Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model.

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1ß and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1ß, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.

Double-Balloon Catheter-Mediated Transarterial Chemotherapy Delivery in a Swine Model: A Mechanism Recruiting the Vasa Vasorum for Localized Therapies.

PURPOSE: Treatment of hypovascular tumors, such as pancreatic adenocarcinoma, is challenging owing to inefficient drug delivery. This report examines the potential mechanism of localized drug delivery via transarterial microperfusion (TAMP) using a proprietary adjustable double-balloon occlusion catheter in a porcine model. MATERIALS AND METHODS: Adult Yorkshire swine (N = 21) were used in the Institutional Animal Care & Use Committee-approved protocols. The RC-120 catheter (RenovoRx, Los Altos, California) was positioned into visceral, femoral, and pulmonary arteries with infusion of methylene blue dye, gemcitabine, or gold nanoparticles. Transmural delivery was compared under double-balloon occlusion with and without side-branch exclusion, single-balloon occlusion, and intravenous delivery. Intra-arterial pressure and vascular histologic changes were assessed. RESULTS: Infusion with double-balloon occlusion and side-branch exclusion provided increased intra-arterial pressure in the isolated segment and enhanced perivascular infusate penetration with minimal vascular injury. Infusates were predominantly found in the vasa vasorum by electron microscopy. CONCLUSIONS: TAMP enhanced transmural passage mediated by localized increase in arterial pressure via vasa vasorum.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31-71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil-to-n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5-20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RF ablation is an option to treat patients with PLE.

The impact of methylene blue in colon cancer: a retrospective multicentric study.

INTRODUCTION: Discussions about the optimal lymph node (LN) count and its therapeutic consequences have persisted over time. The final LN count in colorectal tissues is affected by a variety of variables (patient, tumor, operation, pathologist, immune response). Methylene blue (MB) intra-arterial injection is a simple and inexpensive procedure that can be used to enhance lymph node count. AIM: Analyze whether there is a statistically significant difference between intra-arterial methylene blue injection and conventional dissection for the quantification of lymph nodes and determine if there is a variation in the quality of lymph node acquisition. METHODS AND RESULTS: Between 2015 and 2022, we conducted a retrospective analysis of colon cancer specimens. Data on the tumor's features, the number of lymph nodes, the number of lymph nodes that were positive, and other factors had been collected. The number of identified lymph nodes was highly significantly improved in the study group (P < 0.05). There is not a significant statistical difference between groups regarding the metastatic lymph node harvest. The group with injection of intra-arterial methylene blue shows a significantly decreased (P < 0.05) of the of cases with less than 12 lymph nodes recovered comparing with the control group. CONCLUSION: Colon cancer specimens can be easily evaluated concerning lymph nodes using the methylene blue method. Therefore, we strongly advise this approach as a standard procedure in the histological evaluation of colon cancer specimens in order to maximize the identification of lymph nodes. However, the detection of metastatic lymph nodes was unaffected significantly.

Indocyanine green fluorescence perfusion testing in robot-assisted hepatic arterial infusion pump placement.

BACKGROUND: Hepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field. METHODS: Data was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy. RESULTS: 13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy. DISCUSSION: Liver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement.

Evaluation of the effects of different photosensitizers used in antimicrobial photodynamic therapy on tooth discoloration: spectrophotometric analysis.

BACKGROUND: Tooth discoloration is a common concern in antimicrobial photodynamic therapy (aPDT) using various photosensitizers (PS). Toluidine Blue (TB), Methylene Blue (MB), Phthalocyanine (Pc), and 2-mercaptopyridine-substituted zinc phthalocyanine (TM-ZnPc) are among those studied, but their relative impacts on tooth discoloration remain unclear. AIM: This study aimed to compare the effects of TB, MB, Pc, and TM-ZnPc in aPDT on tooth discoloration, utilizing a controlled experimental setup. MATERIALS AND METHODS: The study comprised seventy-five single-rooted incisors with root canals. Following meticulous preparation, a standardized area on the crown surface was designated for examination, and precise measurements of the initial tooth colors were recorded. Samples were randomly divided into five groups: Negative control, MB, TM, Pc, and TM-ZnPc. Photoactivation was performed using LED light, and color measurements were taken at multiple time points up to 90 days. Data were converted to Lab* color values of the CIE Lab* color system (International Commission on Illumination, Vienna, Austria), and ΔE values were calculated. Statistical analysis was performed using Two-way ANOVA and Post-Hoc Tukey tests (p < 0.05). RESULTS: At day 7 and 30, TM-ZnPc and Pc caused less discoloration compared to MB and TB. TM-ZnPc caused more tooth discoloration compared to Pc (p < 0.05). Compared to baseline, MB and TM-ZnPc caused more tooth discoloration at 30 days and TB caused more tooth discoloration at 90 days (p < 0.05). No significant difference was observed in terms of tooth discoloration at all periods evaluated after Pc application (p > 0.05). All photosensitizers tested in the study caused tooth coloration. CONCLUSION: All PS induced clinically detectable tooth discoloration, with TB and MB causing more significant discoloration compared to Pc and TM-ZnPc at certain time points. TM-ZnPc and Pc demonstrated more stable coloration levels over time, suggesting their potential reliability in aPDT applications. This study highlights the importance of selecting appropriate PS to minimize tooth discoloration in aPDT, with Pc showing promise in this regard.

Ultrasound-guided sciatic nerve block injections in barred owl (Strix varia) cadavers.

OBJECTIVE: To describe an ultrasound-guided approach to the sciatic nerve and the distribution of nerve staining using two injectate volumes of dye in barred owls. STUDY DESIGN: Descriptive, randomized, assessor-blinded, cadaveric study. ANIMALS: Twelve barred owl cadavers. METHODS: The sciatic nerve was visualized with a 13-6 MHz linear ultrasound probe placed on the medial aspect of the proximal femur in barred owl cadavers. A needle was inserted at the proximal caudal thigh, and cranially advanced in-plane until the tip was immediately adjacent and ventral to the sciatic nerve. Eleven owls were injected bilaterally with a 1:1 solution of 1% methylene blue and 0.5% ropivacaine, with high-volume (HV; 0.4 mL kg-1) and low-volume (LV; 0.2 mL kg-1) treatments. Nerve staining ≥ 1 cm circumferentially was determined by dissection 15 minutes post-injection. The coelom was then opened to inspect for aberrant dye spread. In one barred owl cadaver, a 1:1 solution of 1% methylene blue and 74% ioversol contrast was injected, and computed tomography was performed immediately before and 15 minutes after injection for evaluation of injectate spread. RESULTS: The HV treatment (0.4 mL kg-1) resulted in successful nerve staining in 100% of injections, whereas the LV treatment (0.2 mL kg-1) resulted in successful nerve staining in 91% of injections. There was no leakage of injectate into undesired locations (e.g. coelomic cavity) in any cadaver. CONCLUSIONS AND CLINICAL RELEVANCE: In barred owls, the sciatic nerve can be visualized with ultrasound and injecting a ropivacaine/dye solution under ultrasound guidance successfully stained the sciatic nerve in the majority of cases. This technique holds potential for providing analgesia distal to the stifle joint; however, further investigations are necessary to evaluate its practical application in a clinical setting.

Anatomic evaluation to compare the dye spread with ultrasound-guided pericapsular nerve group (PENG) injection with or without an additional suprainguinal fascia iliaca (SIFI) injection in soft embalmed cadavers.

BACKGROUND: Novel interfascial plane blocks like PEricapsular Nerve Group (PENG) and SupraInguinal Fascia Iliaca (SIFI) blocks are effective for management of hip fracture pain. We compared the difference in the distribution of the dye injected and nerves stained by the addition of the SIFI block to the PENG block. METHODS: A total of 24 designated dye injections were performed in eight soft-embalmed cadavers. Under ultrasound guidance 20 ml green ink injected bilaterally in PENG block and 30 ml methylene blue dye was injected in the SIFI block on the right side. The cadavers were dissected 24 h later to assess the extent of dye spread. RESULTS: Extensive spread of dyes was seen on both side of iliacus muscle on the right side, but blue dye was not visible medial to the psoas tendon. The subcostal and iliohypogastric nerves were stained green in the infra-inguinal region. On the left side (PENG alone), the anterior division of the obturator, femoral and saphenous nerve (7/8) and iliohypogastric nerves (3/8) were stained in the infrainguinal region. In the suprainguinal region, the femoral nerve (5/8), accessory obturator nerve (3/8), lateral femoral cutaneous (1/8) and nerve to rectus femoris (4/8) were stained. The main obturator nerve trunk was spared with both injections while its anterior branch and accessory obturator nerve were stained with the PENG injection. CONCLUSION: The study findings indicate that combined PENG + SIFI injections lead to an extensive craniocaudal and longitudinal spread along the iliacus muscle. We perceive that the combination of these two injections will have a superior clinical outcome.

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Ifosfamide induced encephalopathy in a child with osteosarcoma.

BACKGROUND: Ifosfamide (IFO) is an alkylating agent used to treat broad range of malignancies. One of the life-threatening toxic effects is reversible neurotoxicity. In this report; we presented a case report of ifosfamide induced encephalopathy (IIE) in a child with osteosarcoma in order to emphize that it is important to continue ifosfamide treatment as well as the importance of this potentially fatal complication. CASE REPORT: Following the 20th week of ifosfamide treatment, the patient's follow-up with the diagnosis of osteosarcoma developed neurological findings. Laboratory analyzes before and after ifosfamide infusion were normal. No pathological findings were seen on MR imaging. Hypoglycemia, electrolyte disturbances, encephalitis, meningitis, metastasis and posterior reversible encephalopathy syndrome (PRES) were not considered. Electroencephalography was found compatible with neuronal hyperexcitability originating from the left hemisphere. With the diagnosis of ifosfamide induced encephalopathy, prophylaxis with methylene blue was received before the next infusion of ifosfamide. Neurological findings were not observed in the patient's follow-up. CONCLUSION: Patients who develop IIE can continue their treatment protocol with methylene blue prophylaxis and supportive therapy.

Green Discoloration of Human Postmortem Brains: Etiologies and Mechanisms of Discoloration.

ABSTRACT: A variety of gross discolorations of human postmortem brains is occasionally encountered and can have diagnostic implications. We describe 3 cases of green discoloration of the human brain observed on postmortem examination. Two patients who succumbed shortly after administration of methylene blue (MB) showed diffuse green discoloration that was detectable as early as 24 hours and was seen for at least 48 hours after MB administration. Green discoloration was largely in cortical and deep gray matter structures with relative sparing of the white matter. In contrast, a patient with severe hyperbilirubinemia who died after intracerebral hemorrhage showed localized bright green bile stained brain parenchyma in the areas surrounding the hemorrhage. We highlight the distinct patterns of discoloration in different causes of green brain discoloration, including MB, bile staining, and hydrogen sulfide poisoning. Recognition of these patterns by practicing pathologists can be used to differentiate between these etiologies and allow correct interpretation in both the medical and forensic autopsy settings.

Thermo- and pH-Responsive Gelatin/Polyphenolic Tannin/Graphene Oxide Hydrogels for Efficient Methylene Blue Delivery.

Gelatin (GE), amino-functionalized polyphenolic tannin derivative (TN), and graphene oxide (GO) were associated to yield thermo- and pH-responsive hydrogels for the first time. Durable hydrogel assemblies for drug delivery purposes were developed using the photosensitizer methylene blue (MB) as a drug model. The cooling GE/TN blends provide brittle physical assemblies. To overcome this disadvantage, different GO contents (between 0.31% and 1.02% wt/wt) were added to the GE/TN blend at 89.7/10.3 wt/wt. FTIR and RAMAN spectroscopy analyses characterized the materials, indicating GO presence in the hydrogels. Incorporation studies revealed a total MB (0.50 mg/mL) incorporation into the GE/TN-GO hydrogel matrices. Additionally, the proposed systems present a mechanical behavior similar to gel. The GO presence in the hydrogel matrices increased the elastic modulus from 516 to 1650 Pa. SEM revealed that hydrogels containing MB present higher porosity with interconnected pores. Dissolution and swelling degree studies revealed less stability of the GE/TN-GO-MB hydrogels in SGF medium (pH 1.2) than SIF (pH 6.8). The degradation increased in SIF with the GO content, making the polymeric matrices more hydrophilic. MB release studies revealed a process controlled by Fickian diffusion. Our results point out the pH-responsible behavior of mechanically reinforced GE/TN-GO-MB hydrogels for drug delivery systems purposes.

Greenish-blue discoloration of the brain and heart after treatment with methylene blue.

Greenish-blue discoloration of the brain and heart was observed during the autopsy of a 63-year-old woman who had been treated with methylene blue for septic shock following a traffic accident. This "pistachio" or "avatar" discoloration occurs when the colorless metabolite leucomethylene blue is oxidized to methylene blue upon exposure to atmospheric oxygen. Other clinically documented adverse effects of methylene blue include greenish-blue urine and bluish discoloration of the skin and mucosa. In medicine, methylene blue is an inhibitor of nitric oxide synthase and guanylate cyclase with different clinical applications, namely, rapid reversal of circulatory shock that is refractory to fluid administration, inotropic agents, and vasoconstrictors. Postmortem differential diagnosis with putrefaction and hydrogen sulfide poisoning should be made, and forensic pathologists should be aware of methylene blue-related greenish-blue discoloration to avoid unnecessary workup and investigations.

Efficacy of Per-oral Methylene Blue Formulation for Screening Colonoscopy.

BACKGROUND & AIMS: Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral methylene blue formulation (MB-MMX) can be delivered directly to the colorectal mucosa. METHODS: We performed a phase 3 study of 1205 patients scheduled for colorectal cancer screening or surveillance colonoscopies (50-75 years old) at 20 sites in Europe and the United States, from December 2013 through October 2016. Patients were randomly assigned to groups given 200 mg MB-MMX, placebo, or 100 mg MB-MMX (ratio of 2:2:1). The 100-mg MB-MMX group was included for masking purposes. MB-MMX and placebo tablets were administered with a 4-L polyethylene glycol-based bowel preparation. The patients then underwent colonoscopy by an experienced endoscopist with centralized double-reading. The primary endpoint was the proportion of patients with 1 adenoma or carcinoma (adenoma detection rate [ADR]). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for differences in detection between the 200-mg MB-MMX and placebo groups. False-positive (resection rate for non-neoplastic polyps) and adverse events were assessed as secondary endpoints. RESULTS: The ADR was higher for the MB-MMX group (273 of 485 patients, 56.29%) than the placebo group (229 of 479 patients, 47.81%) (OR 1.46; 95% CI 1.09-1.96). The proportion of patients with nonpolypoid lesions was higher in the MB-MMX group (213 of 485 patients, 43.92%) than the placebo group (168 of 479 patients, 35.07%) (OR 1.66; 95% CI 1.21-2.26). The proportion of patients with adenomas ≤5 mm was higher in the MB-MMX group (180 of 485 patients, 37.11%) than the placebo group (148 of 479 patients, 30.90%) (OR 1.36; 95% CI 1.01-1.83), but there was no difference between groups in detection of polypoid or larger lesions. The false-positive rate did not differ significantly between groups (83 [23.31%] of 356 patients with non-neoplastic lesions in the MB-MMX vs 97 [29.75%] of 326 patients with non-neoplastic lesions in the placebo group). Overall, 0.7% of patients had severe adverse events but there was no significant difference between groups. CONCLUSIONS: In a phase 3 trial of patients undergoing screening or surveillance colonoscopies, we found MB-MMX led to an absolute 8.5% increase in ADR, compared with placebo, without increasing the removal of non-neoplastic lesions. Clinicaltrials.gov no: NCT01694966.

Methylene Blue/Collagen Mixture for CT-Guided Presurgical Lung Nodule Marking: High Efficacy and Safety.

PURPOSE: To assess outcomes of computed tomography (CT)-guided methylene blue/collagen marking of preoperative lung nodules before video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS). MATERIALS AND METHODS: A retrospective cohort study assessing 25 methylene blue/collagen solution CT-guided lung nodule localization procedures on 26 nodules in 25 patients was performed. The procedures were performed by a fellowship-trained radiologist 1-2 hours before scheduled surgery under local anesthesia. Approximately 4-6 ml of methylene blue/collagen solution was injected in a perinodular location under CT guidance with a 19-gauge trocar needle and along the track to the visceral pleural surface. Post-procedural CT images confirmed appropriate lung nodule location marking. RESULTS: Perinodular CT-guided trocar needle placement was achieved in all marking procedures (n = 26/26). Increased consolidation near the target nodule was also demonstrated in all patients on the post-procedural localized CT scans. One patient with moderate emphysema developed a small to moderate-sized pneumothorax (∼20%-30%), and an 8-Fr thoracentesis catheter was placed under CT guidance before surgery. There was no bleeding or hemoptysis in any patient. Methylene blue/collagen solution was readily visible by the thoracic surgeon in association with all target nodules. One patient required conversion to open procedure due to the proximal portion of the right lower lobe pulmonary artery segmental branch. Of the 26 identified nodules, pathology specimens confirmed the adequacy of nodule resection in all cases. CONCLUSIONS: Preoperative CT-guided methylene blue/collagen solution injection offers a safe and highly effective technique for marking subpleural lung nodules undergoing VATS or RATS.

Headache and Methemoglobinemia.

AIM: This basic review is intended to summarize the current knowledge of methemoglobinemia as an important cause of secondary headache with the hope of generating a growing interest in studying this phenomenon. BACKGROUND: We describe the pathological underpinnings of headaches generated by hypoxia. Possible mechanisms include cerebral vasodilation-associated stretching of the vessel nociceptors, sensitization of perivascular nociceptors mediated by nitric oxide, cerebral calcitonin gene-related peptide, activation of the cyclic adenosine monophosphate pathway, cortical spreading depression, disruption of the blood-brain barrier, and neurogenic inflammation. We review the clinical features, pathophysiology, and management of methemoglobinemia. We conducted a literature review of reports of symptomatic methemoglobinemia with headache. In addition, we describe a case report of a patient who presented with an acute onset of severe holocranial headache associated with rapidly progressive perioral paresthesia, cyanosis in lips and hands, nausea, and mild dyspnea on exertion. These features can be misinterpreted as an acute attack of migraine with pain-related hyperventilation syndrome and anxiety leading to clinically detrimental delay in the management of the progressive hypoxia. Her symptoms resolved following treatment with methylene blue. The complex relationship of migraine and hypoxia-related headaches is also reviewed. We propose that methemoglobinemia-associated headaches are possibly generated by stretching of the nociceptor nerve endings during cerebral vasodilation and hypoxia-mediated oxidative stress. CONCLUSIONS: The case highlights the need to broaden the formulated differential diagnosis of an acute onset severe holocranial headache and pay careful attention to other signs and symptoms that may provide hints on potential mechanism(s) for secondary headaches. We provide justification for the need to incorporate "Headache attributed to Methemoglobinemia" as a subtype under the section "Headache attributed to hypoxia and/or hypercapnia" of the International Classification of Headache Disorders to support clinical decision making.

Technetium-99m-indocyanine green versus technetium-99m-methylene blue for sentinel lymph node biopsy in early-stage endometrial cancer.

INTRODUCTION: The low accuracy of pre-operative imaging techniques for prediction of nodal status strengthens the relevance of sentinel lymph node (SLN) biopsy in endometrial cancer, although the optimal method for its detection is still under investigation. The increasing use of indocyanine green (ICG) has aroused concern about its enhanced visualization of lymphatic channels, which could lead to a specimen that is thought to be nodal tissue not subsequently yielding a lymph node on pathologic analysis ('empty node packet'). Our main objective was to compare the overall and bilateral detection rates for SLN biopsy using two combined techniques: technetium-99m-ICG (Tc-99m-ICG) versus technetium-99m-methylene blue (Tc-99m-MB). Our secondary aim was to compare the 'empty node packet' rates between the two cohorts. METHODS: A prospective, non-randomized, single-center trial including patients diagnosed with endometrial cancer (any grade or histology) in pre-operative early stage, and operated on between February 2017 and July 2019. All tracers were injected intracervically. Pelvic and aortic lymphadenectomy were performed on patients at intermediate or high risk of recurrence pre-operatively. All SLNs were sent for intra-operative frozen section and afterwards processed following an ultrastaging protocol. RESULTS: Eighty-four patients were included, 58% (n=49) in the Tc-99m-MB group and 42% (n=35) in the Tc-99m-ICG group. Overall detection rate was 93% and was not statistically different between the two groups. A better bilateral detection rate was observed among Tc-99m-ICG patients (69% vs 41%, p=0.012). The 'empty node packet' rate was 4% in the Tc-99m-ICG cohort and 0% in the Tc-99m-MB cohort (p=0.032). DISCUSSION: Tc-99m-ICG is a feasible, safe technique for SLN biopsy in early-stage endometrial cancer, and appears to be superior in terms of bilateral detection to Tc-99m-MB. The addition of Tc-99m to ICG could decrease the rate of 'empty node packets' and better define the anatomic location of SLNs in patients with endometrial cancer.

Electromagnetic Navigation Bronchoscopy Triple Contrast Dye Marking for Lung Nodule Localization.

Small pulmonary lesions can be difficult to localize during video-assisted thoracoscopic surgery. Electromagnetic navigation bronchoscopy (ENB) dye marking of the lesion, particularly when guided by cone beam computed tomography in the hybrid operating room (HOR), is an emerging approach. However, issues with confirmation of dye injection and intraoperative visualization of the colored dye can be unpredictable and challenging. To address these uncertainties, we present our technique of ENB dye marking localization of lung nodule using the triple-contrast dye method in the HOR.

Preoperative Computed Tomography-Guided Localization for Pulmonary Nodules with Glue and Dye.

BACKGROUND: This study was aimed to describe a new localization technique developed using medical glue and methylene blue dye, and characterized the localization results and postoperative outcome to evaluate its safety and usefulness. METHODS: This retrospective study was conducted at our center from January 2016 to April 2018. Totally 346 consecutive patients with 383 nodules who underwent preoperative computed tomography (CT)-guided medical glue and methylene blue dye localization, followed by lung resection, were enrolled in this study. RESULTS: Mean nodule size was 7.7 ± 3.7 mm (range: 2-30 mm), with a mean depth from pleura or fissure of 9.4 ± 9.3 mm (range: 0-60 mm). The success rate of CT-guided localization for pulmonary nodules was 99.5% (381/383) of the nodules. Localization-related complications included mild pneumothorax in 16 (4.6%) patients, mild hemothorax in 7 (2.0%) patients, and hemoptysis in 1 (0.3%) patient. Pleural reaction occurred in 7 (2.0%) and pain in 25 (7.2%) patients. All 383 nodules were resected successfully, with conversion to thoracotomy only required in two patients for adhesion and calcification of lymph nodes. All patients recovered well postoperatively, with a short postoperative hospital stay (3.7 ± 2.0 days) and a low complication rate (2.6%, 9/346). CONCLUSION: CT-guided medical glue and methylene blue dye localization prior to video-assisted thoracoscopic surgery (VATS) lung resection was a novel, safe, and technically feasible method, with a high-technical success rate and a low-complication rate. It allowed surgeons to easily locate and detect the nodules and estimate the surgical margin.

Application of Modified Tailed Microcoil in Preoperative Localization of Small Pulmonary Nodules: A Retrospective Study.

BACKGROUND: The localization of small pulmonary nodules (SPNs) during video-assisted thoracoscopic surgery (VATS) is challenging thoracic surgeon, especially in patients with severe pleural adhesion or visceral pleura pigmentation due to low success rate and future conversion to thoracotomy. This study aims to compare the efficacy and safety between modified microcoil and methylene blue in preoperative localization of small nodules, particularly patients with severe pleural adhesion or visceral pleura pigmentation. MATERIALS AND METHODS: From January 2018 to February 2019 in our institute, 342 patients who underwent computed tomography-guided localization of SPN were recruited in this retrospective cohort study and divided into the modified microcoil group (n = 239) and the methylene blue group (n = 103) according to the localization method. Clinical characteristics and perioperative complications were collected to analyze. RESULTS: All SPNs were successfully marked in both groups. Location-related complications, the duration of localization procedure, and the length of hospital stay were not different between the two groups. The operation time of modified microcoil and the duration of removal of nodule in operation were both shorter than the methylene blue (p = 0.014 and p = 0.047). The analysis stratified by gender showed that similar results were found in male patients (p = 0.01 and p = 0.00), while in female patients, no significant difference was found. Additionally, in senior patients (older than 60 years), the operation time in modified microcoil groups was less than methylene blue group (p = 0.024). CONCLUSION: Compared with methylene blue, modified microcoil achieved a shorter operation time of removal of nodule in VATS, especially for patients with pleural adhesion and the pigmentation of the lung surface as well as the male patients and the patients older than 60 years.