A decade of blood-brain barrier permeability assays: Revisiting old traumatic brain injury rat data for new insights and experimental design.

Increased microvascular permeability at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema following traumatic brain injury (TBI). These pathologic conditions compromise the integrity of the neurovascular unit resulting in severe brain dysfunction. To quantify this permeability and assess ionic equillibrium, preclinical researchers have relied on the use of various molecular weight permeable dyes such as Evans Blue that normally cannot enter the brain parenchyma under homeostatic conditions. Evans Blue, the most cited of the molecular weight dyes, has reported reproducibility issues because of harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra associated with the dye. Our laboratory group transitioned to Alexa Fluor 680, a far-red dye with improved sensitivity compared to Evans Blue and thus improved reproducibility to alleviate this issue. To evaluate our reproducibility and increase the rigor of our experimental design, we retrospectively analyzed our controlled cortical impact (CCI) experiments over the past 10 years to evaluate effect size with larger samples and potential sources of variability. All of our BBB permeability experiments were performed with Male, Sprague Dawley rats weighing between 225 and 300 g. Historically, Sprague Dawleys were randomly divided into treatment groups: SHAM, CCI, and a stem cell-based treatment from years 2007-2020. The assessment of microvascular hyperpermeability were evaluated by comparing the mean at minimum threshold, area at 1 k-2 k, and intensity density obtained from Alexa Fluor 680 permeability data. Studies utilizing Evans Blue were further compared by tip depth, diameter size, and the hemisphere of injury. Statistical evaluation utilizing the G Power software analysis did not yield a significant difference in sample size comparing experimental groups for Evans Blue and Alexa Fluor 680 analyzed brain tissue. Our analysis also demonstrated a trend in that recent studies (years 2018-2020) have yielded more compact sample sizes between experimental groups in Alexa Fluor 680 analyzed rats. This retrospective study further revealed that Alexa Fluor 680 image analysis provides greater sensitivity to BBB permeability following TBI in comparison to Evans Blue. Significant differences in sample size were not detected between Evans Blue and Alexa Fluor 680; there were significant differences found throughout year to year analysis at the lower range of thresholds. SUMMARY STATEMENT: This work provides a comparative analysis of BBB permeability assay techniques after CCI model of injury in rats.

Polymethine dyes for PDT: recent advances and perspectives to drive future applications.

It has been proved that the effectiveness of photodynamic therapy (PDT) is closely related to the intrinsic features of the photosensitizer (PS). Over the recent years, several efforts have been devoted to the discovery of novel and more efficient photosensitizers showing higher efficacy and lower side effects. In this context, squaraine and cyanine dyes have been reported to potentially overcome the drawbacks related to the traditional PSs. In fact, squaraines and cyanines are characterized by sharp and intense absorption bands and narrow emission bands with high extinction coefficients typically in the red and near-infrared region, good photo and thermal stability and a strong fluorescent emission in organic solvents. In addition, biocompatibility and low toxicity make them suitable for biological applications. Despite these interesting intrinsic features, their chemical instability and self-aggregation properties in biological media still limit their use in PDT. To overcome these drawbacks, the self-assembly and incorporation into smart nanoparticle systems are forwarded promising approaches that can control their physicochemical properties, providing rational solutions for the limitation of free dye administration in the PDT application. The present review summarizes the latest advances in squaraine and cyanine dyes for PDT application, analyzing the different strategies, i.e.the self-assembly and the incorporation into nanoparticles, to further enhance their photochemical properties and therapeutic potential. The in vivo assessments are still limited, thus further delaying their effective application in PDT.

C4d as a Practical Marker for Cutaneous Amyloidosis.

ABSTRACT: Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed.

Hydrogen sulfide attenuates hyperhomocysteinemia-induced blood-brain barrier permeability by inhibiting MMP-9.

Backgroud: Hyperhomocysteinemia (HHcy) is implicated in various neurovascular disorders including vascular dementia, subarachnoid hemorrhage and stroke. Elevated homocysteine (Hcy) levels are associated with increased oxidative stress and compromised blood-brain barrier (BBB) integrity. Hydrogen sulfide (H2S) has recently emerged as potent neuroprotective molecule in various neurological conditions including those associated with HHcy. The present study evaluates the protective effect of sodium hydrogen sulfide (NaHS; a source of H2S) on HHcy-induced BBB dysfunction and underpin molecular mechanisms.Materials and methods: Supplementation of NaHS restored the increased BBB permeability in the cortex and hippocampus of HHcy animals assessed in terms of diffused sodium fluorescein and Evans blue tracer dyes in the brain. Activity of matrix metalloproteinases (MMPs) assessed by gelatinase activity and in situ gelatinase assay was restored to the normal in the cortex and hippocampus of HHcy animals supplemented with NaHS.Results: Application of gelatin zymography revealed that specifically MMP-9 activity was increased in the cortex and hippocampus of HHcy animals, which was inhibited by NaHS supplementation. Real-time RT-PCR analysis showed that NaHS administration also decreased mRNA expression of MMP-9 in the hippocampus of HHcy animals. NaHS supplementation was further observed to reduce water retention in the brain regions of Hcy treated animals.Conclusion: Taken together, these findings suggest that NaHS supplementation ameliorates HHcy-induced BBB permeability and brain edema by inhibiting the mRNA expression and activity of MMP-9. Therefore, H2S and H2S releasing drugs may be used as a novel therapeutic approach to treat HHcy-associated neurovascular disorders.

Tailored Engineering of Novel Xanthonium Polymethine Dyes for Synergetic PDT and PTT Triggered by 1064 nm Laser toward Deep-Seated Tumors.

Small molecular dye that simultaneously exerts dual PDT/PTT effects as well as florescence imaging triggered by a single NIR-II light has never been reported to date. Apart from the huge challenge in pushing absorption profile into NIR-II region, fine-tuning dyes' excited state via rational structure design to meet all three functions, especially oxygen photosensitization, remains the most prominent throttle. Herein, five novel NIR-II dyes (BHs) are productively developed by strategically conjugating dyad innovative xanthonium with sequentially extended polymethine bridges, enabling intense absorption from 890 to 1206 nm, significantly 400 nm longer than conventional cyanine dyes with same polymethines. More importantly, owning to high resonance and favorable excited state energy population induced by greater rigidity via ring-fused amino, BH 1024 exhibits best singlet oxygen generation capability, moderate photothermal heating, and considerable fluorescence under 1064 nm laser irradiation. Furthermore, BH 1024 is encapsulated into folate-functionalized polymer, which demonstrated a synergetic PDT/PTT effect in vitro and in vivo, eventually achieving solid tumors elimination under NIR-II fluorescence guide. As far as it is known, this is the first time small molecular dyes for NIR-II PDT or NIR-II PDT/PTT are explored and designed.

Local and regional therapy for primary and locally recurrent melanoma.

In the vast majority of cases, cutaneous melanoma presents as localized disease and is treated with wide excision and sentinel lymph node biopsy, with shared decision making regarding completion lymph node dissection and adjuvant systemic therapy. The treatment of recurrent and in-transit disease is more complex, with further options for regional and systemic therapies and multiple variables to be factored into decisions. Rates of overall and complete response to regional therapies can be quite high in carefully chosen patients, which limits the need for systemic therapies and their inherent side effects. Ongoing trials aim to assess the efficacy of combination regional and systemic therapies and assist in deciding among these options. This review discusses the treatment of primary melanoma and regional nodal disease and offers an in-depth discussion of options for the treatment of recurrent melanoma and in-transit melanoma.

Recent Development of Photothermal Agents (PTAs) Based on Small Organic Molecular Dyes.

Photothermal therapy (PTT) has attracted great attention due to its noninvasive and effective use against cancer. Various photothermal agents (PTAs) including organic and inorganic PTAs have been developed in the last decades. Organic PTAs based on small-molecule dyes exhibit great potential for future clinical applications considering their good biocompatibility and easy chemical modification or functionalization. In this review, we discuss the recent progress of organic PTAs based on small-molecule dyes for enhanced PTT. We summarize the strategies to improve the light penetration of PTAs, methods to enhance their photothermal conversion efficiency, how to optimize PTAs' delivery into deep tumors, and how to resist photobleaching under repeated laser irradiation. We hope that this review can rouse the interest of researchers in the field of PTAs based on small-molecule dyes and help them to fabricate next-generation PTAs for noninvasive cancer therapy.

From Dyestuff Chemistry to Cancer Theranostics: The Rise of Rylenecarboximides.

Fighting cancer with the means of chemistry remains a tremendous challenge and defines a pressing societal need. Compounds based on synthetic organic dyes have long been recognized as vital tools for cancer diagnosis and therapy (theranostics). Fluorescence and photoacoustic imaging of cancer as well as cancer treatment protocols such as photodynamic and photothermal therapy are all photobased technologies that require chromophores. However, a serious drawback of most chromophoric molecules is photobleaching over the course of their use in biological environments, which severely compromises the desired theranostic effects. At this point, rylenecarboximide (RI) dyes with ultrahigh photostability hold enormous promise. RI stands for a homologous series of dyes consisting of an aromatic core and carboximide auxochromic groups. They possess high molar extinction coefficients and finely tunable photophysical properties. RIs such as perylenebiscarboxylic acid monoimide (PMI), perylenetetracarboxylic acid diimide (PDI), terrylenetetracarboxylic acid diimide (TDI), and quaterrylene tetracarboxylic acid diimide (QDI) have attracted great scientific attention as colorants, components of organic photovoltaics and organic field-effect transistors, as well as tools for biological applications. PDI has appeared as one of the most widely studied RI dyes for fluorescence bioimaging. Our recent breakthroughs including chemotherapy with PDI-based DNA intercalators and photothermal therapy guided by photoacoustic imaging using PDI, TDI, or QDI, define urgent needs for further scientific research and clinical translation. In this Account, we tackle the relationship between chemical structures and photophysical and pharmacologic properties of RIs aiming at new contrast and anticancer agents, which then lay the ground for further biomedical applications. First, we introduce the design concepts for RIs with a focus on their structure-property relationships. Chemical structure has an enormous impact on the fluorescent, chemotoxic, photodynamic, and photothermal performance of RIs. Next, based on the resulting performance criteria, we employ RIs for fluorescence and photoacoustic cancer imaging as well as cancer therapies. When carrying electron donating substituents, PDIs and PMIs possess high fluorescence quantum yield and red-shifted emission which qualifies them for use in cancer fluorescence imaging. Also, some fluorescent PDIs are combined with chemodrugs or developed into DNA intercalators for chemotherapy. PDI-based photosensitizers are prepared by "heavy atom" substitution, showing potential for photodynamic therapy. Further, photothermal agents using PDI, TDI, and QDI with near-infrared absorption and excellent photothermal conversion efficiency offer high promise in photothermal cancer therapy monitored by photoacoustic imaging. Finally, looking jointly at the outstanding properties of RIs and the demands of current biomedicine, we offer an outlook toward further modifications of RIs as a powerful and practical platform for advanced cancer theranostics as well as treatment of other diseases.

Early Glottic Cancer Treated by Transoral Laser Surgery Using Toluidine Blue for the Definition of the Surgical Margins: A Pilot Study.

Background and objectives: Transoral laser microsurgery (TLM) is widely accepted for its advantages, which consist of a brief hospital stay, rapid functional recovery, low management costs and the fact that it can be easily repeated in cases of recurrence. However, a high incidence of positive or narrow surgical margins has been reported in the literature, even if controversy still exists on the prognostic significance of positive resection margins. The aim of the study was to evaluate the utility of toluidine blue staining in defining the resection margins of early glottic cancer (T1a-T2) treated with TLM. Materials and Methods: This retrospective study was conducted on patients with early glottic cancer (T1a-T2) managed by TLM. A group of patients treated between 2010 and 2014 underwent toluidine blue staining (TB group) of the lesions before starting the cordectomy by TLM, and a group of patients treated by TLM between 2006 and 2009 was considered the control group. Results: A total of 44 subjects were included in this study: 41 were men, and 3 were women. The mean age was 58 ± 9.0 years (median 59.0, range 41-77). Twenty-three of the 44 patients were included in the TB group and 21 in the case control group. In the TB group, only the positivity of the deep margin was a predictor of local recurrence (p = 0.037), while in the control group, positive or close margins and the type of cordectomy were predictive factors of local recurrence (p = 0.049). Considering the TB group and control cases, the 5-year local recurrence-free survival was 95.6% and 80.9%, respectively (p = 0.14). Conclusions: From this first study, toluidine blue staining seems to be a useful modality to improve the rate of the negative resection margins of early glottic cancer (T1a-T2) treated by TLM.

Quantitative Assessment of Liver Function by Using Gadoxetic Acid-enhanced MRI: Hepatocyte Uptake Ratio.

Purpose To determine whether hepatocyte uptake ratios derived at gadoxetic acid-enhanced MRI correlate with quantitative measures of liver function and can help to identify contraindication to major hepatectomy. Materials and Methods Between August 2016 and October 2016, 50 study participants with chronic liver disease or cirrhosis underwent liver MRI at 3.0 T including T1 mapping and elastography. Liver function was quantitatively assessed by using the indocyanine green retention test (ICG R15). T1 maps were obtained by using the Look-Locker sequence before and 10 minutes after gadoxetic acid administration (0.025 mmol/kg). The relationship between ICG R15 and the following MRI parameters was evaluated: pre- and postcontrast T1 values of the liver, hepatocyte uptake ratio representing the amount of contrast media solely taken into hepatocytes, liver volume, and degree of enhancement at the common bile duct. Diagnostic performance of the hepatocyte uptake ratio to identify patients with ICG R15 greater than 20% (ie, contraindication to hepatectomy) was compared with other parameters by using areas under the receiver operating characteristic curve. Results Hepatocyte uptake ratio showed a negative correlation with ICG R15 r of -0.78 (P < .001). In participants with chronic liver disease or Child-Pugh class A, those with ICG R15 of 20% or less showed higher hepatocyte uptake ratio than those with ICG R15 greater than 20% (P < .001). Hepatocyte uptake ratios demonstrated better performance for helping to detect ICG R15 greater than 20% than did liver volume (area under the curve, 0.96 vs 0.70; P = .01). Conclusion Hepatocyte uptake ratios are negatively correlated with liver function as measured by indocyanine green retention test and provide acceptable diagnostic performance for helping to identify participants who have contraindications to major hepatectomy. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.

Ultra-pH-sensitive indocyanine green-conjugated nanoprobes for fluorescence imaging-guided photothermal cancer therapy.

Photothermal therapy (PTT) has been recognized as a promising approach for cancer treatment due to its minimal invasiveness and low systemic side effects. However, developing a photothermal agent with accurate tumor imaging capability is a prerequisite for the efficient PTT. Here, we developed a series of ultra-pH-sensitive indocyanine green (ICG)-conjugated nanoparticles for fluorescence imaging-guided tumor PTT. These nanoparticles exhibited high fluorescence activation ratio (~100-fold) with sharp pH transition (ΔpHon/off <0.25), and superior temperature response than free ICG. The in vivo imaging experiments demonstrated that the nanoparticles generated excellent tumor-to-normal tissue contrast through pH-triggered fluorescence activation in tumor sites, which provided information on tumor mass location, boundaries, and shape. Moreover, comparing to free ICG, the nanosystem had significantly longer blood circulation time and more accurate tumor targeting, providing efficient photothermal therapeutic effect against A549 tumor in living animals. In conclusion, this nanoplatform offers a potential strategy for imaging-guided cancer PTT.

Application of the selective indocyanine green videoangiography in microsurgical treatment of a craniocervical junction dural arteriovenous fistula.

Craniocervical junction dural arteriovenous fistula (CCJDAVF) is a rare and unique type of intracranial DAVF with complex neurovascular anatomy, making it difficult to identify the arterialized vein during operation. The authors report the case of a 50-year-old male who presented with symptoms of venous hypertensive myelopathy. Angiography demonstrated a left CCJDAVF. The fistula was successfully disconnected via a suboccipital midline approach. The selective indocyanine green videoangiography (SICG-VA) technique was applied to distinguish the fistula site and arterialized vein from adjacent normal vessels. Favorable clinical and angiographic outcomes were attained. The detailed operative technique, surgical nuances, and utility of SICG-VA are illustrated in this video atlas.The video can be found here: https://youtu.be/GJYl_jOJQqU.

Application of Indocyanine Green in Gynecology: Review of the Literature.

The present review aims to analyze the current data available on the different applications of indocyanine green (ICG) in gynecology. A semantic review of English-language publications was performed by searching for MeSH terms and keywords in the PubMed and Google Scholar databases. The studies were finally selected by one author according to the aim of this review. ICG is a highly water-soluble tricarbocyanine dye that fluoresces in the NIR spectrum. Approved by the FDA in 1959, it can be administered either IV (usual dose of 5 mg) or locally/submucosally (usual dose of 5-6.25 mg) according to the pathology or indication. It is used most often in the setting of oncology, endometriosis and other gynecological conditions. In oncological applications, ICG is used to identify sentinel lymph nodes (SLN) using near-infrared light in endometrial, cervical and vulvar cancers. The main advantages that it offers include a reduction of surgical time, improved SLN detection rates, and the ability to avoid radioactivity. In cases of endometrial (submucosal or hysteroscopic applications) or cervical (intracervical administration) cancer, ICG can detect SLN at an accuracy of 95% to 98%. For vulvar cancer, the SLN detection rate can reach 100%. In endometriosis, the lack of good evidence hinders the final evaluation of this method in both diagnostic and therapeutic scenarios. An analytical, well-designed, prospective study is currently underway.

Indocyanine green - guided laparoscopic renal pedicle lymphatic disconnection: A novel, targeted treatment for chyluria.

INTRODUCTION AND OBJECTIVES: Chyluria, or the passage of chyle into the urine from anomalous lymphatic connections, results in a characteristic milky urine. In severe cases, it can cause signifi cant morbidity from nutritional losses and immune suppression. Although predominantly associated with Wuchereria bancrofti infections, non-parasitic cases have also been described. Traditionally, surgical treatment has involved renal lymphatic disconnection using open or minimally invasive methods, occasionally aided by pre-operative imaging techniques like lymphangiography, or by identifi cation of structures with laparoscopic magnifi cation.

Organic Dye Based Nanoparticles for Cancer Phototheranostics.

Phototheranostics, which simultaneously combines photodynamic and/or photothermal therapy with deep-tissue diagnostic imaging, is a promising strategy for the diagnosis and treatment of cancers. Organic dyes with the merits of strong near-infrared absorbance, high photo-to-radical and/or photothermal conversion efficiency, great biocompatibility, ready chemical structure fine-tuning capability, and easy metabolism, have been demonstrated as attractive candidates for clinical phototheranostics. These organic dyes can be further designed and fabricated into nanoparticles (NPs) using various strategies. Compared to free molecules, these NPs can be equipped with multiple synergistic functions and show longer lifetime in blood circulation and passive tumor-targeting property via the enhanced permeability and retention effect. In this article, the recent progress of organic dye-based NPs for cancer phototheranostic applications is summarized, which extends the anticancer arsenal and holds promise for clinical uses in the near future.

Indocyanine Green Fluorescence Angiography and the Incidence of Anastomotic Leak After Colorectal Resection for Colorectal Cancer: A Meta-analysis.

BACKGROUND: Anastomotic leak is a life-threatening complication of colorectal surgery. Recent studies showed that indocyanine green fluorescence angiography might be a method to prevent anastomotic leak. OBJECTIVE: The purpose of this study was to investigate whether intraoperative indocyanine green fluorescence angiography can reduce the incidence of anastomotic leak. DATA SOURCES: Potential relevant studies were identified from the following databases: PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. STUDY SELECTION: This meta-analysis included comparative studies investigating the association between indocyanine green fluorescence angiography and anastomotic leak in patients undergoing surgery for colorectal cancer where the diagnosis of anastomotic leak was confirmed by CT and the outcomes of the indocyanine green group were compared with a control group. INTERVENTION: Indocyanine green was injected intravenously after the division of the mesentery and colon but before anastomosis. MAIN OUTCOME MEASURES: The Newcastle-Ottawa Scale was used to assess methodologic quality of the studies. ORs and 95% CIs were used to assess the association between indocyanine green and anastomotic leak. RESULTS: In 4 studies with a total sample size of 1177, comparing the number of anastomotic leaks in the indocyanine green and control groups, the ORs were 0.45 (95% CI, 0.18-1.12), 0.30 (95% CI, 0.03-2.98), 0.17 (95% CI, 0.01-3.69), and 0.12 (95% CI, 0.03-0.52). The combined OR was 0.27 (95% CI, 0.13-0.53). The difference was statistically significant (p < 0.001), and there was no significant heterogeneity (p = 0.48; I = 0). LIMITATIONS: Data could not be pooled because of the small number of studies; some differences between studies may influence the results. Also, the pooled data were not randomized. CONCLUSIONS: The result revealed that indocyanine green was associated with a lower anastomotic leakage rate after colorectal resection. However, larger, multicentered, high-quality randomized controlled trials are needed to confirm the benefit of indocyanine green fluorescence angiography.

Enhanced photodynamic therapy by encapsulation of perfluorocarbon into PEGylated near-infared dyes.

Near-Infrared (NIR) dyes, with improved tissue penetration, minimal invasiveness and high specificity, have gained great interests in diagnosing and treating tumors. However, the poor solubility in aqueous medium and low 1O2 quantum yields of NIR dyes restrict their application in PDT (photodynamic therapy) research. Herein, a novel nanosystem with modifying the NIR dyes and encapsulating perfluorocarbon is reported for improving the PDT effectiveness of NIR dyes. By adding the PEG2000-SH and the C13 carbon chain to a NIR representative dye IR780, the new formed material PEG-IR780-C13 shows good solubility in water. Then PFTBA was encapsulated into PEG-IR780-C13 to form a nanosystem (PFTBA@PEG-IR780-C13). When exposed to laser irradiation, the nanosystem showed enhanced production of 1O2 and significantly increased PDT both in vivo and in vitro. Therefore, this work provides an approach for design and application of NIR dyes.

The Combination of Trypan Blue and Brilliant Blue G-Assisted Vitrectomy for Macular Pucker: Histopathological Findings.

PURPOSE: To report on the combined use of trypan blue (TB) and brilliant blue G (BBG) for staining the epiretinal membrane (ERM) and internal limiting membrane (ILM) during vitrectomy and to describe the histopathological findings. METHODS: 10 surgical specimens were removed from 10 eyes with macular pucker during vitrectomy using a commercially available combination of TB and BBG for ERM and ILM staining and peeling. Specimens were evaluated using light and transmission electron microscopy. RESULTS: In all cases the combination of TB and BBG was useful for identifying and delineating ERM and ILM. No complications related to the use of the dye were observed during or after surgery. Glial cells were present in all specimens. Hyalocytes were observed in 6 cases and myofibroblasts in 3 of them. In 7 cases native vitreous collagen fibrils were found on the ILM, while in 5 specimens newly formed collagen was present. No clinical evidence of toxicity was observed during the 3-month follow-up. CONCLUSION: The combined use of TB and BBG appeared to be very useful intraoperatively to improve the visualization of ERM and ILM, thus facilitating their complete removal. Anatomical and histopathological findings demonstrated the safety and the efficacy of this vital dye.

Doxorubicin and Indocyanine Green Loaded Hybrid Bicelles for Fluorescence Imaging Guided Synergetic Chemo/Photothermal Therapy.

Hybrid bicelles have been demonstrated to have great potential for hydrophobic drug delivery. Herein, we report a near-infrared light-driven, temperature-sensitive hybrid bicelles co-encapsulating hydrophobic doxorubicin (DOX) and indocyanine green (ICG) (DOX/ICG@HBs). Encapsulation of ICG into the lipid bilayer membrane of DOX/ICG@HBs results in higher photostability than free ICG. DOX/ICG@HBs exhibited temperature-regulated drug release behavior and significant photothermal cytotoxicity. After tail vein injection, such discotic nanoparticles of DOX/ICG@HBs were found to accumulate selectively at the tumor site and act as an efficient probe to enhance fluorescence imaging greatly. The in vivo experiments showed that the DOX/ICG@HBs-mediated chemo- and photothermal combination therapy was more cytotoxic to tumor cells than the photothermal treatment or the chemotherapy alone due to the synergistic effect, reducing the occurrence of tumor metastasis. Therefore, DOX/ICG@HBs can act as a powerful nanotheranostic agent for chemo/photothermal therapy of cancer under the guidance of near-infrared fluorescence imaging.

Subserosal uterine injection of blue dye for the identification of the sentinel node in patients with endometrial cancer: a feasibility study.

OBJECTIVE: To define the detection rate, sensitivity, and negative predictive value (NPV) of the sentinel node technique in patients with endometrial cancer. METHODS: Patients with endometrial cancer after informed consent underwent subserosal injection of blue dye during hysterectomy in a tertiary gynae/oncology department between 2010 and 2014. The procedure was performed in all cases by the same team including two gynae/oncologist consultants and one trainee. All relevant perioperative clinicopathological characteristics of the population were recorded prospectively. The identified sentinel nodes were removed separately and a completion bilateral pelvic lymphadenectomy followed in all cases. Simple statistics were used to calculate the sensitivity and NPV of the method on per patient basis. RESULTS: Fifty-four patients were included in this study. At least one sentinel node was mapped in 46 patients yielding a detection rate of 85.2%. Bilateral detection of sentinel nodes was accomplished in only 31 patients (57.4%). The mean number of sentinel nodes was 2.6 per patient and the commonest site of identification was the external iliac artery and vein area (66%). Six patients (11%) had a positive lymph node, and in five of them, this was the sentinel one yielding a sensitivity of 83.3% and an NPV of 97.5%. The overall detection rate improved significantly after the first 15 cases; however, this was not the case for the bilateral detection rate. CONCLUSION: Our study is in accordance with previous studies of sentinel node in endometrial cancer and further demonstrates and enhances the confidence in the technique. In the current era of an ongoing debate on whether a systematic lymphadenectomy in patients with endometrial cancer is still necessary, we believe that the sentinel node is an acceptable alternative and should be applied routinely in tertiary centres following a strict algorithm.