Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

This editorial contains comments on the article "Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature" in the recent issue of World Journal of Gastrointestinal Surgery. It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation (ELRAT) and systemic therapy, underlying molecular mechanisms for targeted therapy in perihilar cholangiocarcinoma (pCCA) management. pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis. The only curative option is radical surgery. Surgical excision and reconstruction become extremely complicated and not always could be performed even in localized disease. On the other hand, ELRAT takes its place among surgical options for carefully selected pCCA patients. In advanced disease, systemic therapy becomes a viable option to prolong survival. This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with kinase inhibitors and immunotherapy in both palliative and adjuvant settings. Fibroblast grow factor and fibroblast grow factor receptor, human epidermal growth factor receptor 2, isocitrate dehydrogenase, and protein kinase cAMP activated catalytic subunit alpha (PRKACA) and beta (PRKACB) pathways have been actively investigated in CCA in last years. Several agents were introduced and approved by the Food and Drug Administration. They all demonstrated meaningful activity in CCA patients with no global change in outcomes. That is why every successfully treated patient counts, especially those with advanced disease. In conclusion, pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options. ELRAT also brings some hope, but it could be performed in very carefully selected patients. Advanced disease requires systemic anticancer treatment, which is supposed to be individualized according to the genetic and molecular features of cancer cells. Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava (RHIVC) and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.

Ex vivo liver resection and autotransplantation (ELRAT) may provide an opportunity for R0 resection of conventionally unresectable hepatobiliary cancers and hepatic metastases. To date, few studies of the surgery for malignant tumors have been conducted and there are no known reports of in vivo partial hepatectomy followed by ELRAT (IPH-ELRAT) for malignant tumors.

Between December 2021 and November 2022, ten patients with malignant hepatobiliary primary cancers or hepatic metastases underwent ELRAT at our institution. We shared the surgical skills and postoperative prognoses of these patients were assessed.

The types of tumors were biliary tract cancer (BTC, n=8), hepatic metastasis of colonic carcinoma (n=1), and hepatic metastasis of small-bowel stromal tumor (n=1). Five patients underwent in vivo total hepatectomy followed by ex vivo liver resection and autotransplantation (ITH-ELRAT), The other five received in vivo partial hepatectomy followed by ex vivo liver resection and autotransplantation (IPH-ELRAT). Four patients underwent inferior vena cava replacement using artificial blood vessels. The survival rate of all ten patients one month after surgery was 100%. Nine patients (90%) are currently alive, with a median follow-up of 8.5 months (range 6-16.5 months). To date, seven of the nine surviving patients have had no cancer recurrence, including six with BTC.

We report the world first five cases that received IPH-ELRAT for malignancies. We also demonstrated relatively favorable outcomes in patients who underwent ELRAT. ELRAT may be a recommendable surgical option for selected patients with conventionally unresectable hepatobiliary malignant tumors.

Ex situ liver resection and autotransplantation, a surgical technique introduced for managing advanced and unresectable malignant tumors, never became a popular surgical procedure, due mainly to the high incidence of adverse events and postoperative recurrences. This study aims to assess the clinical outcomes of ex situ liver resection and autotransplantation in the currently available literature.

The PubMed electronic database was used to retrieve studies that meet the inclusion criteria for the topic.

Twenty-nine studies were included. The mean (range) 90-day mortality rate was 11.6% (0%-50%) and the mean overall survival was 55.8% (12.5%-100.0%). R0 resection was achieved in 100% of cases. In the overall study sample, the maximum tumor size was found to be positively correlated with the 90-day mortality rate (P = .047) and negatively correlated with the overall survival (P = .048). The mean number of total resected segments appeared to be positively correlated with the length of hospital stay (P = .039). In the malignant tumor sample, there was a significant relationship between the maximum tumor size and postoperative liver failure, 90-day mortality rate (P = .027 and P = .034, respectively), and between the mean length of anhepatic phase and mean length of hospital stay (P = .0092).

The ex situ liver resection and autotransplantation appears to be a valuable option in selected patients with conventionally unresectable hepatic tumors and normal liver function. However, it was not possible to provide clear and unequivocal recommendations about this procedure. To rectify this, an international database to help surgeons in their decision-making process ought to be established.

Intrahepatic cholangiocarcinoma (iCCA) accounts for approximately 10% of all primary liver cancers. Surgery is the only potentially curative treatment, even in cases of macrovascular invasion. Since resection offers the only curative chance, even extended liver resection combined with complex vascular or biliary reconstruction of the surrounding organs seems justified to achieve complete tumour removal. In selected cases, the major vascular resection is the only change to try getting the cure. The best results are achieved by the referral centre with a wide experience in complex liver surgery, such as ALPPS procedure, IVC resection, and ante-situ and ex-situ resections. However, despite aggressive surgery, tumour recurrence occurs frequently and long-term oncological results are very poor. This suggests that significant progress in prognosis cannot be expected by surgery alone. Instead, multimodal treatment including neoadjuvant chemotherapy, radiotherapy, and subsequent adjuvant treatment for iCCA seem to be necessary to improve results.

Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract. To date, surgical treatment remains the only hope for definitive cure of CCA patients. Involvement of major vascular structures was traditionally considered a contraindication for resection. Nowadays, selected cases of CCA with vascular involvement can be successfully approached. Intrahepatic CCA often involves the major hepatic veins or the inferior vena cava and might necessitate complete vascular exclusion, in situ hypothermic perfusion, ex situ surgery and reconstruction with autologous, heterologous or synthetic grafts. Hilar CCA more frequently involves the portal vein and hepatic artery. Resection and reconstruction of the portal vein is now considered a relatively safe and beneficial technique, and it is accepted as a standard option either with direct anastomosis or jump grafts. However, hepatic artery resection remains controversial; despite accumulating positive reports, the procedure remains technically challenging with increased rates of morbidity. When arterial reconstruction is not possible, arterio-portal shunting may offer salvage, while sometimes an efficient collateral system could bypass the need for arterial reconstructions. Keys to achieve success are represented by accurate selection of patients in high-volume referral centres, adequate technical skills and eclectic knowledge of the various possibilities for vascular reconstruction.

Ex vivo hepatectomy is the incorporation of liver transplant techniques in the non-transplant setting, providing opportunity for locally advanced tumors found conventionally unresectable. Because the procedure is rare and reports in the literature are limited, we sought to perform a systematic review and meta-analysis investigating technical variations of ex vivo hepatectomies.

In the literature, there is a split in those performing the procedure between venovenous bypass (VVB) and temporary portacaval shunts (PCS). Of the 253 articles identified on the topic of ex vivo resection, 37 had sufficient data to be included in our review.

The majority of these procedures were performed for hepatic alveolar echinococcosis (69%) followed by primary and secondary hepatic malignancies. In 18 series, VVB was used, and in 18, a temporary PCS was performed. Comparing these two groups, intraoperative variables and morbidity were not statistically different, with a cumulative trend in favor of PCS. Ninety-day mortality was significantly lower in the PCS group compared to the VVB group (p=0.03).

In order to better elucidate these differences between technical approaches, a registry and consensus statement are needed.

Many patients with hepatic tumors cannot benefit from resection owing to the difficult anatomic sites of their lesions. Some of these patients might be eligible for ex vivo liver resection and autotransplantation. This procedure consists of complete hepatectomy, extracorporeal liver resection, and autotransplantation of the remnant liver.

Four databases were searched for studies reporting cases of ex vivo liver resection and autotransplantation. Outcomes of this procedure were evaluated by meta-analysis of proportions with random effects model and individual participant data analysis.

Fifty-three studies were assessed. Meta-analysis revealed an R0 resection rate of 93.4% (95% confidence interval: 81.0-97.9%, I² = 0%), a frequency of major surgical complications of 24.5% (95% confidence interval, 16.9-34.3%, I² = 26%), a 30-day mortality of 9.5% (95% confidence interval: 5.9-14.9%, I² = 0%), and a 1-year survival of 78.4% (95% confidence interval: 62.2-88.8%, I² = 64%). We were able to obtain the individual participant data in 244 patients; R0 resection was achieved in 98.6%, with no obvious difference between analyzed subgroups. The 30-day mortality and 1-year survivals were 7.9% and 82.1%, respectively. For groups with malignant and nonmalignant tumors, the 30-day mortalities were 11.3% vs. 6.3% (P = .181), and 1-year survivals were 65.0% vs. 89.7% (P < .001). When comparing those with malignant versus those with nonmalignant lesions, major surgical complications occurred in 50.0% vs. 21.0%; P < .001). Regression analysis revealed that outcomes of patients with benign tumors were better compared with those with malignant tumors (1-year survival, odds ratio: 4.629; 95% confidence interval: 2.181-10.097, P < .001).

Ex vivo liver resection and autotransplantation facilitates radical treatment in selected patients with conventionally unresectable hepatic tumors and normal liver function. The outcomes of treatment of malignant lesions appear to be less satisfactory.