Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis.

BACKGROUND: Near-infrared (NIR) fluorescence imaging has the potential to overcome the current drawbacks of sentinel lymph node mapping (SLNM) in colon cancer. Our aim was to provide an overview of current SLNM performance and of factors influencing successful sentinel lymph node (SLN) identification using NIR fluorescence imaging in colon cancer. METHODS: A systematic review and meta-analysis was conducted to identify currently used methods and results. Additionally, we performed a single-center study using indocyanine green (ICG) as SLNM dye in colon cancer patients scheduled for a laparoscopic colectomy. SLNs were analyzed with conventional hematoxylin-and-eosin staining and additionally with serial sectioning and immunohistochemistry (extended histopathological assessment). A true-positive procedure was defined as a tumor-positive SLN either by conventional hematoxylin-and-eosin staining or by extended histopathological assessment, independently of regional lymph node status. SLN procedures were determined to be true negatives if SLNs and regional lymph nodes revealed no metastases after conventional and advanced histopathology. SLN procedures yielding tumor-negative SLNs in combination with tumor-positive regional lymph nodes were classified as false negatives. Sensitivity, negative predictive value and detection rate were calculated. RESULTS: This systematic review and meta-analysis included 8 studies describing 227 SLN procedures. A pooled sensitivity of 0.63 (95% CI 0.51-0.74), negative predictive value 0.81 (95% CI 0.73-0.86) and detection rate of 0.94 (95% CI 0.85-0.97) were found. Upstaging as a result of extended histopathological assessment was 0.15 (95% CI 0.07-0.25). In our single-center study, we included 30 patients. Five false-negative SLNs were identified, resulting in a sensitivity of 44% and negative predictive value of 80%, with a detection rate of 89.7%. Eight patients had lymph node metastases, in three cases detected after extended pathological assessment, resulting in an upstaging of 13% (3 of 23 patients with negative nodes by conventional hematoxylin and eosin staining). CONCLUSIONS: Several anatomical and technical difficulties make SLNM with NIR fluorescence imaging in colon cancer particularly challenging when compared to other types of cancer. As a consequence, reports of SLNM accuracy vary widely. Future studies should try to standardize the SLNM procedure and focus on early-stage colon tumors, validation of tracer composition, injection mode and improvement of real-time optical guidance.

Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer.

PURPOSE: Using current optical imaging techniques and gamma imaging modalities, perioperative sentinel lymph node (SLN) identification in colon cancer can be difficult when the SLN is located near the primary tumour or beneath a thick layer of (fat) tissue. Sentinel lymph node mapping using PET/CT lymphoscintigraphy combined with real-time visualization of the SLN using near-infrared imaging has shown promising results in several types of cancer and may facilitate the successful identification of the number and location of the SLN in early colon cancer. METHODS: Clinical feasibility of PET/CT lymphoscintigraphy using preoperative endoscopically injected [89Zr]Zr-Nanocoll and intraoperative injection of the near-infrared (NIR) tracer Indocyanine Green (ICG) was evaluated in ten early colon cancer patients. Three preoperative PET/CT scans and an additional ex vivo scan of the specimen were performed after submucosal injection of [89Zr]Zr-Nanocoll. All SLNs and other lymph nodes underwent extensive pathological examination for metastases. A histopathological proven lymph node visible at preoperative PET/CT and identified at PET/CT of the specimen was defined as SLN. RESULTS: A total of 27 SLNs were harvested in seven out of eight patients with successful injection of both tracers. In one patient no SLNs were assigned preoperatively. In two patients injection of [89Zr]Zr-Nanocoll failed due to incorrect needle positioning. Twenty-one (78%) SLNs were found intraoperatively using NIR-imaging. Eleven of the 27 (41%) SLNs were located near the primary tumour (< 2 cm). Those six SLNs not found intraoperatively with NIR-imaging were all located close to the tumour. In all seven patients at least one SLN could be assigned at preoperative imaging 24 h after tracer administration. One SLN contained metastases detected by immunohistochemistry. No metastases were found in the non-SLNs. CONCLUSIONS: This study shows the potential of preoperative PET/CT lymphoscintigraphy to inform the surgeon about the number and location of SLNs in patients with early colon cancer. The additional use of NIR-imaging allows for intraoperative identification of these SLNs which are invisible with conventional white light imaging. Further research is necessary to improve and simplify the technique. We recommend perioperative SLN identification using a preoperative lymphoscintigraphy scan just before surgery approximately 24 h after injection. Additionally a postoperative scan of the specimen combined with intraoperative real-time NIR-imaging should be performed.

Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: results of a systematic review.

BACKGROUND: Near-infrared imaging with indocyanine green (ICG) has been extensively investigated during laparoscopic cholecystectomy (LC). However, methods vary between studies, especially regarding patient selection, dosage and timing. The aim of this systematic review was to evaluate the potential of the near-infrared imaging technique with ICG to identify biliary structures during LC. METHODS: A comprehensive systematic literature search was performed. Prospective trials examining the use of ICG during LC were included. Primary outcome was biliary tract visualization. Risk of bias was assessed using ROBINS-I. Secondly, a meta-analysis was performed comparing ICG to intraoperative cholangiography (IOC) for identification of biliary structures. GRADE was used to assess the quality of the evidence. RESULTS: Nineteen studies were included. Based upon the pooled data from 13 studies, cystic duct (Lusch et al. in J Endourol 28:261-266, 2014) visualization was 86.5% (95% CI 71.2-96.6%) prior to dissection of Calot's triangle with a 2.5-mg dosage of ICG and 96.5% (95% CI 93.9-98.4%) after dissection. The results were not appreciably different when the dosage was based upon bodyweight. There is moderate quality evidence that the CD is more frequently visualized using ICG than IOC (RR 1.16; 95% CI 1.00-1.35); however, this difference was not statistically significant. CONCLUSION: This systematic review provides equal results for biliary tract visualization with near-infrared imaging with ICG during LC compared to IOC. Near-infrared imaging with ICG has the potential to replace IOC for biliary mapping. However, methods of near-infrared imaging with ICG vary. Future research is necessary for optimization and standardization of the near-infrared ICG technique.

Laparoscopic Imaging Techniques in Endometriosis Therapy: A Systematic Review.

Endometriosis is a common disease associated with pelvic pain and subfertility. Laparoscopic surgical treatment has proven effective in endometriosis, but is hampered by a high rate of recurrence. The aim of this systematic review was to evaluate the intraoperative identification of endometriosis by enhanced laparoscopic imaging techniques, focusing on sensitivity and specificity. A systematic review was conducted according to PRISMA guidelines in PubMed, Embase, Cochrane Library, and Web of Science. Published prospective studies reporting on enhanced laparoscopic imaging techniques during endometriosis surgery were included. General study characteristics and reported outcomes, including sensitivity and specificity, were extracted. Nine studies were eligible for inclusion. Three techniques were described: 5-ALA fluorescence (5-ALA), autofluorescence (AFI), and narrow-band imaging (NBI). The reported sensitivity of 5-ALA and AFI for identifying endometriosis ranged from 91% to 100%, compared with 48% to 69% for conventional white light laparoscopy (WL). A randomized controlled trial comparing NBI + WL with WL alone reported better sensitivity of NBI (100% vs 79%; p < .001). All 9 studies reported an enhanced detection rate of endometriotic lesions with enhanced imaging techniques. Enhanced imaging techniques are a promising additive for laparoscopic detection and treatment of endometriosis. The 5-ALA, AFI, and NBI intraoperative imaging techniques had a better detection rate for peritoneal endometriosis compared with conventional WL laparoscopy. None of the studies reported clinical data regarding outcomes. Future studies should address long-term results, such as quality of life, recurrence, and need for reoperation.

Near infrared fluorescence lymphatic laparoscopy of the colon and mesocolon.

During surgery, a surgeon relies on the vision of his eyes and the touch of his hands. While laparoscopic surgery for colon cancer has proven to be safe and effective, it still remains a technically difficult procedure. Although it is associated with reduced haptic feedback, by enforcing the power of visual guidance, the loss of this feedback can be (partly) compensated for. Here we describe how the use of near-infrared dyes and fluorescence laparoscopy could help improve tumour staging and therefore lead to better selection of patients for postoperative adjuvant chemotherapy. More controversially, and analogous to melanoma and breast cancer surgery with sentinel node biopsy, we speculate that local resection with SLN harvesting in early colon cancer might change the therapeutic and surgical strategy in colon cancer.