Assessing Surgical Innovation. ALPPS: An IDEAL Example of Disruptive Innovation.

Objective: To assess the impact of the IDEAL (Innovation, Development, Exploration, Assessment and Long-term) paradigm on the development of ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) in comparison to the evaluation of two other revolutionary innovations: laparoscopic cholecystectomy (LC) and robotic surgery.

Background And Aims: The assessment and development of disruptive procedures often follow a chaotic and unstructured approach. The IDEAL paradigm has offered a sequential 5-stage process to assess controversial surgical strategies like ALPPS, which was introduced in 2012 to expand liver surgery for primarily non-resectable disease.

Liver transplantation for HCC in cirrhosis: Are Milan criteria outdated?

In Germany, organ allocation is based on the MELD-system and lab-MELD is usually low in patients with hepatocellular carcinoma (HCC) in cirrhosis. Higher medical urgency can be achieved by standard exception for HCC (SE-HCC), if Milan criteria (MC) are met. Noteworthy, UNOS T2 reflects MC, but excludes singular lesions < 2 cm.

Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

Background And Aims: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate.

Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020.

Early Postoperative Serum Phosphate Drop Predicts Sufficient Hypertrophy After Liver Surgery.

Objective: The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD).

Background: Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia.

Parenchyma-Sparing Liver Resection or Regenerative Liver Surgery: Which Way to Go?

Liver resection for malignant tumors should respect oncological margins while ensuring safety and improving the quality of life, therefore tumor staging, underlying liver disease and performance status should all be attentively assessed in the decision process. The concept of parenchyma-sparing liver surgery is nowadays used as an alternative to major hepatectomies to address deeply located lesions with intricate topography by means of complex multiplanar parenchyma-sparing liver resections, preferably under the guidance of intraoperative ultrasound. Regenerative liver surgery evolved as a liver growth induction method to increase resectability by stimulating the hypertrophy of the parenchyma intended to remain after resection (referred to as future liver remnant), achievable by portal vein embolization and liver venous deprivation as interventional approaches, and portal vein ligation and associating liver partition and portal vein ligation for staged hepatectomy as surgical techniques.

Sex Disparities in Outcomes Following Major Liver Surgery: New Powers of Estrogen?

Aim: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies.

Background: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown.

[Hepatocellular carcinoma].

The therapeutic spectrum of hepatocellular carcinoma (HCC) in cirrhosis has expanded over the last decade and consists of surgical, interventional and systemic approaches. The tumor stage and liver function are important for the therapeutic strategy. Curation can be achieved by liver resection or transplantation.

Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry.

Background: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR).

Methods: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018.

Timing of surgical repair of bile duct injuries after laparoscopic cholecystectomy: A systematic review.

Background: The surgical management of bile duct injuries (BDIs) after laparoscopic cholecystectomy (LC) is challenging and the optimal timing of surgery remains unclear. The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature.

Aim: To assess timing of surgical repair of BDI and postoperative complications.

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score: is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?

Background: Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively.

Methods: Thirteen high-volume centers participated in this retrospective multicentric study.

Patients Benefit from Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria without Harming the Health Care System.

Liver transplantation (LT) is the only definitive treatment to cure hepatocellular carcinoma (HCC) in cirrhosis. Waiting-list candidates are selected by the model for end-stage liver disease (MELD). However, many indications are not sufficiently represented by labMELD.

Parenchyma Sparing ALPPS Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Background: Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS).

Materials And Methods: Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance.

Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models.

Platelet-derived peripheral serotonin has pleiotropic effects on coagulation, metabolism, tissue regeneration, and cancer growth; however, the effect of serotonin on the tumor microenvironment remains understudied. Peripheral serotonin–deficient () mice displayed reduced growth of subcutaneous and orthotopically injected syngeneic murine pancreatic and colorectal cancers with enhanced accumulation of functional CD8 T cells compared to control C57BL/6 mice, resulting in extended overall survival. Subcutaneous and orthotopic syngeneic tumors from mice expressed less programmed cell death 1 ligand 1 (PD-L1), suggesting serotonin-mediated regulation.

Regenerative Liver Surgery - ALPPS and Associated Techniques.

Hepatectomy is the only potentially curative treatment of hepatic tumors, but remains challenging in case of multiple, bilobar lesions and those located in the vicinity of the hepatic hilum and hepatic veins. Regenerative liver surgery utilizes the unique ability of the liver to re-grow after tissue loss and vascular deprivation. All concepts subsumed under this term aim to increase the resectability of hepatic tumors by stimulating growth of future liver remnant.

The evolution of surgery for colorectal liver metastases: A persistent challenge to improve survival.

Only a few decades ago, the opinion that colorectal liver metastases were a palliative diagnosis changed. In fact, previously, the prevailing view was strongly resistant against resecting colorectal liver metastases. Constant technical improvement of liver surgery and, much later, effective chemotherapy allowed for a successful wider application of surgery.

Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors.

Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a re-oxygenating compound without apparent toxicity.

Can magnetic resonance imaging radiomics of the pancreas predict postoperative pancreatic fistula?

Objectives: To evaluate whether a magnetic resonance imaging (MRI) radiomics-based machine learning classifier can predict postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) and to compare its performance to T1 signal intensity ratio (T1 SIratio).

Methods: Sixty-two patients who underwent 3 T MRI before PD between 2008 and 2018 were retrospectively analyzed. POPF was graded and split into clinically relevant POPF (CR-POPF) vs.

Induction of liver hypertrophy for extended liver surgery and partial liver transplantation: State of the art of parenchyma augmentation-assisted liver surgery.

Background: Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25-30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure.

Purpose: The aim of this review is to depict the various interventions for liver parenchyma augmentation-assisting surgery enabling extended liver resections.

Repeated hepatectomy after ALPPS for recurrence of colorectal liver metastasis: the edge of limits?

Background: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS.

Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking.

Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe.

Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients.

Variation in complications and mortality following ALPPS at early-adopting centers.

Background: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience.

Methods: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018.