastomotic leakage (P = 0.174, area under the curve = 0.731), and a cut-off value of 98 seconds was derived (specificity: 98%). All times to enhancement at the planned anastomotic site and ICG watershed were significantly predictive for the occurrence of a stricture, however area under the curves were <0.7. CONCLUSIONS: The identified fluorescent threshold can be used for intraoperative decision making or to identify potentially high-risk patients for anastomotic leakage after esophagectomy with gastric conduit reconstruction.

Fluorescence angiography guided resection of small bowel neuroendocrine neoplasms with mesenteric lymph node metastases.

BACKGROUND: Surgery for small bowel neuroendocrine neoplasms (SB-NEN) might result in vascular compromise of the remaining bowel due to resection of lymph node metastases in close proximity to main mesenteric vessels. Fluorescence angiography (FA) has been described as a safe technique to assess perfusion during gastro-intestinal surgery. This study aimed to evaluate the potential value of intraoperative FA during surgery for SB-NEN. METHODS: This study included patients undergoing surgery for SB-NEN of any stage. The planned level of transection was marked by the surgeon, after which FA using indocyanine green (ICG) was performed. The primary study outcome was change in management due to FA. RESULTS: Ten consecutive patients with SB-NEN were included, all with metastatic lymph nodes close to main mesenteric vessels. FA use led to management changes in eight patients (80%); four patients had less bowel resected with a preserved length of 5-35 cm. The other four patients had more extended bowel resections with an additional length varying from 3 to 25 cm. The median postoperative stay was 4 days (interquartile range 4-6). No anastomotic leakage occurred. CONCLUSION: This is the first known series describing preliminary results of FA during SB-NEN surgery. FA led to a management change in 80% of patients with better tailoring the extent of resection of small bowel. Structural implementation of FA to assess small bowel perfusion after dissection for small bowel NET results in change of management, either by preserving small bowel or resecting ill-perfused small bowel.

IMARI: multi-Interventional program for prevention and early Management of Anastomotic leakage after low anterior resection in Rectal cancer patIents: rationale and study protocol.

BACKGROUND: Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program. METHODS: IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power. DISCUSSION: The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL. TRIAL REGISTRATION: Trialregister.nl ( NL8261 ), January 2020.

Optimizing omentoplasty for management of chronic pelvic sepsis by intra-operative fluorescence angiography: a comparative cohort study.

AIM: Pelviperineal wound complications frequently occur after salvage surgery for chronic pelvic sepsis despite using an omentoplasty. Sufficient perfusion of the omentoplasty following mobilization is essential for proper healing. This study investigated the impact on short-term clinical outcomes of fluorescence angiography (FA) using indocyanine green for assessment of omental perfusion in patients undergoing salvage surgery. METHOD: This was a comparative cohort study including consecutive patients who underwent combined abdominal and transanal minimally invasive salvage surgery with omentoplasty at a national referral centre for chronic pelvic sepsis between December 2014 and August 2019. The historical and interventional cohorts were defined based on the date of introduction of FA in April 2018. The primary outcome was pelviperineal non-healing, defined by the presence of any degree of pelviperineal infection at the final postoperative evaluation. RESULTS: Eighty-eight patients underwent salvage surgery with omentoplasty for chronic pelvic sepsis, of whom 52 did not have FA and 36 did have FA. The underlying primary disease was Crohn's disease (n = 50) or rectal cancer (n = 38), with even distribution among the cohorts (P = 0.811). FA led to a change in management in 28/36 (78%) patients. After a median of 89 days, pelviperineal non-healing was observed in 22/52 (42%) patients in the cohort without FA and in 8/36 (22%) patients in the cohort with FA (P = 0.051). Omental necrosis was found during reoperation in 3/52 and 0/36 patients, respectively (P = 0.266). CONCLUSION: After introduction of FA to assess perfusion of the omentoplasty, halving of the pelviperineal non-healing rate was observed in patients undergoing salvage surgery for chronic pelvic sepsis.

Near-infrared fluorescence angiography for intra-operative assessment of pedicled omentoplasty for filling of a pelvic cavity: a pilot study.

BACKGROUND: During creation of a pedicled omentoplasty, blood flow to segments of the omentum might become compromised. If unrecognized, this can lead to omental necrosis. The purpose of this study was to investigate the potential added intra-operative value of the use of fluorescence angiography (FA) with indocyanine green (ICG) to assess omental perfusion. METHODS: All consecutive patients undergoing a pedicled omentoplasty in a 6-month period (April 1 2018-October 1 2018) in a University hospital were included. The primary outcome was change in management due to FA. Secondary outcomes included the amount of additionally resected omentum, added surgical time, and quantitative fluorescent values (time to fluorescent enhancement, contrast quantification). RESULTS: Fifteen patients had pelvic surgery with omentoplasty and FA. Change in management occurred in 12 patients (80%) and consisted of resecting a median of 44 g (range 12-198 g) of poorly perfused omental areas that were not visible by conventional white light. The median added surgical time for the use of FA and subsequent management was 8 min (range 3-39 min). The first fluorescent signal in the omental tissue appeared after a median of 20 s (range 9-37 s) after injection of ICG. The median signal-to-baseline ratio was 23.7 (interquartile range 12.2-29.7) in well perfused and 2.5 (interquartile range 1.7-4.0) in poorly perfused tissue. CONCLUSIONS: FA of a pedicled omentoplasty allows a real-time assessment of omental perfusion and leads to change in management in 80% of the cases in this pilot study. These findings support the conduct of larger studies to determine the impact on patient outcome in this setting.

Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: a systematic review.

BACKGROUND: Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness. METHODS: This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles. RESULTS: The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified. CONCLUSIONS: Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined.

Near infrared fluorescence imaging for early detection, monitoring and improved intervention of diseases involving the joint.

Joints consist of different tissues, such as bone, cartilage and synovium, which are at risk for multiple diseases. The current imaging modalities, such as magnetic resonance imaging, Doppler ultrasound, X-ray, computed tomography and arthroscopy, lack the ability to detect disease activity before the onset of anatomical and significant irreversible damage. Optical in vivo imaging has recently been introduced as a novel imaging tool to study the joint and has the potential to image all kinds of biological processes. This tool is already exploited in (pre)clinical studies of rheumatoid arthritis, osteoarthritis and cancer. The technique uses fluorescent dyes conjugated to targeting moieties that recognize biomarkers of the disease. This review will focus on these new imaging techniques and especially where Near Infrared (NIR) fluorescence imaging has been used to visualize diseases of the joint. NIR fluorescent imaging is a promising technique which will soon complement established radiological, ultrasound and MRI imaging in the clinical management of patients with respect to early disease detection, monitoring and improved intervention.