Rescue of outflow block of the remnant left liver after extended right hemihepatectomy for resection of a tumor in the caudate lobe.

Outflow block of the liver is a life-threatening event after living donor liver transplantation. Herein, we rescued a patient suffering from the outflow block of the remnant left hemiliver caused by bending of the left hepatic vein (LHV) after right hemihepatectomy plus caudate lobectomy combined with resection of the middle hepatic vein (MHV). A metastatic tumor sized 6 cm in the caudate lobe of the liver involving the root of the MHV was found in a 50's year old patient after resection of a right breast cancer eight years ago. Right hemihepatectomy and caudate lobectomy combined with resection of the MHV was performed using a two-stage hepatectomy (partial TIPE ALPPS). On day 1, the total bilirubin value increased to 4.5 mg/dL, and a dynamic computed tomography (CT) scan showed the bent LHV. On the diagnosis of outflow block of the left liver, a self-expandable metallic stent was placed in the LHV using an interventional approach, and the pressure in the LHV decreased from 27 cmH2O to 12 cmH2O. The bilirubin value decreased to 1.2 mg/dL on day 3. Outflow block of the LHV can happen after extended right hemihepatectomy with resection of the MHV. Early diagnosis and interventional stenting treatment can rescue the patient from congestive liver failure.

Liver fibrosis as a predictor of liver failure and outcome following ALPPS among patients with primary liver cancer.

The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

Overcome intraoperative difficulties of ALPPS procedure: a single-center outcomes and technical experience.

Backgrounds/aims: Recently, the ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) has become widely known to achieve hepatic resection by rapid future liver remnant hypertrophy, but it comes with intraoperative difficulties, followed by increased complications. This study aimed to report the outcomes of an oncology center in a low-income and middle-income country with ALPPS in patients with liver tumors and its technical variants, which were invented to overcome intraoperative difficulties of the ALPPS procedure. Patients and methods: A retrospective analysis of patients undergoing ALPPS from September 2022 to December 2023 was performed. Results: A total of 25 patients underwent the ALPPS procedure: 21 procedures for hepatocellular carcinoma (HCC), 3 combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and 1 for small cell neuroendocrine carcinoma (SNEC). The mean postoperative stay was 29.6 ± 9.3 days (range 16-58 days). After stage 1, we counted 8 complications, all of grade II; after stage 2, the number of complications was decreased to 3:2 were of grade I and 1 were of grade IIIB. 3 (12%) patients failed to proceed to ALPPS stage 2. After a median follow-up of 9 months (range 2-25), disease recurrence has been recorded in 3 patients (12%), while 1 patient (4%) died, affected by HCC. The entire group's 2-year overall survival (OS) and disease-free survival (DFS) were 83.3% and 82.5%, respectively. Conclusion: The ALPPS procedure is an approach for large liver tumors with small future liver remnant with acceptable OS and DFS in a low-income and middle-income country.

Correlation between the liver transection line localization and future liver remnant hypertrophy in associating liver partition and portal vein ligation for staged hepatectomy.

Background and aims: Colorectal liver metastases (CRLMs) represent the most prevalent form of secondary liver tumors, and insufficient future liver remnant (FLR) often leads to unresectability. To tackle this challenge, various methods for stimulating liver hypertrophy have been developed including portal vein embolization (PVE), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and the newest one, liver venous deprivation (LVD). ALPPS was thoroughly studied over the last decade and it has been shown to induce rapid and intensive FLR hypertrophy. The objective of this study was to assess whether the localization of the liver transection line during the initial stage of ALPPS correlates with the degree of FLR hypertrophy. Methods: A retrospective, multicentric study was conducted, and we analyzed all consecutive patients with CRLMs who underwent ALPPS over the eight-year period. Patients were categorized into two groups based on the type of resection-right trisectionectomy (ERH) or right hemihepatectomy (RH) respectively. The degree of hypertrophy (DH), its correlation with FLR and postoperative outcomes were assessed. Results: The cohort consisted of 136 patients (72 in the ERH group and 64 in the RH group). Baseline characteristics, hypertrophy interval, and total liver volume showed no significant differences between the groups. DH was greater in the ERH group (83.2% vs. 62.5%, p = 0.025). A strong negative correlation was observed between FLR volume and DH in both groups. Postoperative outcomes and one-year survival were comparable between the groups. Conclusions: FLR hypertrophy is influenced by the localization of the liver transection line in ALPPS. Furthermore, correlation analysis indicated that a smaller estimated FLR is associated with greater DH. No statistical difference in outcomes was noted between the groups.

Full robotic versus open ALPPS: a bi-institutional comparison of perioperative outcomes.

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.

Chylous ascites after associating liver partition and portal vein ligation for stage hepatectomy (ALPPS): overview and case report.

Chylous ascites is an uncommon pathology with low incidence following hepato-pancreato-biliary surgery, there are no cases reported in the international literature following the associating liver partition and portal vein ligation for stage hepatectomy (ALPPS) procedure. It is caused by abnormal intraperitoneal accumulation of lymph fluid in the abdominal cavity secondary to obstruction or injury to the chyle cistern or its tributaries. We describe the case of a 49-year-old woman diagnosed with colon cancer and liver metastasis. ALPPS was performed, on a first and second stage, presenting a high drainage output as well as change in the characteristics of the drainage fluid. The diagnosis of chylous ascites was confirmed by finding triglyceride levels in the drainage fluid at 300 mg/dL. Medical treatment was started based on a hyper-protein diet and fat restriction, supplemented with medium-chain triglycerides and somatostatin analog, with fistula resolution. It can be managed with medical treatment.

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.

Case Report: ALPPS hepatectomy, an alternative to liver transplantation in central PRETEXT III hepatoblastomas: a case series.

Introduction: Hepatoblastoma is the most common malignant primary liver tumor in the pediatric population, accounting for 67% of cases in the United States. Surgical resection is the only curative treatment option; however, it can be performed in only 10% of patients with primary tumors. The two most common limitations for resection are the need for extensive resections and tumors in central locations. The therapeutic hypertrophy of healthy tissue achieved with ALPPS (Associating Liver Partition and Portal vein ligation for Staged Hepatectomy) enables larger resections and has been successfully employed in the pediatric population in recent years. Objective: To present three cases of patients with centrally located PRETEXT II or III hepatoblastomas who underwent ALPPS procedure as a viable therapeutic alternative to liver transplantation. Discussion and results: Central PRETEXT III hepatoblastomas are typically indications for liver transplantation. Transplantation offers high five-year survival rates (73%). However, the associated morbidity, healthcare system costs, and limited availability make it necessary to explore alternative options. Series have reported the successful application of the ALPPS procedure in PRETEXT II and PRETEXT III hepatoblastomas in other locations. Therapeutically induced hypertrophy, characterized by an increase in the volume of healthy tissue in unaffected lobes or segments, enabled the resection of previously deemed unresectable lesions. The patients experienced uncomplicated postoperative courses and expected reduction in tumor markers. Chemotherapy selection followed the guidelines outlined in Block C of the SIOPEL IV protocol. Conclusions: ALPPS hepatectomy is a viable therapeutic option for patients with centrally located PRETEXT III or II hepatoblastomas.

Single center experience with ALPPS and timing with stage 2 in patients with fibrotic/cirrhotic liver.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel procedure for major resection in patients with insufficient future liver remnant (FLR). Effective FLR augmentation is pivotal in the completion of ALPPS. Liver fibrosis/cirrhosis associated with chronic viral hepatitis impairs liver regeneration. To investigate the augmentation of FLR in associating ALPPS between patients with fibrotic/cirrhotic livers (FL) and non-fibrotic livers (NFL) and compare their short-term clinical outcomes and long-term survival. Patients were divided into two groups based on the Ishak modified staging: non-fibrotic liver group (NFL, stage 0) and fibrotic/cirrhotic liver group (FL, stage 1-5/6). Weekly liver regeneration in FLR, perioperative data, and survival outcomes were investigated. Twenty-seven patients with liver tumors underwent ALPPS (NFL, n = 7; FL, n = 20). NFL and FL patients had viral hepatitis (28.6% [n = 2] and 95% [n = 19]), absolute FLR volume increments of 134.90 ml and 161.85 ml (p = 0.825), and rates of hypertrophy were 16.46 ml/day and 13.66 ml/day (p = 0.507), respectively. In the FL group, baseline FLR volume was 360.13 ml, postoperatively it increased to a plateau (542.30 ml) in week 2 and declined (378.45 ml) in week 3. One patient (3.7%) with cirrhotic liver (stage 6) failed to proceed to ALPPS-II. The overall ALPPS-related major complication rate was 7.4%. ALPPS is feasible for fibrotic liver patients classified by Ishak modified stages ≤ 5. After ALPPS-I, 14 days for FLR augmentation seems an appropriate waiting time to reach a maximum FLR volume in these patients.

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.

Robotic Complete ALPPS (rALPPS)-First German Experiences.

BACKGROUND: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. MATERIAL AND METHODS: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. RESULTS: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. CONCLUSION: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Is ALPPS still appropriate for large or locally advanced hepatocellular carcinoma in an era of targeted agents and immunotherapy?

Therapeutic options for large or locally advanced hepatocellular carcinoma (HCC) have limited efficacy. This study investigated the efficacy and safety of drug-eluting beads trans-arterial chemo-embolization (dTACE), portal vein embolization (PVE), tyrosine kinase inhibitor (TKI), and immune checkpoint inhibitors (ICI) compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for large or locally advanced HCC.Data regarding clinicopathological details, safety, and oncological outcomes were reviewed for the quadruple therapy (dTACE-PVE-TKI-ICI) and compared with ALPPS.From 2019 to 2020, 10 patients with large or locally advanced HCC underwent future remnant liver (FRL) modulation (dTACE-PVE-TKI-ICI: 5; ALPPS: 5). All five dTACE-PVE-TKI-ICI cases responded well, with patients #4 and #5 achieving complete tumor necrosis. The overall response rate (ORR) was 5/5. Patients #1-4 underwent hepatectomy, while #5 declined surgery due to complete tumor necrosis. Mean FRL volume increased by 75.3% (range 60.0%-89.4%) in 2-4 months, compared to 104.6% (range 51.3%-160.8%) in 21-37 days for ALPPS (P = 0.032). Major postoperative complications occurred in 1/5 ALPPS patients. Resection rates were 4/4 for quadruple therapy and 5/5 for ALPPS. 2-year progression free survival for dTACE-PVE-TKI-ICI and ALPPS were 5/5 and 3/5, respectively.Quadruple therapy is a feasible, effective strategy for enhancing resectability by downsizing tumors and inducing FRL hypertrophy, with manageable complications and improved long-term prognosis. In addition, it provokes the re-examination of the application of ALPPS in an era of molecular and immune treatments.

ALPPS en cáncer colorrectal sincrónico en tiempos de COVID-19 / ALPPS in synchronous colorectal cancer in times of COVID-19

RESUMEN Durante la pandemia por SARS-CoV-2 evidenciamos un aumento de la morbimortalidad secundario a procedimientos quirúrgicos. Se estima una mortalidad a los 30 días del 19,1% en cirugías programadas y del 26% en procedimientos quirúrgicos de emergencia, y alrededor de la mitad de los pacientes que se someten a cirugía estando infectados con SARS-CoV-2 experimentan complicaciones pulmonares posoperatorias. Los tratamientos oncológicos sufrieron deficiencias en nuestro país debido a las limitantes secundarias a la emergencia sanitaria, en cuanto a capacidad de internación e implementación de los tratamientos quimioterápicos. Informamos la primera cirugía de ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) realizada en el nordeste argentino en una paciente con metástasis colorrectales múltiples en contexto de la pandemia por SARS-CoV-2, con buenos resultados.

ABSTRACT During the SARS-CoV-2 pandemic, we observed an increase in morbidity and mortality secondary to surgical procedures. The mortality rate for elective surgery is estimated at 19.1% and is 26% for emergency procedures. Additionally, approximately half of patients who undergo surgery while infected with SARS-CoV-2 experience postoperative pulmonary complications. Due to limitations caused by the health emergency, cancer treatments in our country have been affected in terms of hospitalization capabilities and implementation of chemotherapy treatments. We report the first ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure performed in northeastern Argentina on a patient with multiple colorectal metastases during the SARS-CoV-2 pandemic, with successful outcomes.

Promising Results of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Perihilar Cholangiocarcinoma in a Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.

BACKGROUND & AIMS: Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. METHODS: Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. RESULTS: Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. CONCLUSIONS: The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. IMPACT AND IMPLICATIONS: In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

Liver Venous Deprivation for Rapid Liver Hypertrophy Before Major Hepatectomy: A Case Report.

Liver venous deprivation (LVD) is an emerging, minimally invasive strategy to induce rapid liver hypertrophy of the future liver remnant (FLR) before a major hepatectomy. LVD (aka "double vein embolization") entails same-session percutaneous embolization of the portal and hepatic veins of the planned liver resection. This report discusses LVD's utilization and technical challenges in managing a 49-year-old male with recurrent multifocal colorectal liver metastases (CRLM). The patient initially underwent neoadjuvant FOLFOX chemotherapy followed by a simultaneous laparoscopic sigmoid colectomy and liver surgery (microwave ablation of segment V and wedge resections of segment one and IVb), followed by completion of chemotherapy. The patient had an R0 resection with clear colon and liver surgical margins. Nine months after the initial surgery, the patient had a rise in tumor markers, and surveillance imaging demonstrated recurrence of liver metastases in segments I and V. LVD was performed by interventional radiology, which led to a 28% increase in FLR (segments II, III, and IV); initially measuring 464 cm3 before LVD and measuring 594 cm3 on post-procedure day 21. The patient underwent right hemi-hepatectomy and caudate resection on post-procedure day 29. The patient did not have any complications and was discharged on postoperative day 6. The patient remains disease-free with no evidence of recurrence at 12 months follow-up.

Promising Outcomes of Modified ALPPS for Staged Hepatectomy in Cholangiocarcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

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.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

Vessel-Guided Mesohepatectomy for Liver Partition and Staged Major Parenchyma-Sparing Hepatectomies with Super-Selective Portal Vein Embolization or Enhanced ALPPS to Achieve R0 Resection for Colorectal Liver Metastases at the Hepatocaval Confluence.

Background. R0 minor parenchyma-sparing hepatectomy (PSH) is feasible for colorectal liver metastases (CRLM) in contact with hepatic veins (HV) at hepatocaval confluence since HV can be reconstructed, but in the case of contact with the first-order glissonean pedicle (GP), major hepatectomy is mandatory. To pursue an R0 parenchyma-sparing policy, we proposed vessel-guided mesohepatectomy for liver partition (MLP) and eventually combination with liver augmentation techniques for staged major PSH. Methods. We analyzed 15 consecutive vessel-guided MLPs for CRLM at the hepatocaval confluence. Patients had a median of 11 (range: 0-67) lesions with a median diameter of 3.5 cm (range: 0.0-8.0), bilateral in 73% of cases. Results. Grade IIIb or more complications occurred in 13%, median hospital stay was 14 (range: 6-62) days, 90-day mortality was 0%. After a median follow-up of 17.5 months, 1-year OS and RFS were 92% and 62%. In nine (64%) patients, MLP was combined with portal vein embolization (PVE) or ALPPS to perform staged R0 major PSH. Future liver remnant (FLR) volume increased from a median of 15% (range: 7-20%) up to 41% (range: 37-69%). Super-selective PVE was performed in three (33%) patients and enhanced ALPPS (e-ALPPS) in six (66%). In two e-ALPPS an intermediate stage of deportalized liver PSH was necessary to achieve adequate FLR volume. Conclusions. Vessel-guided MLP may transform the liver in a paired organ. In selected cases of multiple bilobar CRLM, to guarantee oncological radicality (R0), major PSH is feasible combining advanced surgical parenchyma sparing with liver augmentation techniques when FLR volume is insufficient.