The clinical application of sentinel node navigation surgery (SNNS) for patients with gastric cancer requires accurate intraoperative diagnosis of lymph node metastasis. However, the clinical significance of the diagnosis of lymph node micrometastasis for gastric cancer has not been established. In this study, we evaluated lymph nodes dissected during SNNS by immunohistochemistry with anti-cytokeratin antibody (IHC) staining for gastric cancer to investigate the usefulness of SNNS.The subjects were 130 patients with gastric cancer (3,381 lymph nodes) who underwent SNNS with infrared ray observation and lymph node dissection of D1+α or more. The dissected lymph nodes were stained with IHC (CAM 5.2), and the results were compared with intra- and postoperative diagnoses by hematoxylin and eosin (H&E) staining. In addition, the association of metastatic lymph nodes and ICG-positive lymph nodes was examined.The number of patients (lymph nodes) with lymph node metastasis by HE and IHC staining was 16 (52 nodes) and 31 (91 nodes), respectively. Fifteen patients (27 nodes) diagnosed with pN0 by HE staining were diagnosed to be metastatic by IHC staining. The tumor depth of these patients was pT1 in ten patients (m, 3; sm, 7) and pT2 in five (mp, 4; ss, 1). Regarding the histological type, three patients were classified as well-differentiated type, while six patients each had moderately and poorly differentiated types. The grade of lymphatic invasion was ly0 in 5, ly1 in 6, and ly2 in 4, respectively. Histological assessment of 27 IHC-positive and HE-negative cells indicated 5 single cells, 16 clusters, and 6 micrometastases. These lymph nodes were all included in the sentinel nodes (SN) identified during surgery. All but one patient (0.8%) were recurrence-free at 2-8 years after surgery (median 74.7 months). The one patient developed anastomotic recurrence 4.5 years after the first operation and died.Since all 27 lymph nodes in 15 patients with metastasis by IHC staining but not by HE staining were micrometastasis or less and included in the SN, ICG-positive lymphatic basin dissection by SNNS with infrared ray observation seems to be an adequate method of lymph node dissection for gastric cancer.

This meta-analysis was conducted to evaluate the diagnostic value of near-infrared (NIR) or fluorescent indocyanine green (ICG) guided sentinel lymph node (SLN) mapping in gastric cancer (GC).This meta-analysis was registered at the PROSPERO. Clinical studies were retrieved from the electronic database Pubmed, Embase, Medline, Web of science, and the Cochrane Library. Quality assessment was conducted by an adapted checklist of QUADAS-2. A bivariate mixed-effects model was used to pool the data. Evaluation of articles quality, analysis for publication bias, summary receiver operator characteristic (SROC) curves, and meta-regression were also performed. Subgroup analysis was used to explain the heterogeneities.A total of 13 clinical studies (971 patients) were included. The NIR or fluorescent imaging (FI) involved infrared ray electronic endoscopy (IREE), infrared ray laparoscopic system (IRLS), and FI system. Significant evidence of heterogeneity was found for sensitivity and specificity (I  = 91.1% and I  = 98.2%), respectively. The pooled SLN sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.94(95%CI: 0.80-0.99), 1.00(95%CI: 0.60-1.00), 34.0(95%CI: 9.25-125.29), 0.06(95%CI:0.02-0.22), and 252.50(95%CI: 94.93-671.61), respectively. Area under curve (AUC) of SROC curve was 1.00 (95%CI: 0.99-1.00), and the summary operating point (cut-off value) was SENS = 0.94(95%CI: 0.80-0.99) and SPEC = 1.00(95%CI: 0.60-1.00). Subgroup analysis showed that NIR imaging, imaging performed 20 minutes after intraoperative injection, preoperative injection (especially for FI imaging), stained with immunohistochemistry (IHC) (+hematoxylin-eosin [HE]), cT1 stage, submucosa injection (especially for cT1), mean number of SLN ≥ 5, study size > 26 were associated with higher SLN sensitivity. In terms of ICG concentration, diluted ICG concentration that 0.5 mg/mL (compared with 5 mg/mL) in NIR imaging and 0.05 mg/mL (compared with 0.5 mg/mL) in FI system showed higher sensitivities. However, the differences in tumor diameter (≤30 mm vs >30 mm), gastrectomy methods (opening vs laparoscopy), lymphadenectomy methods (LBD vs pick-up), and publication year (≥2010 vs <2010) did not achieve statistical significance.ICG combined with NIR or FI guided SLN mapping is technically feasible for GC. Based on the small sample size evidence, the IREE and IRLS devices may have higher sensitivity than FI in current clinical studies; and there may be an excessive ICG concentration used for current SLN mapping in GC. However, well-designed further studies with large sample size are needed to confirm the best procedure and suitable criteria.This meta-analysis was registered at PROSPERO. Clinical studies on this topic were retrieved from the electronic database Pubmed, Embase, Medline, Web of Science, and the Cochrane Library. The NIR or FI involved IREE, IRLS, and FI techniques. A total of 13 clinical studies (971 patients) were included. Based on the small sample size evidence, NIR or FI ICG guided SLN mapping in GC is technically feasible.© 2018 Wiley Periodicals, Inc.

Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients.

Fluorescence videography is a promising technique for assessing bowel perfusion. Fluorescence-based enhanced reality (FLER) is a novel concept, in which a dynamic perfusion cartogram, generated by computer analysis, is superimposed on to real-time laparoscopic images. The aim of this experimental study was to assess the accuracy of FLER in detecting differences in perfusion in a small bowel resection–anastomosis model.

The aim of the study was to evaluate laser-assisted fluorescent-dye angiography (LAA) to assess perfusion in the gastric graft and to correlate perfusion with subsequent anastomotic leak.Anastomotic leaks are a major source of morbidity after esophagectomy with gastric pull-up (GPU). In large part, they occur as a consequence of poor perfusion in the gastric graft.Real-time intraoperative perfusion was assessed using LAA before bringing the graft up through the mediastinum. When there was a transition from rapid and bright to slow and less robust perfusion, this site was marked with a suture. The location of the anastomosis relative to the suture was noted and the outcome of the anastomosis ascertained by retrospective record review.Intraoperative LAA was used to assess graft perfusion in 150 consecutive patients undergoing esophagectomy with planned GPU reconstruction. An esophagogastric anastomosis was performed in 144 patients. A leak was found in 24 patients (16.7%) and were significantly less likely when the anastomosis was placed in an area of good perfusion compared with when the anastomosis was placed in an area of less robust perfusion by LAA (2% vs 45%, P < 0.0001). By multivariate analysis perfusion at the site of the anastomosis was the only significant factor associated with a leak.Intraoperative real-time assessment of perfusion with LAA correlated with the likelihood of an anastomotic leak and confirmed the critical relationship between good perfusion and anastomotic healing. The use of LAA may contribute to reduced anastomotic morbidity.

The aim of this study is to present our preliminary experience with indocyanine green fluorescence (IGF) imaging in laparoscopic sleeve gastrectomy. After dissection of the greater curve sleeve, gastrectomy is performed using a linear articulated stapler. Once the stomach is resected, an indocyanine green solution is prepared and injected in a periferic vein. A laparoscopic system with a high-definition camera system connected to a laparoscope equipped with a specific filter for optimal detection of the near-infrared fluorescence was used at all times as previously reported in a paper of Boni et al. A methylene blue test is routinely performed after near-infrared fluorescence, and a routine gastrografin upper gastrointestinal study is performed on postoperative day 2. We retrospectively identified 15 patients undergoing laparoscopic sleeve gastrectomy between April and October 2014. IGF imaging was used for all patients. A regular and homogeneous perfusion was observed along the entire gastric sleeve including the esophago-gastric junction. On the contrary, the excised specimen appeared devascularized at IGF imaging as expected. Intraoperative methylene blue test was negative in all cases. The contrast swallow did not document any leak. Neither clinical leak nor other complications occurred postoperatively (minimum follow-up of 2 months). IGF is a recent development in minimally invasive surgery. In this preliminary experience, IGF results resemble to intraoperative methylene blue test and postoperative contrast swallow ones. IGF allows a real-time assessment and gives a direct image of tissue perfusion and vascularization. Moreover, IGF may be helpful to explain the exact pathogenesis of gastric leak.

The absorption spectrum of indocyanine green depends on the nature of the solvent medium and on the dye concentration. Binding to plasma proteins causes the principal peaks in the absorption spectrum to shift about 25 nm toward the higher wavelengths. The much greater influence on the spectrum of the dye concentration results from progressive aggregate formation with increasing concentration. Indocyanine green solutions therefore do not follow Lambert-Beer's law above 15 mg-I-1 (in plasma). Indocyanine green solutions in plasma and concentrated (1,000 mg-I-1) solutions in distilled water are stable for at least 4 h. In long-term experiments the optical density of indocyanine green solutions in plasma as well as in distilled water generally diminishes, even in the dark. On the 7th day a new absorption maximum starts to appear at gamma=900 nm, possibly caused by further aggregate formation leading to much larger particles. Spectral stabilization after injection of a concentrated solution into the blood is most rapid when the dye is dissolved in distilled water. Spectral stabilization slows down with decreasing temperature. As rapid spectral stabilization is essential in quantitative dye dilution studies, the practice of adding a albumin and/or isotonic saline solution to the injectate should be discontinued. When a 10 g-1(-1) aqueous solution of indocyanine green is used, spectral stabilization takes less than 1.5 a (at 37 degrees C), which is sufficiently fast for almost any application.

Optical imaging using near-infrared (NIR) fluorescence provides new prospects for general and oncologic surgery. ICG is currently utilised in NIR fluorescence cancer-related surgery for three indications: sentinel lymph node (SLN) mapping, intraoperative identification of solid tumours, and angiography during reconstructive surgery. Therefore, understanding its advantages and limitations is of significant importance. Although non-targeted and non-conjugatable, ICG appears to be laying the foundation for more widespread use of NIR fluorescence-guided surgery.Copyright © 2011 Wiley-Liss, Inc.

Safety and efficiency are important topics in minimally invasive surgery. Apart from its advantages, laparoscopic surgery has the following drawbacks: two-dimensional imaging, challenging eye-hand coordination, and absence of tactile feedback. Enhanced imaging with earlier and clearer identification of essential tissue types can partly overcome these disadvantages. Research groups worldwide are investigating new technologies for image-guided surgery purposes. This review article gives an overview of current developments in surgical optical imaging for improved anatomic identification and physiologic tissue characterization during laparoscopic gastrointestinal surgery.A systematic literature search in the PubMed database was conducted. Eligible studies reported on any kind of novel optical imaging technique applied for anatomic identification or physiologic tissue characterization in laparoscopic gastrointestinal surgery. Gynecologic and urologic procedures also were included whenever vascular, nerve, ureter, or lymph node imaging was concerned.Various surgical imaging techniques for enhanced intraoperative visualization of essential tissue types (i.e., blood vessel, bile duct, ureter, nerve, lymph node) and for tissue characterization purposes such as assessment of blood perfusion were identified. An overview of preclinical and clinical experiences is given as well as the potential added value for intraoperative anatomic localization and characterization during laparoscopy.Implementation of new optical imaging methods during laparoscopic gastrointestinal surgery can improve intraoperative anatomy navigation. This may lead to increased patient safety (preventing iatrogenic functional tissue injury) and procedural efficiency (shorter operating time). Near-infrared fluorescence imaging seems to possess the greatest potential for implementation in clinical practice in the near future.

Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). The authors aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy.

An aberrant left hepatic artery is frequently encountered during upper gastrointestinal surgery, and researchers have yet to propose optimal strategies with which to address this arterial variation. The objective of this study was to determine whether the areas perfused by an aberrant left hepatic artery can be visualized in real-time using near-infrared fluorescence imaging with indocyanine green.Patients with gastric adenocarcinoma who underwent minimally invasive radical gastrectomy from May 2018 to August 2019 were enrolled and retrospectively analyzed at a single-center. Patients with an aberrant left hepatic artery and normal preoperative liver function were examined. After the clamping of an aberrant left hepatic artery, indocyanine green was administered via a peripheral intravenous route during surgery. Fluorescence at the liver was visualized under near-infrared fluorescence imaging.In 31 patients with aberrant left hepatic arteries, near-infrared fluorescence imaging was used without adverse events associated with indocyanine green. Six (19%) patients were reported to have an aberrant left hepatic artery upon preoperative CT imaging, while all other instances were detected during surgery. Fluorescence excitation on the liver was, on average, visible after 43 s (range, 25-65). Fluorescence across the entire surface of the liver was noted in 20 (65%) patients in whom the aberrant left hepatic artery could be ligated. Aberrant left hepatic arteries were safely preserved in 10 (32%) patients who showed areas of no or partial fluorescence excitation. Guided by near-infrared fluorescence imaging, ligation of aberrant left hepatic arteries elicited no significant changes in postoperative liver function.Near-infrared fluorescence imaging facilitates the identification of aberrant left hepatic arterial territories, guiding decisions on the preservation or ligation of this arterial variation.

Injury to the right gastroepiploic artery (RGEA) graft during gastrectomy after coronary artery bypass grafting (CABG) can cause critical coronary failure. A man in his 60s with advanced gastric cancer and a history of CABG was admitted to our hospital. His cardiac blood flow was dependent on RGEA, and a gastrectomy with RGEA preservation was necessary. Robot‐assisted distal gastrectomy with real‐time vessel navigation using indocyanine green (ICG) fluorescence imaging and Da Vinci Firefly technology was planned. Intraperitoneal observation revealed severe adhesions around the graft. Two milliliters ICG (2.5 mg/mL) was injected intravenously, and RGEA was visualized. An RGEA‐preserving robot‐assisted distal gastrectomy was successfully performed. The operation time was 279 minutes, and the blood loss was 5 mL. The postoperative course was good and there were no complications.

&lt;b&gt;<i>Purpose:</i>&lt;/b&gt; To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. &lt;b&gt;<i>Methods:</i>&lt;/b&gt; ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 &lt;smlcap&gt;M&lt;/smlcap&gt;). &lt;b&gt;<i>Results:</i>&lt;/b&gt; BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p &lt; 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. &lt;b&gt;<i>Conclusions:</i>&lt;/b&gt; BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.

Recently, totally laparoscopic gastrectomy has been gradually accepted by surgeons worldwide for gastric cancer treatment. Complete dissection of the lymph nodes and the establishment of the surgical margin are the most important considerations for curative gastric cancer surgery. Previous studies have demonstrated that indocyanine green (ICG)-traced laparoscopic gastrectomy significantly improves the completeness of lymph node dissection. However, it remains difficult to identify the tumor location intraoperatively for gastric cancers that are staged ≤T3. Here, we investigated the feasibility of ICG fluorescence for lymph node mapping and tumor localization during totally laparoscopic distal gastrectomy.Preoperative and perioperative data from consecutive patients with gastric cancer who underwent a totally laparoscopic distal gastrectomy were collected and analyzed. The patients were categorized into the ICG (n=61) or the non-ICG (n=75) group based on whether preoperative endoscopic mucosal ICG injection was performed.The ICG group had a shorter operation time and less intraoperative blood loss. Moreover, significantly more lymph nodes were harvested in the ICG group than the non-ICG group. No pathologically positive margin was found and there was no significant difference in either the proximal or distal surgical margins between the 2 groups.Near-infrared fluorescence imaging with ICG can be successfully used in totally laparoscopic distal gastrectomy, and it contributes to both the completeness of D2 lymph node dissection and confirmation of the gastric transection line. Well-designed prospective randomized studies are needed in the future to fully validate our findings.Copyright © 2020. Korean Gastric Cancer Association.

Indocyanine green (ICG) fluorescence lymphography can be used to visualize the lymphatic drainage of gastric cancer. Few studies have been performed to identify lymphatic drainage patterns after endoscopic submucosal dissection (ESD). ESD results in changes to lymphatics owing to fibrosis of the submucosal layer. This study aimed to evaluate the efficacy of ICG fluorescence lymphography for visualization of lymphatic drainage after ESD, and to assess its clinical application in additional gastrectomy after ESD for early gastric cancer.All patients who underwent gastrectomy after ESD between 2014 and 2017 in a single centre were reviewed. ICG was injected endoscopically into the submucosal layer around the ESD scar the day before surgery. At the time of surgery, lymph nodes (LNs) were visualized and lymphadenectomy was performed with near-infrared imaging. Ex vivo, all LNs were examined for the presence of fluorescence. Number of LNs resected and number of tumour-positive LNs were compared between patients who underwent near-infrared imaging and those who had conventional lymphadenectomy without intraoperative imaging.Some 290 patients underwent gastrectomy after ESD, 98 with fluorescence lymphography-guided lymphadenectomy and 192 with conventional lymphadenectomy. Fluorescence lymphography visualized lymphatic drainage in all patients, without complications related to ICG injection or near-infrared imaging. Fluorescence lymphography visualized all stations containing metastatic LNs. The sensitivity for detecting LN metastasis in fluorescent stations was 100 per cent (9 of 9 stations), and the negative predictive value was 100 per cent (209 of 209). One patient with LN metastasis had one non-fluorescent metastatic LN within a fluorescent station.Fluorescence lymphography successfully visualized all draining LNs after ESD, with high sensitivity and negative predictive value for detecting LN metastasis. Fluorescence lymphography-guided lymphadenectomy could be an alternative to systematic lymphadenectomy during additional surgery after ESD.© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.

Application of indocyanine green (ICG) fluorescence imaging is effective in guiding laparoscopic radical lymphadenectomy for gastric cancer. However, the optimal approach for indocyanine green injection is controversial. Therefore, the objective of this study was aimed to compare the efficacy and ICG injection between the preoperative submucosal and intraoperative subserosal approaches for lymph node (LN) tracing during laparoscopic gastrectomy.

Near-infrared (NIR) fluorescence lymphography-guided minimally invasive gastrectomy using indocyanine green (ICG) is employed to visualize draining lymphatic vessels and lymph nodes. Endoscopically injected ICG spreads along the gastric wall and emits fluorescence from the serosal surface of the stomach. We aimed to assess the efficacy of ICG diffusion in securing the resection margin. We retrospectively analyzed 503 patients with early gastric cancer located in the body of the stomach who underwent fluorescence lymphography-guided gastrectomy from 2018 to 2021. One day before surgery, ICG was endoscopically injected into four points of the submucosal layer peritumorally. We measured the extent of resection and the resection line based on the ICG diffusion area from the specimen using NIR imaging. The mean area of the ICG diffusion was 82.7 × 75.3 and 86.7 × 80.2 mm2 on the mucosal and serosal sides, respectively. After subtotal gastrectomy, the length of the proximal resection margin was 38.1 ± 20.1, 33.4 ± 22.2, and 28.7 ± 17.2 mm in gastroduodenostomy, loop gastrojejunostomy, and Roux-en-Y gastrojejunostomy, respectively. The ICG diffusion area along the gastric wall secured a resection margin of &gt;28 mm. The ICG diffusion range can be used as a simple and easy method for determining the resection margin during gastrectomy using NIR imaging.

Securing the surgical margin is the most essential and important task in curative surgery. However, it is difficult to accurately identify the tumor location during laparoscopic surgery for gastric cancer, and existing methods, such as preoperative endoscopic marking with tattooing and clipping, have multiple disadvantages.We investigated the feasibility and safety of indocyanine green (ICG) fluorescence marking for determining the tumor location during laparoscopic gastrectomy.We retrospectively analyzed preoperative and perioperative data from consecutive patients with gastric cancer undergoing planned laparoscopic distal gastrectomy. Data was maintained in a prospectively compiled surgical database, and patients were categorized into ICG (n = 84) or non-ICG (n = 174) groups based on whether they underwent preoperative endoscopic mucosal ICG injection. One-to-one propensity score matching (PSM) was performed to compare outcomes between the two groups.We included 84 patient pairs after PSM, and there were no significant differences in preoperative patient characteristics. The ICG group had shorter procedure time (p < 0.001), lower estimated blood loss (p = 0.005), and significantly shorter postoperative hospital stay (p < 0.001). Positive resection margins were confirmed in five cases (6.0%) in the non-ICG group, whereas there were none in the ICG group (p = 0.008). Real-time confirmation was possible during laparoscopy, and the injected ICG did not affect the surgical procedure or result in adverse events.ICG fluorescence imaging is feasible and safe and can potentially be used as a tumor-marking agent for determining the surgical resection line.

Fluorescent imaging with indocyanine green can be used to visualize lymphatics. Peritumoral injection of indocyanine green may allow for visualization of every draining lymph node from a primary lesion on near-infrared imaging.To evaluate the role of fluorescent lymphography using near-infrared imaging as an intraoperative tool for achieving complete lymph node dissection and compare the number of lymph nodes retrieved with the use of near-infrared imaging and the number of lymph nodes retrieved without the use of near-infrared imaging.This prospective single-arm study was conducted among 40 patients who underwent robotic gastrectomy between August 30, 2013, and July 21, 2014, at a single-center, tertiary referral teaching hospital. After propensity score matching, the results of these 40 patients were compared with the results of 40 historical control patients who underwent robotic gastrectomy without indocyanine green injection between January 1, 2012, and August 31, 2013. Statistical analysis was performed from January 1, 2015, to July 31, 2016.Robotic gastrectomy with systemic lymphadenectomy and retrieval of lymph nodes under near-infrared imaging after peritumoral injection of indocyanine green to the submucosal layer 1 day before surgery.The primary outcome was the number of retrieved lymph nodes in each nodal station.Among the 40 patients in the study (19 women and 21 men; mean [SD] age, 52.2 [11.7] years), no complications related to indocyanine green injection or near-infrared imaging were observed. On completion of the lymphadenectomy, the absence of fluorescent lymph nodes in the dissected area was confirmed. A mean (SD) total of 23.9 (9.0) fluorescent lymph nodes were recorded among a mean (SD) total of 48.9 (14.6) overall lymph nodes retrieved. The mean number of overall lymph nodes retrieved was larger in the near-infrared group than in the historical controls (48.9 vs 35.2; P < .001), with a significantly greater number of lymph nodes retrieved at stations 2, 6, 7, 8, and 9. In the near-infrared group, 5 patients exhibited lymph node metastases, and all metastatic lymph nodes were fluorescent.This study's findings suggest that fluorescent lymphography may be useful intraoperatively for identifying and retrieving all necessary lymph nodes for a complete and thorough lymphadenectomy.

Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique.Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines.Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure.The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

The double-tracer method has been established for sentinel node (SN) mapping in gastric cancer surgery. However, there remain several unresolved issues that prevent its widespread use in clinical practice. In this study, we aimed to demonstrate the feasibility of single-tracer SN mapping in laparoscopic surgery for gastric cancer, using indocyanine green (ICG) fluorescence imaging with a one-step nucleic acid amplification (OSNA) assay intraoperatively.Patients with clinical T1N0M0 gastric adenocarcinoma preoperatively were considered for inclusion if they had a single primary lesion 4 cm or less in maximal diameter. Immunohistochemical staining with the anti-cytokeratin 19 antibody was performed on preoperative biopsy specimens, and patients with faint positive reactions were excluded. Intraoperatively, single-tracer SN biopsy with ICG fluorescence imaging was performed, followed by laparoscopic gastrectomy with modified D1+ or D2 lymph node dissection.Twenty eligible patients underwent SN biopsy and laparoscopic gastrectomy. SNs were identified in 17 cases (85%), with a median number of three SNs per patient. The median times for SN mapping and OSNA assay were 19 and 35 min, respectively. OSNA assay detected one metastatic lymph node, but all other nodes were negative. No adverse effects were observed in relation to SN mapping.Single-tracer SN mapping by ICG fluorescence imaging with intraoperative diagnosis by OSNA assay is feasible and safe. SNs can be identified in most patients, without producing false-negative results. Further clinical trial to demonstrate the sensitivity is ongoing.

Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC.The study enrolled 129 GC patients undergoing total or partial gastrectomy with D2 lymphadenectomy and indocyanine green fluorescence-guided SLN mapping. The primary outcomes were the negative predictive value (NPV) and sensitivity of SLN mapping. The secondary outcomes were clinicopathologic factors associated with SLN mapping accuracy and successful SLN mapping.The SLN detection rate in this study was 86.8 %. The study had an overall NPV of 83.1 % and an overall sensitivity of 65.8 %. The NPV was found to be significantly higher in the patients with no lymphovascular invasion (LVI) than in those with LVI (96.0 % vs 59.3 %; p < 0.001) and in the patients whose pathologic T (pT) stage lower than 3 than in those whose T stage was 3 or higher (92.0 % vs 66.7 %; p = 0.009). The sensitivity of SLN mapping was 50 % in the patients with no LVI and 33 % in the patients with a pT stage lower than 3.The study results showed that for patients with early-stage GC with no LVI, negative SLN findings may represent a potential additive predictor indicating the absence of regional LN metastasis. However, given the low sensitivity rates noted, further research is needed to identify specific patient populations that may benefit from SLN mapping in GC.© 2024. Society of Surgical Oncology.

To compare postoperative complications, long-term survival, and quality of life (QOL) after laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG).

Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection.

Prognosis of potentially curable (M0), completely resected gastric cancer is primarily determined by pathologic T and N staging criteria. The optimal regional dissection extent during gastrectomy for gastric adenocarcinoma continues to be debated.A gastric cancer data set was created through structured queries to the Surveillance, Epidemiology, and End Results database (1973 to 1999). Relationships between the number of lymph nodes (LNs) examined and survival were analyzed for the stage subgroups T1/2N0, T1/2N1, T3N0, and T3N1.In every stage subgroup, overall survival was highly dependent on the number of LNs examined. Multivariate prognostic variables in the T1/2N0M0 subgroup were number of LNs examined, age (for both, P <.0001), race (P =.0004), sex (P =.0006), and tumor size (P =.02). A linear trend for superior survival based on more LNs examined could be confirmed for all four stage subgroups. Baseline model-predicted 5-year survival with only one LN examined was 56% (T1/2N0), 35% (T1/2N1), 29% (T3N0), or 13% (T3N1). For every 10 extra LNs dissected, survival improved by 7.6% (T1/2N0), 5.7% (T1/2N1), 11% (T3N0), or 7% (T3N1). A cut-point analysis yielded the greatest survival difference at 10 LNs examined but continued to detect significantly superior survival differences for cut points at up to 40 LNs, always in favor of more LNs examined.Although the impact of stage migration versus improved regional disease control cannot be separated on basis of the available information, the data provide support in favor of extended lymphadenectomy during potentially curative gastrectomy for gastric cancer.

The seventh edition of the tumor, lymph node (LN), metastasis (TNM) staging system increased the required number of examined LNs in gastric cancer from 15 to 16. However, the same staging system defines lymph node-negative gastric cancer regardless of the number of examined LNs. In this study, the authors evaluated whether gastric cancer can be staged properly with fewer than 15 examined LNs.The survival rates of 10,010 patients who underwent curative gastrectomy from 1987 to 2007 were analyzed. The patients were divided into 2 groups according to the number of examined LNs, termed the "insufficient" group (≤15 examined LNs) and the "sufficient" group (≥16 examined LNs). The survival curves of patients from both groups were compared according to the seventh edition of the TNM classification.Three hundred sixteen patients (3.2%) had ≤15 examined LNs for staging after they underwent standard, curative lymphadenectomy. Patients who had T1 tumor classification, N0 lymph node status, and stage I disease with an insufficient number of examined LNs after curative gastrectomy had a significantly worse prognosis than patients who had ≥16 examined LNs. Moreover, having an insufficient number of examined LNs was an independent prognostic factor for patients who had T1, N0, and stage I disease.Lymph node-negative cancers in which ≤15 LNs were examined, classified as N0 in the new TNM staging system, could not adequately predict patient survival after curative gastrectomy, especially in patients with early stage gastric cancer.Copyright © 2012 American Cancer Society.

Indocyanine green (ICG) fluorescence imaging is effective in increasing the number of lymph node dissections during laparoscopic radical gastrectomy; however, no studies have attempted to explain this phenomenon.

Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients.Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups.Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group.FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.

To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC).

Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P &lt; 0.001). Both OS and DFS in the ICG group are significantly better than that in the non-ICG group (log-rank P = 0.015; log-rank P = 0.012, respectively). There is a difference in the overall recurrence rates between the ICG and non-ICG groups (17.8% vs 31.0%). Compared with conventional lymphadenectomy, ICG guided laparoscopic lymphadenectomy is safe and effective in prolonging survival among patients with resectable GC.

Anastomotic leak is one of the most serious postoperative complications, and intraoperative adequate perfusion plays a key role in preventing its development in gastric cancer surgery. This study aimed to investigate the relationships between anastomotic leak and the parameters defined by an assessment of intraoperative anastomotic perfusion using a near-infrared indocyanine green (ICG) fluorescence system and to evaluate the usefulness of this ICG fluorescence assessment in gastric cancer surgery.We retrospectively reviewed data of 100 patients who underwent gastric cancer surgery. In a visual assessment based on fluorescence intensity, we classified ICG fluorescence image patterns as homogeneous, heterogeneous, or faint. In a chronological assessment, the first or second time point of ICG fluorescence appearance on one or the other side of the anastomosis was defined as FT or ST, respectively. The time difference in ICG fluorescence appearance between FT and ST was defined as TD. The relationships between anastomotic leak and the evaluated clinical factors, including the parameters identified by the ICG fluorescence assessment, were evaluated using univariate or multivariate analysis.Although no signs of leak were found by surgeons' subjective judgments, four patients developed postoperative anastomotic leak of Clavien-Dindo grade III or IV. Multivariate analysis revealed that TD was an independent predictor of anastomotic leak (odds ratio 35.361, 95% confidence interval 1.489-839.923, p = 0.027).A novel parameter identified using near-infrared ICG fluorescence assessment may be useful to predict anastomotic leak in gastric cancer surgery.UMIN Clinical Trials Registry: #UMIN000030747 ( https://www.umin.ac.jp/ctr/index.htm ).

Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery.The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature.This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (Grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population.Between December 2018 and February 2021, A total of 850 patients were enrolled and randomized. After exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (Grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P=0.041). The rate of anastomotic leakage (Grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group (P=0.044), and the respective reoperation rates were 0.5% and 2.4% (P=0.021).Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

<i>Background:</i> Recently, gastrointestinal cancer has also been identified as a target for sentinel node navigation surgery (SNNS). This study is the first to determine the feasibility of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in gastrointestinal cancer. <i>Methods:</i> Our series consisted of 22 patients with gastric cancer and 26 patients with colorectal cancer who had undergone standard surgical resection. ICG solution was injected intraoperatively into the subserosa around the tumor. Fluorescence imaging was obtained by a charge-coupled device (CCD) camera with a light-emitting diode with a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. <i>Results:</i> Immediately after the ICG injection, lymphatic vessels draining the tumor and round-shaped SNs were visualized by their bright fluorescence. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. The SN detection rate and mean number of SNs were 90.9% and 3.6 ± 4.5 (mean ± SD), respectively, in patients with gastric cancer, and 88.5% and 2.6 ± 2.4, respectively, in patients with colorectal cancer. Among the patients with gastric cancer, the accuracy and false-negative rates were 88.9 and 33.3%, respectively, in patients with T<sub>1&lt;/sub&gt; stage cancer, and 70.0 and 60.0%, respectively, overall, in all the patients. Among the patients with colorectal cancer, the corresponding values were 100 and 0%, respectively, in patients with T<sub>1&lt;/sub&gt; stage cancer, and 82.6 and 66.7%, respectively, overall, in all the patients. <i>Conclusions:</i> Our preliminary results show that ICG fluorescence imaging allows easy, highly sensitive and real-time imaging-guided SN mapping in patients with gastric or colorectal cancer. SN mapping guided by ICG fluorescence imaging could be a promising tool deserving further clinical exploration.

In this study, we determined the possible usefulness of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the management of gastric cancer.ICG fluorescence imaging system has recently been developed for obtaining biochemical information from living tissues.Our series consisted of 56 patients with gastric cancer who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG solution (0.5%) was injected into the submucosa around the tumor endoscopically before the operation or into the subserosa intraoperatively. ICG fluorescence imaging was conducted using a charge-coupled device camera with a light-emitting diode having a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector.SNs were detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/- 7.0. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. cT1-stage cancers were associated with a significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3-stage cancers. Preoperative ICG injection was associated with a significantly higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P < 0.0001), a higher accuracy rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%, P = 0.0345) as compared with intraoperative ICG injection.This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

To evaluate the feasibility and accuracy of diagnosis using sentinel node (SN) biopsy in T1 gastric cancer, a multicenter trial was conducted by the Japan Clinical Oncology Group (JCOG).Sentinel node biopsy with indocyanine green (ICG) was performed in patients with T1 gastric cancer. Green-stained nodes (GNs), representing SNs, were removed first, and gastrectomy with lymphadenectomy was then performed. GNs in one plane (with the largest dimension) were histologically examined intraoperatively by frozen section with hematoxylin and eosin (H&E) stain. All harvested lymph nodes (GNs and non-GNs) were histologically examined by paraffin section after surgery. The primary endpoint was to determine the proportion of false negatives, which was defined as the number of patients with negative GNs by frozen section divided by those with positive GNs and/or positive non-GNs by paraffin section. The sample size was set at 1,550, based on the expected and threshold value as 5 and 10 % in the proportion of false negatives.Accrual was suspended when 440 patients were enrolled because the proportion of false negatives was high. In the primary analysis, the proportion of false negatives was 46 % (13/28) after a learning period with 5 patients for each institution. Seven of 13 patients had nodal metastases outside the lymphatic basin. False negatives remained at 14 % (4/28) even by examining additional sections of GNs by paraffin section.The proportion of false negatives was much higher than expected. Intraoperative histological examination using only one plane is not an appropriate method for clinical application of SN biopsy in gastric cancer surgery.

Endoscopic full-thickness gastric resection (EFTGR) with regional lymph node dissection (LND) has been used for early gastric cancer (EGC) exceeding the indications for endoscopic submucosal dissection (ESD). The extent of the dissected lymph nodes is crucial. A 3D near-infrared (NIR) video robot system significantly enhances visualization of the lymphatic system. However, this system has not been used in EFTGR with LND. Thus, this study assessed the benefits of the 3D NIR video robot system in a clinical setting.Between February 2015 and September 2018, 24 patients with EGC exceeding the indications for ESD were treated with EFTGR and LND using a 3D NIR video system with the da Vinci surgical robot. Indocyanine green (ICG) was injected endoscopically around the tumor, and basin node (BN) dissection around the nodes was examined using the 3D NIR video system of the da Vinci Si surgical robot. Subsequently, robot-assisted EFTGR was performed. The primary outcome was the 5-year survival rate.During a 5-year follow-up of all 24 patients, an 80-year-old patient with an ulcer and T2 invasion was lost to follow-up. Among the remaining 23 patients, no mortality or recurrence was observed.No metastasis or mortality occurred using the da Vinci robot-assisted EFTGR with LLND and a 3D NIR video system for patients who required radical gastrectomy for EGC in over 5 years. Hence, this may be a safe and effective method for radical gastrectomy; further studies are required confirming its effectiveness.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.