Background: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. Methods: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. Results: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). Conclusions: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.

The liver plays an important role in maintaining homeostasis during endotoxin-triggered systemic inflammatory response. To study the effects of phosphocreatine on hepatic energy metabolism after endotoxin administration, we used transgenic mice whose livers express creatine kinase (CK). CK catalyzes a phosphocreatine/creatine reaction, that is, an adenosine triphosphate (ATP) reservoir system. Because dietary supplementation with creatine leads to an accumulation of creatine and phosphocreatine in transgenic livers, we compared the CK transgenic mice fed with creatine with the normally fed CK transgenic mice. In the creatine-fed mice, hepatic ATP, energy charge ([ATP + 0.5 adenosine diphosphate (ADP)]/[ATP + ADP + adenosine monophosphate (AMP)]), and mitochondrial oxidative phosphorylation activities remained at high levels after injection of 10 mg/kg of lipopolysaccharide (LPS) as compared with those in normally fed mice. Furthermore, there were beneficial effects on the functional reserve for ATP synthesis and work-cost performance, as calculated by free cytoplasmic ADP and the Michaelis constant (Km). Interestingly, a reduction of tissue necrosis factor alpha and interleukin-lalpha (IL-lalpha), and suppression of the decrease in glucose levels after LPS injection were observed in the creatine fed mice. Survival rates at 72 hours after injection of 10 mg/kg of LPS significantly increased in the creatine fed mice compared with the normally fed mice (80% vs. 24%, P < .001). Therefore, we concluded that the presence of phosphocreatine in the liver maintains energy metabolism and attenuates cytokine response, resulting in endotoxin tolerance.

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Background) Sentinel lymph node (SLN) biopsy using indocyanine green fluorescence (fICG) method showed equal or better identification rate compared with blue dye or radioisotope (RI) method. In the fICG method, lymphatic vessels which drain into the SLNs can be seen through skin or subcutaneous tissue using near infrared camera (Photodynamic Eye®: PDE), and we can easily find the SLNs. However, whenever we observe the fluorescence images, we have to hold the PDE, turn off the operating light, and look at a monitor because fluorescence images cannot be seen directly. Medical imaging projection system (MIPS) is a new device which detects fluorescent emission from the organ and projects their images on the location of the fluorescence emission (Panasonic Connected Solutions Company, Japan). Projected images can be adjusted following the body movement or deformation of the organ. Therefore, MIPS could provide an option for real-time navigation for the SLN biopsy. The aim of this study was to evaluate the clinical utility of the MIPS. Patients and methods) Patients with clinically node-negative primary breast cancer underwent the fICG SLN biopsy using MIPS. Primary endpoint was identification rate of the fICG method using MIPS. At first, the study was conducted as an interventional study because the MIPS was the unapproved medical device. After approval of the MIPS, this study was conducted as an observational study. The study protocol was approved by the institutional review board at Kyoto University Hospital. All patients provided informed consent to participate in this study. Results) Between March 2016 and May 2017, 39 patients (40 procedures) underwent the fICG method SLN biopsy using MIPS. The median age was 55 years (range 32–74 years), and the median body mass index was 20.4 kg/m2 (range 17.7–27.7 kg/m2). About half had tumor stage T1 (58%) and 8 (20.0%) had DCIS. 8 procedures (20%) were performed after preoperative systemic therapy (PST). As MIPS itself can illuminate the operating field, SLN biopsy using MIPS was successfully performed without operating light in all procedures. At least one SLN was detected using MIPS for all procedures and the identification rate was 100% (95% CI: 91–100%). Median number of SLNs detected by MIPS was 3 (range 1–9) for all procedures, and 3 (range 2–8) for procedures after PST. Two pathologically positive SLNs and one SLN which included isolated tumor cells were detected by MIPS. In 25 procedures, RI was also used. 62 of 97 SLNs detected by MIPS (64%) were also detected by RI. However, no SLNs were detected only by RI. Conclusions) Although we still may not be able to avoid RI method because 25/40 (62.5%) procedures required the combined use of RI method, the fICG methods SLN biopsy using MIPS, which showed comparable identification rate of SLN with the conventional methods, could be useful tool with a view of allowing us to perform a real-time navigation surgery. Acknowledgements) This study was supported by Acceleration Transformative research for Medical innovation, Japan Agency for Medical Research and Development (AMED). Citation Format: Takada M, Takeuchi M, Suzuki E, Sato F, Matsumoto Y, Torii M, Sakita-Kawaguchi N, Nakayama Y, Okuda T, Nishino H, Seo S, Hatano E, Toi M. Real-time navigation for sentinel lymph node biopsy in breast cancer patients using projection mapping with indocyanine green fluorescence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-07.