Christmas article: Minimally invasive (Christmas) heart surgery.

Introduction The woven Christmas heart is a cherished tradition and an iconic symbol of Danish Christmas. The common approach is to weave Christmas hearts by hand, however, as surgery is moving towards a minimally invasive approach, we wished to assess whether Christmas hearts could be weaved in a minimally invasive approach. Methods A single-blinded randomized crossover trial. All participants had to weave three Christmas hearts; one by hand, one laparoscopic, and one by a robotic approach within eight minutes. The hearts were assessed visually by a Danish Christmas expert and designer. Two trained surgeons received additional attempts, with no time limit, at weaving Christmas hearts by a laparoscopic and by a robotic approach. Results The study showed that it was possible to weave Christmas hearts by a minimally invasive approach. However, Christmas hearts woven by hand were significantly more elegant (p less-than 0.001 for both), as well as significantly faster to weave (p less-than 0.001 for both) than hearts woven by a laparoscopic or robotic approach. Furthermore, experienced surgeons tended to weave more elegant Christmas hearts than inexperienced surgeons (p = 0.051). Conclusion Minimally invasive approaches to surgery can be used to weave Christmas hearts, however, these approaches did not lead to more elegant or faster weaving of the Christmas hearts. Furthermore, surgical experience and experience with minimally invasive surgical approaches led to more elegant Christmas hearts. Funding none. Trial registration none.

Anastomotic perfusion assessment with indocyanine green in robot-assisted low-anterior resection, a multicenter study of interobserver variation.

BACKGROUND: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL. METHOD: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion. RESULTS: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04). CONCLUSION: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04766060.

Normalization of Time-Intensity Curves for Quantification of Foot Perfusion Using Near-Infrared Fluorescence Imaging With Indocyanine Green.

PURPOSE: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower extremity arterial disease (LEAD). However, the absolute fluorescence intensity is influenced by patient-and system-related factors limiting reliable and valid quantification. To enhance the quality of quantitative perfusion assessment using ICG NIR fluorescence imaging, normalization of the measured time-intensity curves seems useful. MATERIALS AND METHODS: In this cohort study, the effect of normalization on 2 aspects of ICG NIR fluorescence imaging in assessment of foot perfusion was measured: the repeatability and the region selection. Following intravenous administration of ICG, the NIR fluorescence intensity in both feet was recorded for 10 mins using the Quest Spectrum platform®. The effect of normalization on repeatability was measured in the nontreated foot in patients undergoing unilateral revascularization preprocedural and postprocedural (repeatability group). The effect of normalization on region selection was performed in patients without LEAD (region selection group). Absolute and normalized time-intensity curves were compared. RESULTS: Successful ICG NIR fluorescence imaging was performed in 54 patients (repeatability group, n = 38; region selection group, n = 16). For the repeatability group, normalization of the time-intensity curves displayed a comparable inflow pattern for repeated measurements. For the region selection group, the maximum fluorescence intensity (Imax) demonstrated significant differences between the 3 measured regions of the foot (P = .002). Following normalization, the time-intensity curves in both feet were comparable for all 3 regions. CONCLUSION: This study shows the effect of normalization of time-intensity curves on both the repeatability and region selection in ICG NIR fluorescence imaging. The significant difference between absolute parameters in various regions of the foot demonstrates the limitation of absolute intensity in interpreting tissue perfusion. Therefore, normalization and standardization of camera settings are essential steps toward reliable and valid quantification of tissue perfusion using ICG NIR fluorescence imaging.

Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial.

BACKGROUND: The proadaptive effects of glucagon-like peptide-2 (GLP-2) include stimulation of intestinal mucosal growth as well as intestinal blood flow and angiogenesis. We have recently reported that daily subcutaneous injections of glepaglutide, a long-acting GLP-2 analog, improved intestinal absorptive function in patients with short bowel syndrome (SBS). As secondary and exploratory end points, the effects of glepaglutide on intestinal morphology and perfusion are reported. METHODS: The following assessments were done in 18 patients with SBS in a randomized, crossover, dose-finding, phase 2 trial before and after three weeks of treatment with glepaglutide: plasma citrulline and mucosa biopsies to assess changes in (1) intestinal morphology by immunohistochemistry and (2) gene expressions associated with absorption, proliferation, and markers of tight-junction integrity by quantitative polymerase chain reaction. Intestinal perfusion was assessed in stoma nipples by laser speckle contrast imaging and quantitative fluorescence angiography with indocyanine green. RESULTS: In the 1- and 10-mg dose groups, glepaglutide significantly increased plasma citrulline by 15.3 µmol/L (P = 0.001) and 15.6 µmol/L (P = 0.001), respectively. Trends toward an increase in villus height, crypt depth, and epithelium height were seen in the same groups. No significant changes were seen in gene expressions or intestinal perfusion. CONCLUSION: The increase in plasma citrulline and the morphological improvements may partly account for improvement in the intestinal absorptive function. However, the finding of a stability in perfusion after three weeks of treatment with glepaglutide may have been preceded by a more profound acute-phase increase in intestinal perfusion at treatment initiation.

Intraoperative near-infrared lymphography with indocyanine green may aid lymph node dissection during robot-assisted resection of gastroesophageal junction cancer.

BACKGROUND: Adequate lymphadenectomy during gastroesophageal junction (GEJ) cancer resection is essential, because lymph node (LN) metastasis correlates with increased recurrence risk. Fluorescence lymphography with indocyanine green (ICG) has been used for LN mapping in several surgical specialties; however, reports on GEJ cancer are lacking. Therefore, we investigated whether intraoperative ICG lymphography could facilitate LN harvest during robot-assisted resection of GEJ cancer. METHODS: Patients scheduled for robot-assisted resection of GEJ cancer were included, and outcomes were compared with historical controls. After intraoperative endoscopic submucosal ICG injection, standard D1 + LN dissection was performed under white light. Then, near-infrared (NIR) fluorescence imaging was activated, and each LN dissection area was re-examined. Any tissue within the D1 + field exhibiting distinctly increased ICG fluorescence compared with background tissue was dissected and sent for pathology review. RESULTS: We included 70 patients between June 2020 and October 2021. Three cases were aborted due to disseminated disease, and two were converted to open resection and excluded from the analysis. Additional tissue was dissected after NIR review in 34 of 65 (52%) patients. We dissected 43 fluorescent tissue samples, and after pathology review, 30 were confirmed LNs; none were metastatic. The median number of LNs harvested per patient (34, interquartile range [IQR] = 26-44) was not significantly different from that harvested from historical controls (32, IQR = 24-45; p = 0.92), nor were there any differences between these two groups in the duration of surgery, intraoperative blood loss, or comprehensive complication scores (p = 0.12, p = 0.46, and p = 0.41, respectively). CONCLUSIONS: Intraoperative NIR lymphography with ICG may aid LN detection during robot-assisted resection of GEJ cancer without increasing surgical risk. Although NIR lymphography may facilitate LN dissection, none of the LN removed after the NIR review was metastatic. Hence, it remains uncertain whether NIR lymphography will improve oncological outcomes.

Intestinal perfusion assessed by quantitative fluorescence angiography in piglets with necrotizing enterocolitis.

BACKGROUND: Reduced intestinal perfusion is thought to be a part of the pathogenesis in necrotizing enterocolitis (NEC). This study aims to evaluate the intestinal perfusion assessment in NEC-lesions by quantitative fluorescence angiography with indocyanine green (q-ICG) during laparoscopy and open surgery. METHODS: Thirty-four premature piglets were delivered by cesarean section and fed with parenteral nutrition and increasing infant formula volumes to induce NEC. During surgery, macroscopic NEC-lesions were evaluated using a validated macroscopic scoring system (1-6 for increasing NEC severity). The intestinal perfusion was assessed by q-ICG and quantified with a validated pixel intensity computer algorithm. RESULTS: Significantly higher perfusion values were found in healthy areas of the colon (score 1) compared to those with NEC scores of 4, 5, and 6 (p < 0.05). Similarly, in the small intestine, perfusion was higher in the intestine with areas scored 1 compared to scores of 3 and 4 (p < 0.05). A cut-off value was found between NEC score of 1-2 vs. 3-4 for the small intestine at 117 and for colon at 107 between NEC scores 12 vs. scores of 36 with an area less than the curve value at 0.9 (p < 0.05). CONCLUSIONS: q-ICG seems to be a feasible and valuable technique to evaluate the perfusion of tissue with NEC-lesions. We found a cut-off between intestine with scores 1-2 and intestine with NEC scores 3-6 in colon, and NEC score 3-4 in the small intestine. LEVEL OF EVIDENCE: II.

Quantitative fluorescence angiography aids novice and experienced surgeons in performing intestinal resection in well-perfused tissue.

BACKGROUND: Anastomotic leakage (AL) after gastrointestinal resection is a devastating complication with huge consequences for the patient. As AL is associated with poor blood supply, tools for objective assessment of perfusion are in high demand. Indocyanine green angiography (ICG-FA) and quantitative analysis of ICG-FA (q-ICG) seem promising. This study aimed to investigate whether ICG-FA and q-ICG could improve perfusion assessment performed by surgeons of different experience levels. METHODS: Thirteen small bowel segments with a varying degree of devascularization, including two healthy sham segments, were constructed in a porcine model. We recruited students, residents, and surgeons to perform perfusion assessment of the segments in white light (WL), with ICG-FA, and after q-ICG, all blinded to the degree of devascularization. RESULTS: Forty-five participants fulfilled the study (18 novices, 12 intermediates, and 15 experienced). ICG and q-ICG helped the novices correctly detect the healthy bowel segments to experienced surgeons' level. ICG and q-ICG also helped novice surgeons to perform safer resections in healthy tissue compared with normal WL. The relative risk (RR) of leaving ischemic tissue in WL and ICG compared with q-ICG, even for experienced surgeons was substantial, intermediates (RR = 8.9, CI95% [4.0;20] and RR = 6.2, CI95% [2.7;14.1]), and experienced (RR = 4.7, CI95% [2.6;8.7] and RR = 4.0, CI95% [2.1;7.5]). CONCLUSION: Q-ICG seems to guide surgeons, regardless of experience level, to safely perform resection in healthy tissue, compared with standard WL. Future research should focus on this novel tool's clinical impact.

Time to maximum indocyanine green fluorescence of gastric sentinel lymph nodes and feasibility of combined indocyanine green/sodium fluorescein gastric lymphography.

PURPOSE: Indocyanine green (ICG) and sodium fluorescein (SF) are fluorescent dyes used for sentinel lymph node mapping. In oncological gastric surgery, ICG lymphography has increased the number of resected lymph nodes. However, the optimal time to administer ICG is unclear, and both preoperative and intraoperative injections have been practised. As dye spillage will diminish lymphogram visibility, a second dye with different excitation and emission spectra may present a clinical alternative. We measured the time until maximum ICG fluorescence of gastric sentinel lymph nodes and investigated the feasibility of combined lymphography with two fluorescent dyes: ICG and SF. METHODS: Ten Danish Landrace/Yorkshire pigs were used in this study. After completion of the laparoscopic setup, ICG and then SF were endoscopically injected into the gastric submucosa. Lymphograms for both dyes were recorded, and the time until maximum ICG sentinel lymph node fluorescence was determined. RESULTS: The mean time until maximum ICG fluorescence of gastric sentinel lymph nodes was 50 s (± 12.5), and the fluorescent signal then remained stable until the end of the recorded period (45 min). A lymphogram showing both ICG and SF was acquired for eight of the ten pigs. CONCLUSIONS: Because of the short time until maximum ICG fluorescence of sentinel lymph nodes, intraoperative injections could be a sufficient alternative to preoperative injections for oncological gastric surgery. Combined ICG and SF lymphography was feasible and resulted in clear lymphograms with no interference between the two dyes. The ability to use multiple dyes during a surgical procedure offers the exciting prospect of simultaneously assessing perfusion and performing fluorescence lymphography.

Hypotension Associated with MTS is Aggravated by Early Activation of TEA During Open Esophagectomy.

OBJECTIVE: A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI2)-induced vasodilation and identified by facial flushing, tachycardia, and hypotension during abdominal surgery. We evaluated whether thoracic epidural anesthesia (TEA) influences the incidence of MTS. DESIGN: Randomized, blinded controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Fifty patients undergoing open esophagectomy. INTERVENTIONS: Patients were randomized to either early (EA, after induction of general anesthesia) or late activation of TEA (LA, after re-established gastric continuity). Plasma 6-keto-PGF1α, a stable metabolite of PGI2 and interleukine-6 (IL6) were measured in plasma during surgery along with hemodynamic variables and MTS graded according to facial flushing together with plasma C-reactive protein on the third post-operative day. RESULTS: Forty-five patients met the inclusion criteria. Development of MTS tended to be more prevalent with EA (n=13/25 [52%]) than with LA TEA (n=5/20 [25%], p=0.08). For patients who developed MTS, there was a transient increase in plasma 6-keto-PGF1α by 15 min of surgery and plasma IL6 (p<0.001) as C-reactive protein (P<0.009) increased. EA TEA influenced the amount of phenylephrine needed to maintain mean arterial pressure >60 mmHg in patients who developed MTS (0.16 [0.016-0.019] mg/min vs MTS and LA TEA 0.000 [0.000-0.005] mg/min, p<0.001). CONCLUSION: The incidence of MTS is not prevented by TEA in patients undergoing open esophagectomy. On the contrary, the risk of hypotension is increased in patients exposed to TEA during surgery, and the results suggest that it is advantageous to delay activation of TEA. Also, MTS seems to be associated with a systemic inflammatory response, maybe explaining the aggravated post-operative outcome.

Severe mesenteric traction syndrome is associated with increased systemic inflammatory response, endothelial dysfunction, and major postoperative morbidity.

This study aimed to determine if mesenteric traction syndrome (MTS) triggers increased systemic inflammation and endothelial cell dysfunction. Patients developing severe MTS had pronounced early IL6 elevations followed by endothelial cell damage. Furthermore, these processes were associated with increased postoperative morbidity. OBJECTIVE: To determine whether mesenteric traction syndrome (MTS) leads to increased systemic inflammation and dysfunction of the glycocalyx and endothelial cell and whether this correlates with the degree of postoperative morbidity. INTRODUCTION: Severe MTS is associated with increased postoperative morbidity following major gastrointestinal surgery, but the pathophysiological mechanism has not been previously explored. Systemic inflammatory response and impaired glycocalyx and endothelial cells may be responsible for the development of symptoms. METHODS: The study analyzed prospectively collected data from two cohorts (n = 67). The severity of the MTS response was graded intraoperatively and blood samples for PGI2, catecholamines, IL6, and endothelial biomarkers obtained at predefined time points. RESULTS: Patients undergoing either esophagectomy (n = 45) or gastrectomy (n = 22) were included. Surgery led to significantly increased plasma concentrations of all biomarkers. Yet, patients who developed severe MTS had higher baseline epinephrine levels (p < 0.05) and higher levels of PGI2 (p < 0.05), Syndecan-1 (p < 0.001), and sVEGFR1 (p < 0.001). Peak values of IL6, Syndecan-1, sVEGFR1, and sTM all correlated to peak PGI2. Lastly, patients with high postoperative morbidity had higher baseline epinephrine (p = 0.009) and developed higher plasma IL6 (p = 0.007) and sTM (p = 0.022). CONCLUSION: The development of severe MTS during upper gastrointestinal surgery is associated with preoperative elevated plasma epinephrine and further a more pronounced proinflammatory response and damage to the vascular endothelium. The increased postoperative morbidity seen in patients with severe MTS may thus, in part, be explained by an inherent susceptibility towards an inappropriate secretion of PGI2, which leads to an increased surgical stress response and endothelial damage. These findings must be confirmed in a new prospective cohort.

Quantification of fluorescence angiography: Toward a reliable intraoperative assessment of tissue perfusion - A narrative review.

BACKGROUND: Accurate intraoperative assessments of tissue perfusion are essential in all forms of surgery. As traditional methods of perfusion assessments are not available during minimally invasive surgery, novel methods are required. Here, fluorescence angiography with indocyanine green has shown promising results. However, to secure objective and reproducible assessments, quantification of the fluorescent signal is essential (Q-ICG). This narrative review aims to provide an overview of the current status and applicability of Q-ICG for intraoperative perfusion assessment. RESULTS: Both commercial and custom Q-ICG software solutions are available for intraoperative use; however, most studies on Q-ICG have performed post-operative analyses. Q-ICG can be divided into inflow parameters (ttp, t0, slope, and T1/2max) and intensity parameters (Fmax, PI, and DR). The intensity parameters appear unreliable in clinical settings. In comparison, inflow parameters, mainly slope, and T1/2max have had superior clinical performance. CONCLUSION: Intraoperative Q-ICG is clinically available; however, only feasibility studies have been performed, rendering an excellent usability score. Q-ICG in a post-operative setting could detect changes in perfusion following a range of interventions and reflect clinical endpoints, but only if based on inflow parameters. Thus, future studies should include the methodology outlined in this review, emphasizing the use of inflow parameters (slope or T1/2max), a mass-adjusted ICG dosing, and a fixed camera position.

Quantitative fluorescence angiography detects dynamic changes in gastric perfusion.

INTRODUCTION: The use of Indocyanine green (ICG) fluorescence angiography (ICG-FA) is an applied method to assess visceral perfusion during surgical procedures worldwide. Further development has entailed quantification of the fluorescence signal; however, whether quantified ICG-FA can detect intraoperative changes in perfusion after hemorrhage has not been investigated previously. In this study, we investigated whether a quantification method, developed and validated in our department (q-ICG), could detect changes in gastric perfusion induced by hemorrhage and resuscitation. METHODS: Ten pigs were included in the study. Specific regions of interest of the stomach were chosen, and three q-ICG measurements of gastric perfusion obtained: 20 min after completion of the laparoscopic setup (baseline), after reducing the circulating blood volume by 30%, and after reinfusion of the withdrawn blood volume. Hemodynamic variables were recorded, and blood samples were collected every 10 min during the procedure. RESULTS: The reduction in blood volume generated decreased gastric perfusion (q-ICG) from baseline (p = 0.023), and gastric perfusion subsequently increased (p < 0.001) after the reintroduction of the withdrawn blood volume. Cardiac output (CO) and mean arterial blood pressure (MAP) shifted correspondingly and the gastric perfusion correlated to CO (r = 0.575, p = 0.001) and MAP (r = 0.436, p = 0.018). CONCLUSION: We present a novel study showing that the q-ICG method can detect dynamic changes in local tissue perfusion induced by hemorrhage and resuscitation. As regional gastrointestinal perfusion may be significantly reduced, while hemodynamic variables such as MAP or heart rate remain stable, q-ICG may provide an objective, non-invasive method for detecting regional early ischemia, strengthening surgical decision making.

Quantification of ICG fluorescence for the evaluation of intestinal perfusion: comparison between two software-based algorithms for quantification.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) can be used to evaluate intestinal perfusion prior to anastomosis. Several software for the quantification of fluorescence have emerged, but these have not previously been compared. The aim of this study was to compare the results from quantitative ICG-FI analysis of relative perfusion in an experimental setting using two different software-based quantification algorithms (FLER and Q-ICG). METHODS: Twenty pigs received a laparotomy, and ischemic areas were created in three segments of the small intestine of each pig. For each ischemic area, fluorescence imaging was performed and the fluorescence recordings were quantitatively analyzed using FLER and Q-ICG. The quantitative analysis resulted in a set of perfusion lines for each software for either 30%, 60% or 100% relative perfusion. The perfusion lines were compared by registering the normalized slope for each set of perfusion lines, calculating the relative perfusion percentage in the FLER perfusion line according to Q-ICG, and measuring the length of the ischemic area for each analysis. RESULTS: Fifty-four fluorescence recordings from 18 pigs were included. The ischemic segment for FLER was significantly longer in the 30% perfusion group and significantly shorter in the 100% perfusion group as compared to Q-ICG. The normalized slope for the FLER perfusion lines was significantly higher in the 30% perfusion group and significantly lower in the 100% perfusion group as compared to the Q-ICG perfusion lines. For the perfusion lines defined by FLER as 30%, 60%, and 100%, Q-ICG found 35.2% (p = 0.07), 63.7% (p = 0.31), and 84.1% perfusion (p = 0.003) respectively. CONCLUSION: The two software demonstrated significant differences in quantitative fluorescence analysis when perfusion was either very high or very low. The clinical relevance of these differences is unclear.

Fluorescence guided intraluminal endoscopy in the gastrointestinal tract: A systematic review.

BACKGROUND: Conventional endoscopy is based on full spectrum white light. However, different studies have investigated the use of fluorescence based endoscopy systems where the white light has been supplemented by infrared light and the use of relevant fluorophores. Fluorescence endoscopy utilizes the fluorescence emitted from a fluorophore, visualizing what is not visible to the naked eye. AIM: To explore the feasibility of fluorescence endoscopy and evaluate its use in diagnosing and evaluating gastrointestinal disease. METHODS: We followed the PRISMA guidelines for this systematic review. The research covered five databases; PubMed, Scopus, Web of Science, Embase, and the Cochrane Collection, including only studies in English and Scandinavian languages. Authors screened title and abstract for inclusion, subsequently full-text for inclusion according to eligibility criteria listed in the protocol. The risk of bias was assessed for all studies according to the Newcastle-Ottawa Scale. The authors extracted the data and reported the results in both text and tables. RESULTS: We included seven studies in the systematic review after screening a total of 2769 papers. The most prominent fluorophore was indocyanine green (n = 6), and whereas one study (n = 1) used Bevacizumab 800-CW. Three studies investigated fluorescence endoscopy in detecting varices, adenomas in patients with familial adenomatous polyposis and neoplasms in the gastrointestinal tract. Four studies evaluated the usefulness of fluorescence endoscopy in assessing tumor invasion. Three of the four studies reported an exceptional diagnostic accuracy (93%, 89% and 88%) in assessing tumor invasion, thus representing better visualization and more correct diagnosis by fluorescence endoscopy compared with the conventional endoscopy. The relationship between the endoscopic findings, tumor invasion, and tumor vascularity was evaluated in two studies showing a significant correlation (d P < 0.05 and b P < 0.01). CONCLUSION: The use of fluorescence endoscopy is a promising method adding diagnostic value in the detection of neoplasia, adenomas, and assessment of tumor invasion within the gastrointestinal tract. More studies are needed to utilize the feasibility of fluorescence endoscopy compared with other endoscopic methods.

Optimizing quantitative fluorescence angiography for visceral perfusion assessment.

BACKGROUND: Compromised tissue perfusion is a significant risk factor for anastomotic leakage after intestinal resection, leading to prolonged hospitalization, risk of recurrence after oncologic resection, and reduced survival. Thus, a tool reducing the risk of leakage is highly warranted. Quantitative indocyanine green angiography (Q-ICG) is a new method that provides surgeons with an objective evaluation of tissue perfusion. In this systematic review, we aimed to determine the optimal methodology for performing Q-ICG. METHOD: A comprehensive search of the literature was performed following the PRISMA guidelines. The following databases were searched: PubMed, Embase, Scopus, and Cochrane. We included all clinical studies that performed Q-ICG to assess visceral perfusion during gastrointestinal surgery. Bias assessment was performed with the Newcastle Ottawa Scale. RESULTS: A total of 1216 studies were screened, and finally, 13 studies were included. The studies found that intensity parameters (maximum intensity and relative maximum intensity) could not identify patients with anastomotic leakage. In contrast, the inflow parameters (time-to-peak, slope, and t1/2max) were significantly associated with anastomotic leakage. Only two studies performed intraoperative Q-ICG while the rest performed Q-ICG retrospectively based on video recordings. Studies were heterogeneous in design, Q-ICG parameters, and patient populations. No randomized studies were found, and the level of evidence was generally found to be low to moderate. CONCLUSION: The results, while heterogenous, all seem to point in the same direction. Fluorescence intensity parameters are unstable and do not reflect clinical endpoints. Instead, inflow parameters are resilient in a clinical setting and superior at reflecting clinical endpoints.

Feasibility and usability of real-time intraoperative quantitative fluorescent-guided perfusion assessment during resection of gastroesophageal junction cancer.

PURPOSE: Anastomotic leakage after resection of gastroesophageal junction cancer is a dangerous complication, and leakage rates have remained stable for decades. Perfusion is crucial for anastomotic healing, but traditional perfusion assessment is limited in a minimally invasive environment. New methods as indocyanine green fluorescence angiography (ICG-FA) have proven promising, but quantitative analysis has been challenging. This study aimed to demonstrate the feasibility and usability of real-time intraoperative quantitative fluorescence angiography (q-ICG) with a touchscreen tablet. METHODS: A software for q-ICG was previously developed and validated. Ten patients underwent perfusion assessment in white light (WL), with ICG-FA, and with q-ICG during Ivor-Lewis esophageal resection. The usability of the tablet-based software was tested with the System Usability Scale (SUS®). Furthermore, we investigated the differences in perfusion assessment as the distance from the conduit margin to a surgeon selected point of sufficient perfusion for anastomosis using the different modalities. RESULTS: Q-ICG was successful in all patients, with an excellent median SUS® of 82.5 (77.5-93.8). Significant differences in distances from the conduit margin to points of sufficient perfusion selected by the surgeons were found: ICG: WL = 14.1 mm (p = 0.048), q-ICG: WL = 32.08 mm (p < 0.001), and q-ICG: ICG = 17.95 mm (p = 0.002). Furthermore, significant differences of perfusion were found between the points, when q-ICG was performed retrospectively in the surgeon selected areas (p = 0.008-0.013). CONCLUSION: Real-time intraoperative touchscreen-based q-ICG was feasible with excellent usability, and differences in sufficient perfusion points selected by the surgeons between modalities were found. Further studies should focus on clinical relevance and determine cutoff values associated with anastomotic leakage.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Laparoscopy to Assist Surgical Decisions Related to Necrotizing Enterocolitis in Preterm Neonates.

Aim of the Study: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that mainly affects preterm infants. Despite advancements in neonatal care, mortality of NEC remains high and controversies exist regarding the most appropriate time for surgical intervention and challenging of diagnosing NEC. Using a pig model of NEC, we aimed to examine if laparoscopy is feasible for diagnosis of NEC. Methods: Preterm caesarean-delivered piglets (n = 42) were fed with increasing amounts of infant formula up to 5 days to induce NEC. On days 3-5, we examined the intestine by laparoscopy under general anesthesia. The bowel was examined by tilting the pigs from supine position to the left and right side. Macroscopic NEC lesions were identified and graded according to a macroscopic scoring system, then a laparotomy was performed to rule out any organ injury and missed NEC lesions. Results: Visible NEC lesions (scores 4-6) were found in 26% (11/42) of the piglets. A positive predictive value of 100% was found for laparoscopy as a diagnostic marker of NEC in both colon and the small intestine. One piglet had a higher NEC score in the small intestine found at laparotomy, than at laparoscopy, resulting in a sensitivity of 67%, and a specificity of 100% for the small intestine. Conversely, both the sensitivity and specificity for colon was 100%. Acceptable levels of agreement was found, with minimal proportional bias in both colon and the small intestine for laparoscopy and laparotomy. Ultrasound examination had a lower sensitivity of 67% and specificity of 63%. All piglets were respiratory and circulatory stable during the procedure. Conclusions: In preterm piglets, laparoscopy is a feasible tool to diagnose NEC with a high positive predictive value and a high specificity.

Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome: findings from a randomised phase 2 trial.

BACKGROUND: With the introduction of glucagon-like peptide-2 (GLP-2) in the treatment of short bowel syndrome (SBS), there is emerging evidence that GLP-2 may play a role in the restoration of the disturbed homeostatic feedback in the gut-liver axis and may ameliorate SBS-associated liver damage. We have previously presented that daily subcutaneous injections with 1 and 10 mg of glepaglutide improved intestinal function in patients with SBS. As exploratory endpoints, we here assessed the effect of glepaglutide on liver function. METHODS: Liver tests, transient elastography (TE) with controlled attenuation parameter (CAP), indocyanine green (ICG) kinetics, soluble CD163 (sCD163), soluble mannose receptor (sMR), and lipopolysaccharide binding protein (LBP) were assessed in 18 patients with SBS in a randomised, cross-over, dose-finding phase 2 trial before and after three weeks of treatment with glepaglutide. This trial is completed and registered at ClinicalTrials.gov: NCT02690025. FINDINGS: Between Feb 2016 and Jan 2017, 22 patients with SBS were screened. Of these, 18 patients were randomised and treated with glepaglutide; 16 patients completed the trial. Treatment with glepaglutide was associated with increase in TE and ICG-elimination. In the 10 mg dose group, glepaglutide increased sCD163 by 0·44 mg/mL (P = 0·0498), and alkaline phosphatase (ALP) decreased in the 1 mg dose group by 33 U/L (P = 0·032). CAP, sMR, LBP, liver transaminases, and INR were not affected. INTERPRETATION: Glepaglutide may improve hepatic excretory function, but at the same time activate resident liver macrophages and increase liver stiffness. The excretory and the stiffness findings may to some extent relate to increased splanchnic blood flow which would not influence the marker of macrophage activation. Thus, glepaglutide exerted diverse effects on liver status that call for attention in future studies. FUNDING: Zealand Pharma.

Laser speckle contrast imaging and quantitative fluorescence angiography for perfusion assessment.

PURPOSE: Indocyanine green fluorescence angiography (ICG-FA) is an established technique for assessment of intestinal perfusion during gastrointestinal surgery, whereas quantitative ICG-FA (q-ICG) and laser speckle contrast imaging (LSCI) are relatively unproven. The study aimed to investigate whether the techniques could be applied interchangeably for perfusion assessment. METHODS: Nineteen pigs underwent laparotomy, two minor resections of the small bowel, and anastomoses. Additionally, seven pigs had parts of their stomach and small intestine de-vascularized. Data was also collected from an in vivo model (inferior caval vein measurements in two additional pigs) and an ex vivo flow model, allowing for standardization of experimental flow, distance, and angulation. Q-ICG and LSCI were performed, so that regions of interest were matched between the two modalities in the analyses, ensuring coverage of the same tissue. RESULTS: The overall correlation of q-ICG and LSCI evaluated in the porcine model was modest (rho = 0.45, p < 0.001), but high in tissue with low perfusion (rho = 0.74, p < 0.001). Flux values obtained by LSCI from the ex vivo flow model revealed a decreasing flux with linearly increasing distance as well as angulation to the model. The Q-ICG perfusion values obtained varied slightly with increasing distance as well as angulation to the model. CONCLUSIONS: Q-ICG and LSCI cannot be used interchangeably but may supplement each other. LSCI is profoundly affected by angulation and distance. In comparison, q-ICG is minimally affected by changing experimental conditions and is more readily applicable in minimally invasive surgery.