Real-Time Lymphography by Indocyanine Green Fluorescence

BackgroundAccurate lymph node detection plays a critical role in the staging and prognosis of gastric cancer, yet conventional techniques often suffer from limited sensitivity or operator dependency. Indocyanine green (ICG) fluorescence imaging has emerged as a promising tool to enhance intraoperative lymph node visualization, while endoscopic ultrasound (EUS) offers real-time structural assessment. This study aims to investigate the effectiveness of a precise intraoperative navigation system for gastric cancer, constructed using ICG fluorescence tracing technology in conjunction with EUS.MethodsA total of 26 patients who underwent radical gastric cancer surgery at Northern Jiangsu People’s Hospital from September 1 to October 31, 2024, were included in this study and randomly divided into two groups: the ICG group (n=13) and the non-ICG group (n=13). The ICG group utilized ICG fluorescence tracing technology during the operation, which was subsequently combined with EUS to evaluate the lymph nodes postoperatively. The main observation indicators included the total number of lymph nodes, the number of positive lymph nodes, and the correlation between the ICG tracing results and the presence of positive lymph nodes. Additionally, a comparative analysis of the pathological tissue morphology and EUS images in the ICG group was performed.ResultsThere were no statistically significant differences in the baseline characteristics [age, sex, body mass index (BMI), clinical stage] between the two patient groups (P>0.05). The number of lymph nodes detected in the ICG group was significantly higher than that in the non-ICG group (41.15 vs. 26.62, P<0.05). Although the number of positive lymph nodes detected (7.38 vs. 4.77) was higher, there was no significant difference (P>0.05). The sensitivity of EUS in determining the depth of infiltration was 84.62%, the specificity was 92.31%, and the consistency was good (Kappa =0.76). The lymph node detection rates for ICG and ICG combined with EUS were 85.78% and 94.71% respectively (P<0.05), with coverage rates of 58.95% and 67.92% respectively (P<0.05), and Kappa values were 0.77 and 0.89. ICG combined with EUS showed significant advantages in identifying tumor boundaries, positive lymph nodes, and subfat lymph nodes. These findings were supported by both histomorphological analysis and EUS imaging.ConclusionsThe combination of ICG and EUS navigation systems can significantly enhance the accuracy and quality of lymph node detection during radical gastric cancer surgery, thereby offering a novel approach for precise navigation.Trial RegistrationThe project has been registered with the Chinese Clinical Trial Registry (ChiCTR2400090495).

Secure methods for clinical detection of the sentinel node (SN) are in great demand to avoid unnecessary resection. This was a clinical exploration/feasibility study of a novel detection system for SN biopsy using indocyanine green (ICG) fluorescence imaging in gastric cancer surgery. SN biopsy using ICG dye was performed in three patients who had gastric cancer. ICG fluorescence images were obtained using a detection system comprising a charge-coupled device (CCD) camera with a cut filter as the detector and light emitting diodes (LED) as the light source. The nodes were also examined simultaneously by an infrared (IR) imaging videoscope. Immediately after intraoperative ICG injection, the fluorescence imaging system allowed easy visualization of the lymphatic vessels draining from the primary gastric tumor toward the lymph nodes and tracing of the moving injected dye. Some lymph vessels and nodes were hardly recognized by ICG green color or IR imaging. The ICG fluorescence system also allowed visualization of the lymph node when ICG was injected the day before surgery, similar to the radio-guided method. Detection of SNs in gastric cancer surgery using the ICG fluorescence imaging system is a promising novel technique and may perhaps prove useful for laparoscopic surgery.

Introduction: In laparoscopic colectomy for colorectal cancer, appropriate lymph node dissection and prevention of anastomotic leak are very important. Indocyanine green (ICG) images obtained through the laparoscopic procedure helped visualize lymphatic drainage vessels and inform decision-making to determine the vessels. Intracorporeal anastomosis has advantages such as earlier recovery of postoperative bowel function, shorter length of wound incision, reduction of intestinal mobilization range, and fewer incisional hernias. Background: We report the surgical technique and short-term results of 48 patients who underwent laparoscopic colectomy and intracorporeal anastomosis using the double ICG fluorescence technique from July 2020 to September 2023. Methods: Two injections of ICG (0.75 mg ×2) into the proximal and distal subserosa of the tumor preceded the surgical procedure after pneumoperitoneum. Intraoperative lymph node mapping by the Stryker1588, 1688AIM camera imaging system was visualized. Laparoscopic colectomy was performed according to the Complete Mesocolic Excision and Central Vascular Ligation concepts. Complete intracorporeal anastomosis was performed by a functional end-to-end or overlap or Delta anastomosis. After anastomosis, ICG (12.5 mg) was injected intravenously to check the intestinal blood perfusion at the anastomosis site. Results: Forty-eight patients (Sex; male: 23 and female: 25) (Tumor location; C: 20, A: 11, T: 8, D: 7, S:2) (pStage0:2, I:15, II: 16, III:10, and IV:5) were underwent. The median age was 74. median body mass index was 23. Median number of dissected lymph nodes was 18. The median operative time was 246 min. The median wound length was 3.5 cm. The median postoperative hospital stay was 7 days. Visualization of lymphatic flow was observable in 24 of 28 cases (85.7%). The transection line was changed in 2/48 cases (4.1%) after ICG fluorescence angiography. There were no intraoperative complications, and two patients had postoperative paralytic ileus. Discussion: We introduce a novel technique of double ICG administration during laparoscopic colon resection for colon cancer that enables improved lymphadenectomy and warrants the extent of intestinal resection. It contains the intrinsic solution to the potential risks related to more intense dissection for extended lymphadenectomy. This is an immediate assessment of blood supply to the anastomosed intestinal walls. ICG fluorescence has immanent advantages as a result of its very low toxicity, high sensitivity, fast feedback, and absence of radiation. It is helpful to determine the extent of a bowel resection and can avoid leaving positive lymph nodes behind. It was revealed that ICG accurately evaluates the blood supply to anastomotic sites in real time and can detect organ ischemia before reconstruction is performed. This is particularly useful in laparoscopic surgery, as detection of impaired blood supply is difficult and even more for intracorporeal anastomosis. Lower anastomotic leak and reoperation rates were revealed with the use of ICG in several studies. Lymph nodes’ metastases are the most important prognostic factor in colon cancer, which has a poor prognosis and high recurrence. The use of ICG in the identification of lymph flow and lymphadenectomy basin in colon cancer patients has been previously reported. Lymph drainage of the transverse colon is complicated, and understanding this lymphatic drainage system is difficult, making ICG fluorescence particularly useful in right-sided and splenic flexure colon cancer patients. Conclusion: ICG fluorescence lymphangiography in laparoscopic colectomy for colon cancer allows visualization of lymphatic flow and may complement more reliable lymph node dissection. In addition, the evaluation of intestinal perfusion using ICG contributes to the reduction of anastomotic leakage and enables safer intracorporeal anastomosis.

BackgroundThere is a lack of comparative analyses on the use of carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) tracer technology for lymph node detection and their perioperative safety in robotic radical gastrectomy.MethodsA retrospective analysis was performed on patients who underwent robotic distal gastrectomy between November 2019 and November 2020. Patients were assigned to the CNSI group, the ICG group, or the control group. The number of lymph nodes detected, number of lymph nodes detected at each station, number of micro lymph nodes detected, rate of lymph node metastasis, and inoperative and postoperative recovery were compared.ResultsOf the 93 patients analyzed, 34 were in the CNSI group, 27 were in the ICG group, and 32 were in the control group. The mean number of lymph nodes retrieved in the CNSI group (48.44) was higher than that in the ICG (39.19) and control (35.28) groups (P = 0.004; P < 0.001), and there was no difference between the ICG and control groups (P = 0.102). The mean number of micro lymph nodes retrieved in the CNSI group (13.24) was higher than that in the ICG (5.74) and control (5.66) groups (P < 0.001). The lymph node metastasis rates in the CNSI, ICG, and control groups were 5.03, 4.63, and 5.93%, respectively (P > 0.05).ConclusionThe effect of CNSI on lymph node dissection and sorting was better than that of ICG, and CNSI improved the surgical quality and reduced lymph node staging deviation to a greater extent. CNSI was better than ICG in terms of improving the number of micro lymph nodes detected.

Management of the regional lymph nodes remains the most controversial aspect of treating patients with intermediate-thickness cutaneous melanoma. Prospective studies have failed to demonstrate a significant survival advantage for patients undergoing elective lymph node dissection. The sentinel lymph node dissection (SLND) technique has been proposed as a method of accurately identifying patients with occult metastases in whom a regional lymph node dissection would be indicated. The majority of studies evaluating this technique have come from academic centers, most with dedicated melanoma clinics. This report describes the initial experience with SLND at a community hospital. Fifteen patients with intermediate-thickness primary cutaneous melanoma underwent preoperative lymphoscintigraphy with 99Tc-sulfur colloid. In addition, intraoperative lymphatic mapping using intradermally injected isosulfan blue was performed. Dissection was guided by radioactivity levels (in counts per second) as measured by a hand-held gamma probe. The resected lymph node or nodes were evaluated for micrometastases using routine hematoxylin and eosin staining and immunohistochemistry with S-100 and HMB-45. All patients were followed clinically for any evidence of recurrence. A sentinel node(s) was identified on preoperative lymphoscintigraphy in all 15 patients (100%). A single sentinel node was identified in 11 of 15 (73%), two nodes in 3 (20%), and one node in 1 (6.7%). The hand-held gamma probe reading correlated well with the site marked the "hot spot" (600-15,320 cps for the hot spot versus 10-350 cps for background). The sentinel lymph node was successfully identified and resected in all 15 patients. Blue-stained lymphatics and/or lymph nodes were present in 8 of 15 (53%) cases. Histopathology was negative for evidence of occult micrometastases in all patients. At mean follow-up of 221 days, all 15 patients remain with no evidence of disease. The outcomes for mapping and harvesting the sentinel node at a community institution compare favorably with results at major academic institutions. SLND may therefore be offered to patients with intermediate-thickness cutaneous melanoma in the community hospital setting with regional lymph node dissection and adjuvant interferon alpha-2b as options for patients with nodal micrometastases.

PD18-02 THE EFFECTIVENESS OF TEMPLATE-BASED REGIONAL LYMPH NODE DISSECTION IN REDUCING LOCOREGIONAL RECURRENCE IN PATIENTS WITH CLINICALLY NODE-NEGATIVE UPPER URINARY TRACT UROTHELIAL CARCINOMA

Colon cancer is one of the most common malignancies of the alimentary tract, and one main metastatic route is lymph node metastasis. Thorough dissections of regional lymph nodes is one of the core surgical treatment of right colon cancer. D3 lymphadenectomy and complete mesocolic excision (CME) are generally accepted surgical methods for right colon cancer, which can improve the standardization of surgery, improve the quality of tumor resection, and provide more lymph nodes dissectal. Colon cancer of hepatic flexure is likely to have metastasis of the infrapyloric lymph nodes (No.206), which are not regional lymph nodes. Lymph node dissection of No.206 group belongs to extended right hemicolectomy, which involves many vascular variations and complicated peripheral anatomical structure. The theory of fascial surgery provides surgeons with anatomic basis and a clear understanding of the anatomical structure of the infrapyloric region, which is an important theoretical basis for the thorough dissection of lymph nodes in No.206 group, and can completely remove the mass, regional lymph nodes and adipose connective tissue, so as to achieve the goal of non-bleeding surgery. Lymph nodes in No.206 group were dissected, not just the visible lymph nodes, but the entire lymph nodes and lymphatic vessels in the region, including adipose tissue. Extended right hemicolectomy requires higher surgical techniques. The survival benefits of extended right hemicolectomy are not supported by high-level evidence. It is still controversial whether the infrapyloric lymph node dissection should become routine for colon cancer of hepatic flexure. In this article, the metastasis and dissection of infrapyloric lymph node in colon cancer of hepatic flexure is elucidated.

The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN. Seventy-four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1-2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty-one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not. Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.

Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

Enucleation of primary lesion and neck dissection of regional lymph nodes are required in operating on a tumor. As a result, rehabilitation is very difficult following treatment of a tumor, because of the large defect and the side effects. The dissection of regional lymph nodes is required in the operation of mammary cancer and uterine cancer, causing edema of the limb. In other words the quality of life of a patient is adversely affected by current surgical methods. This has been improved by the use of Sentinel navigation surgery, but it is reported that this method is impossible to use in the head and neck region due to the existence of the lymphatic network. We surmised that the quality of life of the patient could be maintained by using the lymph vessels as a drug delivery route after involving the lymphatic network. From our past reports [1–4], we are able to elucidate, to a great extent, the detailed architecture of lymphatic vessels in the tongue. However, the network of the lymph nodes in the neck region is very complicated and at present is far from being elucidated. On the other hand, the lymph vessels from every organ connect with the regional lymph nodes as stated in the theory of Sentinel navigation

Lymphography by radioisotope or dye is a well-known technique for visualizing the lymphatic drainage pattern in a neoplastic lesion and it is in use in gastric cancer. Indocyanine green (ICG) more recently has been validated in fluorescent lymphography studies and is under evaluation as a novel tracer agent in gastric cancer. The amount and dilution of ICG injected as well as the site and the time of the injection are not standardized. In our unit, endoscopic submucosal injections of ICG are made as 0.5 mg in 0.5 mL at four peritumoral sites the day before surgery (for a total of 2.0 mg in 2.0 mL). Detection instruments for ICG fluorescence are evolving. Near-infrared systems integrated into laparoscopic or robotic instruments (near-infrared fluorescence imaging) have shown the most promising results. ICG fluorescence recognizes the node that receives lymphatic flow directly from a primary tumor. This is defined as the sentinel lymph node, and it has a high predictive negative value at the cT1 stage, able to reduce the extent of gastrectomy and lymph node dissection. ICG also enhances the number of lymph nodes detected during extended lymphadenectomy for advanced gastric cancer. Nevertheless, the practical effects of ICG use in a single patient are not yet clear. Standardization of the technique and further studies are needed before fluorescent lymphography can be used extensively worldwide. Until then, current guidelines recommend an extensive lymphadenectomy as the standard approach for gastric cancer with suspected metastasis.

Purpose: This study aims to determine if ICG fluorescence can detect fibrosis and inflammatory changes and if it is associated with histopathologic evidence of endometriosis in patients undergoing minimally invasive excision of suspected endometriosis. Methods: This retrospective cohort study reviewed 178 medical records from July 1, 2014, to December 31, 2023, at three community-based hospitals, conducted by a single fellowship-trained MIGS surgeon. Institutional Review Board approval was obtained (#RIL20220137). Inclusion criteria were reproductive-aged females (18-50 years) undergoing planned robotic-assisted excision of suspected endometriosis. Exclusion criteria included a prior histopathologic diagnosis of endometriosis (n=33), history of major abdominal or pelvic surgery (n=39), gynecologic and non-gynecologic inflammatory conditions (n=16), and use of ICG without peritoneal biopsy (n=2). Data on patient demographics, clinical symptoms, duration of symptoms, and medical and surgical history was collected. Operative reports confirmed the use of ICG and its correlation with pathology findings. In the ICG and Control cohorts, peritoneal biopsies were analyzed for histopathologic evidence of endometriosis, fibrosis, or inflammatory changes. Statistical analysis determined the sensitivity, specificity, NPV, and PPV of ICG-detected fibrosis. Chi-square and logistic regression were used to analyze the data and control for confounding variables. Results: Of the 178 charts that met inclusion criteria, 88 charts were analyzed after applying exclusion criteria. These were divided into two cohorts: ICG cohort (n=49) and Control cohort (No ICG use; n=39). In the ICG group, 40 charts demonstrated histopathological findings of endometriosis. Additionally, 21 charts presented histopathological evidence of fibrosis, and 14 charts showed concurrent endometriosis and fibrosis. Among the 9 charts without endometriosis, 7 exhibited histopathological evidence of fibrosis or inflammation. The most common symptoms reported by patients were dysmenorrhea (56%), chronic pelvic pain &gt; 6 months (40.9%), and abnormal uterine bleeding (AUB) (31.8%). Chi-square analysis demonstrated statistical significance in ICG’s ability to detect fibrosis when examining all eligible records from ICG use and control cohorts (χ² = 9.412, df = 1, Goodman and Kruskal tau = 0.107, Pearson’s R value = 0.327, p-value &lt; 0.002). Furthermore, when assessing the differences in the relationship between fibrosis and endometriosis between the ICG use and control cohorts, chi-square analysis demonstrated a statistical significance between the presence of fibrosis and endometriosis when ICG is used (ICG cohort: χ² = 5.490, df = 1, p-value &lt; 0.019) versus control group (Control cohort: χ² = 0.310, df = 1, p-value = 0.578) and maintains significance even when cohorts are pooled together (Composite: χ² = 7.019, df = 1, p-value = 0.008, likelihood ratio = 0.012). Analysis of all 258 peritoneal biopsies between ICG use cohort and control cohort further supported ICG’s ability to detect fibrosis, with a sensitivity of 85.1%, negative predictive value of 92.5%, specificity of 40.8%, and positive predictive value of 24.2%. Logistic regression analysis identified significant predictors of fibrosis including clinical symptoms of dysmenorrhea (OR=7.995, df = 1, p-value &lt; .005), history of chronic pelvic pain (OR=5.014, p-value &lt; .025), presence of histopathologic-proven endometriosis at time of surgery (OR=7.490, df = 1, p-value&lt;0.006), and history of depression/anxiety (OR=4.096, df = 1, p-value &lt; 0.015). Overall, the findings suggest that ICG fluorescence significantly improves the detection of fibrosis, which is strongly associated with the presence of endometriosis. ICG can enhance diagnostic accuracy and aid in a thorough and directed removal of endometriosis and related fibrosis and inflammatory changes. Conclusion: Significant associations from chi-square and logistic regression analyses support the use of ICG fluorescence as a helpful adjunct to white light laparoscopy for the intraoperative identification of endometriosis-related fibrosis and inflammation. The high sensitivity and NPV of ICG fluorescence in detecting fibrotic and inflammatory changes highlight its potential value in identifying fibrosis even when endometriosis is not confirmed on histopathology. In the absence of histopathological evidence of glands and stroma, the presence of fibrosis or inflammatory changes may suggest that the presence of endometriosis cannot be definitively excluded. These findings support the growing literature proposing that fibrosis and inflammation are integral to the natural history and pathogenesis of endometriosis. Larger prospective studies are warranted to validate our findings and assess patient outcomes such as pain relief, quality of life, fertility, and re-operation. Further quantitative studies are needed to analyze ICG perfusion time and intensity and their impact on detecting endometriosis and related fibrosis and inflammatory changes.

PELVIC LYMPH NODE DISSECTION CAN BE CURATIVE IN PATIENTS WITH NODE POSITIVE BLADDER CANCER

The experience of the Sydney Melanoma Unit (SMU) is documented to offer quality assurance (QA) standards and an acceptable range for lymph node yield for regional lymph node dissection (RLND) in melanoma patients. Surgery is the most effective treatment for melanoma involving lymph nodes (LN). QA for RLND procedures, including adequacy of surgery and histopathology, is not well developed. The number of LN removed is one auditable measurement, known as a reliable predictor of surgical quality in other tumors. Data were retrieved from the SMU prospective database for patients treated from 1993 to 2006. There were 2039 RLND by SMU surgeons and 324 by non-SMU surgeons. The axilla, groin, cervical dissections of < or = 3 levels (CD < or = 3) and cervical dissections > or = 4 levels (CD > or = 4) were assessed. At axillary dissection the mean number of LN resected by SMU surgeons was 21.9 (median 21; range 1-83; 90% of cases > or = 10 LN), groin dissection mean 14.5 LN (median 13; range 1-54; 90% of cases > or = 7 LN), CD < or = 3 dissection mean 19.5 LN (median 18.5; range 1-52; 90% of cases > or = 6 LN) and CD > or = 4 dissection mean 38.9 LN (median 36; range 5-103; 90% of cases > or = 20 LN). SMU surgeons retrieved significantly more LN than non-SMU surgeons for axillary and groin dissections (P < 0.0005). These data benchmark performance for melanoma RLND. Cases with a low node count (below the 90 percentile) should be assessed critically. Standard RLND operations should have a reproducible mean and predictable distribution of LN retrieved.

Indocyanine green (ICG) fluorescence imaging is increasingly being used in various areas of abdominal surgery. The constant improvement in the technology enables easy intraoperative use and progressively influences operative decision-making, also in robotically assisted colorectal surgery. Summation of current evidence on the use of ICG fluorescence imaging in robotically assisted colorectal surgery. The assessment of evidence is based on acomprehensive literature search (PubMed). First individual studies (feasibility, case matched, prospective cohort, multicenter phaseII, single center randomized controlled study/trial) showed asignificant reduction in the incidence of anastomotic leakage (AL) after colorectal anastomosis through the use of ICG fluorescence angiography (FA, 9.1% vs. 16.3%; p = 0.04). First feasibility studies demonstrated lymph node detection or navigation as well as ureter visualization. The ICG-FA reliably detects tissue perfusion, quickly and effectively with few side effects. It can influence intraoperative decision-making and reduce AL rates. In addition, patients may be offered more precise tumor therapy via ICG sentinel lymph node (SLN) detection and lateral pelvic lymph node (LPN) mapping and navigation. Iatrogenic lesions, such as ureteral injuries can be sufficiently prevented by appropriate visualization; however, valid data in order to be able to derive standardized operative consequences require further convincing multicenter, randomized controlled trials (mRCT).