Search Results (61)

This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article

Background/Objectives: Glioblastoma (GBM) is the most common primary malignant central nervous system tumor, accounting for 50.9% of malignant CNS diagnoses and carrying a median survival of 15 months despite maximal standard therapy. High recurrence rates are driven by residual infiltrative tumor cells at the resection margin. Fluorescence-guided surgery (FGS) has emerged as a key innovation to improve intraoperative tumor visualization and maximize the extent of resection (EOR). This review examines the historical development, current clinical applications, and future directions of FGS in GBM surgery. Methods: A comprehensive literature review was conducted, covering the evolution of fluorophores (fluorescein, indocyanine green [ICG], and 5-aminolevulinic acid [5-ALA]), visualization technologies (wide- and narrow-field modalities), therapeutic adjuncts (photodynamic and sonodynamic therapies), and clinical adoption patterns and outcomes. Results: Early intraoperative fluorescence using fluorescein dates to 1947. ICG angiography has broad surgical utility, while 5-ALA received FDA approval in 2017, with phase III trials demonstrating gross total resection rates of 65% versus 36% with white-light surgery. Adjunct technologies—3D exoscopes, FGS-compatible loupes, and quantitative spectroscopy probes—enhance detection of residual tumor. Preliminary studies of intraoperative photodynamic and sonodynamic therapies show feasibility and potential survival benefits. Global adoption of 5-ALA FGS exceeds 75% among surveyed neurosurgeons. Conclusions: FGS significantly improves EOR in GBM surgery, translating into better patient outcomes. Ongoing clinical trials and technological refinements—novel fluorophores, quantitative imaging, and therapeutic applications—promise to further optimize tumor visualization and treatment. Full article

Background/Objectives: Indocyanine green fluorescence angiography (ICG-FA) enables the real-time visualization of tissue perfusion. However, objective research on microscope-integrated fluorescence angiography (FA) has not been conducted before. This study aims to evaluate the fluorescence light distribution in images formed by ICG-FA in two surgical microscopes using a phantom, and to provide recommendations for their application. Methods: An 11.8 by 6.8 cm ICG and Intralipid phantom was made to evaluate overall spatial fluorescence sensitivity in two surgical microscopes in multiple working distances (WDs) and magnification factors (MFs). The signal was quantified using a tailor-made software in Python 3.8.10. Results: A clear center–periphery effect was present in most settings in both microscopes, with the highest peripheral fluorescence signal loss in the lowest MF: 100% in the Tivato and 83% in the Pentero. Increasing the MF improved homogeneity, where the biggest difference was seen between the first and second MF. A 30 cm WD and 3.5× MF produced the most homogeneous images suitable for free-flap surgery. Manually opening the light beam diameter also reduced the center–periphery effect. Conclusions: Peripheral signal loss in microscope-integrated ICG-FA must be considered during clinical interpretation and for the quantification of tissue perfusion. In clinical practice during reconstructive free-flap surgery, a 30 cm WD, 3.5 MF, and manually opened light beam diameter should be applied to achieve the most homogeneous image. Full article

Planning and harvesting anterolateral thigh flaps (ALT) requires precise perforator selection and accurate tissue perfusion assessment. Unfortunately, variable perforator anatomy and perfusion patterns often result in extensive exploratory dissection. We aimed to assess the impact of preoperative color-coded duplex sonography (CCDS) and intraoperative indocyanine green fluorescence angiography (ICGFA) on perforator selection and operative morbidity. Fifty-three ALTs were performed with preoperative CCDS and intraoperative ICGFA. Flaps had one, two, or three suitable perforators. Additional perforators were either included, or ligated following temporary clamping with ICGFA-based perfusion assessment. If perfusion was sufficient, further dissecting of additional perforators of unfavorable course was abstained from. The impact on perforator selection and operative outcomes was studied. Seven flaps were raised on a single, 34 on 2, and 12 on 3 perforators. There was no flap loss. Comparing the subgroups of fully dissected versus partially clamped and subsequently ligated perforators revealed significantly shorter harvest times in the latter (268 ± 71 versus 216 ± 47 min, p = 0.006). The unnecessary dissection of 21 additional perforators in 16 cases was avoided. Combining preoperative CCDS and intraoperative ICGFA aids in designing ALTs and guarantees the intraoperative selection of suitable perforators. This allows for significant reductions in operative time and donor-site morbidity by limiting unnecessary dissection. Full article

Background:Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative damage and inflammation in AMD models, thereby offering therapeutic potential. Materials and Methods: Adult retinal pigmented epithelial cells (ARPE-19) were pre-treated with phlorizin (0.01–0.1 μM) and subjected to oxidative stress induced by ultraviolet A (UVA) radiation or sodium iodate (NaIO₃). Cell viability, reactive oxygen species (ROS) production, MAPK/NF-κB signaling, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-angiogenic factors (VEGF, MMP2, MMP9) expression were assessed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. In vivo, a laser-induced choroidal neovascularization (CNV) mouse model was used to evaluate phlorizin’s effects on CNV formation and vascular leakage via fundus photography and fluorescence angiography. Result: Phlorizin significantly enhanced cell viability, reduced ROS production, inhibited MAPK/NF-κB activation, and downregulated inflammatory and angiogenic mediators. In vivo studies confirmed the reduced CNV formation and vascular leakage following the phlorizin treatment. Conclusions: Phlorizin demonstrated significant protective effects against oxidative stress and inflammation, highlighting its therapeutic potential for treating AMD. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss globally, with early detection and intervention critical to preventing severe outcomes. This narrative review examines the role of retinal biomarkers—molecular and imaging—in improving early diagnosis, tracking disease progression, and advancing personalized treatment for DR. Key biomarkers, such as inflammatory and metabolic markers, imaging findings from optical coherence tomography and fluorescence angiography and genetic markers, provide insights into disease mechanisms, help predict progression, and monitor responses to treatments, like anti-VEGF and corticosteroids. While challenges in standardization and clinical integration remain, these biomarkers hold promise for a precision medicine approach that could transform DR management through early, individualized care. Full article

Background: Esophageal cancer, the seventh most common malignancy globally, requires esophagectomy for curative treatment. However, esophagectomy is associated with high postoperative morbidity and mortality, highlighting the need for minimally invasive approaches. Robotic-assisted surgery has emerged as a promising alternative to traditional open and minimally invasive esophagectomy (MIE), offering potential benefits in improving clinical and oncological outcomes. This review aims to assess the postoperative morbidity and outcomes of robotic surgery. Methods: A comprehensive review of the current literature was conducted, focusing on studies evaluating the role of robotic-assisted surgery in esophagectomy. Data were synthesized on the clinical outcomes, including postoperative complications, survival rates, and recovery time, as well as technological advancements in robotic surgery platforms. Studies comparing robotic-assisted esophagectomy with traditional approaches were analyzed to determine the potential advantages of robotic systems in improving surgical precision and patient outcomes. Results: Robotic-assisted esophagectomy (RAMIE) has shown significant improvements in clinical outcomes compared to open surgery and MIE, including reduced postoperative pain, less blood loss, and faster recovery. RAMIE offers enhanced thoracic access, with fewer complications than thoracotomy. The RACE technique has improved patient recovery and reduced morbidity. Fluorescence-guided technologies, including near-infrared fluorescence (NIRF), have proven valuable for sentinel node biopsy, lymphatic mapping, and angiography, helping identify critical structures and minimizing complications like anastomotic leakage and chylothorax. Despite these benefits, challenges such as the high cost of robotic systems and limited long-term data hinder broader adoption. Hybrid approaches, combining robotic and open techniques, remain common in clinical practice. Conclusions: Robotic-assisted esophagectomy offers promising advantages, including enhanced precision, reduced complications, and faster recovery, but challenges related to cost, accessibility, and evidence gaps must be addressed. The hybrid approach remains a valuable option in select clinical scenarios. Continued research, including large-scale randomized controlled trials, is necessary to further establish the role of robotic surgery as the standard treatment for resectable esophageal cancer. Full article

Background and Objectives: This study aimed to determine the minimal effective dose of indocyanine green (ICG) required for accurately assessing colonic perfusion during laparoscopic colorectal surgery using a laser-assisted laparoscopic near-infrared (NIR) camera system. Materials and Methods: In 15 patients with colorectal cancer undergoing right hemicolectomy, the left branch of the middle colic artery was preserved, and ICG angiography was performed in the transverse colon. To determine the optimal ICG dose, experimental doses of 0.01, 0.02, 0.03, 0.04, and 0.05 mg of ICG per patient’s body weight (kg) were administered intravenously in each group. Additionally, a conventional dose of 0.2 mg/kg was administered in the same patients more than 30 min after the initial dose. For quantitative analysis, the fluorescent expression region was extracted, and fluorescence intensity was analyzed using automatic image processing. Analysis accessibility, T_1/2MAX, perfusion time ratio, slope, artificial intelligence (AI)-based perfusion pattern analysis, and washout time were measured in 150 detailed regions of interest in each image. Results: Group 1 (0.01 mg/kg) showed significantly lower accessibility rates for quantitative analysis (48.0%) compared with Groups 2–5 (84.7–100%). The mean slope value in Group 1 was 3.7, which fell below the acceptable threshold (>4) and was significantly lower than that of the other groups (p < 0.001). An acceptable AI-based perfusion pattern was 14.2% in Group 1, significantly lower than in Groups 2–5 (66.4–100%). Washout time was significantly faster with minimal doses compared with conventional doses (39.0 ± 15.8 s vs. 117.5 ± 4.9 s, respectively, p < 0.001). Conclusions: This study supports the use of minimal ICG doses, ranging from 0.02 to 0.05 mg/kg, to optimize repetitive ICG angiography using a laser-assisted laparoscopic NIR camera. Full article

Background/Objectives: Indocyanine green video angiography, integrated into the operative microscope, is frequently used in cerebrovascular surgery. This technology is often preferred, for cost or availability, to Doppler or intraoperative DSA (digital subtraction angiography). With the same assumption it was possible, in our preliminary experience, to partially vicariate the aforementioned devices using the SPY mode of the Stryker endoscope; it allowed the visualization of fluorescence in high definition. Methods: A retrospective analysis was conducted on a series of five patients suffering from cerebral aneurysm or AVM (arteriovenous malformation) who underwent, during the last year, surgical treatment with the aid of the microscope supported by the Stryker endoscope in the SPY mode for the visualization of the fluorescence emitted by indocyanine green. Results: All aneurysms were completely excluded from the cerebrovascular circulation in the absence of residues in the collar and occlusion of adjacent vessels; the complete removal of the nidus in all the AVMs was achieved with no residues. Conclusions: The intraoperative use of indocyanine green was a safe, rapid, and effective technique within a preliminary case study of “regular—not giant” aneurysms and superficially located AVM. The endoscopic technique in the SPY mode has allowed to partially vicariate the use of Doppler, intraoperative angiography, and integrated microscope video angiography. For these purposes, we propose, in selected cases, the support of the endoscope in the SPY mode during the microsurgical procedure in order to visualize the green fluorescence of indocyanine. Full article

Introduction: Intraoperative fluid management is one of the most important factors affecting optimal perfusion in the microcirculatory area in patients that undergo flap surgery. While insufficient fluid administration in the intraoperative period leads to flap complications and organ dysfunction, volume load can cause complications such as edema in the denervated flap tissue, the opening of the sutures, or fat necrosis. The Infrared Fluorescent Angiography Perfusion Evaluation Device (SPY) is one of the many noninvasive techniques that evaluate the well-being of microcirculation at the tissue level. This device monitors and scores the perfusion distribution in the flap area. This retrospective study aimed to investigate the effect of fluid resuscitation in head and neck free flap transfer surgery on flap quality and patient outcomes according to the change in SPY scores. Material and Method: This study included 39 ASA I–II patients who were aged 18–60 years and underwent simultaneous free flap reconstruction of the head and neck between 2015 and 2021. Patients’ blood pressure, body temperature, hemoglobin, pH, and lactate values were recorded at both baseline and end of the operation. Also, the SPY “Infrared Fluorescent Angiography Perfusion Evaluation Device” scores, the amount of intraoperative fluid and transfusion, bleeding and urine output, and the duration of mechanical ventilation, anesthesia and surgery, and the duration and amount of drainage, the length of stay in hospital and intensive care unit, and the presence of flap infection, detachment, necrosis and loss, and re-exploration rate were recorded for the patients. Results: The difference between the first and last measured SPY values was observed to be positively correlated with the length of stay in the hospital and intensive care unit and the duration of drainage. There was a positive correlation between the length of stay in the hospital and intensive care unit and the duration of drainage, the amount of drainage, as well as the duration of anesthesia and the duration of surgery (p < 0.001). A positive correlation was found between the amount of drainage and the amount of crystalloid solution administered (r = 0.36, p < 0.05). In patients with flap infection, the difference between SPYfirst and SPYlast, the duration of anesthesia, and the duration of surgery were significantly higher. The amount of crystalloid solution given and bleeding and the duration of anesthesia and surgery were found to be significantly higher in mechanically ventilated patients (p < 0.05). Conclusions: It has been concluded that SPY-guided fluid management can be beneficial in preventing morbidities, such as extended hospital and intensive care stay, by reducing flap infection, mechanical ventilation duration, and drainage, with early diagnosis of insufficient perfusion. Full article

Objectives: The main objective of this study was to report and investigate the characteristics and longitudinal changes in dark-without-pressure (DWP) fundus lesions in patients with autoimmune diseases using multimodal imaging techniques. Methods: In this retrospective observational case series, five patients affected by ocular and systemic autoimmune disorders and DWP were examined. DWP was assessed by multimodal imaging, including color fundus photography (CFP), near-infrared reflectance (NIR), blue reflectance (BR), blue autofluorescence (BAF), optical coherence tomography (OCT), OCT-angiography (OCT-A), fluorescein angiography (FA) and indocyanine green angiography (ICGA), and functional testing, including standard automated perimetry (SAP) and electroretinography (ERG). Follow-up examinations were performed for four out of five patients (range: 6 months–7 years). Results: DWP fundus lesions were found in the retinal mid-periphery and were characterized by the hypo-reflectivity of the ellipsoid zone on OCT. DWP appeared hypo-reflective in NIR, BR and BAF, and exhibited hypo-fluorescence in FA in two patients while showing no signs in one patient. ICGA showed hypo-fluorescent margins in one patient. SAP and ERG testing did not show alterations attributable to the DWP lesion. Follow-up examinations documented rapid dimensional changes in DWP even in the short term (1 month). Conclusions: This study suggests a possible association between autoimmune diseases and DWP. New FA and ICGA features were described. The proposed pathogenesis hypotheses may operate as a basis for further investigation of a lesion that is still largely unknown. Large population studies would be necessary to confirm whether there is a higher incidence of DWP in this patient category. Full article

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called “shine-through radioactivity” of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining ^99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with ^99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical “roadmap”. In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted. Full article

The number of solid organ transplant recipients (SOTRs) is growing as a consequence of an increase in transplantations and longer survival; these patients, thus, frequently suffer various comorbidities and are subjected to the detrimental effects of immunosuppressive agents, which expose them to a higher risk of developing malignancies. These drugs also complicate the surgical treatment of neoplasms, as they can hinder wound healing, especially when associated with other unfavorable factors (e.g., previous radiotherapy, diabetes, etc.). We herein present our experience with a 74-year-old SOTR who underwent a radical extended parotidectomy and reconstruction with a submental island flap for a persistent cutaneous squamous carcinoma after radiotherapy; his complicated clinical course was characterized by incredibly slow wound healing. The current literature was reviewed to provide a succinct overview of the main difficulties of head and neck surgery in SOTRs. In particular, the immunosuppressive regimen can be tapered considering the individual risk and other elements should be carefully assessed, possibly prior to surgery, to prevent cumulative harm. New developments, including intraoperative monitoring of flap vascularization through indocyanine green fluorescence video-angiography and the prophylactic application of negative pressure wound therapy, when feasible, may be particularly beneficial for high-risk patients. Full article

Indocyanine green (ICG) is a fluorescent dye used for sentinel lymph node assessment and the assessment of perfusion in skin flaps and bowel anastomoses. ICG binds serum proteins and behaves as a macromolecule in the circulation. Tumour tissue has increased vascular permeability and reduced drainage, causing macromolecules to accumulate within it. MIRRORS ICG is designed to determine whether indocyanine green (ICG) helped identify metastatic deposits in women undergoing robotic interval cytoreductive surgery for advanced-stage (3c+) ovarian cancer. Peritoneal surfaces of the abdominal and pelvic cavity were inspected under white light and near-infrared light (da Vinci Si and Xi Firefly Fluorescence imaging, Intuitive Surgical Inc.) following intravenous injection of 20 mg ICG in sterile water. Visibly abnormal areas were excised and sent to histopathology, noting IGC positivity. In total, 102 biopsies were assessed using ICG. Intravenous ICG assessment following neoadjuvant chemotherapy had a sensitivity of 91.1% (95% CI [82.6–96.4%]), a specificity of 13.0% (95% CI [2.8–33.6%]), a positive predictive value of 78.3% (95% CI [68.4–86.2%]), and a negative predictive value of 30.0% (95% CI [6.7–65.2%]) False-positive samples were seen in 9/20 patients. Psammoma bodies were noted in the histopathology reports of seven of nine of these patients with false-positive results, indicating that a tumour had been present (chemotherapy-treated disease). This study demonstrates the appearance of metastatic peritoneal deposits during robotic cytoreductive surgery following the intravenous administration of ICG in women who have undergone neoadjuvant chemotherapy for stage 3c+ advanced ovarian cancer. A perfusion assessment using indocyanine green (ICG) peritoneal angiography during robotic interval cytoreductive surgery for advanced ovarian cancer did not clinically improve metastatic disease identification in patients with high-volume disease. The use of ICG in patients with excellent response to chemotherapy where few tumour deposits remained shows some promise. The potential of molecular imaging to enhance precision surgery and improve disease identification using the robotic platform is a novel avenue for future research. Full article

Objectives: This review aims to explore recent advancements in optical imaging techniques for monitoring the viability of Deep Inferior Epigastric Perforator (DIEP) flap reconstruction. The objectives include highlighting the principles, applications, and clinical utility of optical imaging modalities such as near-infrared spectroscopy (NIRS), indocyanine green (ICG) fluorescence angiography, laser speckle contrast imaging (LSCI), hyperspectral imaging (HSI), dynamic infrared thermography (DIRT), and short-wave infrared thermography (SWIR) in assessing tissue perfusion and oxygenation. Additionally, this review aims to discuss the potential of these techniques in enhancing surgical outcomes by enabling timely intervention in cases of compromised flap perfusion. Materials and Methods: A comprehensive literature review was conducted to identify studies focusing on optical imaging techniques for monitoring DIEP flap viability. We searched PubMed, MEDLINE, and relevant databases, including Google Scholar, Web of Science, Scopus, PsycINFO, IEEE Xplore, and ProQuest Dissertations & Theses, among others, using specific keywords related to optical imaging, DIEP flap reconstruction, tissue perfusion, and surgical outcomes. This extensive search ensured we gathered comprehensive data for our analysis. Articles discussing the principles, applications, and clinical use of NIRS, ICG fluorescence angiography, LSCI, HSI, DIRT, and SWIR in DIEP flap monitoring were selected for inclusion. Data regarding the techniques’ effectiveness, advantages, limitations, and potential impact on surgical decision-making were extracted and synthesized. Results: Optical imaging modalities, including NIRS, ICG fluorescence angiography, LSCI, HSI, DIRT, and SWIR offer a non- or minimal-invasive, real-time assessment of tissue perfusion and oxygenation in DIEP flap reconstruction. These techniques provide objective and quantitative data, enabling surgeons to monitor flap viability accurately. Studies have demonstrated the effectiveness of optical imaging in detecting compromised perfusion and facilitating timely intervention, thereby reducing the risk of flap complications such as partial or total loss. Furthermore, optical imaging modalities have shown promise in improving surgical outcomes by guiding intraoperative decision-making and optimizing patient care. Conclusions: Recent advancements in optical imaging techniques present valuable tools for monitoring the viability of DIEP flap reconstruction. NIRS, ICG fluorescence angiography, LSCI, HSI, DIRT, and SWIR offer a non- or minimal-invasive, real-time assessment of tissue perfusion and oxygenation, enabling accurate evaluation of flap viability. These modalities have the potential to enhance surgical outcomes by facilitating timely intervention in cases of compromised perfusion, thereby reducing the risk of flap complications. Incorporating optical imaging into clinical practice can provide surgeons with objective and quantitative data, assisting in informed decision-making for optimal patient care in DIEP flap reconstruction surgeries. Full article