Right hepatectomy with preservation of the entire caudate lobe in patients with metastatic liver tumors: a case of a new hepatectomy technique and treatment strategy for patients with marginal liver function

Background Performing major hepatectomy for patients with marginal hepatic function is challenging. In some cases, the procedure is contraindicated owing to the threat of postoperative liver failure. In this case report, we present the first case of marginal liver function (indocyanine green clearance retention rate at 15 min [ICGR15]: 28%) successfully treated with right hepatectomy, resulting in total caudate lobe preservation. Case presentation A 71-year-old man was diagnosed with sigmoid colon cancer with three liver metastases (S5, S7, and S8). All of metastatic lesions shrunk after chemotherapy, but his ICGR15 and indocyanine green clearance rate (ICGK) were 21% and 0.12, respectively. Moreover, the remnant liver volume was only 39%. Therefore, portal venous embolism (PVE) of the right portal vein was suggested. Portography showed divergence of the considerably preserved right caudate lobe branch (PV1R) from the root of the right portal vein. The liver function was reevaluated 18 days after PVE was suggested. During this time, the ICGR15 (21–28%) and ICGK rate (0.12–0.10) deteriorated. The right caudate lobe was significantly enlarged; thus, a total caudate lobe-preserving hepatectomy (TCPRx) was performed. Patients eligible for TCPRx included those with (1) hepatocellular carcinoma or metastatic liver cancer, (2) no tumor in the caudate lobe, (3) marginal liver function (ICG Krem greater than 0.05 if TCPRx was adapted; otherwise, less than 0.05) and Child–Pugh classification category A, and (4) preserved PV1R and right caudate bile duct branch. The procedure was performed through (A) precise estimation of the remnant liver volume preoperatively, (B) repeated intraoperative cholangiography to confirm the biliary branch of the right caudate lobe (B1R) conservation, and (C) stapler division of posterior and anterior Glisson’s pedicles laterally to avoid injuries to the PV1R and B1R. Conclusions Right hepatectomy with total caudate lobe preservation, following PVE, was a safe and viable surgical technique for patients with marginal liver function.

Quantitative washout in patients with hepatocellular carcinoma undergoing TACE: an imaging biomarker for predicting prognosis?

Background The delayed percentage attenuation ratio (DPAR) was recently identified as a novel predictor of an early complete response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). In this study, we aimed to validate the role of DPAR as a predictive biomarker for short-, mid-, and long-term outcomes after TACE. Methods We retrospectively reviewed laboratory and imaging data for 103 treatment-naïve patients undergoing initial TACE treatment at our tertiary care center between January 2016 and November 2020. DPAR and other washin and washout indices were quantified in the triphasic computed tomography performed before the initial TACE. The correlation of DPAR and radiologic response was investigated. Furthermore, the influence of DPAR on the 6-, 12-, 18-, and 24-month survival rates and the median overall survival (OS) was compared to other established washout indices and estimates of tumor burden and remnant liver function. Results The DPAR was significantly of the target lesions (TLs) with objective response to TACE after the initial TACE session was significantly higher compared to patients with stable disease (SD) or progressive disease (PD) (125 (IQR 118–134) vs 110 (IQR 103–116), p < 0.001). Furthermore, the DPAR was significantly higher in patients who survived the first 6 months after TACE (122 vs. 115, p = 0.04). In addition, the number of patients with a DPAR > 120 was significantly higher in this group (n = 38 vs. n = 8; p = 0.03). However, no significant differences were observed in the 12-, 18-, and 24-month survival rates after the initial TACE. Regarding the median OS, no significant difference was observed for patients with a high DPAR compared to those with a low DPAR (18.7 months vs. 12.7 months, p = 0.260). Conclusions Our results confirm DPAR as the most relevant washout index for predicting the short-term outcome of patients with HCC undergoing TACE. However, DPAR and the other washout indices were not predictive of mid- and long-term outcomes.

Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module and the lightcyan module were found positively correlated with not extended hepatectomy but major hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and verified the down-regulation in the remnant liver following extended hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.

Technique of vessel-skeletonized parenchyma-sparing hepatectomy for the oncological treatment of bilobar colorectal liver metastases

Background To aid in the oncological management of multiple bilobar colorectal liver metastases (CRLMs), we describe a new surgical procedure, VEssel-Skeletonized PArenchyma-sparing Hepatectomy (VESPAH). Study design Of 152 patients with CRLMs treated with hepatectomy, 33 patients had multiple bilobar liver metastases (≥8 liver metastases); their surgical procedures and clinical outcomes were retrospectively summarized and compared between those who underwent VESPAH and those who underwent major hepatectomy (Major Hx). Results Of the 33 patients, 20 patients were resected by VESPAH (the VESPAH group) and 13 patients by major hepatectomy (Major Hx group). The median number of CRLMs was 13 (range, 8–53) in the VESPAH group and 10 (range, 8–41) in the Major Hx group (P=0.511). No operative mortality nor severe morbidity was observed in either group. The VESPAH group showed earlier recovery of remnant liver function after surgery than the Major Hx group; the incidence of grade B/C post hepatectomy liver failure was 5% in the VESPAH group and 38% in the Major Hx group, P=0.048). Intrahepatic tumor recurrence was confirmed in 14 (70%) and 7 (54%) patients in the VESPAH and Major Hx groups, respectively (P=0.416). There was no significant difference in median overall survival (OS) after hepatectomy between the two groups; the median OS was 47 months in the VESPAH group and 33 months in the Major Hx group (P=0.481). The VESPAH group showed the higher induction rate of adjuvant chemotherapy within 2 months after surgery (P=0.002) and total number of repeat hepatectomy for intrahepatic recurrence (P=0.060) than the Major Hx group. Conclusions VESPAH enables us to clear surgical navigation by hepatic vessel skeletonization and may enhance patient tolerability of not only adjuvant chemotherapy but also repeat hepatectomies during the patients’ lifetimes.

The Protective Effect of Dexmedetomidine Against Ischemia-Reperfusion Injury after Hepatectomy: A Meta-Analysis of Randomized Controlled Trials

Background: Hepatic inflow occlusion proceeded to reduce blood loss during hepatectomy induces ischemia-reperfusion (IR) injury in the remnant liver. Dexmedetomidine, a selective α2-adrenoceptor agonist used as an anesthetic adjuvant, has been shown to attenuate IR injury in preclinical and clinical studies. However, a meta-analysis is needed to systematically evaluate the protective effect of perioperative dexmedetomidine use on IR injury induced by hepatectomy.Methods: A prospectively registered meta-analysis following Cochrane and PRISMA guidelines concerning perioperative dexmedetomidine use on IR injury after hepatectomy was performed via searching Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, Web of Science, CNKI, WanFang, and Sinomed for eligible randomized controlled trials up to 2021.3.31. The main outcome is postoperative liver function. Risk of bias was assessed by the Cochrane Risk of Bias tool. Review Manager 5.3 and Stata12.0 were applied to perform data analyses.Results: Eight RCTs enrolling 468 participants were included. Compared with 0.9% sodium chloride, dexmedetomidine decreased serum concentration of ALT (WMD = −66.54, 95% CI: −92.10–−40.98), AST (WMD= −82.96, 95% CI: −106.74–−59.17), TBIL (WMD = −4.51, 95% CI: −7.32–−1.71), MDA (WMD = −3.09, 95% CI: −5.17–−1.01), TNF-α (WMD = −36.54, 95% CI: −61.33–−11.95) and IL-6 (WMD = −165.05, 95% CI: −225.76–−104.34), increased SOD activity (WMD = 24.70, 95% CI: 18.09–31.30) within postoperative one day. There was no significant difference in intraoperative or postoperative recovery parameters between groups.Conclusions: Perioperative administration of dexmedetomidine can exert a protective effect on liver IR injury after hepatectomy. Additional studies are needed to further evaluate postoperative recovery outcomes of dexmedetomidine with different dosing regimens.

The prognostic significance of a histological response to preoperative chemotherapy in patients with synchronous colorectal liver metastases

Objective: Preoperative chemotherapy (PC) for colorectal liver metastasis (CRLM) is widely used to improve prognosis, but its clinical benefit has not been fully established. This study aimed to assess the effectiveness of PC for synchronous CRLM and the correlation between the histological response to PC and survival. Summary of Background Data: We enrolled 69 patients who underwent initial hepatectomy for synchronous CRLM between 2004 and 2018 at Gifu University Hospital. Methods: We retrospectively analyzed the clinicopathological factors and outcomes of 69 patients who underwent hepatectomy after receiving PC (PC group: n = 43) or who underwent upfront hepatectomy (non-PC group: n = 26). In the PC group, the patients were divided into the Grade 1 (n = 27) and Grade 2/3 (n = 16) groups according to their histological responses to PC. Results: The median survival and 5-year overall survival (OS) rates were 80.9 months and 61.5%, respectively, in the PC group and 71.7 months and 61.5%, respectively, in the non-PC group ( P = 0.867). Regarding recurrence-free survival (RFS) and remnant liver-RFS, there were no significant differences between the two groups ( P = 0.087 and 0.291). However, in a subgroup analysis, the median 5-year OS, RFS, and remnant liver RFS were significantly longer in the Grade 2/3 than Grade 1 group ( P = 0.008, P = 0.002, and P &lt; 0.001, respectively). Conclusions: Some patients benefit from PC, and the histological response to PC had prognostic significance for patients with synchronous CRLM.

Isolated Caudate Lobectomy: Glissonean Pedicle Transection Method, and Combined Right–left Side Approach. A Case Series Report

Tumors located in caudate lobe may be primary tumors, or metastases from other sites. Isolated caudate lobectomy (ICL) is a challenging procedure due to its complex structure and location. The access route to caudatelobe has an important role in the success of the operation. A combined right and left side approach is recommended for benign or suspected malignant tumor located anterior to the vena cava or entirely in the caudate lobe, which radical resection of the caudate is necessary. We report two cases of successfully with Glissonean pedicle transection method described by Takasaki and combined right and left side approach. We found this to be a safe and effective approach, which can be applied to all case of benign tumors; or in the case of malignant tumors located entirely in the caudate lobe when extended hepatic resection is not possible due to poor liver function. or small remnant liver volume.

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy

Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3–13) mmHg vs. 4 (2–6) mmHg and 4 (2–6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.