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.

A Single Institution’s Experience With Robotic Minor and Major Hepatectomy

Background Minimally invasive liver resection is gradually becoming the preferred technique to treat liver tumors due its salutary benefits when compared with traditional “open” method. While robotic technology improves surgeon dexterity to better perform complex operations, outcomes of robotic hepatectomy have not been adequately studied. We therefore describe our institutional experience with robotic minor and major hepatectomy. Materials and Methods We prospectively study all patients undergoing robotic hepatectomy from 2016 to 2020. Results A total of 220 patients underwent robotic hepatectomy. 138 (63%) were major hepatectomies while 82 (37%) were minor hepatectomies. Median age was 63 (62 ± 13) years, 118 (54%) were female. 168 patients had neoplastic disease and 52 patients had benign disease. Lesion size in patients who had undergone minor hepatectomy was 2 (3 ± 2.5) cm, compared to 5 (5 ± 3.0) cm in patients who undergone major hepatectomy ( P < .001). 97% of patients underwent R0 resections while none of the patients had R2 resection. Operative duration was 226 (260 ± 122.7) vs 282 (299 ± 118.7) minutes ( P ≤ .05); estimated blood loss was 100 (163 ± 259.2) vs 200 (251 ± 246.7) mL ( P ≤ .05) for minor and major hepatectomy, respectively. One patient had intraoperative bleeding requiring “open” conversion. Nine (4%) patients had experienced notable postoperative complications and 2 (1%) patients died postoperatively. Length of stay was 3 (5 ± 4.6) vs 4 (5 ± 2.8) days for minor vs major hepatectomy ( P = .84). Reoperation and readmission rate for minor vs major hepatectomy was 1% vs 3% ( P = .65) and 9% vs 10% ( P = .81), respectively. Discussion Robotic major hepatectomy is safe, feasible, and efficacious with excellent postoperative outcomes.

Recurrent Colorectal Liver Metastases in the Liver Remnant After Major Liver Surgery—IRE as a Salvage Local Treatment When Resection and Thermal Ablation are Unsuitable

Purpose To examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation. Patients and Methods Twenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively. Results Complete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases. Conclusion In this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable.