Kiyohiko Omichi

In Situ Cross-Linkable Hydrogel of Hyaluronan Produced via Copper-Free Click Chemistry

Injectable hydrogels are useful in biomedical applications. We have synthesized hyaluronic acids chemically modified with azide groups (HA-A) and cyclooctyne groups (HA-C), respectively. Aqueous HA-A and HA-C solutions were mixed using a double-barreled syringe to form a hydrogel via strain-promoted [3 + 2] cycloaddition without any catalyst at physiological conditions. The hydrogel slowly degraded in PBS over 2 weeks, which was accelerated to 9 days by hyaluronidase, while it rapidly degraded in a cell culture media with fetal bovine serum within 4 days. Both HA-A and HA-C showed good biocompatibility with fibroblast cells in vitro. They were administered using the double-barreled syringe into mice subcutaneously and intraperitoneally. Residue of the hydrogel was cleared 21 days after subcutaneous administration, while it was cleared 7 days after intraperitoneal administration. This injectable HA hydrogel is expected to be useful for tissue engineering and drug delivery systems utilizing its orthogonality.

Differential diagnosis of liver tumours using intraoperative real-time tissue elastography.

Real‐time tissue elastography is an innovative tool that informs the surgeon about tissue elasticity by applying the principle of ultrasonography. The aim of this study was to investigate the accuracy of intraoperative real‐time tissue elastography (IORTE) for the detection and characterization of liver tumours.

Asunaprevir/daclatasvir and sofosbuvir/ledipasvir for recurrent hepatitis C following living donor liver transplantation

This study aimed to clarify the efficacy and safety of interferon‐free therapy using asunaprevir and daclatasvir, or sofosbuvir and ledipasvir for post living donor liver transplantation (LDLT) recipients with hepatitis C virus (HCV).

Salvage Liver Transplantation or Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma: An Intent‐to‐treat Analysis

The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention‐to‐treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5‐year intention‐to‐treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5‐year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5‐year disease‐free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P < 0.001). Similar results were observed after propensity score matching. In conclusion, although the 5‐year OS rates were similar in the salvage LT and second resection groups, the salvage LT strategy still achieves better DFS. Second resection for recurrent HCC might be considered to be the best alternative option to LT in the current organ shortage. Liver Transplantation 23 1553–1563 2017 AASLD.

Neutrophil-to-lymphocyte ratio predicts prognosis after neoadjuvant chemotherapy and resection of intrahepatic cholangiocarcinoma

Background. Previous studies have demonstrated a strong association between the preoperative neutrophil‐to‐lymphocyte ratio and the outcomes of patients with resected hepatocellular carcinoma and colorectal liver metastases. However, the predictive ability of neutrophil‐to‐lymphocyte ratio in patients with intrahepatic cholangiocarcinoma, especially those treated with preoperative chemotherapy, has been less well described. Methods. The clinicopathological characteristics, overall survival, and recurrence free survival of all patients with intrahepatic cholangiocarcinoma resected between 2000–2015, were compared between those with elevated (≥3.0) and normal (<3.0) neutrophil‐to‐lymphocyte ratio. Results. Among 119 patients who met the inclusion criteria, 64 (53.8%) had neutrophil‐to‐lymphocyte ratio <3.0 and 55 (46.2%) had neutrophil‐to‐lymphocyte ratio ≥3.0. Patients with neutrophil‐to‐lymphocyte ratio ≥3.0 were more likely to be female and have lymph node metastasis (P < .05). Cumulative 5‐year overall survival and recurrence free survival rates were 87% and 60%, respectively in patients with neutrophil‐to‐lymphocyte ratio <3.0, compared with 64% and 39%, respectively in patients with neutrophil‐to‐lymphocyte ratio ≥3.0 (P = .049 and .038). Among 43 patients treated with preoperative chemotherapy and resection, 21 (48.8%) had neutrophil‐to‐lymphocyte ratio <3.0 and 22 (51.2%) had neutrophil‐to‐lymphocyte ratio ≥3.0. In this subgroup, cumulative 5‐year overall survival and recurrence free survival rates were 95% and 70%, respectively in the patients with neutrophil‐to‐lymphocyte ratio <3.0 compared with 50% and 26%, respectively in the patients with neutrophil‐to‐lymphocyte ratio ≥3.0 (P = .002 and P = .004). On multivariate analysis, a neutrophil‐to‐lymphocyte ratio ≥3.0 was associated significantly with worse overall survival among all patients as well as overall survival and recurrence free survival among the subgroup who received preoperative chemotherapy. Conclusion. Neutrophil‐to‐lymphocyte ratio is associated independently with worse survival in patients with intrahepatic cholangiocarcinoma undergoing resection or neoadjuvant chemotherapy prior to resection.

Efficacy of Hyaluronic Acid/Carboxymethyl Cellulose-Based Bioresorbable Membranes in Reducing Perihepatic Adhesion Formation: A Prospective Cohort Study

Background: Perihepatic adhesions induced by hepatectomy make the subsequent repeat hepatectomy technically demanding. The aim of this study was to verify the effect of hyaluronic acid/carboxymethyl cellulose-based bioresorbable membrane (HA membrane) in preventing posthepatectomy adhesion formation by focusing on the ease of the adhesiolysis in subsequent hepatectomy for recurrent tumors. Methods: A total of 201 patients who underwent hepatectomy using HA membrane were prospectively followed-up for 3 years. Thirty of the 201 patients underwent a repeat hepatectomy for recurrence. The operative data of 85 cases of repeat hepatectomy, the primary hepatectomy of which had been performed without the use of HA membrane, served as the historical control data. The primary endpoint was the time interval between the skin incision and the start of hepatic parenchymal transection (the preparation time) including adhesiolysis. Secondary endpoints were blood loss during the operation, incidence of postoperative complications, and the biochemical data. Results: The median preparation time (183 vs. 228 min; p = 0.027) and total operation time (374 vs. 439 min; p = 0.041) were significantly shorter in the HA membrane group than in the control group. Conclusion: Use of HA membranes during hepatectomy enabled significant shortening of the adhesiolysis time during the sequential hepatectomy performed for recurrent tumors.

Loss of muscle mass during preoperative chemotherapy predicts worse recurrence-free survival in patients with resectable colorectal liver metastases

MTA and 9.7% in the RFA group (p = 0.85). There was no mortality. Median hospital stay was 1 day for both groups. For the RFA vs MTA groups, local recurrence (LR) rate per lesion was 20.3% and 8.5%, respectively (p = 0.01). On Cox Proportion Hazards model, ablation modality was an independent predictor of LR following risk adjustment. Conclusion: To our knowledge, this is the first comparison of RFA and MTA in the treatment of CRLM. Our results demonstrates MTA achieves better local tumor control with shorter operative and ablation time.