Search Results (23)

Background/Objectives: Lymphedema is characterized by edema; in severe cases, skin changes and ulceration significantly impair patients’ quality of life. Although several experimental rodent models for lymphedema have been established, a reproducible and practical model remains essential for evaluating new therapeutic and imaging agents. This study aimed to establish a lymphedema animal model and to evaluate the efficacy of a newly synthesized dual-mode imaging reagent as a potential alternative to indocyanine green (ICG). Methods: Eleven Sprague-Dawley rats were classified into two groups. Full-thickness skin excision was performed on the tails of nine rats to induce lymphedema; two rats served as controls. Five rats received ICG injections for 1 week postoperatively, while the remaining six rats were administered tail injections of chemically synthesized indocyanine green-methylene blue (ICG-MB) reagent. Lymphatic flow was photographed using a SPY camera. After euthanasia, tail segments were analyzed by microcomputed tomography (micro-CT) to measure volume and by hematoxylin–eosin staining for histological evaluation. Results: On postoperative day 7, lymphatic flow was confirmed in the ICG-MB group using the SPY Elite^® fluorescence imaging system. On micro-CT scans, the preoperative rat tail volume was 3992.72 ± 144.80 mm³. Rat tail volume was 5216.71 ± 1131.88 and 4614.76 ± 468.29 mm³, respectively, at 1 and 2 weeks after lymphedema was induced. Histology revealed lymphocyte infiltration, inflammatory reaction, and thickened subcutaneous adipose tissue, with no significant difference between groups. Conclusions: The rat tail lymphedema model proved valuable for studying lymphedema pathology and diagnostic agents. The ICG-MB reagents demonstrate stable performance and favorable biocompatibility. Full article

Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates the SLN detection rates, perioperative outcomes, and 12-month oncologic outcomes oncologic results of retroperitoneal vNOTES mapping in presumed early-stage EC. Materials and Methods: This single-center retrospective cohort study analyzed consecutive patients undergoing retroperitoneal vNOTES staging (hysterectomy, BSO, and SLN mapping) for presumed EC between February 2023 and January 2024. Eligible patients had radiologically uterine-confined disease and were candidates for transvaginal surgery. Following cervical methylene blue injection, SLN mapping was executed via the retroperitoneal vNOTES route. Mapped and suspicious nodes were excised, with side-specific lymphadenectomy performed for failed mapping per algorithm. While perioperative outcomes were assessed for the full cohort, oncologic analyses (FIGO 2023 staging, nodal metastasis) were restricted to patients with confirmed carcinoma. Results: Of 98 patients (median age 54; BMI 31 kg/m²), final pathology confirmed carcinoma in 78 (73 endometrioid, 5 serous) and EIN in 20. Bilateral SLN mapping succeeded in 87.8% (86/98), necessitating side-specific lymphadenectomy in the remaining 12.2%. The obturator fossa was the predominant nodal basin (43.9%). Within the carcinoma cohort (n = 78), 57.7% were Grade 1 and 74.4% FIGO Stage I. Nodal metastases (FIGO IIIC1) were identified in 12.8% (10/78), all prompting adjuvant therapy. At a median follow-up of 12 months, no disease recurrences were observed. The complication rate was 6.1% (5.1% Clavien–Dindo ≥ III), with no conversions required. At 12-month follow-up, no recurrences were detected, though the absence of systematic lymphadenectomy precluded formal sensitivity analysis. Conclusions: Retroperitoneal vNOTES represents a feasible and safe strategy for SLN mapping in early-stage EC, demonstrating high bilateral detection with minimal morbidity. However, reliance on methylene blue and limited follow-up necessitate caution. Broader implementation requires validation through prospective, comparative trials utilizing indocyanine green and long-term oncologic surveillance. Full article

Failure of the endodontic treatment is often associated with persistent polymicrobial biofilms, particularly those involving Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans), which display synergistic pathogenicity and resistance to standard disinfection methods. This in vitro study compared the antimicrobial activity and oxidative damage induced by indocyanine green (ICG)–mediated laser ablation (LA) with that produced by antimicrobial photodynamic therapy (aPDT) using methylene blue (MB) or curcumin (CUR) in root canals infected with dual-species biofilms. The samples were divided into five experimental groups (n = 20): Group A—Methylene Blue + Red Laser (RL), Group B—Curcumin + Blue LED (BL), Group C—Indocyanine Green + Infrared Diode Laser (DL), Group D—saline solution (Negative Control—NC), Group E—2.5% sodium hypochlorite (Positive Control—PC). One hundred treated bovine incisors (20 per group) were analyzed for microbial viability (colony-forming unit (CFU/mL)), the metabolic functionality of biofilms was assessed through the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) based reduction method, and oxidative stress markers, including Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyl content, total oxidant capacity (TOC), and total protein levels. All experimental treatments significantly reduced microbial load compared to the negative control (p < 0.05), with ICG achieving the greatest reduction. ICG also induced the highest levels of oxidative stress across all parameters (p < 0.05). These findings suggest that LA with ICG is more effective than aPDT with MB or CUR, achieving disinfection outcomes comparable to those of 2.5% sodium hypochlorite, and warrant further investigation in complex clinical models. Full article

Background: Sentinel lymph node (SLN) biopsy often combines technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB), but few contemporary audits quantify the performance of each tracer when used together in routine practice. Methods: We conducted a single-center retrospective audit of 111 consecutive SLN procedures for breast cancer patients undergoing SLNB using a triple-tracer approach with technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB). We evaluated sentinel lymph node detection rates, the number of nodes retrieved, tracer concordance, and subgroup performance (including those with mastectomy and post-neoadjuvant therapy). Results: Identification was 96.4% for 99mTc (107/111), 93.7% for ICG (104/111), and 78.4% for MB (87/111). Performance was heterogeneous (Q = 26.2, p < 0.001); 99mTc and ICG each outperformed MB (Holm-adjusted p < 0.001), while 99mTc and ICG did not differ significantly. Triple-tracer workflows were associated with higher odds of detection; cross-validated AUCs reached 0.98 for 99mTc and 0.82 for ICG. Conclusions: Technetium remains a foundational tracer for SLNB, with ICG serving as a valuable adjunct that enhances nodal visualization and overall detection efficacy, and MB adds redundancy. Triple-tracer mapping achieved the best overall nodal identification and was associated with fewer sentinel nodes excised when complete tracer concordance was observed. Full article

Background and Objectives: To summarize the evidence on in vivo uterine pelvic lymphatic drainage. Materials and Methods: A literature search was performed in multiple electronic databases from inception to December 2024. We included all the studies that compared two different uterine injection sites in the mapping of pelvic sentinel lymph nodes by injecting two different tracers into two distinct injection sites. The primary outcomes included the concordance and discordance rates in the mapped pelvic sentinel lymph nodes between the pairs of injection sites. The secondary outcomes were the detection rates per injection site and tracer. Four reviewers independently reviewed the records for inclusion, assessed the risk of bias, and extracted the data. Pooled concordance, discordance, and detection rates with 95% confidence intervals (CIs) were estimated using the random effects model. Heterogeneity was quantified using the I² tests. Results: Out of 2512 records, we included 4 studies (172 patients and 344 hemipelves). Three studies injected the cervix with the technetium-99m and the uterine corpus with methylene blue; one study injected the cervix with indocyanine green and the utero-ovarian ligament with methylene blue. Both tracers/injection sites successfully identified a sentinel lymph node in 132 hemipelves (132/344; 38.4%), identifying the same sentinel lymph node in 116 cases (116/132; 87.9%). The pooled concordance rate per hemipelvis was 91.8% (95% CI 0.665–1.000; I² = 92%; chi² p-value < 0.01). Two different sentinel lymph nodes were identified in the remaining 16 hemipelves, with a pooled hemipelvis discordance rate of 8.2% (95% CI 0.000–0.335; I² = 92%; chi² p-value < 0.01). The cervix and technetium-99m were the injection site and tracer with the highest pooled detection rate. Conclusions: Different uterine injection sites appear to share a common pelvic lymphatic pathway and sentinel lymph node in most cases, consistent with the current practice in endometrial cancer. Future research will confirm whether cervical injections might be proposed for pelvic sentinel lymph node mapping in all gynecological cancers. Full article

Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases. Full article

The term “fluorescence” was first proposed nearly two centuries ago, yet its application in clinical medicine has a relatively brief history coming to the fore in the past decade. Nowadays, as fluorescence is gradually expanding into more medical applications, fluorescence image-guided surgery has become the new arena for this technology. It allows surgical teams to real-time visualize target tissues or anatomies intraoperatively to increase the precision of resection or preserve vital structures during open or laparoscopic surgeries. In this review, we introduce the concept of near-infrared fluorescence guided surgery, discuss the recent and ongoing clinical trials of molecular fluorophores (indocyanine green, 5-aminolevulinic acid, methylene blue, IR-dye 800CW, pafolacianine) and their surgical goals, highlight key chemical and medical factors for imaging agent optimization, deliberate challenges and potential advantages, and propose a framework for integrating this technology into routine surgical care in the near future. The notable clinical achievements of these fluorophores over the past decade strongly indicates that the future of fluorescence in surgery is bright with many more patient benefits to come. Full article

Background: Sentinel lymph node (SLN) biopsy is recommended over systematic lymphadenectomy in early-stage endometrial cancer due to its lower morbidity and comparable detection rate. The objective of this study was to identify clinical factors associated with unsuccessful mapping. Methods: Between April 2020 and June 2024, 120 patients over the age of 18 and diagnosed with early-stage endometrial cancer were enrolled in this prospective study at a single institution. Demographic, clinicopathologic, and treatment data were collected and analyzed using descriptive statistics. Univariate and multiple linear regressions were performed to identify predictors of failed mapping. Results: The mean age of the patient cohort was 62.5 years (range 33 to 83), and the mean body mass index (BMI) was 32 kg/m² (range 18 to 50). Patients underwent intracervical injections with methylene blue (MB), indocyanine green (ICG), or a combination of both tracers, with 40 patients in each group. A total of 108 patients (90.0%) were diagnosed with endometrioid carcinoma and 12 (10.0%) with non-endometrioid cancers. Additionally, 110 patients (91.7%) were diagnosed in early stages of the disease. The overall SLN detection rate was 73.4%, with bilateral detection at 49.2% and unilateral detection at 24.2%. Univariate analysis showed that older age (p < 0.001), menopause (p = 0.001), the use of MB as the sole tracer (p = 0.006), a shorter tumor-to-serosa distance (p = 0.048), and bulky lymph nodes (p = 0.18) were associated with unsuccessful mapping. Multiple linear regression model analysis identified age (p = 0.007), tracer type (p = 0.013), and enlarged lymph nodes (p = 0.013) as independent predictors of SLN mapping failure. Conclusions: Advanced age, tracer type, and intraoperative detection of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping. Full article

Background: Sentinel lymph node (SLN) biopsy in early-stage endometrial cancer is recommended over systematic lymphadenectomy due to reduced morbidity and comparable detection rates. The main objective of this study was to compare the overall and bilateral detection rates of SLN in early-stage endometrial cancer using three techniques. Methods: a prospective cohort study was designed to detect the difference in SLN detection rate in three cohorts: Indocyanine green (ICG), methylene blue (MB), and tracer combination (ICG + MB). Mapping characteristics, detection rate, number of SLNs, and positive SLNs of the three cohorts were compared. Results: A total of 99 patients were enrolled. A total of 109 SLN sites with 164 lymph nodes were detected. No differences were found between the three cohorts in terms of age, BMI, tumor diameter, or other histologic characteristics. The overall SLN detection rate (DR) was 54.3% in the MB group, 72.7% in ICG, and 80.6% in the ICG-MB group. Bilateral DR was 22.9%, 39.4%, and 54.8% in groups, respectively, with the MB method yielding significantly inferior results. Conclusions: The ICG-MB group demonstrated superior overall and bilateral detection rates, but a significant difference was found only in the MB cohort. Combining tracer agents can enhance the accuracy of SLN identification in initial-stage endometrial cancer without additional risk to the patient. Full article

Targeted drug delivery to visceral organs offers the possibility of not only limiting the required dose, but also minimizing drug toxicity; however, there is no reliable method for delivering drugs to the surface of visceral organs. Here, we used six color tracers and the chick chorioallantoic membrane (CAM) model to investigate the use of the heteropolysaccharide pectin to facilitate tracer diffusion across the glycocalyceal charge barrier. The color tracers included brilliant blue, Congo red, crystal violet, indocyanine green, methylene blue, and methyl green. The direct application of the tracers to the CAM surface or embedding tracers into linear-chain nanocellulose fiber films resulted in no significant diffusion into the CAM. In contrast, when the tracers were actively loaded into branched-chain pectin films, there was significant detectable diffusion of the tracers into the CAM. The facilitated diffusion was observed in the three cationic tracers but was limited in the three anionic tracers. Diffusion appeared to be dependent on ionic charge, but independent of tracer size or molecular mass. We conclude that dye-loaded pectin films facilitated the diffusion of color tracers across the glycocalyceal charge barrier and may provide a therapeutic path for drug delivery to the surface of visceral organs. Full article

Background: Despite intensive research, the ideal protocol applied to maximize the overall benefits of antimicrobial photodynamic therapy (aPDT) remains unexplored. Evidence exists that following aPDT, the diffused light beyond the photosensitizer can exert a secondary therapeutic effect known as photobiomodulation (PBM), which stimulates the healing of the surrounding tissues. Therefore, the aim of this study was to examine the attenuation properties of five different photosensitizers activated by their corresponding laser wavelengths. Methods: The illumination of various concentrations of chosen photosensitizers, curcumin, methylene blue, toluidine blue, indocyanine green and a methylene blue derivative, irradiated by their respective laser wavelengths (445 nm, 635 nm, 660 nm and 808 nm) was explored via a spectrophotometric analysis. The onward transmitted light intensities for each combination of a photosensitizer and laser wavelength were assessed. The attenuation percentages observed were statistically evaluated using an analysis-of-variance (ANOVA) model. A Tukey’s post hoc test was performed to determine the significance of differences between individual group mean values. Results: With the exception of toluidine blue illuminated by an 808 nm laser, which showed the lowest intensity loss, all the other photosensitizers presented an attenuation range of 63% to 99%. Conclusions: At appropriate concentrations, all the examined photosensitizers may allow the passage of sufficient wavelength-dependent light transmission. Calculated fluences are proposed to achieve secondary, beneficial PBM effects. Full article

Near-infrared fluorescence (NIRF) image-guided surgery is a useful tool that can help reduce perioperative complications and improve tissue recognition. Indocyanine green (ICG) dye is the most frequently used in clinical studies. ICG NIRF imaging has been used for lymph node identification. However, there are still many challenges in lymph node identification by ICG. There is increasing evidence that methylene blue (MB), another clinically applicable fluorescent dye, can also be useful in the intraoperative fluorescence-guided identification of structures and tissues. We hypothesized that MB NIRF imaging could be used for lymph node identification. The aim of this study was to evaluate the feasibility of intraoperative lymph node fluorescence detection using intravenously (IV) administered MB and compare it to ICG via a camera that has two dedicated near-infrared (NIR) channels. Three pigs were used in this study. ICG (0.2 mg/kg) was administered via a peripheral venous catheter followed by immediate administration of MB (0.25 mg/kg). NIRF images were acquired as video recordings at different time points (every 10 min) over an hour using the QUEST SPECTRUM^® 3 system (Quest Medical Imaging, Middenmeer, The Netherlands), which has two dedicated NIR channels for simultaneous intraoperative fluorescence guidance. The 800 nm channel was used to capture ICG fluorescence and the 700 nm channel was used for MB. The target (lymph nodes and small bowel) and the background (vessels-free field of the mesentery) were highlighted as the regions of interest (ROIs), and corresponding fluorescence intensities (FI) from these ROIs were measured. The target-to-background ratio (TBR) was then computed as the mean FI of the target minus the mean FI of the background divided by the mean FI of the background. In all included animals, a clear identification of lymph nodes was achieved at all time points. The mean TBR of ICG in lymph nodes and small bowel was 4.57 ± 1.00 and 4.37 ± 1.70, respectively for the overall experimental time. Regarding MB, the mean TBR in lymph nodes and small bowel was 4.60 ± 0.92 and 3.27 ± 0.62, respectively. The Mann-Whitney U test of the lymph node TBR/small bowel TBR showed that the TBR ratio of MB was statistically significantly higher than ICG. The fluorescence optical imaging technology used allows for double-wavelength assessment. This feasibility study proves that lymph nodes can be discriminated using two different fluorophores (MB and ICG) with different wavelengths. The results suggest that MB has a promising potential to be used to detect lymphatic tissue during image-guided surgery. Further preclinical trials are needed before clinical translation. Full article

Aim: to evaluate the adjunctive effects of photodynamic therapy (aPDT) on nonsurgical mechanical treatment in patients with periodontitis. Materials and methods: The search strategy was conducted according to the PRISMA guidelines to answer research questions regarding the effectiveness of aPDT in association with non-surgical periodontal therapy. The mean values and standard deviations were collected by data extraction. A descriptive comparison between aPDT in association with periodontal treatment and periodontal treatment alone was performed, and meta-analyses of PPD were also performed. Both randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) were included. Results: Out of 2059 records, 14 articles on adjunctive photodynamic therapy were included because they met the eligibility criteria. A comparison between the aPDT data and the control group showed improved PPD for photodynamic therapy (SMD −0.76, p = 0.003; I² = 88%). Statistical analysis was then applied to the three PPD subgroups. The first group included studies that used indocyanine green in association with a wavelength of 810 nm (SMD −1.79, p < 0.00001, I² = 88%). The second group included studies that used phenothiazine chloride at a wavelength of 660 nm (SMD −0.03, p = 0.84, I² = 0%). The last group included studies that used methylene blue photosensitizers treated with a wavelength 628–670 nm were included (SMD −0.13, p = 0.38; I² = 0%). Conclusions: despite the limited number of RCTs and the great heterogeneity between them, it can be concluded that aPDT in association with nonsurgical periodontal treatment improved the clinical parameters at 3 months. Full article

In this study, we propose a single camera-based dual-channel near-infrared (NIR) fluorescence imaging system that produces color and dual-channel NIR fluorescence images in real time. To simultaneously acquire color and dual-channel NIR fluorescence images of two fluorescent agents, three cameras and additional optical parts are generally used. As a result, the volume of the image acquisition unit increases, interfering with movements during surgical procedures and increasing production costs. In the system herein proposed, instead of using three cameras, we set a single camera equipped with two image sensors that can simultaneously acquire color and single-channel NIR fluorescence images, thus reducing the volume of the image acquisition unit. The single-channel NIR fluorescence images were time-divided into two channels by synchronizing the camera and two excitation lasers, and the noise caused by the crosstalk effect between the two fluorescent agents was removed through image processing. To evaluate the performance of the system, experiments were conducted for the two fluorescent agents to measure the sensitivity, crosstalk effect, and signal-to-background ratio. The compactness of the resulting image acquisition unit alleviates the inconvenient movement obstruction of previous devices during clinical and animal surgery and reduces the complexity and costs of the manufacturing process, which may facilitate the dissemination of this type of system. Full article

The treatment of gastric cancer mainly depends on radical gastrectomy. Determination of appropriate surgical margins and adequate lymph node (LN) resection are two major surgical steps that directly correlate with prognosis in gastric cancer. Due to the expanding use of minimally invasive procedures, it is no longer possible to locate tumors and LNs through touch. As an alternative, tracers have begun to enter the field due to their capacities for intraoperative visualization. Herein, we summarize the application of contemporary tracers in gastric cancer surgery, including isosulfan blue, methylene blue, patent blue, indocyanine green, carbon particles, and radioactive tracers. Their mechanisms, administration methods, detection efficiency, and challenges, as well as perspectives on them, are also outlined. Full article