{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:14:23Z","timestamp":1792422863923,"version":"4.5.0"},"reference-count":86,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its\u2019 function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.<\/jats:p>","DOI":"10.3390\/jcm9113538","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T09:04:46Z","timestamp":1604307886000},"page":"3538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Methylene Blue\u2014Current Knowledge, Fluorescent Properties, and Its Future Use"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-9735","authenticated-orcid":false,"given":"Tomasz","family":"Cwalinski","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Polom","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-9588","authenticated-orcid":false,"given":"Luigi","family":"Marano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53-100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giandomenico","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Florence, viale Pieraccini 6, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Cwalina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Ascension St. John Children\u2019s Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Matuszewski","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53-100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Jaskiewicz","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Polom","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Gdansk, 80-214 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alkan G\u00fcrsel, S., Yang, Z., Choudhury, B., Roelofs, M.G., and Scherer, G.G. (2006). Radiation-Grafted Membranes Using a Trifluorostyrene Derivative. J. Electrochem. Soc.","DOI":"10.1149\/1.2335626"},{"key":"ref_2","first-page":"42","article-title":"Methylene blue mediated photodynamic therapy for resistant plaque psoriasis","volume":"81","author":"Salah","year":"2009","journal-title":"J. Drugs Dermatol."},{"key":"ref_3","unstructured":"ASTM International (2015). Standard Test Method for Rapid Determination of the Methylene Blue Value for Fine Aggregate or Mineral Filler Using a Colorimeter, ASTM International. ASTM C1777-15."},{"key":"ref_4","unstructured":"Brayfield, A. (1883). Methylthioninium chloride. Martindale: The Complete Drug Reference, Pharmaceutical Press."},{"key":"ref_5","first-page":"4119","article-title":"Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer","volume":"29","author":"Mathelin","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chen, W., Chen, L., Yang, S., Chen, Z., Qian, G., Zhang, S., and Jing, J. (2007). A novel technique for localization of small pulmonary nodules. Chest.","DOI":"10.1378\/chest.06-1017"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prokop, E.K., Buddemeyer, E.U., Strauss, H.W., and Wagner, H.N. (1974). Detection and localization of an occult vesicoenteric fistula. Am. J. Roentgenol.","DOI":"10.2214\/ajr.121.4.811"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Raja, S., Rice, T.W., Neumann, D.R., Saha, G.B., Khandekar, S., MacIntyre, W.J., and Go, R.T. (1999). Scintigraphic detection of post-pneumonectomy bronchopleural fistulae. Eur. J. Nucl. Med.","DOI":"10.1007\/s002590050379"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1001\/archderm.1975.01630210090012","article-title":"Eczema herpeticum. Treatment with methylene blue and light","volume":"111","author":"Chang","year":"1975","journal-title":"Arch. Dermatol."},{"key":"ref_10","first-page":"E126","article-title":"Treatment of oral lichen planus with photodynamic therapy mediated methylene blue: A case report","volume":"11","author":"Aghahosseini","year":"2006","journal-title":"Med. Oral Patol. Oral Cir. Bucal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-60761-697-9_13","article-title":"Photodynamic therapy of bacterial and fungal biofilm infections","volume":"635","author":"Biel","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11046-011-9434-6","article-title":"Photodynamic antifungal therapy against chromoblastomycosis","volume":"172","author":"Lyon","year":"2011","journal-title":"Mycopathologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/pho.2009.2522","article-title":"High-intensity laser and photodynamic therapy as a treatment for recurrent herpes labialis","volume":"28","author":"Marotti","year":"2010","journal-title":"Photomed. Laser Surg."},{"key":"ref_14","unstructured":"Shannon, M.W., and Borron, S.W.B.M. (2007). Haddad and Winchester\u2019s Clinical Management of Poisoning and Drug Overdose, Elsevier. [4th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2165\/00139709-200322010-00003","article-title":"Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue","volume":"22","author":"Bradberry","year":"2003","journal-title":"Toxicol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4037\/ccn2011799","article-title":"A review of acute cyanide poisoning with a treatment update","volume":"31","author":"Hamel","year":"2011","journal-title":"Crit. Care Nurse"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Peter, C., Hongwan, D., K\u00fcpfer, A., and Lauterburg, B.H. (2000). Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur. J. Clin. Pharmacol.","DOI":"10.1007\/s002280000124"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bai, S.W., Huh, E.H., Park, J.H., Rha, K.H., Kim, S.K., and Park, K.H. (2006). Urinary tract injuries during pelvic surgery: Incidence rates and predisposing factors. Int. Urogynecol. J.","DOI":"10.1007\/s00192-005-0015-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/med.20177","article-title":"Cellular and molecular actions of Methylene Blue in the nervous system","volume":"31","author":"Oz","year":"2011","journal-title":"Med. Res. Rev."},{"key":"ref_20","unstructured":"Akorn Inc. (2011). Methylene Blue Injection, USP 1% Prescribing Information, Akorn Inc."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jangjoo, A., Forghani, M.N., Mehrabibahar, M., and Sadeghi, R. (2010). Anaphylaxis reaction of a breast cancer patient to methylene blue during breast surgery with sentinel node mapping. Acta Oncol.","DOI":"10.3109\/02841861003769964"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gould, E.A., Winship, T., Philbin, P.H., and Kerr, H.H. (1960). Observations on a \u201csentinel node\u201d in cancer of the parotid. Cancer.","DOI":"10.1002\/1097-0142(196001\/02)13:1<77::AID-CNCR2820130114>3.0.CO;2-D"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cabanas, R.M. (1977). An approach for the treatment of penile carcinoma. Cancer.","DOI":"10.1002\/1097-0142(197702)39:2<456::AID-CNCR2820390214>3.0.CO;2-I"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chung, A., and Giuliano, A.E. (2018). Lymphatic mapping and sentinel lymphadenectomy for breast cancer. The Breast: Comprehensive Management of Benign and Malignant Diseases, Elsevier.","DOI":"10.1016\/B978-0-323-35955-9.00042-8"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Morton, D.L., Wen, D.R., Wong, J.H., Economou, J.S., Cagle, L.A., Storm, F.K., Foshag, L.J., and Cochran, A.J. (1992). Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma. Arch. Surg.","DOI":"10.1001\/archsurg.1992.01420040034005"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00423-017-1641-2","article-title":"Use of methylene blue and near-infrared fluorescence in thyroid and parathyroid surgery","volume":"403","author":"Hillary","year":"2018","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/bjs.4217","article-title":"Sentinel lymph node mapping in colorectal cancer","volume":"90","author":"Mulsow","year":"2003","journal-title":"Br. J. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/00000658-199409000-00015","article-title":"Lymphatic mapping and sentinel lymphadenectomy for breast cancer","volume":"220","author":"Giuliano","year":"1994","journal-title":"Ann. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nedu, M.-E., Tertis, M., Cristea, C., and Georgescu, A.V. (2020). Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications. Diagnostics, 10.","DOI":"10.3390\/diagnostics10040223"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nguyen, J.Q.M., McWade, M., Thomas, G., Beddard, B., Herington, J.L., Paria, B.C., Schwartz, H.S., Halpern, J.L., Holt, G.E., and Mahadevan-Jansen, A. (2018). Development of a modular fluorescence overlay tissue imaging system for wide-field intraoperative surgical guidance. J. Med. Imaging.","DOI":"10.1117\/1.JMI.5.2.021220"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vahrmeijer, A.L., Hutteman, M., Van der Vorst, J.R., Van de Velde, C.J.H., and Frangioni, J.V. (2013). Image-guided cancer surgery using near-infrared fluorescence. Nat. Rev. Clin. Oncol.","DOI":"10.1038\/nrclinonc.2013.123"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Van Manen, L., Handgraaf, H.J.M., Diana, M., Dijkstra, J., Ishizawa, T., Vahrmeijer, A.L., and Mieog, J.S.D. (2018). A practical guide for the use of indocyanine green and methylene blue in fluorescence-guided abdominal surgery. J. Surg. Oncol.","DOI":"10.1002\/jso.25105"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/jso.21943","article-title":"The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery","volume":"104","author":"Schaafsma","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Polom, K., Murawa, D., Nowaczyk, P., Rho, Y.S., and Murawa, P. (2012). Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green-human serum albumin in comparison with gamma emitting radioactive colloid tracer. Eur. J. Surg. Oncol.","DOI":"10.1016\/j.ejso.2011.11.004"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4103\/0970-9185.74599","article-title":"Methylene blue: Revisited","volume":"26","author":"Ginimuge","year":"2010","journal-title":"J. Anaesthesiol. Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Barnes, T.G., Hompes, R., Birks, J., Mortensen, N.J., Jones, O., Lindsey, I., Guy, R., George, B., Cunningham, C., and Yeung, T.M. (2018). Methylene blue fluorescence of the ureter during colorectal surgery. Surg. Endosc.","DOI":"10.1007\/s00464-018-6219-8"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jpha.2016.07.006","article-title":"Bile salt induced solubilization of methylene blue: Study on methylene blue fluorescence properties and molecular mechanics calculation","volume":"7","author":"Selvam","year":"2017","journal-title":"J. Pharm. Anal."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Stummer, W., Pichlmeier, U., Meinel, T., Wiestler, O.D., Zanella, F., and Reulen, H.J. (2006). Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol.","DOI":"10.1016\/S1470-2045(06)70665-9"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Shimizu, S., Kamiike, W., Hatanaka, N., Yoshida, Y., Tagawa, K., Miyata, M., and Matsuda, H. (1995). New method for measuring ICG Rmax with a clearance meter. World J. Surg.","DOI":"10.1007\/BF00316992"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Al-Awadi, K.A., Kehinde, E.O., Al-Hunayan, A., and Al-Khayat, A. (2005). Iatrogenic ureteric injuries: Incidence, aetiological factors and the effect of early management on subsequent outcome. Int. Urol. Nephrol.","DOI":"10.1007\/s11255-004-7970-4"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Palaniappa, N.C., Telem, D.A., Ranasinghe, N.E., and Divino, C.M. (2012). Incidence of iatrogenic ureteral injury after laparoscopic colectomy. Arch. Surg.","DOI":"10.1001\/archsurg.2011.2029"},{"key":"ref_42","first-page":"169","article-title":"Iatrogenic ureter injuries: Eleven years experience in a tertiary hospital","volume":"67","author":"Mahendran","year":"2012","journal-title":"Med. J. Malays."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Marcelissen, T.A.T., Den Hollander, P.P., Tuytten, T.R.A.H., and Sosef, M.N. (2016). Incidence of Iatrogenic Ureteral Injury during Open and Laparoscopic Colorectal Surgery: A Single Center Experience and Review of the Literature. Surg. Laparosc. Endosc. Percutaneous Tech.","DOI":"10.1097\/SLE.0000000000000335"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1177\/014107688808100904","article-title":"The \u201cHoly Plane\u201d of Rectal Surgery","volume":"81","year":"1988","journal-title":"J. R. Soc. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Delacroix, S.E., and Winters, J.C. (2010). Urinary tract injures: Recognition and management. Clin. Colon Rectal Surg.","DOI":"10.1055\/s-0030-1254297"},{"key":"ref_46","first-page":"49","article-title":"The implications of lighted ureteral stenting in laparoscopic colectomy","volume":"6","author":"Chahin","year":"2002","journal-title":"J. Soc. Laparoendosc. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Verbeek, F.P.R., Van der Vorst, J.R., Schaafsma, B.E., Swijnenburg, R.J., Gaarenstroom, K.N., Elzevier, H.W., van de Velde, C.J., Frangioni, J.V., and Vahrmeijer, A.L. (2013). Intraoperative near infrared fluorescence guided identification of the ureters using low dose methylene blue: A first in human experience. J. Urol.","DOI":"10.1016\/j.juro.2013.02.3187"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Al-Taher, M., van den Bos, J., Schols, R.M., Bouvy, N.D., and Stassen, L.P.S. (2016). Fluorescence Ureteral Visualization in Human Laparoscopic Colorectal Surgery Using Methylene Blue. J. Laparoendosc. Adv. Surg. Tech.","DOI":"10.1089\/lap.2016.0264"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yeung, T.M., Volpi, D., Tullis, I.D.C., Nicholson, G.A., Buchs, N., Cunningham, C., Guy, R., Lindsey, I., George, B., and Jones, O. (2016). Identifying ureters in situ under fluorescence during laparoscopic and open colorectal surgery. Ann. Surg.","DOI":"10.1097\/SLA.0000000000001513"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Matsui, A., Tanaka, E., Choi, H.S., Kianzad, V., Gioux, S., Lomnes, S.J., and Frangioni, J.V. (2010). Real-time, near-infrared, fluorescence-guided identification of the ureters using methylene blue. Surgery.","DOI":"10.1016\/j.surg.2009.12.003"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bach, K.K., Lindsay, F.W., Berg, L.S., and Howard, R.S. (2004). Prolonged postoperative disorientation after methylene blue infusion during parathyroidectomy. Anesth. Analg.","DOI":"10.1213\/01.ANE.0000134860.73875.CF"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Majithia, A., and Stearns, M.P. (2006). Methylene blue toxicity following infusion to localize parathyroid adenoma. J. Laryngol. Otol.","DOI":"10.1017\/S0022215105005098"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Khan, M.A., North, A.P., and Chadwick, D.R. (2007). Prolonged postoperative altered mental status after methylene blue infusion during parathyroidectomy: A case report and review of the literature. Ann. R. Coll. Surg. Engl.","DOI":"10.1308\/147870807X160434"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Slooter, M.D., Janssen, A., Bemelman, W.A., Tanis, P.J., and Hompes, R. (2019). Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: A systematic review. Tech. Coloproctol.","DOI":"10.1007\/s10151-019-01973-4"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"McWade, M.A., Thomas, G., Nguyen, J.Q., Sanders, M.E., Sol\u00f3rzano, C.C., and Mahadevan-Jansen, A. (2019). Enhancing Parathyroid Gland Visualization Using a Near Infrared Fluorescence-Based Overlay Imaging System. J. Am. Coll. Surg.","DOI":"10.1016\/j.jamcollsurg.2019.01.017"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dudley, N.E. (1971). Methylene Blue for Rapid Identification of the Parathyroids. Br. Med. J.","DOI":"10.1136\/bmj.3.5776.680"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Harrison, B.J., and Triponez, F. (2009). Intraoperative adjuncts in surgery for primary hyperparathyroidism. Langenbeck\u2019s Arch. Surg.","DOI":"10.1007\/s00423-009-0532-6"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"De Leeuw, F., Breuskin, I., Abbaci, M., Casiraghi, O., Mirghani, H., Lakhdar, A.B., Laplace-Builh\u00e9, C., and Hartl, D. (2016). Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study. World J. Surg.","DOI":"10.1007\/s00268-016-3571-5"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zhang, C., Jiang, D., Huang, B., Wang, C., Zhao, L., Xie, X., Zhang, Z., Wang, K., Tian, J., and Luo, Y. (2019). Methylene Blue-Based Near-Infrared Fluorescence Imaging for Breast Cancer Visualization in Resected Human Tissues. Technol. Cancer Res. Treat.","DOI":"10.1177\/1533033819894331"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/jso.25874","article-title":"Real-time near-infrared fluorescence imaging mediated by blue dye in breast cancer patients","volume":"121","author":"Jiang","year":"2020","journal-title":"J. Surg. Oncol."},{"key":"ref_61","unstructured":"Hariharan, U., Sood, R., Choudhury, A., Garg, R., and Kaur, J. (2011). Oxygen desaturation following methylene blue injection: Not always spurious. Saudi J. Anaesth."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Varon, A.J., Anderson, H.B., and Civetta, J.M. (1989). Desaturation noted by pulmonary artery catheter oximeter after methylene blue injection. Anesthesiology.","DOI":"10.1097\/00000542-198911000-00029"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Salhab, M., Al Sarakbi, W., and Mokbel, K. (2005). Skin and fat necrosis of the breast following methylene blue dye injection for sentinel node biopsy in a patient with breast cancer. Int. Semin. Surg. Oncol.","DOI":"10.1186\/1477-7800-2-26"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1742-1241.1974.tb09205.x","article-title":"Necrotic subcutaneous abscesses following injections of methylene blue","volume":"28","author":"Perry","year":"1974","journal-title":"Br. J. Clin. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1524-4741.2007.00519.x","article-title":"Methylene blue dye\u2014A safe and effective alternative for sentinel lymph node localization","volume":"14","author":"Varghese","year":"2008","journal-title":"Breast J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Patel, H.P., Chadwick, D.R., Harrison, B.J., and Balasubramanian, S.P. (2012). Systematic review of intravenous methylene blue in parathyroid surgery. Br. J. Surg.","DOI":"10.1002\/bjs.8814"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Vutskits, L., Briner, A., Klauser, P., Gascon, E., Dayer, A.G., Kiss, J.Z., Muller, D., Licker, M.J., and Morel, D.R. (2008). Adverse effects of methylene blue on the central nervous system. Anesthesiology.","DOI":"10.1097\/ALN.0b013e3181684be4"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sidi, A., Paulus, D.A., Rush, W., Gravenstein, N., and Davis, R.F. (1987). Methylene Blue and Indocyanine Green Artfactually Lower Pulse Oximetry Readings of Oxygen Saturation. Studies in Dogs. J. Clin. Monit.","DOI":"10.1007\/BF03337379"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Paras, C., Keller, M., White, L., Phay, J., and Mahadevan-Jansen, A. (2011). Near-infrared autofluorescence for the detection of parathyroid glands. J. Biomed. Opt.","DOI":"10.1117\/1.3583571"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"McWade, M.A., Paras, C., White, L.M., Phay, J.E., Mahadevan-Jansen, A., and Broome, J.T. (2013). A novel optical approach to intraoperative detection of parathyroid glands. Surgery.","DOI":"10.1016\/j.surg.2013.06.046"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Van der Vorst, J.R., Schaafsma, B.E., Verbeek, F.P.R., Swijnenburg, R.J., Tummers, Q.R., Hutteman, M., Hamming, J.F., Kievit, J., Frangioni, J.V., and van de Velde, C.J. (2014). Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue. Head Neck.","DOI":"10.1002\/hed.23384"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Winer, J.H., Choi, H.S., Gibbs-Strauss, S.L., Ashitate, Y., Colson, Y.L., and Frangioni, J.V. (2010). Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light. Ann. Surg. Oncol.","DOI":"10.1245\/s10434-009-0868-8"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gordon, D.L., Airan, M.C., and Suvanich, S. (1974). Visual identification of an insulinoma using methylene blue. Br. J. Surg.","DOI":"10.1002\/bjs.1800610508"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Handgraaf, H.J.M., Boogerd, L.S.F., Shahbazi Feshtali, S., Sarasqueta, A.F., Snel, M., Swijnenburg, R.J., Vahrmeijer, A.L., Bonsing, B.A., and Mieog, J.S.D. (2018). Intraoperative Near-Infrared Fluorescence Imaging of Multiple Pancreatic Neuroendocrine Tumors: A Case Report. Pancreas.","DOI":"10.1097\/MPA.0000000000000951"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Van der Vorst, J.R. (2012). Near-infrared fluorescence imaging of a solitary fibrous tumor of the pancreas using methylene blue. World J. Gastrointest. Surg.","DOI":"10.4240\/wjgs.v4.i7.180"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Tummers, Q.R.J.G., Boonstra, M.C., Frangioni, J.V., van de Velde, C.J.H., Vahrmeijer, A.L., and Bonsing, B.A. (2015). Intraoperative near-infrared fluorescence imaging of a paraganglioma using methylene blue: A case report. Int. J. Surg. Case Rep.","DOI":"10.1016\/j.ijscr.2014.12.002"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Brouwer de Koning, S.G., Vrancken Peeters, M.J.T.F.D., J\u00f3\u017awiak, K., Bhairosing, P.A., and Ruers, T.J.M. (2018). Tumor Resection Margin Definitions in Breast-Conserving Surgery: Systematic Review and Meta-analysis of the Current Literature. Clin. Breast Cancer.","DOI":"10.1016\/j.clbc.2018.04.004"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Houvenaeghel, G., Lambaudie, E., Bannier, M., Rua, S., Barrou, J., Heinemann, M., Buttarelli, M., Piana, J.T., and Cohen, M. (2019). Positive or close margins: Reoperation rate and second conservative resection or total mastectomy?. Cancer Manag. Res.","DOI":"10.2147\/CMAR.S190852"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ejso.2014.02.225","article-title":"Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue","volume":"40","author":"Tummers","year":"2014","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"B\u00e9zu, C., Coutant, C., Salengro, A., Dara\u00ef, E., Rouzier, R., and Uzan, S. (2011). Anaphylactic response to blue dye during sentinel lymph node biopsy. Surg. Oncol.","DOI":"10.1016\/j.suronc.2010.10.002"},{"key":"ref_81","unstructured":"Mu\u00f1iz-Diaz, E., and Puig, L. (2014). Allergic and anaphylactic reactions to methylene-blue-treated plasma in Catalonia in the period 2008\u20132013. Blood Transfus."},{"key":"ref_82","unstructured":"Barras, A.C.H., Walder, B., and Seeck, M. (2010). Serotonin syndrome following methylene blue infusion: A rare complication of antidepressant therapy. J. Neurol. Neurosurg. Psychiatry."},{"key":"ref_83","unstructured":"Polymedica Pharmaceuticals USA Inc. (1990). Product Information. Urised Tablets (Methylene Blue), Polymedica Pharmaceuticals USA Inc."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Youngster, I., Arcavi, L., Schechmaster, R., Akayzen, Y., Popliski, H., Shimonov, J., Beig, S., and Berkovitch, M. (2010). Medications and glucose-6-phosphate dehydrogenase deficiency: An evidence-based review. Drug Saf.","DOI":"10.2165\/11536520-000000000-00000"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1542\/peds.97.5.717","article-title":"Methylene blue-induced phototoxicity: An unrecognized complication","volume":"97","author":"Porat","year":"1996","journal-title":"Pediatrics"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"George, M. (2000). Methylene-blue-induced hyperbilirubinemia and phototoxicity in a neonate. Clin. 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