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Chen Y, Liu G, Wu Y, Cai H. Assessment of liver injury using indocyanine green fluorescence imaging. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1167. [PMID: 34430608 PMCID: PMC8350635 DOI: 10.21037/atm-21-3049] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/14/2021] [Indexed: 12/25/2022]
Abstract
Background To investigate whether indocyanine green (ICG) fluorescence imaging can be used to evaluate chronic and acute liver injury induced by either a high-fat (HF) diet or carbon tetrachloride (CCl4). Methods Sprague-Dawley (SD) rats were randomly divided into three groups: control group, HF diet-induced model group, and CCl4-induced model group. The chronic and acute liver injury models were induced by a HF diet and intraperitoneal injection of CCl4, respectively. After HF feeding, the liver index, levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the rats were determined. The livers were also collected to evaluate histopathology damage by hematoxylin and eosin (H&E) staining. After in vitro perfusion of the liver and ICG administration, the liver fluorescence intensity and corresponding spectral value were measured by using real-image guided system (REAL-IGS). Results After HF feeding, the liver index and levels of serum ALT and AST were significantly increased, and the livers of the rats showed severe histopathological changes. Compared with the control group, the hepatic lobes of the model rats exhibited incomplete green fluorescence, and the corresponding spectral value was markedly reduced. Conclusions ICG fluorescence imaging can be used to evaluate liver injury induced by either a HF diet or CCl4.
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Affiliation(s)
- Yan Chen
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Ge Liu
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yulin Wu
- Nanjing Nuoyuan Medical Devices Co., Ltd., Nanjing, China
| | - Huiming Cai
- Nanjing Nuoyuan Medical Devices Co., Ltd., Nanjing, China
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Tokunaga A, Miyamoto H, Fumoto S, Nishida K. Effect of Chronic Kidney Disease on Hepatic Clearance of Drugs in Rats. Biol Pharm Bull 2021; 43:1324-1330. [PMID: 32879206 DOI: 10.1248/bpb.b20-00124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The pharmacokinetics of some hepatically cleared drugs have been reported to fluctuate in patients with renal impairment, but the definitive factors have not been clarified. We compared the pharmacokinetics of some drugs with different hepatic elimination processes in a chronic kidney disease (CKD) rat model, to optimize their administration during kidney injury. We chose indocyanine green (ICG), midazolam (MDZ), and acetaminophen (APAP) as reference drugs to determine changes in hepatic clearance pathways in presence of CKD. Drugs were intravenously administered via the jugular vein to the CKD model rats, previously established by adenine administration, and then, blood, bile, and urine samples were collected. The plasma concentration of ICG, which is eliminated into the bile without biotransformation, increased; and its total body clearance (CLtot) significantly decreased in the CKD group compared to the control group. Moreover, the plasma concentrations of MDZ and APAP, metabolized in the liver by CYP3A and Ugt1a6 enzymes, respectively, were higher in the CKD group than in the control group. The biliary clearances of APAP and its derivative APAP-glucuronide increased in the CKD group, whereas their renal clearances were markedly decreased with respect to those in the control group. Altogether, plasma concentrations of some hepatically eliminated drugs increased in the CKD rat model, but depending on their pharmacokinetic characteristics. This study provides useful information for optimizing the administration of some hepatically cleared drugs in CKD patients.
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Affiliation(s)
- Ayako Tokunaga
- Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University
| | - Hirotaka Miyamoto
- Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University
| | - Shintaro Fumoto
- Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University
| | - Koyo Nishida
- Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University
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Salehi O, Kazakova V, Vega EA, Conrad C. Indocyanine green staining for intraoperative perfusion assessment. Minerva Surg 2021; 76:220-228. [PMID: 34080819 DOI: 10.23736/s2724-5691.21.08673-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Indocyanine green (ICG) is a fluorescent iodide-based dye which is used in hepatic surgery to evaluate the biliary tree, liver perfusion, and function. While liver perfusion assessment and delineation of anatomic regions has been performed using ultrasound, ischemic demarcation, or indigo carmine/methylene blue staining, ICG staining can overcome limitations associated with these techniques, such as rapid washout, lack of precision, non-demarcation in damaged livers, and lack of intraparenchymal fidelity. ICG can be used to fluoresce target segments/tumors (Positive staining) or counterstain normal liver tissue leaving areas of interest unstained (negative staining). Moreover, ICG enhancement patterns vary for different tumors, such as colorectal liver metastases vs. hepatocellular carcinoma, providing not only help with detection but also assessment of differentiation. In the field of oncology, benefits of ICG include detection of small radiographically occult tumors, distinction between cirrhotic nodules and cancer, identification of necrotic tumors in chemotherapy-damaged livers, and determining margins when intraoperative ultrasound is inadequate. While ICG has important and expanding indications in hepatic surgery, limitations include small depth of penetrance, need for special monitors/equipment, and potential for dye spillage. ICG is well tolerated, has a small learning curve, minimally invasive surgical integration, and options of both portal vein and peripheral vein injection and hence is a safe and versatile method of anatomic liver mapping, tumor visualization, and liver graft perfusion evaluation in oncologic surgery and liver transplantation. Advancements in technique and technology associated with ICG will aid in increasing the indications in hepato-biliary surgery.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Vera Kazakova
- Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA -
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Perioperative Non-Invasive Indocyanine Green-Clearance Testing to Predict Postoperative Outcome after Liver Resection. PLoS One 2016; 11:e0165481. [PMID: 27812143 PMCID: PMC5094749 DOI: 10.1371/journal.pone.0165481] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Accepted: 10/12/2016] [Indexed: 02/06/2023] Open
Abstract
Background Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting. Study Design 137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests. Results Preoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome. Conclusion PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications.
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Uthaman S, Bom JS, Kim HS, John JV, Bom HS, Kim SJ, Min JJ, Kim I, Park IK. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors. J Biomed Mater Res B Appl Biomater 2016; 104:825-34. [PMID: 26743660 DOI: 10.1002/jbm.b.33607] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Revised: 11/16/2015] [Accepted: 12/03/2015] [Indexed: 12/13/2022]
Abstract
Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.
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Affiliation(s)
- Saji Uthaman
- Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
| | - Joon-suk Bom
- Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
| | - Hyeon Sik Kim
- Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
| | - Johnson V John
- Department of Polymer Science and Engineering, BK 21 PLUS Center for Advanced Chemical Technology, Pusan National University, Pusan 609-735, Republic of Korea
| | - Hee-Seung Bom
- Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
| | - Seon-Jong Kim
- Department of Korean Medicine Rehabilitation, Mokpo Oriental Hospital of Dongshin University, 313 Baengnyeon-daero, Mokpo 530-822, Korea
| | - Jung-Joon Min
- Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
| | - Il Kim
- Department of Polymer Science and Engineering, BK 21 PLUS Center for Advanced Chemical Technology, Pusan National University, Pusan 609-735, Republic of Korea
| | - In-Kyu Park
- Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
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Fluorescent imaging of the biliary tract during laparoscopic cholecystectomy. ANNALS OF SURGICAL INNOVATION AND RESEARCH 2014; 8:5. [PMID: 25317203 PMCID: PMC4196113 DOI: 10.1186/s13022-014-0005-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Accepted: 07/16/2014] [Indexed: 01/28/2023]
Abstract
The introduction of laparoscopic cholecystectomy was associated with increased incidences of bile duct injury. The primary cause appears to be misidentification of the biliary anatomy. Routine intra-operative cholangiography has been recommended to reduce accidental duct injury, although in practice it is more often reserved for selected cases. There has been interest in the use of fluorescent agents excreted via the biliary system to enable real-time intra-operative imaging, to aid the laparoscopic surgeon in correctly interpreting the anatomy. The primary aim of this review is to evaluate the ability of fluorescent cholangiography to identify important biliary anatomy intra-operatively. Secondary aims are to investigate its ability to detect important intra-operative pathology such as bile leaks, identify potential alternative fluorophores, and evaluate the evidence regarding patient outcomes.
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Çelebi N, Muğlalı M, Aksoy A, Yarım G, Yarım M, Güvenç D. Comparison of lidocaine metabolism for different anesthesia techniques in rabbits with liver disease. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 116:e23-6. [PMID: 22819454 DOI: 10.1016/j.oooo.2011.11.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Revised: 10/22/2011] [Accepted: 11/06/2011] [Indexed: 11/18/2022]
Abstract
OBJECTIVE This study was designed to investigate the serum lidocaine concentrations (SLC) after local infiltration anesthesia (IA) and mandibular anesthesias (MA) in rabbits with carbon tetrachloride (CCl₄)-induced chronic liver damage (CLD). STUDY DESIGN Fourteen rabbits were administered CCl₄ in group 1, MA (CLD-MA; n = 7); in group 2, IA (CLD-IA; n = 7); in group 3, MA (H-MA; n = 7); and in group 4, IA (H-IA; n = 6) was performed. SLC were measured. RESULTS SLC showed difference over time. At the 10th minute, mean SLC in IA groups were higher than in MA groups. At the 120th minute, the highest mean concentration was found in the CLD-IA group. CONCLUSIONS SLC increases in CLD, and serum lidocaine concentration after IA in the mandibular anterior region is higher than it is after MA.
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Affiliation(s)
- Nükhet Çelebi
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, Turkey.
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Akl TJ, King TJ, Long R, McShane MJ, Nance Ericson M, Wilson MA, Coté GL. Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma. JOURNAL OF BIOMEDICAL OPTICS 2012; 17:077008. [PMID: 22894521 PMCID: PMC3394684 DOI: 10.1117/1.jbo.17.7.077008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2011] [Revised: 06/06/2012] [Accepted: 06/14/2012] [Indexed: 06/01/2023]
Abstract
An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.
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Affiliation(s)
- Tony J. Akl
- Texas A&M University, Department of Biomedical Engineering, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843-3120
| | - Travis J. King
- Texas A&M University, Department of Biomedical Engineering, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843-3120
| | - Ruiqi Long
- Texas A&M University, Department of Biomedical Engineering, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843-3120
| | - Michael J. McShane
- Texas A&M University, Department of Biomedical Engineering, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843-3120
| | - M. Nance Ericson
- Oak Ridge National Laboratory, P.O. Box 2008, MS 6006, Oak Ridge, Tennessee 37831-6006
| | - Mark A. Wilson
- University of Pittsburgh, Department of Surgery, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213
- University Dr. C-1w142, Veterans Affairs Healthcare System, Pittsburgh, Pennsylvania 15240
| | - Gerard L. Coté
- Texas A&M University, Department of Biomedical Engineering, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843-3120
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A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012; 2012:940585. [PMID: 22577366 PMCID: PMC3346977 DOI: 10.1155/2012/940585] [Citation(s) in RCA: 864] [Impact Index Per Article: 66.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 02/01/2012] [Indexed: 02/07/2023] Open
Abstract
The purpose of this paper is to give an overview of the recent surgical intraoperational applications of indocyanine green fluorescence imaging methods, the basics of the technology, and instrumentation used. Well over 200 papers describing this technique in clinical setting are reviewed. In addition to the surgical applications, other recent medical applications of ICG are briefly examined.
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Vollmar B, Menger MD. The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev 2009; 89:1269-339. [PMID: 19789382 DOI: 10.1152/physrev.00027.2008] [Citation(s) in RCA: 368] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The complex functions of the liver in biosynthesis, metabolism, clearance, and host defense are tightly dependent on an adequate microcirculation. To guarantee hepatic homeostasis, this requires not only a sufficient nutritive perfusion and oxygen supply, but also a balanced vasomotor control and an appropriate cell-cell communication. Deteriorations of the hepatic homeostasis, as observed in ischemia/reperfusion, cold preservation and transplantation, septic organ failure, and hepatic resection-induced hyperperfusion, are associated with a high morbidity and mortality. During the last two decades, experimental studies have demonstrated that microcirculatory disorders are determinants for organ failure in these disease states. Disorders include 1) a dysregulation of the vasomotor control with a deterioration of the endothelin-nitric oxide balance, an arterial and sinusoidal constriction, and a shutdown of the microcirculation as well as 2) an overwhelming inflammatory response with microvascular leukocyte accumulation, platelet adherence, and Kupffer cell activation. Within the sequelae of events, proinflammatory mediators, such as reactive oxygen species and tumor necrosis factor-alpha, are the key players, causing the microvascular dysfunction and perfusion failure. This review covers the morphological and functional characterization of the hepatic microcirculation, the mechanistic contributions in surgical disease states, and the therapeutic targets to attenuate tissue injury and organ dysfunction. It also indicates future directions to translate the knowledge achieved from experimental studies into clinical practice. By this, the use of the recently introduced techniques to monitor the hepatic microcirculation in humans, such as near-infrared spectroscopy or orthogonal polarized spectral imaging, may allow an early initiation of treatment, which should benefit the final outcome of these critically ill patients.
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Affiliation(s)
- Brigitte Vollmar
- Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
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Hori T, Yagi S, Iida T, Taniguchi K, Yamagiwa K, Yamamoto C, Hasegawa T, Yamakado K, Kato T, Saito K, Wang L, Torii M, Hori Y, Takeda K, Maruyama K, Uemoto S. Optimal systemic hemodynamic stability for successful clinical outcomes after adult living-donor liver transplantation: prospective observational study. J Gastroenterol Hepatol 2008; 23:e170-e178. [PMID: 18422962 DOI: 10.1111/j.1440-1746.2008.05394.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM Most living-donor liver transplantation (LDLT) recipients show characteristic systemic hemodynamics due to liver cirrhosis, and systemic hemodynamics after LDLT influenced postoperative graft function corresponding to outcomes. However, identities of optimal systemic hemodynamics for excellent outcomes and precise parameters for clinical strategy remain unclear. METHODS Therefore, we performed prospective study in adult LDLT recipients from 2003. Hemodynamic parameters were prospectively recorded, and were analyzed in 40 recipients classified into three groups: cirrhotic (group I-C) or non-cirrhotic recipients (group I-NC) with good outcomes, and cirrhotic recipients (group II-C) without good outcomes. RESULTS Group I-C retained characteristic hyperdynamics even after LDLT. However, absolute values of parameters revealed no significant differences between groups I-C and II-C, because group II-C also tended to show hyperdynamics. It is suggested that successful outcomes in cirrhotic recipients require maintenance of optimal hyperdynamic stability after LDLT, because cirrhotic vascular alterations still occurred. Because hemodynamic behaviors were different between groups I-C and I-NC, absolute values were also significantly different even in these successful two groups. Thus, absolute values themselves were not necessarily satisfactory for accurate evaluation of optimal hemodynamic stability. Cirrhotic hyperdynamics are symbolized in large blood volume (BV) circulated by high cardiac output (CO); therefore, we standardized CO against BV. CO/BV was significantly different between groups I-C and II-C, reflecting subtle variability of hyperdynamics in groups II-C, and was interestingly constant in the two successful groups. Therefore, CO/BV reliably evaluated optimal hemodynamic stability after LDLT, and accurately predicted outcomes. CONCLUSION Identification of inappropriate hemodynamics after LDLT is advantageous to further improve LDLT outcomes.
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Affiliation(s)
- Tomohide Hori
- Department of Hepato-pancreato-biliary Surgery and Transplantation, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
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A liquid chromatography tandem mass spectrometry method for the quantification of indocyanine green in dog plasma and bile. J Pharm Biomed Anal 2008; 47:351-9. [DOI: 10.1016/j.jpba.2008.01.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2007] [Revised: 01/04/2008] [Accepted: 01/07/2008] [Indexed: 11/19/2022]
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Hashimoto T, Miki K, Imamura H, Sano K, Satou S, Sugawara Y, Kokudo N, Makuuchi M. Sinusoidal perfusion in the veno-occlusive region of living liver donors evaluated by indocyanine green and near-infrared spectroscopy. Liver Transpl 2008; 14:872-80. [PMID: 18508355 DOI: 10.1002/lt.21460] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Split liver transplantation and living donor liver transplantation (LDLT) commonly use a right liver graft without the middle hepatic vein (MHV). Although tributaries of the MHV are not reconstructed in the majority of cases, the alterations of the microcirculation and its regional functions remain unknown. We addressed these issues by assessing liver tissue indocyanine green (ICG) uptake with near-infrared spectroscopy (NIRS) in 21 donors. After graft procurement, visual inspection (before and after hepatic arterial clamping) and Doppler examination of the veno-occlusive region were performed. Bolus ICG (100 microg/kg) was then administered intravenously. Blood ICG at the finger tip was measured with pulse dye densitometry, whereas the liver ICG concentrations in the veno-occlusive and non-veno-occlusive regions were simultaneously measured for 15 minutes by NIRS. We estimated the hepatic ICG uptake rate constants in the veno-occlusive region (Ku-oc) and non-veno-occlusive region (Ku-non). Changes in sinusoidal perfusion in the veno-occlusive region were expressed by the ratio of Ku-oc to Ku-non (Roc/non). The median value of Roc/non was 0.47, although it ranged from 0.13 to 0.94. Roc/non was related to the extent of liver surface discoloration before and after hepatic arterial clamping (P = 0.03 and 0.01, respectively). In conclusion, sinusoidal perfusion was impaired in the veno-occlusive regions of living donor livers, but the magnitude of the effect varied greatly. Measurement of hepatic ICG uptake by NIRS could become a valuable tool for assessing the indication for venous reconstruction in LDLT and/or split donor liver transplantation.
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Affiliation(s)
- Takuya Hashimoto
- Artificial Organ and Transplantation Surgery, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan
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Hori T, Yagi S, Iida T, Taniguchi K, Yamagiwa K, Yamamoto C, Hasegawa T, Yamakado K, Kato T, Saito K, Wang L, Torii M, Hori Y, Takeda K, Maruyama K, Uemoto S. Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis. World J Gastroenterol 2007; 13:5918-5925. [PMID: 17990357 PMCID: PMC4205438 DOI: 10.3748/wjg.v13.i44.5918] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2007] [Revised: 08/15/2007] [Accepted: 10/17/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT. METHODS Systemic hemodynamics, indocyanine green (ICG) elimination rate (K ICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function. RESULTS Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased K ICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow. CONCLUSION We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.
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15
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Nanashima A, Shibasaki S, Sakamoto I, Sueyoshi E, Sumida Y, Abo T, Nagasaki T, Sawai T, Yasutake T, Nagayasu T. Clinical evaluation of magnetic resonance imaging flowmetry of portal and hepatic veins in patients following hepatectomy. Liver Int 2006; 26:587-94. [PMID: 16762004 DOI: 10.1111/j.1478-3231.2006.01273.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Hepatic blood flow was associated with degree of hepatic damage. Measurements of blood flow using ultrasonography (US) may vary due to any observer's and patient's conditions. The utility of magnetic resonance imaging (MRI) flowmetry in portal and hepatic veins was assessed. PATIENTS AND METHODS Using the phase-contrast method, the mean flow velocity of portal (PVF) and hepatic vein (HVF) were determined by MRI and US in 75 consecutive patients with liver diseases, including 58 patients undergoing hepatectomy. The correlations between these parameters and clinicopathological findings were examined. RESULTS PVF and HVF measured by MRI flowmetry were 12.8+/-4.5 and 14.7+/-5.3 cm/s, respectively. There was no significant correlation of both flows between MRI and US. PVF correlated significantly with portal pressure (r = -0.722; P < 0.05). There was a negative correlation between HVF and histological activity index score (r = -0.366; P < 0.05). PVF and HVF were lower in patients with cirrhosis and higher staging score (2-4) and PVF was lower in patients with higher grading score (2-3; P < 0.05). PVF and HVF were not significantly associated with postoperative complications. CONCLUSIONS Our results suggest that MRI flowmetry is a potentially useful tool for measurement of hepatic blood flow and recommend its use for estimation of liver cirrhosis-associated impairment.
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Affiliation(s)
- A Nanashima
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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16
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Hori T, Iida T, Yagi S, Taniguchi K, Yamamoto C, Mizuno S, Yamagiwa K, Isaji S, Uemoto S. K(ICG) value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation. Liver Transpl 2006; 12:605-613. [PMID: 16555326 DOI: 10.1002/lt.20713] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Reliable monitoring enabling evaluation of graft function is crucial after living-donor liver transplantation (LDLT). A method to identify poor graft function at an early postoperative period would allow opportune intensive clinical management to bring about further improvements in LDLT outcomes. This study assessed the reliability of the indocyanine green (ICG) elimination rate constant (K(ICG)) value as an estimator of graft function and determined the actual temporal changes of K(ICG) after LDLT. K(ICG) values were measured using a noninvasive method in 30 adult recipients up to 28 days after LDLT. The receptor index (LHL15) based on liver scintigraphy, and graft parenchymal damage score based on histopathological findings were evaluated after LDLT and correlated well with simultaneous K(ICG). Thus, K(ICG) measured by noninvasive method was confirmed as accurately evaluating graft function. Changes of K(ICG) after LDLT in recipients with good graft function were maintained, after some falls in the early periods, and had a significant difference compared with those for recipients without good graft function; moreover, there were already significant differences in K(ICG) 24 hours after LDLT. Mean transit time reflecting systemic hemodynamics revealed that recipients without good outcomes fell into an unstable systemic hemodynamic state, and effective hepatic blood flow has a large influence on liver regeneration after LDLT. In conclusion, we suggested that K(ICG) values can predict clinical outcomes at the early postoperative period after LDLT by sharply reflecting the influence of systemic dynamics on splanchnic circulation.
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Affiliation(s)
- Tomohide Hori
- First Department of Surgery, School of Medicine, Mie University, Tsu City, Mie Prefecture, Japan.
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17
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Yang W, Koti R, Glantzounis G, Davidson BR, Seifalian AM. Arterialization of the portal vein improves hepatic microcirculation and tissue oxygenation in experimental cirrhosis. Br J Surg 2003; 90:1232-9. [PMID: 14515292 DOI: 10.1002/bjs.4209] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Abstract
Background
Arterialization of the portal vein (APV) has shown beneficial effects on liver regeneration and function in selected patients undergoing liver resection and transplantation. Whether APV improves liver perfusion and function in cirrhosis is unclear. This study investigated the effect of APV on hepatic haemodynamics and liver function in a rat model of cirrhosis.
Methods
Male Sprague–Dawley rats (250–300 g) were divided into three groups: normal controls (n = 7), cirrhosis with sham laparotomy (sham; n = 7) and cirrhosis with APV (APV; n = 9). Portal venous blood flow, portal vein pressure and hepatic parenchymal microcirculation (HPM) were measured before and after APV. Hepatic parenchymal oxygenation was assessed by near-infrared spectroscopy and hepatocellular injury by standard liver function tests. Measurements were taken at baseline, after APV and 7 days after surgery.
Results
APV increased portal blood flow and pressure in cirrhotic rats without altering intrahepatic portal resistance. APV increased the HPM in cirrhotic rats by a mean(s.e.m.) of 28·5(0·1) per cent on day 0 and 54·6(0·1) per cent by day 7 (P = 0·001). Liver tissue oxygenation was increased by APV and the plasma γ-glutamyltranspeptidase level was reduced (mean(s.e.m.) 6·0(0·5) versus 3·8(0·3) units/l before and after APV respectively; P = 0·006) at day 7.
Conclusion
APV increases portal blood flow, tissue perfusion and oxygenation in cirrhosis.
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Affiliation(s)
- W Yang
- Hepatic Haemodynamic Laboratory, University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London, UK
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18
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Chen MS, Li JQ, Zhang YQ, Lu LX, Zhang WZ, Yuan YF, Guo YP, Lin XJ, Li GH. High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol 2002; 8:74-8. [PMID: 11833075 PMCID: PMC4656630 DOI: 10.3748/wjg.v8.i1.74] [Citation(s) in RCA: 79] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct a randomized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization(TACE) in the treatment of large hepatocellular carcinoma (HCC).
METHODS: From January 1993 to June 1998, 473 patients with unresectable hepatocellular carcinoma were divided into two groups: 216 patients in group A received more than 20mL iodized oil during the first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the same way. The Child’s classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment. During the TACE procedure the catheters was inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography. The anticancer drug mixed with iodized oil (Lipiodol) were Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10 mL Lipiodol, 138 cases received 11-15 mL, and the average dose was 11.8 mL.
RESULTS: High-dose Lipiodol chemoembolization caused tolerable side effects and a little hurt to the liver function in the patients with Child grade A or ICG-R15 < 20. But the patients with child grade B or ICG-R15 > 20 had higher risk of liver failure after high-dose TACE. More type I and type II lipiodol accumulations in CT scan after 4 weeks of TACE were seen in the group A patients than those in the group B patients (P < 0.01). The resection rate and complete tumor necrosis rate in group A were higher than those of group B (P < 0.05). The 1-,2-,3-year survival rates of group A patients with Child grade A were 79.2%, 51.8% and 34.9%, respectively, better than those of group B (P < 0.001).
CONCLUSION: High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor. High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose. For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol is recommended.
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Affiliation(s)
- Min-Shan Chen
- Department of Hepatobiliary Cancer Center of Sun Yet-sen University of Medical Sciences, 651 Dongfeng Road East, Guangzhou 510060, China.
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19
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Abstract
Although the study of hepatic circulation is complicated by the dual blood supply and complex anatomy of the liver, many distinct methods are available to facilitate its study. Before embarking on an investigation of hepatic hemodynamics, the investigator must be familiar with the available methods and their applications. All methods have their own attributes and limitations. No one method is superior to the others, but, depending on the aspect of hepatic hemodynamics to be investigated, a particular methodology may yield distinct advantages.
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Affiliation(s)
- N Garcia
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Medical College of Virginia, Virginia Commonwealth University, USA.
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