Adjuvant chemotherapy is associated with better oncological outcomes after ALPPS for colorectal liver metastases.

ALPPS enables complete tumor resection in a shorter interval and a larger number of patients than classic two-stage hepatectomies. However, there is little evidence regarding long-term outcomes in patients with colorectal liver metastases (CLM). This study aims to evaluate the short and long-term outcomes of ALPPS in patients with CRM. Single-cohort, prospective, observational study. Patients with unresectable CLM due to insufficient liver remnant who underwent ALPPS between June 2011 and June 2021 were included. Of 32 patients treated, 21 were male (66%) and the median age was 56 years (range = 29-81). Both stages were completed in 30 patients (93.7%), with an R0 rate of 75% (24/32). Major morbidity was 37.5% and the mortality nil. Median overall survival (OS) and recurrence-free survival (RFS) were 28.1 and 8.8 months, respectively. The 1-3, and 5-year OS was 86%, 45%, and 21%, and RFS was 42%, 14%, and 14%, respectively. The only independent risk factor associated with poor RFS (5.7 vs 11.6 months; p = 0.038) and OS (15 vs 37 months; p = 0.009) was not receiving adjuvant chemotherapy. KRAS mutation was associated with worse OS from disease diagnosis (24.3 vs. 38.9 months; p = 0.025). ALPPS is associated with favorable oncological outcomes, comparable to traditional strategies to increase resectability in patients with CLM and high tumor burden. Our results suggest for the first time that adjuvant chemotherapy is independently associated with better short- and long-term outcomes after ALPPS. Selection of patients with KRAS mutations should be performed with caution, as this could affect oncological outcomes.

Current Perspectives and Progress in Preoperative Portal Vein Embolization with Stem Cell Augmentation (PVESA).

Portal vein embolization with stem cell augmentation (PVESA) is an emerging approach for enhancing the growth of the liver segment that will remain after surgery (i.e., future liver remnant, FLR) in patients with liver cancer. Conventional portal vein embolization (PVE) aims to induce preoperative FLR growth, but it has a risk of failure in patients with underlying liver dysfunction and comorbid illnesses. PVESA combines PVE with stem cell therapy to potentially improve FLR size and function more effectively and efficiently. Various types of stem cells can help improve liver growth by secreting paracrine signals for hepatocyte growth or by transforming into hepatocytes. Mesenchymal stem cells (MSCs), unrestricted somatic stem cells, and small hepatocyte-like progenitor cells have been used to augment liver growth in preclinical animal models, while clinical studies have demonstrated the benefit of CD133 + bone marrow-derived MSCs and hematopoietic stem cells. These investigations have shown that PVESA is generally safe and enhances liver growth after PVE. However, optimizing the selection, collection, and application of stem cells remains crucial to maximize benefits and minimize risks. Additionally, advanced stem cell technologies, such as priming, genetic modification, and extracellular vesicle-based therapy, that could further enhance efficacy outcomes should be evaluated. Despite its potential, PVESA requires more investigations, particularly mechanistic studies that involve orthotopic animal models of liver cancer with concomitant liver injury as well as larger human trials.

Contemporary Surgical Management of Colorectal Liver Metastases.

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.

Complete regression of intrahepatic cholangiocarcinoma after right portal vein ligation. Case report.

INTRODUCTION: Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. PRESENTATION OF CASE: We present the case of a 72-years-old male patient presenting with a bulky hepatic tumor mass located in segment V and extending into segments IVb and VI with MRI features of atypical cholangiocarcinoma with a liver metastasis in segment III. In first surgical step, excision of the metastasis, and ligation of the right portal vein was done. A new MRI examination performed 5 weeks later shows significant tumor regression, and 2 weeks later, during the second surgery, the tumor was not found. Under these conditions we performed a limited segment V liver resection, in the area indicated by the radiologist as the site of the tumor. No viable malignant cells existed in the tumor specimen, and a third MRI examination didn't identify any residual tumor. DISCUSSION: From our literature study this is the only case of complete tumor regression of an intrahepatic cholangiocarcinoma following portal vein ligation. We believe the portal vein ligation resulted in a marked regression/deficiency in the tumor blood supply. CONCLUSION: Serial MRI examinations demonstrated the regression of intrahepatic cholangiocarcinoma after portal vein ligation. Intrahepatic cholangiocarcinoma should be included in the tumors that could extremely rarely spontaneously regress.

[Laparoscopic downstaging surgery for colorectal cancer with synchronous liver metastases: what value in two-stage hepatectomies?] / La chirurgie laparoscopique de downstaging pour cancer colorectal avec métastases hépatiques synchrones: quel intérêt dans les hépatectomies en deux temps? à propos d'une série de 6 cas.

Bilobar hepatic metastases from colorectal cancer pose a problem in terms of management, with curative surgery often requiring several stages. The purpose of our study was to evaluate laparoscopic approach with portal vein ligation in the first step of two-stage hepatectomy in the treatment of patients with synchronous liver metastases from colorectal cancers (SLMCRC). We conducted a single-center retrospective study from August 2016 to January 2020. It included patients with SLMCRC requiring two-stage curative surgery due to insufficient future liver remnant volume (FRL). The primary endpoint was to evaluate postoperative morbidity and mortality following first step laparoscopy at 30 days. The secondary endpoints were to evaluate conversion rate, FRL hypertrophy following laparoscopic portal vein ligation, postoperative morbidity and mortality of 2nd step of two-stage hepatectomy and finally treatment completion rate. We included six patients (4 men and 2 women) with a mean age of 64 (44-72) years. The first step of surgery consisted of a laparoscopic colonic resection associated with right portal vein ligation in 5 patients and left portal vein ligation in one patient. The postoperative morbimortality was zero. The conversion rate was zero. After portal vein ligation, 5 of the 6 patients had significantly enlarged FRL, with a mean gain in FRL volume of 59.48% (31.02%-68.71%). Two of the six patients had severe morbidity after 2nd step hepatectomy (Clavien IIIb). All patients completed the treatment.

ALPPS Procedure for the Treatment of Bilobar Multiple Liver Metastasis from Colorectal Cancer: First Case in RN Macedonia.

Introduction: ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy), is a recently developed procedure, first performed by HJ Schlitt in Regensburg, Germany. The technique developed two stages of hepatectomy. The ALPPS procedure has been introduced to increase the volume of future liver remnant, much more than the other technique, such as PVE (portal vein embolization). The first ALPPS in our country was introduced and performed by our team on May 15th, 2018. Results: The 60-year-old patient was previously operated on for rectal cancer in 2017 at another institution. The operation was performed with anterior resection and the patient was in long term adjuvant chemotherapy. One year after surgery, the patient has multiple bilobar liver metastases and increased tumor markers that led to instant admission to our institution for liver resection. In the first stage, we performed four metastasectomies on the left lobe with right portal vein ligation and transection on the Cantlie line. The second stage was performed after a CT evaluation on the eighth day, with significant hypertrophy on the left lobe. Pathological findings reported ten metastases on the right lobe with a diameter 1-3 cm. The patient was on the long-term chemotherapy, and after one year he had other MS in the IVa segment of the liver. We also performed a metastasectomy. The patient died 32 months after ALPPS. Conclusion: ALPPS is a safe and feasible procedure for the treatment of bilobar liver metastasis from colorectal cancer. It could provide long-term survival for patients.

Bile Acid Overload Induced by Bile Duct and Portal Vein Ligation Improves Survival after Staged Hepatectomy in Rats.

OBJECTIVE: Compared to portal vein ligation (PVL), simultaneous bile duct and portal vein ligation (BPL) can significantly enhance hypertrophy of the intact liver. This study aimed to investigate whether BPL could improve survival after extended hepatectomy independently of an increased remnant liver. METHODS: We adopted rat models of 90% BPL or 90% PVL. To investigate the role of bile acids (BAs) the BA pools in the PVL and BPL groups were altered by the diet. Staged resection preserving 10% of the estimated liver weight was performed 3 days after BPL; PVL; or sham operation. Histology, canalicular network (CN) continuity; and hepatocyte polarity were evaluated. RESULTS: At 3 days after BPL; PVL; or sham operation when the volumetric difference of the intended liver remained insignificant, the survival rates after extended hepatectomy were 86.7%, 47%, and 23.3%, respectively (P<0.01). BPL induced faster restoration of canalicular integrity along with an intensive but transient BA overload. Staged hepatectomy after BPL shortened the duration of the bile CN disturbance and limited BA retention. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the BA pools of rats that underwent PVL could induce similar effects. The changes in CN restoration were associated with activation of LKB1. CONCLUSION: In addition to increasing the future remnant liver, BPL shortened the duration of the spatial disturbance of the CN and could significantly improve the tolerance of the hypertrophied liver to staged resection. BPL may be a safe and efficient future option for patients with an insufficient remnant liver.

Dual transformation therapy for giant hepatocellular carcinoma: Two case reports and review of literature.

BACKGROUND: In the translational therapy of giant hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKI) after laparoscopic portal vein ligation (PVL) is extremely rare. This is a dual conversion therapy that combines surgery and oncology. Here, we report two cases of successful surgical completion after dual conversion therapy. CASE SUMMARY: We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis (case 2 also combined with fatty liver) on physical examination. Due to the insufficient residual liver volume assessed before surgery, laparoscopic right PVL was performed, followed by HAIC combined with anti-PD-1 immunotherapy and TKI. Finally, surgical resection was successfully completed, and pathology confirmed that the tumor was mostly necrotic (90%) in one case, and no live tumor tissue was found in the other case. CONCLUSION: In the process of surgical transformation, our treatment plan takes into account the control and transformation of oncology at the same time, which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.

Surgical management of hilar cholangiocarcinoma: Controversies and recommendations.

Hilar cholangiocarcinomas are highly aggressive malignancies. They are usually at an advanced stage at initial presentation. Surgical resection with negative margins is the standard of management. It provides the only chance of cure. Liver transplantation has increased the number of 'curative' procedures for cases previously considered to be unresectable. Meticulous and thorough preoperative planning is required to prevent fatal post-operative complications. Extended resection procedures, including hepatic trisectionectomy for Bismuth type IV tumors, hepatopancreaticoduodenectomy for tumors with extensive longitudinal spread, and combined vascular resection with reconstruction for tumors involving hepatic vascular structures, are challenging procedures with surgical indications expanded. Liver transplantation after the standardization of a neoadjuvant protocol described by the Mayo Clinic has increased the number of patients who can undergo operation.

CD4+CD25+ regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative surgical approach for the treatment of massive hepatocellular carcinoma (HCC), the key to successful planned stage 2 ALPPS is future liver remnant (FLR) volume growth, but the exact mechanism has not been elucidated. The correlation between regulatory T cells (Tregs) and postoperative FLR regeneration has not been reported. AIM: To investigate the effect of CD4+CD25+ Tregs on FLR regeneration after ALPPS. METHODS: Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS. Flow cytometry was performed to detect changes in the proportion of CD4+CD25+ Tregs to CD4+ T cells in peripheral blood before and after ALPPS. To analyze the relationship between peripheral blood CD4+CD25+ Treg proportion and clinicopathological information and liver volume. RESULTS: The postoperative CD4+CD25+ Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume, proliferation rate, and kinetic growth rate (KGR) of the FLR after stage 1 ALPPS. Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion (P = 0.006); patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion (P = 0.043). The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume, proliferation rate, and KGR were all greater than 0.70. CONCLUSION: CD4+CD25+ Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients' livers. Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.

Case Report: The application of associating liver partition and portal vein ligation for staged hepatectomy in patients with hepatitis b virus-related hepatocellular carcinoma after undergoing treatment with an immune checkpoint inhibitor: a report of two cases.

Hepatocellular carcinoma (HCC) is often diagnosed at an unresectable stage without opportunities for curative therapy. Future liver remnant (FLR) insufficiency limits the range of patients who can undergo radical resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can ultimately achieve short-term hypertrophy of the FLR in patients with viral hepatitis-related fibrosis/cirrhosis and R0 resection. However, the influence of immune checkpoint inhibitors (ICIs) on liver regeneration remains unknown. We report two patients diagnosed with Barcelona Clinic Liver Cancer (BCLC)-B stage hepatitis B virus (HBV)-related HCC who underwent pioneering ALPPS after immunotherapy without posthepatectomy liver failure (PHLF). ALPPS has been shown to be safe and feasible in patients with HCC who underwent immunotherapy previously for the first time and might provide an alternative salvage option for future conversion therapy of HCC.

Recent advances in surgical strategies and liver transplantation for hepatoblastoma.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although the development of treatment strategies with advances in chemotherapy has greatly improved the prognosis of HB, surgical resection and liver transplantation still play a vital role in the treatment of HB. In recent years, technological innovations have led to the development of new surgical approaches for HB. In this review, we describe the latest research on the surgical management of HB, including new imaging technologies, minimally invasive approaches, and the application of associating liver partition portal vein ligation for staged hepatectomy. We also discuss the current role of liver transplantation, use of ante-situm or ex-situ liver resection with auto-transplantation, and management of metastatic HB.

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis.

BACKGROUND: Although numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM). METHODS: Main electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded. RESULTS: A total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04-2.06, I2 = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64-3.62, I2 = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09-1.61, I2 = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13-2.30, I2 = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68-1.27, I2 = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47-2.49, I2 = 54%), respectively. CONCLUSION: ALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results.

Research progress of accelerated liver regeneration induced by associating liver partition and portal vein ligation for staged hepatectomy / 中华肝胆外科杂志

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce accelerated regeneration of future liver remnant (FLR) and provide the opportunity of radical resection for previously inoperable patients with liver cancer, which has been considered to be one of the most important breakthroughs in liver surgery during the 21st century. It is of great significance to fully understand the mechanism of accelerated liver regeneration induced by ALPPS. This article comprehensively reviews the research progress in this field during the past 10 years.

Research progress of three techniques for hepatic hyperplasia / 中华肝胆外科杂志

Surgical resection is one of the important means to achieve long-term survival for patients with liver malignant tumor. However, most of the liver malignant tumor has been diagnosed in the middle and late stage, and lose the chance of surgical treatment. For these patients who have lost the chance of surgery, some surgeons have proposed the concept of planned liver resection, which is to reduce tumor stage and increase future liver remnant (FLR) in a planned way, so as to improve the safety of surgery and prolong the survival time of patients after surgery. For patients with FLR insufficiency after prior evaluation or/and treatment, the technique of hepatic hyperplasia is an important part of planned hepatectomy, that is, to effectively increase FLR in a short period of time by various means. Portal vein ligation (PVL) and portal vein embolization (PVE), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) are three main techniques for hepatic hyperplasia. This article reviews the principle, effect and safety of three liver augmentation techniques.